Infertility Blog

Clomid vs Letrozole: The Last Words

2012-01-22T17:04:00.002-05:00

Hello everyone! Today I will conclude the entries on Letrazol and Clomid, emphasizing the warnings related to letrazole.

“Femara* (the trade name for letrozole) is contraindicated and should not be used in women who may become pregnant, during pregnancy and/or while breastfeeding, because there is a potential risk of harm to the mother and the fetus, including risk of fetal malformations.”

Who says so? Novartis, the company that makes the drug, put out this warning.

There are 2 elements to this statement. First and accurately, the drug has been shown to cause malformations in mice and rats when given in low doses during pregnancy. If is for this reason that we all believe that giving it to pregnant women is not indicated. Clomid also carries a warning that it is not to be used in pregnancy for fear of birth defects, although the potential for defects seems to be lower than for Femara. Nonetheless, Clomid carries a warning.

The second element has to do with taking the drug before pregnancy, as in the case of induction of ovulation. In 2006, the company issued a statement to physicians specifically stating that Femara is not indicated for use in the induction of ovulation.

How did this second statement from Novartis come ot be? In 2005 a very short abstract was presented at a scientific meeting showing the birth defect rate was higher in 150 women who took Femara as compared to the general population. That’s 150 births, not 150 birth defects. Now, no one wants to ignore important birth defect data, however 7 birth defects in 150 women is just too small a group to rely on. Based on this one preliminary study, Novartis quickly issued the warning to physicians.

Soon after the Novartis letter, another physician, Dr Tulandi, examined pregnancy outcome of 911 babies conceived after Clomid or letrozole treatment in infertile women. Here is the data directly quoted from the writings of Dr.Tulandi. “Overall, congenital malformations and chromosomal abnormalities were found in 14 of 514 newborns in the letrozole group (2.4%) and in 19 of 397 newborns in the CC group(4.8%). The major malformation rate in the letrozole group was 1.2% (6 of 514) and in the CC group was 3.0% (12 of 397). These differences did not reach statistical significance because of the relatively small sample size.”

Well then, it seems that clomid has a birth defect rate that is at leat equal to that of Femara, and yet Clomid is used much more and without and warnings. The point being that the early small study was not informative enough and Femara seems safe to use, at least as safe as Clomid. Now this second study was not perfect either, but it was bigger and better than the first.

These are not the only studies published on Femara. There have been dozens all showing that the drug can be very effective and none others have shown an increase in birth defects.

Why would the drug company want to sell Femara if there is controversy over its safety?

As we discussed previously, Femara is a medication that blocks estrogen production, which is very helpful for many women with breast cancer. Most women have the type of breast cancer that grows faster in the presence of estrogen. Blocking the body’s ability to produce estrogen using Femara can significantly slow the growth of the tumor. This is why the company produces the drug. Unfortunately, there is a tremendous market for such a product.

On the other hand, the fertility business is comparatively very small and it is associated with very large liability risks. Even if the data relating the drug to birth defects is poor, I can see why the company would want to protect itself from potentially crippling birth defect lawsuits.

The good news is that the drug is available and a licensed MD can prescribe any drug “off label”, as long as there is good evidence that the drug is helpful and there is no harm.

Tons of drugs are used off label. One fertility example is Lupron for endometriosis. This drug is mostly used to treat men with prostate cancer as it lowers testosterone levels which may help restrict tumor growth. Lupron is also used in women with endometriosis because it lowers estrogen levels, and endometriosis needs estrogen to grow. Many women take it and the literature is loaded with scientific articles supporting its use in medical studies. And yet, Lupron it not FDA approved for the treatment of endometriosis. (For those of you thinking ahead, yes Femara is used by some to treat endometriosis). Another example is the use of antiepileptic drugs to treat anxiety and depression. Believe me; the list goes on and on.

So where does this all take us?
1) Femara works for the induction of ovulation.
2) Femara should not be given during pregnancy.
3) Femara does not thin the lining of the uterus as may Clomid
4) Femara is relatively new and associated with more warnings.

It is the last statement that makes doctors understandably nervous about using it, especially when there is a close alternative (Clomid) that has been around since the 1960’s.

As time has gone by, I have used Femara more and more, but still use Clomid first. As more time passes and more studies are done, this may change, and it is possible that Femara may become the first line treatment over Clomid for all fertility doctors. Importantly, no one yet has proven that Femara leads to a higher pregnancy rate than Clomid.

Thanks for reading and don’t forget to read the disclaimer from 5.17.06.

Dr. Licciardi

Clomid and Letrozole Part 2

2011-12-17T07:34:00.002-05:00

Now a bit more about Letrozol (also known as Femara). Letrozol and Clomid have the same end result: ovulation, but they go about it in a much different way. Letrozol acts by decreasing the body’s ability to make estrogen, whereas with Clomid estrogen is produced but its actions are blocked.

Letrozol is an aromatase inhibitor. Aromatase is the enzyme that makes estrogen. Now there are many steps to making estrogen, but aromatase is the last and most important step. Aromatase takes testosterone and slightly changes it to become estrogen. Yes, women have some testosterone, but men have more. To me it’s amazing that testosterone and estrogen, two hormones that are so different, are just one step away from each other. Nevertheless, that’s the case and the system somehow works.

As Letrazol inhibits the formation of estrogen, estrogen levels fall. And this helps women become pregnant? Crazy as it sounds that answer is yes, and this happens in a way similar to the workings of Clomid. Once again, the brain sees no estrogen (this time because there really is very little). The brain reacts, and puts out more FSH to stimulate the ovary to make estrogen, which the ovary can only do my making a follicle, that just so happens to contain an egg. Just as with the Clomid, the follicle grows, the egg matures and ovulation usually comes next.

How can you get pregnant if you are taking a drug that is blocking (Clomid) or eliminating (Letrozol) estrogen? You do not need estrogen to ovulate. Estrogen is a buy-product of the growing follicle. The reason estrogen is made by the follicle is so that the lining of the uterus (the endometirum) can grow. And yes you need the endometrium, but for most women only a small amount of estrogen is needed to get a good lining. Plus, the aromatase inhibitors do not make the estrogen go to zero, and Clomid does no completely block estrogen. These drugs may cause the endometrium to see much less estrogen than usual but enough gets through for adequate growth.

In addition, Letrazol and Clomid are only taken for 5 days, usually until day 7-9. This leaves 5-6 days for the follicle to grow a bit more and produce more estrogen, all while the drugs are leaving the body.

There are some differences in the negative effects between Clomid and Letrozol. Clomid has a long half life meaning it stays in the body for days after the last dose. Its half life is 5-7 days, so blood levels go up and up each day the pill is taken and significant amounts are present around ovulation. Therefore conditions around the time of ovulation can be effected by the Clomid i.e. the cervical mucus can be too thick and the lining of the uterus can be too thin. The half life of Letrozol is shorter.

The good news is that for most women these drugs work quite well. We do not know why some women have more side effects than others. Subtle genetic differences between women lead to very subtle differences in the shapes of one or more of the proteins involved in binding.

Letrozol also has fewer mental side effects. Common Clomid side effects include headaches, hot flashes, depression, seeing spots, jitteriness, trouble sleeping, and there are a few others. Letrozol does not cause as many of these symptoms.

If Letrozol seems to be better for the mucus, lining of the uterus, and has fewer side effects, why don’t we use it as our first line of therapy over Clomid? This requires a little more discussion which will come in the next entry.

Thanks for reading and don’t forget the disclaimer 5.17.06.

Dr. Licciardi

Dr. Licciardi Performing Surgery to Repair Uterine Septum

2011-11-19T15:47:00.004-05:00

Hello Everyone,

Today’s blog is a little different, as it is the first one of mine that uses a video. What you will see is actual footage of me performing surgery to repair a large uterine septum. I have viewed many such videos on line and feel that they leave room for improvement. The explanations are not clear; plus I am not impressed with the techniques of many of the surgeons.

Not everyone likes watching surgery, but you will see that this very easy to view and there is no bleeding to worry about. If you were told that you have a septum and want to know how they are treated, this is a good tool for you.

It’s very hard for a patient to rate the quality of the surgery they are viewing so I just have to come out and say that what you will see here is surgery of a very high standard. The 3 important things are that I work quickly, I don’t cut away too little, and I don’t cut away too much. If you are curious, you can look at other videos on line and with time you can easily see the differences. Many of the videos show the septum treated by burning it away. I do not like that technique because I think that burning is more likely to lead to scaring. And once you get scar in the uterus, it may be hard for normal function to ever return. You will see I cut with a scissors, which allows for better healing.

I have been working on this video for over a month, and every day see parts that I would like to improve and update (not the surgery part, but the intro photos and some of my voice-overs) . So in time, updated versions will be published, but there is more than enough here to publish now. So here it is; I hope you enjoy it. Feel free to show it to your doctors, I think they will like it too.

Because there is a difference among surgeons, it is wise to seek a second opinion always. Even if you love your own doctor, I would be happy to give you the peace of mind of a second opinion. I have seen many, many women avoid surgery all together simply by taking the extra precaution of a second opinion. It’s well worth it.

Click the link and the video will appear.

http://www.youtube.com/watch?v=pf0XIPNnPlo&feature=feedu

For more important information, see my other blogs about uterine septums.

Thanks for viewing, and please read disclaimer 5.17.06.

Dr. Licciardi

Clomid vs Letrozol

2011-10-19T07:06:00.002-04:00

Hello everyone, here we are with the latest installment of The Infertility Blog, which will discuss the differences between Clomid and Letrozol.

This one is a little medical, but I think I can get everyone through it just fine. I'll start by saying both do the same thing, they both stimulate ovulation, but each does it in it's own way. Both are pills, both can work great in women who are anovulatory, both work only fairly well for regularly menstruating infertile women.

Let's go over Clomid first. The generic name of Clomid is clomiphene citrate. It also goes by Serophene. Clomid is a drug that has been around since the 60’s. In the lab it was discovered that this compound blocks estrogen. This does not sound like a good fertility drug if it’s blocking estrogen. In fact the developers thought that since it blocks estrogen , it may be a good contraceptive. Well it had the opposite effect. Why? After swallowing Clomid, it gets taken through the blood stream to all parts of the body, including the brain. The brain is important because that is where all of the control of ovulation starts. Normal ovulation can not happen without signals from the brain and pituitary gland. When Clomid, the "anti-estrogen", gets to the brain, things start happening.

More about this in a moment, first a bit about how estrogen works. Estrogen, like all hormones, exerts its influence by landing on a receptor. A receptor is a protein either on the surface or inside the cell that recognizes a hormone and binds to the hormone. It is the receptor/hormone combination that then causes the cell to do what the hormone says to do. For example, after estrogen binds to the estrogen receptor the combined hormone/receptor can get the cervical cells make mucus for example. It's very much like a lock and key. The estrogen is a key that only works in the estrogen lock (the estrogen receptor). Other hormones, like progesterone and testosterone, float around and then only bind with their receptors. Like a key, different hormones have slightly different shapes, and the receptors will only connect with a hormone if the hormone has the right shape.

OK, back to Clomid and the brain. When Clomid gets to the brain, because the Clomid molecule has a similar shape as the estrogen molecule, Clomid binds to the estrogen receptor. But because the shape of the Clomid molecule is not exactly the same as the estrogen molecule , the estrogen receptor Clomid combination is faulty, and can not signal the cell to do anything. Elsewhere in the body, the cervical cells will not make mucus. for example. The Clomid takes up all of the available places on the receptor so that the estrogen has nowhere to land, thus the actions of estrogen are blocked.

No estrogen, that is what the brain thinks. The brain says, “Hey, what happened, who turned off the estrogen?” So the brain tries to make more. Estrogen only comes from the ovary, with a few small exceptions, so the only way for the body to get estrogen is to stimulate the ovaries to start ovulating. This is accomplished by the brain stimulating the pituitary gland to put out bursts of FSH, which then travels through the blood stream to the ovaries and gets ovulation going. For most women, this estrogen block is not 100%. Its enough of a block to get ovulation going, but usually the Clomid can spare complete havoc the endometrium (uterine lining) and cervical mucus. In some women, but a small percentage, there is complete havoc; the cervical mucus completely dries up (overcome by insemination) and the uterine lining becomes too thin (can not be overcome).

This is why some doctors give estrogen and Clomid at the same time. It is believed that the Clomid will get the ovulation started and the given estrogen will counteract the Clomid in the uterus and cervix. I have not had much success with this method. I have found that if the Clomid creates havoc, adding estrogen does not help.

Clomid works wonders for women who have irregular cycles, Clomid allow for more frequent, predictable ovulation, and this ups the odds of conception. Women with PCO are excellent candidates for Clomid because they have irregular cycles, which could be anywhere from every 35 days to every 6 months to never. Women who have irregular cycles but are not exactly PCO also have excellent results with Clomid. Women who do not get their periods due to exercise, eating disorders or other types of women with “hypothalamic amenorrhea” usually do not respond to Clomid. This is because their brains do not respond to the Clomid because the brain knows that if there is severe stress or no food coming in, it’s not a good time to get pregnant, so even clomid will not work.

We ask women to take Clomid (and letrozol) early in the cycle because we want to give the boost in FSH early so that maybe we can coax the ovary to make more than one egg that month. FSH rises from Clomid, and it's the FSH that really does all of the work to initiate ovulation. In women who get periods every 4 months, it really does not matter if Clomid is given days 5, 10 20 or 30. We would prefer if you were not pregnant when taking Clomid (although it happens and probably not a problem), that’s why we wither give Provera to bring on a period or do a pregnancy test before you start. So that’s a little about Clomid. It works by blocking estrogen from it’s receptor. More to come next time.

Thanks for reading and please read disclaimer 5/17/06.

Dr. Licciardi

Back to School, Back to Questions

2011-09-23T21:49:00.002-04:00

Hello Everyone! I hope you had a nice summer.

I’m going to start the fall off with answering some very interesting and important questions. Then I have the next few blogs already mapped out. Here we go.

PCOs. Can you have PCOS if you have regular cycles and no symptoms, just ovaries that have many follicles? No, you need to have one other symptom: irregular infrequent periods or androgen excess, the later being demonstrated by increased facial/body hair, acne, or more rare symptoms. I frequently see women who have healthy ovaries on ultrasound, meaning they look good because they have many follicles, probably enough to fit the criteria for PCOS. But without the other symptoms, these women are just lucky.

Uterine Abnormalities. If your uterus is bicornuate or dydelphic, a singleton is highly preferred over multiples. Sometimes the best way to achieve this is by having IVF and a single embryo transfer.
FSH. If you were told you have a high level, you must repeat the test. Odds are that the results will be similar; however that is not always the case. I’ve seen many women who were dismissed from other practices for having high FSH levels only to have better results on repeat: some became pregnant.

Amenorrhea. If your ovulation stopped due to weight loss, it may not return after weight gain. We don’t know why, but in some but not most cases, the changes in the brain that occur with weight loss become permanent. I am not sure about the term Ovarian Insensitivity, I would get another opinion.

Endometriosis. Most doctors today do not do a laparoscopy on women who just started trying and have no evidence of endometriosis. Evidence means very painful periods and or visible cysts of endometriosis on the ovaries seen on ultrasound. If the hysterogram is normal, i.e. the tubes are open, and the history and findings do not point to endometriosis, the odds of finding significant endometriosis on laparoscopy are very low. This does not mean you can’t have the laparoscopy if you wish, but in most cases it is recommended only as an option.

Ectopic Pregnancy. If during IVF, embryos are placed in the uterus, how is it possible to have an ectopic pregnancy in the tube? Unfortunately this does happen, probably because the embryos float into the tube sometime after the transfer. The uterus is a muscle and this muscle does undergo slight but regular contractions. It’s possible that the embryo gets squeezed up into the uterus. There are fewer ectopic after IVF these days, for a few reasons. One big one is that we put in fewer embryos these days. Fewer means there are lower odds of one ending up in the tube. Another is that many women who need IVF because of big blocked tubes (hydrosalpinx) have these tubes removed prior to IVF. A hydrosalpinx is a swollen tube damaged from infection, very severe endometriosis or previous surgery. The interior of these blocked tubes becomes damaged, making ectopics more likely.

Cervical Mucus. Most infertility doctors are not concerned with cervical mucus. We all understand that women who have no treatment or minimal treatment get pregnant on their own. Some women who get their mucus in some way adjusted get pregnant, but the rate of pregnancy may not be higher than baseline.

Thyroid. So far there is no good evidence showing a relationship between thyroid abnormlaites and embryo quality. Certainly, the thyroid should be close to normal while attempting and during pregnancy. It is very difficult to get accurate TSH level during IVF stimulation because during and IVF cycle, the estrogen levels become higher than normal, and this interferes with accurate assessment of TSH.

Embryo Quality. Are poorly growing embryos more likely to be genetically abnormal? The answer is yes, but not by much. This means that the way an embryo looks is not tightly related to chromosomal normality. A poor looking embryo is a little more likely to be genetically abnormal, but you can’t count on it. So if your best embryos are slow growing, we transfer them.

Early Pregnancy Failure. Women with pregnancy losses should have a karyotype, which is the blood test done on both partners to check for possible chromosomal abnormalities. Another necessary test is the hysterogram which will test for uterine abnormalities.
Should women with repeated loss keep trying on their own, do fertility drugs and iui, or move to IVF, possible with PGD? This one of the most difficult questions in our field. I tend to feel that if you are getting pregnant easily on your own, keep trying on your own. However, there is a place for IVF with PCG depending on your situation and age. Certainly finances come into play.

Cervical Stenosis. Usually improves after a vaginal birth because the cervix stretches so much. If the baby is born via c-section, the cervix may not have opened enough to make an improvement. Sometimes even in women without stenosis, healing post c-section can greatly increase the angle between the cervix and the uterus. This is not really stenosis, but this acute angle can make it very difficult to get a catheter, say for iui or embryo transfer, from the cervix into the uterus.

Anti-sperm antibodies. Most fertility doctors these days do not see a relationship between anti-sperm antibodies and infertility. If these antibodies are a factor, most of the time the antibodies that are the biggest problem are those that are in the cervical mucus. The antibodies in the mucus grab the sperm trying to swim through. Therefore, avoiding the cervical mucus via iui can do the trick. You do not need to take fertility drugs if it is felt your only problem is antibodies; an iui without the drugs may suffice.

Uterine lining. All experienced fertility doctors have many women who have become pregnant with “thin” linings. No one knows what the cutoff should be. One problem is that the studies are not done correctly. For instance, let’s say an IVF program analyzes their pregnancy rates according to the thickness of the uterine lining. What happens is the different thicknesses become grouped. They may look at pregnancy rates for women with linings greater than 10mm, 7-10 mm and less than 7 (this is just one example: some may do >9, 6-9 and <6, or any other way they wish). The problem with this is less than seven includes women with 4s and 5’s. So to say less than seven is a cutoff may not be accurate because the pregnancy rate at 7 may be just fine, but it will be lower in women with 4’s and 5’s, but they are all grouped together. The reason the studies are not set up as the pregnancy rates for 6 mm and 7 mm and 8 mm etc. is that the overall number of women in each study is small, so number of women in each group becomes too small to calculate a difference.

Why is my lining thinner today than yesterday? This is very common. The most likely reason is that the lining was measured in a different location on each day. When we scan, we quickly look for the thickest part and write it down. Most fertility doctors are not really interested in progression from day to day. If we glance at it and it looks ok without even measuring it, we quickly find a spot, any spot, and get a measurement. Another reason for differences is that you may have a different person measuring on different days. Different people may measure differently; the measurement should be close, but not exactly the same.
Another possibility is that the lining grows and shrinks a little from day to day. I’ve noticed, usually in cases where the lining is thick, that linings change from day to day. The lining does usually grow thicker as the cycle progresses. Sometimes there is a quick growth such that by day 7 it’s nice and thick and stays at about that level through the next week or so. Sometimes the lining is thin on day 10, but after 2-3 more days it has a late improvement and looks great.

AMH. How can your FSH level be normal and you AMH be very low? Because we don’t know yet what normal and abnormal levels of AMH are. The values also vary considerably from lab to lab. I have not yet started doing AMH levels for this reason. I have seen levels of 0.16 along with FSH levels of 7 in young women. In some labs, over 1 is good, I others lower levels are normal. More time is necessary to work this one out.

Ovulation Induction. You can get pregnant in an iui cycle if the follicle is 16 mm. It’s a little on the small side, but in most cases it’s big enough. One reason we wait on a 16 mm follicle is that there may be others that are even smaller. In those cases, we much prefer to wait.

IVF Failure. Are there some women who will just never get pregnant? Unfortunately the answer is yes. But we have no idea in advance who these women are, unless there is an obvious reason for their infertility. There probably a few men or women who have a hidden untestable genetic problem that prevents pregnancy. Some women just can’t catch a break. They have problems that seem correctable with surgery or IVF, but they don’t get pregnant, or they have miscarriages. It’s a terrible cast, one of many that life sets us into.

IUI Clomid at 41? Cross my heart, we have a woman in our practice that got pregnant and had a baby at age 47 on clomid, after every other treatment under the sun. That being said, taking clomid in your 40’s may not be the best thing. Even with iui, the odds are less than 5%, and every month you are not pregnant, you are one month older.

Blastocyst Transfer. Would embryos that stop growing from day 3 to day 5 have been better off getting transferred on day 3? It depends on the experience of the IVF clinic. At NYU we are very experienced and successful with day 5 (also called blastocyst) transfer. I feel very confident that the lab is as good as the uterus from days 3-5. Very rarely I have a patient who I prefer to transfer on day 3. This is happens when the embryos look close to perfect on day 3 but terrible on day 5, a very rare occurrence. Many IVF programs are not as experienced or successful with culturing to day 5, and in these cases, a day 3 transfer may be better.

Agonist vs Antoginist. (Lupron vs Cetritide or Ganirelix). I use some but not much lupron anymore. One reason has to do with patient convenience; lupron is just one more shot people have to take. Cetritide and Ganirleix are given by injection, but only a few doses are necessary. Plus lupron can cause an ovarian cyst to grow interfering with the timing of the cycle start. In some cases, especially in older women, I believe that lupron can suppress the number of developing eggs. But the lupron protocol is still one that I go to at times.

Low estradiol on day 3? Hard to explain why the level is so low if you are having normal ovulation. If indeed you are having normal ovulation and respond with normal estrogen levels to fertility drugs, the low level on day 3 may not be a problem.

7 miscarriages. Very sorry to hear of your problem. I assume you both had karyotype testing. You may want to consider IVF with PGD. I understand that there may be financial barriers to that service and doing IVF/PGS does not guarantee pregnancy much less a successful pregnancy.

2 Miscarriages after IVF with good egg number and nice embryos. Talk to your doctor, it sounds to me like things can happen in the positive for you.

Thanks for reading and don’t forget to read the disclaimer 5/17/06.
Dr. Licciardi

Tension

2011-07-23T10:22:00.002-04:00

Hello again to everyone.

Tension is the pressure that slowly builds up around us and within us. It’s a pressure that begins on the outside, sometimes very far away, but it somehow finds its way inside us. At first it’s not perceivable, then we notice something but don’t quite know what it is. Then, as things build further, we know what is but want to ignore it. Then and after feeling things are mostly out of hand, we finally we admit to ourselves that yes, we are wound dangerously tight. Some of us are good at then identifying the problem and fixing things back at the source. If things are unfixable we find another controlled and logical way to release the stress. And some of us are not good at identification and self correction, so we just explode, usually after it’s too late. Either way, if we could at least detect the problem earlier, or at least see that there is a problem earlier, we could make things better in the end. Sounds easy.

Over the past week I have been thinking of a few of my own interactions with tension, and helpful things I have heard from others. The key here is betting in better touch with the early signs that tension is brings to your body. Even the least amount of mental tension gives us physical tension. Noticing the physical tension early, so that an early correction can be made, will do wonders for relieving the mental tension. I’ll use a few very simple non-fertility related scenarios as examples of little ways we can understand ourselves better.

1) Some of you may know that I practice Bikram Yoga. It’s not a religion for me, I get there when I can. Frankly, I don’t really love being there. But I was born remarkably inflexible, so I do gain a tremendous benefit, primarily improving my performance in a slew of recreational activities. Bikram also builds strength around the joints, a few of which are in disrepair. During a yoga practice, the instructor typically leads the class through a number of positions, the order of which is deliberately organized. For each position there is the ideal form and degree of bend, and the instructor goes through a list of points for the body and mind directing the students towards these goals. Of course most of us are far from ideal, but getting close, or closer, is quite a workout. If you are involved in formal instruction of any type i.e. music languages, sports; you have recognized that instructors repeat the same thing over and over. Even after months or years into practicing we still are told the same things. This works because as we progress, we hear things differently and eventually things start to click, but it really may take quite some time. So this week, in the middle of my 90 minute class, I am putting on my usual miserable display of form, and sweating insanely. Vowing to stick with it, I strain to align my body and put body parts in places they should never be. Obviously struggling, the instructor says, “relax your face”. “My face, my face? “I say to myself, “are you crazy, my face is the last thing on my mind right now.” But then, after hearing it now for probably the 200th time, it finally made sense. I relaxed my face and my whole body followed along. So the point here is when you feel the infertility tension perking up, check you face first. It may be difficult to melt your body stiffness instantaneously, but the face is more controllable, and if you can start there, the something good may follow.

2) Most of you don’t know that I like to play golf. I play well enough to move along but that’s about it. I like to sink my teeth into my hobbies, so I try to get in a few lessons and practice here and there. Like many players in my bracket, non-relaxation can be a big problem. Last time out I noticed something that I hope will help me considerably. I found that while waiting to tee off, my shoulders were so shrugged up that they almost were touching my ears. There was absolutely no reason for me to be in such a knot. But in anticipation for my next shot, I was doing something that was only making things worse, and until that day, I had no idea it was even happening. I still do it, but I catch myself and let my shoulders fall, which makes me feel better and may, let’s hope, help my game. So try to be conscious of your body in stressful times. Maybe there is muscle group that is acting out, without you being aware. Maybe you sit in an uncomfortable position or bend you back in an awkward way. When the body is out of kilt the mind is right along with it. Taking away hidden physical tension will free up some of the mental tension. Now it would be nice if we could just release the mental tension first so that our physical tightness could resolve, but we all know that is not the reality.

3) Many of you may know that I love to ski. Of all my many little distractions, skiing is my favorite. Over the years I have been involved with ski clubs, ski groups and lessons. One day I was working with a coach and I was in the starting gate for an amateur race. I put my poles over the timing wand, visualized the hill and turns, bent back and awaited the countdown. My coach, who I didn’t even think was watching, looked over and said, “for how long are you going to hold your breath?” That was a big awakening for me. As I prepared for my start, I was doing everything except the most important thing: breathing. How is it possible to initiate a mentally or physically challenging task without oxygen? Not only should we breath, we should take in extra strong deep breaths ahead of time to make our bodies really ready for whatever job is at hand. Getting in shape involves having our bodies become accustomed to an increase in demands, but half of that is just getting our lungs to work earlier and faster to get the air in. Tension pulls away our awareness of basic breathing. Then, after becoming oxygen starved we become more tense irritated and short tempered, all while we have no clue as to what even is going on.

So that’s it for today. Three little personal vignettes relating tension to body tightness and breathing. I used examples related to athletic activity, but the principals apply to having blood drawn, getting an injection or having an embryo transfer. It can even apply when talking to your boss, family member, contractor, and the list goes on and on. Try to pick up the stress signals as early as you can, and this will hopefully lead to easier traveling.

Thanks for reading,

Dr. Licciardi

Being Positive

2011-06-21T06:59:00.002-04:00

Welcome back.

Well, as some of you may have guessed the previous story has a happy ending. While weighing her options Sheri became pregnant. 9 months ago she had a girl, and all is well.

I talked to Sherri about the whole ordeal. She reminded me that she had done many IUIs and 4 IVF cycles. She believes her success was aided by sticking with trying the old fashioned way when not in a medical/IVF cycle.

She is resistant to sayings like, “it’s easier to get pregnant once you stop with our doctor”. And she did want people to know that she did not change her diet or add any holistic therapies, it just happened. (Just a note about this. Of course I believe in the benefits of life-improvement techniques, but they may work best when used in conjunction with conventional therapies Using unconventional therapies alone has some, but limited benefit, and counting on them as you are aging is not recommended. If two groups of 41 year olds try holistic vs holistic plus fertility treatments, both groups will have pregnancies, but there will be more in the second group).

So what are my comments? Every infertility patient has a built in “on-your-own” pregnancy rate. People do get pregnant without treatment. For some the rates are very low, but as long as there is at least one tube and some sperm, the rates are rarely zero. Sheri had an edge; she produced an excellent number of eggs during her ivf cycles and this meant the overall status of her ovaries was well above average. Plus we all understand the Sheri is an exception, not the rule. The fact is, most women her age with a longstanding history of infertility do not get pregnant using their own eggs, even with the most aggressive treatments.

But when it happens it’s wonderful. Plus, in her case to get through the increased risk of miscarriage that goes along with being 43 is a big relief.

But why and how she did it may not be the most important point here. I think we should take time out to celebrate and hope that everyone has the potential to be successful as quickly and as easily as possible.

I’ve had a few other surprises in the past months. I have had my share of patients who responded poorly to the medications causing us to cancel their IVF cycles. With the few eggs that we had, we did an iui “just in case”. Sure enough, 3 women became pregnant and they are all doing well.

Two years ago I had a woman in her 40’s get cancelled from an FSH iui cycle. Her estrogen did not budge after 10 days on drug. Four weeks later her home pregnant test was positive and she had the baby. Apparently, her normal cycle started the day she stopped the injections and without even knowing she ovulated, and without monitoring or exact timing, she became pregnant.

And on the IVF side, I have one woman whose pregnancy is doing well despite her having her retrieval at age 45. Plus, I have had a slew of women whose embryos did not look very good at all, but went on to be successful.
And just yesterday I did a pregnancy ultrasound on a woman who did absolutely nothing except try. I met the couple about 3 months ago. He had a few medical problems that were resolving. Things turned around and they were successful on their own.

One point here is that busy infertility doctors, who promote surgery, fertility drugs, inseminations and in vitro, have many patients who get pregnant without their help. We suggest IVF to some who decide to do iui instead, and some of them get pregnant. We have older patients who have failed many cycles. We may ask them to consider other options, but they persist with IVF, and a few do get pregnant. We have women on our donor egg list who call to come off because they became pregnant.

I don’t want to confuse the luck of a few with the harsh reality of many. But I think it’s important to hear about the potential positives that do exist among people who did not have the best chances. Will being positive up your odds? Some say yes. If not, at least it will give you more strength as you continue on your difficult path.

Another person needs to be very positive, and that person is your doctor. I think most are. You need a doctor who is honest and can communicate the reality of your situation and the odds of success. If you and she believe it’s in your best interest to initiate or continue treatment, then she needs to be behind you 100%. Unfortunately, there are some doctors who do not have the correct mindset to be positive and an advocate for women whose odds are low. No one can really predict who will or will not get pregnant, so why not go in saying it will work. Your doctor should work with everyone as if they will be the one. Again, I think most infertility doctors are very good at this, but if yours is not, try another.

I don’t know if Sheri became pregnant because she was always positive. But I like using her as an example of how good things do happen to people who have one or more factors hindering their chances. Most infertility patients are not optimal candidates for success. Most patients have some barrier, known or unknown, to getting pregnant. Work with what you have, and good things may come your way.

Thanks for reading,

Dr. Licciardi

Update on a Past Story

2011-06-05T09:31:00.004-04:00

Hello everyone once again.

Last week I received some new information about an old story, going back to August 2009. Here is the reprint of a past blog. Read it through, and soon I will post the follow-up information.

Dr. Licciardi

It wasn’t supposed to end this way. We all knew going in that nothing was guarantied, but we felt good and optimistic about starting. Together, we believed that if we just obeyed the rules and had faith, that good things can happen to good people. We anticipated sacrificing time, emotion and money, for a process that was logically the most reliable way to go. We figured it was the best option, and we were “all in” to work towards success.

Shari was 41 when we first met and she was already at it for more than a year. She was very smart and informed. Shari understood the small details of each treatment, but didn’t dwell on the negativity. She was super practical. The plan, which she started at 39, was to start with iui, and move to IVF if nothing happened. She eagerly and compliantly stuck to the plan, and had 2 IVFs under her belt by the time she first saw me.

At our consultation I definitely saw hopeful signs from her previous cycles. She made 15 eggs the second time. Plus her embryo quality was very nice. I explained that 3 things really help when you are trying to get pregnant with IVF at 41; a high egg number, good looking embryos and chromosomally normal embryos. We knew off the bat that she at least had 2/3. More eggs means more selection. We all know that a large percentage of embryos have bad chromosomes, so if you have more embryos, you are increasing your odds of at least one of them being normal. And if they look nice, all the better.

Wow, she called to tell me she got pregnant on her own. Sweet. But there was no heartbeat at 7 weeks, and she needed a D and C. This caused her to pause, and logically concluded that maybe FSH iui could work. So she tried to no avail.

Doing more IVF cycles was not an easy decision. She had some infertility insurance coverage, but that was all gone, so she had to pay for anything else, including the medications. But she weighed the options and decided to proceed with more IVF based on her good response, recent pregnancy and advancing age.

So off she went into her 3rd and 4th IVF cycle with me. Each time producing eggs and very good embryos. We changed the protocol a bit, but in the end she had cycles that most other women could not achieve.

Except for the two negative pregnancy tests.

And that’s the end of the story.

When we last spoke she was again very practical. She just didn’t see the value in going into a 5th IVF cycle. She could not afford donor egg. She was very kind, expressing her gratitude for the treatment she received. But this was it; she was done. She had ended her quest for a baby. Stated differently, she was probably not going to have a baby.

So why am I bringing this story to you, as this is not the first tale of woe in the infertility world.

I think this one was tough for me because she had to stop, but I still had some hope in the chest. For many, stopping becomes the best option because multiple attempts have given me information saying that it really may not be worth continuing. Few eggs, very poor embryo quality, advanced age etc. When younger women have to throw it in, I can at least feel that with time their situation will change, and although it looks like the end now, they may get another shot later on. It’s also easier when the best option is donor egg, and donor egg is agreeable and affordable to the patient.

Now every doctor does get very disappointed every time a patient has a negative pregnancy test. But the story about Shari just left me hanging a little more than usual. Many eggs, nice embryos, and my sense that if she could just do more cycles her time would come. Maybe. The thing was, I couldn’t tell her it would happen, and that always makes it tough. And I couldn’t lay on the optimism thing, even though had some. After 4 cycles, the energy and drive to continue has to come from the patient.

But I will continue to have hope for her. Maybe she will fall into an insurance program that will get her at least one more cycle. She doesn’t have much time for that. May be her financial situation will change and she will get to donor egg. This she has a little time for. And maybe, she will get pregnant on her own, which is not out of the realm of possibilities.

Thanks for reading, and Shari is a substitute name.

Dr. Licciardi

Infertility Questions from Readers

2011-05-04T06:48:00.002-04:00

Hello to all. If you are new to this blog, welcome and please take a moment to browse the previous entries.

Today I have answered the more interesting questions over the past few weeks.

What do I think about cervical mucus? This is tricky question. I would not make any treatment plans based on cervical mucus. Some women have “normal” mucus and others have mucus that is a little thicker, and for some it gets thin only for a short amount of time. Most infertility doctors do not look into mucus problems because no studies have shown that thicker mucus is bad. No studies have shown that trying to fix "mucus problems" does anything. There are some infertility doctors who take their time and really work with mucus and have some pregnancies. However most of us understand that some women seeing fertility doctors do get pregnant on their own and that dealing with the mucus may be immaterial.

Can you have both hypothalamic amenorrhea and polycystic ovaries? The answer is that there are some women who have polycystic looking ovaries and do not ovulate, but do not have other criteria for PCO. In some cases it is hard to distinguish if the underlying problem is PCO or hypothalamic amenorrhea. However, treatment is usually similar in that we use the same medications to induce ovulation for both problems.

I am not familiar with endometriosis causing fevers. Some more rare autoimmune diseases may present with fever, but I am assuming that if you have any suspicious findings would have been tested for those things.

Is a HSG the best test to see polpys? It depends. If your baseline ultrasound and HSG are totally clean, a sonohysterogram is probably not indicated. However if the first 2 tests give ambiguous or conflicting results, a sonohystergram would be the best test to diagnose polyps. Of course it always depends on who is doing the scan.

What if your first FSH is 20? You need to have the level repeated. Strange things happen every day.

What if you get regular periods and your ultrasound is normal, but the doctors cannot do the HSG because they cannot ”get in”? Get another opinion, someone else may be better at doing the HSG.

What if you do a donor egg cycle and the donor performs in a much less positive way than she has in the past? For example, she may have produced fewer eggs, or the fertilization rate was lower or the embryo quality may not have been as good? Unfortunately, this happens occasionally. We usually do not have an explanation for such an occurrence. We hope that after the transfer the pregnancy test is positive, but we understand that the cycle was a big disappointment and a financial burden as well. Pregnancies from marginal looking embryos happen every day.

What if hydros (hydrosalpinx) are seen on HSG but not on ultrasound? This is the usual scenario. The tubes need to be especially large and damaged to be seen on ultrasound.

If you have proximal tubal occlusion, what are your options? One important option is tubal recanulization via a special HSG. The other option is laparoscopic surgery. I usually recommend the HSG because it is less risky and less invasive. Plus there are cases where the patient shows up for recanulization only to have the first part of the test (repeating the hsg) show normal open tubes, therefore obviating the canalization part. There may have been a little tubal spasm during the first test keeping a tube closed, when in fact it was really open. However, all doctors have their own ideas so speak to your caregiver.

Do we treat secondary infertility any differently than the way we treat primary infertility? We do not, it’s all the same. I realize that primary and secondary infertility may be a little different, and we always treat our patients individually, but if you can’t get pregnant you can’t get pregnant. If you are having trouble the second time around, we do all the same tests and offer all the same services as if you had never been pregnant.

What if the sperm is moving but slowly? It depends on how slow. If it is a little off, there is no problem. If your doctor says the sperm is moving very slowly, that is more cause for concern and you may need to get to IUI or IVF sooner.

The E tegrity test? I am waiting for a convincing paper to show its superiority.

What if your lining is surprisingly thin? This is another tough one. I can say that you want to be sure your HSG and sonohysterogram (not just the sonohysterogram) are normal.

Will refleology help? We are not sure but if it improves your quality of life and helps you get through the infertility saga, then I encourage its use. We had a nurse practitioner who performed reflexology and was very well received.

Does DHEA work? It sounded great when the information was first published but like many things in medicine, further good studies showing success have not been published. I do not recommend it, however I have patients who use it, so far without noticeable success.

If you are 30 and your FSH is 11, your odds of hyperstimulation are low. You may need to be more aggressive with your stimulation, but you need to discuss this with your doctor.

Frozen embryos in a natural vs. medicated cycle: a blog to come.

What if you have become pregnant with IVF, but only once despite multiple attempts and good embryo quality? Does this mean that many of your embryos are bad and more likely to result in a malformation or miscarriage? Should you not temp fate? It may mean that there is some unknown problem with your eggs, sperm or embryos that is causing you difficulty in reproducing. It is possible that there is a relationship between infertility and poor pregnancy outcome. Some of the science behind these theories is very preliminary but the ideas are very interesting. For instance, there may be women who have very subtle genetic problems that cause infertility, and these same genetic abnormalities may cause problems with fetal development. At this point, however, there are no tests for this. I understand and your concerns and they may be valid, however I have not had a woman decide to stop treatment because of these potential problems.

What if your doctor uses Lupron for most IVF cycles? I do not use much lupron. If however, you are with a program that has excellent pregnancy rates and uses Lupron, that’s OK, it’s what they do and it works out well for them and their patients. I suspect that over time they will slowly see the benefits of getting away from Lurpon. Without Lupron there are fewer injections and none of the flare reactions than can delay cycles. Plus, I believe that in some women, primarily poor responders, lupron suppresses the response a bit.

Does stress affect FSH levels? It probably has no effect at all. However, if there were an effect the FSH levels would decrease not elevate.

Thanks for reading and please read disclaimer 5/17/06.

Dr. Licciardi

Preventing Ovarian Hyperstimulation: The Lupron Trigger

2011-04-10T15:37:00.002-04:00

Hello everyone, this is another important article on Ovarian Hyperstimulation. The response from readers on this subject has been very positive, thanks for your support.

Saving the best for last, an excellent way to prevent OHSS is to use Lurpon. This requires some explanation.

As many of you have experienced, Lupron is a drug that can be used during an IVF cycle. It is typically started about 1 week before the IVF cycle starts (day 21) or it can be started on day 2. The dose varies, but the usual options are regular lupron, low dose lupron or microdose lupron. None of these have anything to do with reducing OHSS, but I will get to that.

Lupron works by suppressing the pituitary’s ability to produce LH. This is good because in all of the Lupron protocols I just mentioned, one important job of Lupron is to prevent the premature surge of LH. The surge of LH causes ovulation, which is bad for an IVF cycle. If LH surges before the hCG injection, we cancel the cycle for premature ovulation.

We can’t get the eggs when we want them if they have ovulated prior to the retrieval. Lupron prevents this. Before Lupron was invented, we needed to cancel about 15% of IVF cycle for early ovulation.

Some of you are wondering why we trigger ovulation if we want to get eggs from the ovary. LH, hCG and Lupron cause the eggs to mature and then ovulate. For an IVF cycle, we need those medications to get the eggs to mature while still in the ovary, but we grab them before they are released.

Over the past decade we have been using other drugs, like Cetrotide and Ganarelix, to prevent the premature LH surge. These are easier to use than the Lupron because they are only given 2-4 days prior to the hCG. Some doctors still prefer to use Lupron.

Now on to OHSS and Lupron. In a natural ovulation cycle using no drugs, the follicle develops over about 2 weeks, and then a strong surge in LH causes ovulation. While Lupron causes the pituitary to cease LH secretion, in the first 1-2 days of Lupron use, there is a strong release of LH. That’s why we normally give it early in the cycle, before follicles have developed. Premature ovulation does not occur when we give it early because there are no follicles to ovulate.

It is this strong release of LH that makes Lupron great as a hCG substitute for the trigger shot. The quick surge results in a very short blast of LH, which could take place over 1-2 hours. This is very similar to the body’s LH surge that takes place in a natural cycle. After that, the LH has left the system, ovulation occurs 36 hours later, and ovarian stimulation stops. hCG, on the other hand, stays in the body for days, even up to 2 weeks. All of this time, hCG stimulates and stimulates the ovaries, which is too much for ovaries that have released many eggs.

Why give an hCG instead of a LH injection? For iui and IVF we use hCG as opposed to LH because hCG is easier to make and cheaper than LH, and hCG works just as well. The molecules of hcg and LH are very similar and act in similar ways. Plus, the drug companies have not yet figured out how to get the necessary large amounts of LH cheaply into one little vial.

The bottom line is that Lupron, because it causes just a short burst of LH, works very well in preventing OHSS. We are using it more and more and are very pleased with the results. We commonly use it for our egg donors.

One down side to lupron is that, in very small percentage of cases, it may not cause ovulation. This is a rare occurrence and is more likely to happen in women who are hypothalamic, i.e. they do not get regular ovulation due to exercise, dieting or some other factor. In these cases, there is no LH in the pituitary for Lupron to trigger.

In cases where the threat of OHSS is evident, it’s worth taking a chance with the Lupron. We measure LH levels the day after the Lupron injection. If they are very low, the lupron did not work, and there is no LH surge. Therefore we can give hCG the next day, unless the fear of OHSS causes us to cancel the cycle.

Another detail of Lupron use is that for luteal support, we add estrogen. The ovaries just shut down after Lupron use, and therefore estrogen and progesterone are produced in very low quantities. Typically we prescribe progesterone post IVF, but with Lupron we also give estrogen. Not much of a big deal, as estrogen can be given in the form of a pill three times per day. Estrogen patches can also be used.

Lupron cannot be used for triggering if Lupron has been used in the same cycle. So you are taking Lupron starting on day 21, day 2 or using microflare lupron, a Lupron trigger will not work at all. Here hCG would be the only option.

Many other physicians have been increasing their use of Lupron for ovulation triggering. You should ask your doctor if Lupron is used in his practice to prevent ovarian hyperstimulation.

That’s it for today, thanks for reading, and please read disclaimer 5/17/06.
Dr. Licciardi

Preventing Ovarian Hyperstimulation

2011-03-18T09:33:00.003-04:00

Hello again, today we will continue our discussion of ovarian hyperstimulation syndrome (OHSS). We will review ways to minimize its occurrence and eventually get to the best ways to treat the symptoms. As we said last time, OHSS can occur in women undergoing fertility drug use for IUI or IVF.

I will start by saying that OHSS is not preventable in every case. Even with the best intentions of proper medical care and a focus on patient safety, OHSS can occur. Some of you reading this may have had OHSS and are concerned that your difficulties may have been preventable. While this may be true for some, for others the outcome was unexpected.

I am providing general information about this topic; therefore my experiences and protocols cannot take the place of the medical advice provided by your personal physician.

The first step in preventing OHSS is to use the lowest dose of medication that is expected to give a reasonable response.

The good news is that I believe that the incidence of OHSS has been decreasing. One reason is that doctors understand the value of using lower doses of medication. We are more aware of the problems associated with multiple gestations, and try to reduce follicle number to reduce multiples. We are also more cognizant of the problems and risks of OHSS, and are working harder to avoid it.

My goal in an iui cycle using FSH is to stimulate the ovaries to produce about 3-5 follicles. Other physicians have similar goals, but others may give higher doses of drugs to obtain more eggs. I typically use doses of 75, 100 or 150 units for my iui cycles, meaning I am not afraid to start a suspected good responder on a very low dose of drug. Worst case scenario, the response is lower than expected and we need to perform another cycle with a higher dose.

The same principals apply on the IVF side. Women do not need 25 eggs to become pregnant with IVF. Poor responders or women near and over 40 may need more drug, but in this group, even more drug is less likely to cause OHSS. Women in their mid 30’s or younger, with normal FSH levels and good antral follicle counts, should be given lower doses of medication. In this group, and again, these are my personal protocols, 225 units is the highest amount of drug I use, unless there is a history of a poor response. In women with a large amount of resting follicles, the starting dose may be 150-200 units. Body size also comes into play, with small women getting lower doses. I do give 225 usually to donors, because it’s hard to take a chance on low egg production, and donors will not get pregnant from the cycle, and not being pregnant diminishes the symptoms of OHSS.

All of this being said, there are women who escape the vigilance, and over-respond to low doses of medication. This brings us to the next step in preventing OHSS. When a woman has more eggs than desired for an iui cycle, the number one option is stopping or cancelling the cycle. Cancelling and withholding the hCG injection prevents OHSS from even starting. hCG stimulates ovulation, but it has a long life in the body and the prolonged exposure to hCG causes the follicles to continue to grow and make the hormones that contribute to OHSS.

A second option, used less frequently, is to continue with the meds, and hCG, but converting the iui cycle to an IVF cycle. This is sometimes difficult because a patient may not be mentally prepared to jump from iui to IVF. Additionally, IVF is a much more costly option, and even if insurance will cover IVF, the last minute change may by problematic for pre-approvals etc. I typically do not like converting, because while the number of eggs present may be too many for an iui cycle, there may be fewer than desired for an IVF cycle.

Why would converting from an IUI cycle to an IVF cycle reduce the risk of OHSS? Certainly many women hyperstimulate with IVF, but the risks are greater with iui for a couple of reasons. First, during IVF, a needle is placed into each follicle, removing the egg and some granulosa cells, which are the estrogen producing cells of the ovary. So disturbing the follicle lowers its estrogen-producing capabilities thus lowering the risk of OHSS. In addition, with IVF we can control the number of embryos reaching the uterus. Pregnancy makes OHSS worse, and the more fetuses, the more risk. If there are too many follicles in an iui cycle, the odds of twins or more increases, increasing the OHSS risk.

How do we reduce the OHSS risk in an IVF cycle? Choosing the correct dose of drug is the first step. Not giving hCG could be an option, but again this cancels the cycle. Another option is to give hCG a little early, by 1-2 days. When taking fertility injections a woman’s estrogen level rises every day until she gets hCG. So if she gets her hCG a little early, there is less time for the estrogen levels to become higher than desired. This may translate into more immature eggs, but usually women who hyperstimulate have >15-20 eggs, leaving room for some of them to be immature.

Lowering the dose of hCG is commonly done for women at risk. However, the literature does not convincingly support this strategy as effective.

Having the retrieval, but cancelling the transfer is another way to lower the risk of OHSS. Here the embryos are frozen, and thawed 1-2 months later, after the ovaries are no longer over stimulated. This works well, and pregnancy rates are very good in these cases. One potential problem here is that OHSS can still be moderate to severe even in the case of no immediate pregnancy, however in almost all cases, the symptoms are less than if pregnancy had been initiated. For instance, egg donors who do not become pregnant during their ivf cycle, sometimes develop significant hyperstimulation, however their condition resolves in a predictable way.

Transferring fewer embryos and reducing multiples is thought to reduce the risk of OHSS. Since most women who are at risk are younger, an acceptable pregnancy rate can still be achieved by transferring only one embryo.

Next time we will discuss a new alternative method to prevent OHSS, and talk a little about treatment.

Thanks for reading and please read disclaimer 5/17/06.

Dr. Licciardi

Ovarian Hyperstimulation

2011-02-15T15:26:00.002-05:00

Hello again to everyone, today I am bringing to you the topic of Ovarian Hyperstimulation Syndrome (OHSS). Here you will read about the definition of OHSS, the causes and risks. You will see why OHS is what every good doctor strives to avoid, and of course, what every patient would like to avoid as well.

I would like to start by saying that you will read some things that may be frightening, because the most severe forms of OHSS can lead to significant medical problems. However, OHSS does not occur with great frequency and the severe forms are very rare. The next blog will review ways to lower the risks. In many cases it is preventable, although even when your doctor is very careful, OHSS can still occur.

OHSS occurs as a result of taking fertility drugs. These cause the ovaries to become larger than normal and to leak fluid. The more eggs that are produced in the cycle, the higher the risk of OHSS. The leaking fluid can cause significant abdominal swelling, and some of the fluid could make its way to the lungs. We will get back to these and other problems with OHSS in a bit.

OHSS, except for some very rare instances, can only be caused by fertility drugs. When we use infertility drugs, clomid or the injectables, we are hyperstimulating the ovaries. The goal of fertility treatment is to get the ovaries to make more eggs per month than usual. Sometimes we use the drugs to try to just make one egg, but usually we are going for more. In fact,therapy with any of these drugs is called Controlled Ovarian Hyperstimulation. Controlled is the key word. Therefore we expect all women receiving fertility drugs to have enlarged ovaries with the possibility of a small amount of fluid leaving the ovaries, and some cramping. When Controlled Ovarian Hyperstimulation becomes less controlled, OHSS can result.

The development of OHSS through the use of clomid is quite rare, but it has been known to occur. However,the injectables (examples are Follistim, Gonal-F, Menopur, Bravelle) pose much more of a threat. Clomid is a very different drug than the injectables. Clomid nudges along the normal ovulation process by getting the brain (actually the pituitary gland) to put out a little extra FSH. Because there is only so much FSH stored in the pituitary, usually 1-3 eggs will ovulate, as opposed to the one egg that ovulates when no drugs are used. For almost all women, this is not enough stimulation to cause OHSS. The injectables, on the other hand, are more powerful. They are FSH (sometimes with a bit of LH), and more FSH is delivered to the ovaries than in a natural cycle or with Clomid. The injections directly stimulate the ovaries to develop a larger number of eggs for ovulation. Because more eggs are produced, the injectables carry a higher risk of OHSS.

Who is at risk for OHSS? Women who are most likely to make a high number of eggs. The first and obvious group is younger women. For better or for worse, young women have more eggs, and develop more eggs for ovulation when given the injectables. Women with polycystic ovaries (PCO) are at higher risk for OHSS. This is because women with PCO have a very large number of eggs. These eggs are in follicles that have reached the stage just prior to entering the ovulation process. The fertility drugs can get many of these “almost ready” eggs to come up at once. And there are the exceptions, women who do not have risk factors, yet hyperstimulate when exposed to drug.

The severity of OHSS varies widely. Most textbooks divide the various degrees into mild, moderate and severe. Mild does not cause medical problems but may cause a woman to take notice of the changes in her body. In the mild form, the ovaries produce a few eggs and as a result have enlarged slightly. The ovaries have released some fluid, which the patient perceives as bloating. Cramping is mild. Many women have mild hyperstimulation, however they are not at all bothered by the symptoms and they go about business feeling no need to contact a physician for evaluation. The majority of women who take the injectable medications fall into this category. Some women with the same degree of mild hyperstimulation, are more bothered and concerned and may let us know that they do not feel well. Like many things in medicine, we can’t explain why 2 women with the same number of eggs and the same amount of fluid around the ovaries feel differently.

The two worse forms of OHSS are moderate and severe. In these cases, the problems are more complex than just large ovaries and a bit of fluid in the pelvis. In these cases, the OHSS can affect other areas of the body. Dehydration comes into play, and can be very problematic. This occurs as the ovaries leak larger amounts of fluid. The abdomen becomes noticeably distended. Women gain weight as the tummy accumulates more and more fluid. This probably doesn’t sound like dehydration to you, but it is. What’s happening is the leaking fluid comes from the blood which is circulating through the ovaries. As more fluid leaks out, less is fluid is in the blood and the blood becomes thicker, thus the dehydration. Not only does the blood lose water, but with the water flows sodium, so in the blood, sodium levels are low. Proper levels of sodium are necessary for normal function of the brain.

As the blood becomes more concentrated, levels of clotting factors increase. Clotting factors are proteins that are necessary for us to prevent excessive bleeding when injured; they make the blood clot. If the levels of these proteins get too high, the blood will be more likely to clot without any injury. For instance, clots can occur spontaneously in the legs, arms,neck and lungs. The worse the OHSS, the greater the risk if blood clotting.

OHSS can have a big effect on the kidneys. As the dehydration progresses, the overall volume of the blood decreases. Good blood volume is necessary for the normal kidney function of cleaning the blood. Decreased blood volume means that less blood is getting to the kidneys, and therefore the kidneys have trouble doing their job. The blood cannot be cleared of its waste, which is bad for the body.

OHSS has an effect on the lungs. The sheer volume of fluid in the abdomen can make breathing a problem for a couple of reasons. The first has to do with the pressure that builds in the chest as the abdomen fills. We’ve all heard that we breathe with our diaphragm, which is true statement. The abdominal fluid pushes up putting pressure on the diaphragm, making it harder to freely breathe in and out. The second problem has to do with fluid getting into the lungs. When the abdomen gets packed with fluid, it can squeeze through the diaphragm, into the spaces around the lungs. A small amount of fluid around the lungs is tolerable, but larger amounts make it harder to breathe and can cause chest pain.

If you have never taken these drugs, I do not want this blog to discourage you from taking the medicine you may need. If you have any concerns, talk to your doctor about the possible side effects and complications of these medications.
Next time we will discuss ways to prevent and treat OHSS.

Thanks for reading and don’t forget disclaimer 5.17.06.

Dr. Licciardi

Answering Some Infertility Questions

2011-01-07T13:46:00.016-05:00

Hello Again to Everyone.

I hope the holidays treated you as well as possible.

Today I will go through some past comments and answer some of the frequently asked questions that I have not yet answered on my previous blogs. I will enter one more cervical stenosis blog later. I realize that topic is very narrow; only applying to a small percentage of you. Like some of my other entries,the topic is not common but the information vital to some and very lacking on the web.

Hyperstimulation: I have not yet addressed this topic and will do so in the very near future. In many, but not all cases, hyperstimulation can be avoided or at least reduced in severity. I'll discuss how.

Should you hatch your embryos? Don't get hung up on this one. We really don't know the details about the benefits of hatching. At NYU we hatch in selected cases, and we have a "sense" that we are doing the right thing. If a clinic has good pregnancy rates, take their advice on hatching. They may never do it, they may always do it, both are acceptable in today's fertility world.

The pros and cons of septum surgery: also to be addressed. I have written a bit about septums and septum surgery, but I will add another post later. I recently have had the privilege to perform surgery on some women with large septums.

42, high FSH and no response to the IVF fertility drugs. Should you try again? If you need to try again, go ahead. Worst case scenario is that you are where you are now. Your odds of success are very low and you may lose money, and the unemotional answer is that you should consider stopping. So first get informed, including getting a second opinion, then you can decide and proceed as you wish.

Could a low vitamin B level increase the FSH level? I have not read anything supporting that, but increase your B levels and repeat the FSH.

PCO and low sperm morphology. If one doctor recommended clomid, and you agree, the approach is reasonable. Going straight to IVF is not crazy, but less commonly the first step.

Clomid for the treatment of unexplained pregnancy loss. Clomid may be prescribed for women with pregnancy loss, usually to increase the progesterone levels. If you are taking progesterone, clomid may not be needed. I am not aware that clomid will increase the viability of an egg or embryo. It may give you more than one egg, which may help in one of the eggs is abnormal. However, in general, clomid is not on the list of treatments for recurrent pregnancy loss. As you know there is not much on that list anyway. I don't think it will hurt.

Fluid in the uterus at the time of transfer. This usually can be detected prior to transfer.

An estradiol level of 7,000 on the day of hcg is very high. I'll talk more about this in my hyperstimulation bog. Starting on a lower dose of medicine is the fundamental issue.

What if you have one blocked tube, became pregnant with IVF and now want to try for a second child? Should try on your own first? If that was your only known problem, talk to your doctor. Waiting at least for a few months may be ok.

7 years of trying and your only workup consists of an hsg? Yes, get your partner checked and get to a fertility doctor.

Odds with injectables at 34. It's about 15-20%. Twins? If you are anovulatory, get on a very low dose. This should produce 1 egg. Check with the ultrasound, if there is more than one follicle, you would have the option to cancel the cycle. One egg can not be guaranteed every time.

Spotting and PCOS? Get an endometrial biopsy if you have not already had one. And a hsg and maybe a sonohysterogram to rule out a polpy. If that's all ok, then discuss progesterone or alternative treatments with your doctor.

A good sonohysterogram should pick up a septum.

Do women increase their odds of pregnancy after a HSG? I have not seen that frequently. I do so many, that occasionally someone gets pregnant afterwards, but I don't think the test was the solution.

To my "twice as nice" patient (double cervix etc who happens to be very nice too) thanks for writing and keep me posted. Dr. Licciardi

The best test to diagnose fibroids is the ultrasound. If your ultrasound is normal, you do not have fibroid.

Will egg freezing work with an FSH of 15? This is not good. For more details, refer to the egg freezing blogs.

Are embryos that are transferred on day 5 better than the embryos that were frozen on day 6? Yes they are, but it was still worth freezing. Obviously you make a good "batch". Give them a chance, at least one of them may do just fine.

How telling is the antral follicle count? It's a guide but not the final say. I have seen 6 resting follicles turn into 15 eggs, and 4 turn into 1. You can't ignore your count, but don't make any important decisions based on the antral follicle count only. Age, FSH, and possibly AMH are more important. Many people feel you can measure the antral follicle count anytime in the cycle.

Does the fertilization rate, or number of polyspermy embryos, or number slow growing embryos have any impact on your chance of pregnancy if in the end you have a couple of nice embryos to transfer? Maybe. At the most recent meeting of the American Society of Reproductive Medicine, there was one report showing a higher pregnancy rate when the fertilization rate was very high. However my overall feeling is that if you can get to a couple very nice embryos, the quality of the remaining unused eggs and embryos is not that indicative of success.

29 years old, an estradiol level on the hcg of 2993, 6 eggs, one embryo for transfer. The main issue here is the disconnect between your age/estradiol level and your egg number. I have seen a few women from other centers who come to me with a similar history. When I repeat their stimulation, they get many more eggs. I don't know if it was something we did better at NYU, or the first cycle was just a fluke.

If you have follicles on ultrasound, at least one of which is 16 mm or greater, and take an hcg shot, you will almost always ovulate. An progesterone level of 7 confirms ovulation.

What if you have only one vial of sperm remaining, is there something you can do to conserve your resource? You can thaw and refreeze, talk to your doctor about the pros and cons. At NYU, our embryologists sometimes scrape some of the frozen specimine to get just enough sperm for the case, leaving most of it unthawed. ICSI would be required. Ask you doctor about that too.

What if your only sign of PCO is a blood test? I wouldn't worry too much about it. If you are getting regular cycles an abnormal blood test should not impact your fertility. If the test is indicative of other medical issues make sure you get that checked out. You will have to ask your doctor for the details.

What if the first cycle of clomid did not work? If you are OK with the concept of clomid for your situation, it's ok to try a few cycles. Now the plan should never be written in stone, so if you are getting nervous about another cycle it's ok to change course. But I would not worry that it will never work based on a failed first try; stick with it a little longer.

That's it for now, I'll write again soon. Thanks for reading and please read disclaimer 5.17.06.

Dr. Licciardi

Cervical Stenosis from a Cone or LEEP

2010-12-12T21:36:00.012-05:00

Hello again, today we are going to talk more about blockage of the cervical canal: Cervical Stenosis. We will concentrate on the most common causes of cervical stenosis; scaring that results from the treatment of an abnormal pap smear.

Please refer back to the previous post on the cervix to get some background for this blog.

Treatment of an abnormal pap can cause scarring of the lower part of the cervix, the external os. This type of scar is a problem for 2 reasons. First, it reduces the number of mucus producing cells, sometimes lowering natural fertility. Second, it may make fertility procedures, such as insemination or embryo transfer, more difficult.

Most cases of cervical stenosis occur as a result of improper healing from a surgical procedure. It may not be that the procedure was done improperly; it’s just that the healing did not cooperate

It is cells in the area of the external os that are tested during a pap smear. When these cells look abnormal, we need to remove them before they progress to cervical cancer. We treat the abnormal cells by either by destroying them or removing them: both processes can cause scarring. Examples of destroying the tissue include cauterization (basically burning away with electricity or a laser) and Cryo.

Cautery just basically fries the cells away, some abnormal and some normal tissue. Cryo literally freezes off some of the tissue of the external os, removing abnormally growing cells and some normal tissue. Cryo and Cautery are not popular because they do not give you any tissue to send to the lab.

Rather than destroying cervical tissue, there are other procedures that remove a small piece. Examples of tissue removal include a cone biopsy or a LEEP (Loop Electrosurgical Excision Procedure). The cone procedure and LEEP are basically the same thing, however if necessary the LEEP can be a little more precise and remove a smaller amount of normal tissue. The LEEP and the cone biopsy cut away pieces of tissue that can be further evaluated under the microscope.

A cone involves and old fashioned scalpel, and takes away a larger piece in the shape of a cone (pictures to follow). The LEEP uses a thin wire loop that scoops out a little piece. However, sometimes using a LEEP the doctor needs to take a larger area as if a cone were being performed. Today, most procedures are LEEP procedures because the biopsy can be directed; in other words, only a small area can be removed if necessary. In addition, the LEEP can be performed in the office as opposed to the hospital. Finally, there is a lower chance of bleeding with a LEEP.

No matter which of these procedures is performed, a small percentage of people can have post-op scarring that leads to cervical stenosis. The more tissue removed or destroyed, the greater the chance of a scar.

Why do some people scar an others not? Some people are just more prone to it. Scaring is the normal way we heal. For some women, the scarring is more robust and progresses enough to cover over the cervical canal. Certainly, if any of these procedures are followed by infection, scarring will be more likely.

Let’s go through the pictures.

Here is our uterine drawing showing the uterus and cervix.

The next picture is a drawing of what your doctor sees when she puts in the speculum. It’s the cervix, actually the very bottom of the cervix.

Let’s say your pap comes back abnormal. This usually means that there are some cells around the external os that are abnormal. Depending on the severity of the pap, these cells may need to be removed. Using some special techniques, you doctor would look very carefully at your cervix under magnification to try to determine the extent and location of the abnormality.
This picture is an example of abnormal cells in a very small area.

Here, the doctor does not need to remove much tissue, and this is not likely to lead to scarring. The doctor will probably use the LEEP procedure, but only a small amount of cervix needs to be removed. This picture shows a cervix with a small abnormality and a small LEEP.

This picture shows a case where there is a larger amount abnormal cells and they take up a larger area on the cervix.

In this case, the abnormal cells are all around the external os. Here, the doctor needs to take away much more tissue.

You can see that the shape of the removed tissue is in the shape of a cone, thus the term cone biopsy. A larger LEEP will also make a cone shaped biopsy. While the odds of scaring remain low, if it does happen, it is more likely to come from taking more tissue. The next picture shows a post-LEEP scar.

The good news is that in most cases, scarring at the external os is the easiest to deal with. Unlike scar tissue that forms higher up in the cervix, scarring at the external os can be seen with a speculum and the scar is usually shallow. The scar is usually on the thin side and can be easily opened, usually in the office.

After opening, the scar may have a tendency to return, but re-opening is not that difficult. In the case of fertility treatments such as insemination and embryo transfer, the scar can be opened just prior to these procedures without much difficulty. Unfortunately some women can have more serious scarring after these procedures that is not so easy to deal with. Additionally, some women need to have multiple biopsies, and this will increase the scar risk.

More on Cervical Stenosis next time.

Thanks for reading and please read disclaimer 5.17.06.

Dr. Licciardi

Cervical Stenosis

2010-11-12T12:33:00.015-05:00

Hello Everyone, Dr. Licciardi here with today’s message.

In this blog we will discuss a topic that I have been waiting to write about for quite some time, Cervical Stenosis. This is an important topic because it affects a large number of women in a negative way. Cervical stenosis is responsible for infertility, pain, and IVF failure. It can even cause endometriosis. And like most things I write about, the subject is rarely discussed in a way that is clear and understandable. Here we go.

Let’ start with some pictures. Below is a drawing of the ovaries uterus and cervix.

As you can see the cervix is really just the lower part of the uterus. But the structure of the cervix is very different from the structure of the uterus. The uterus is a nice fleshy muscle whose job is to stretch during pregnancy. The cervix is the opposite, the tissue is tough and firm, and it is designed not to stretch during pregnancy. If you squeeze the bulb of your nose you can feel the approximate consistency of the cervix.

The cervix has a narrow hollow center that is basically a tunnel from the vagina to the uterus. Because it is so narrow, even the slightest scarring can partially or fully block off the tunnel, and that’s what stenosis is.

Stenosis is a problem because it keeps things form coming out, like menstrual blood, and it keeps things from going in, like sperm or catheters for insemination or embryo transfer.

Let’s use some more pictures to make thing a little more clear. Here is another basic drawing of the uterus and cervix.

This is the view as seen from front to back. I took out the tubes and ovaries to make things simpler.

This is a picture of the same thing, it’s just a side view.

I wanted make this familiar to you because many pictures published in books and on the net show one view or the other.

Just two more new words to know: the external os and the internal os.

Os means opening or hole. The external os is the opening of the cervix going from the vagina upwards. This is where the pap smear is taken.
The internal os is the opening of the cervix from the uterus downwards. This is usually the first part of the cervix to open during childbirth. This is usually not a significant distinct area of the cervix, it’s just the place where the cervix and uterus meet.

These are the two most common locations for cervical stenosis to occur.

The next drawing is here to emphasize that while the os are the 2 most common sites of stenosis, anywhere along the cervical canal can be stenotic.

Here is another drawing showing typical scenarios

Next time we will go over the causes and treatments of cervical stenosis.
Thanks for reading and please read disclaimer 5.17.06

Dr. Licciardi

Checking Tubes: The HSG is better than the Saline Sonogram

2010-10-10T14:24:00.012-04:00

Hello again everyone.
Today we are going to finish discussing the difference between the HSG and saline sonogram. Last time we highlighted the differences as they relate to studying uterine problems. Today I will point out the differences as they relate to the tubes. We will see how the biggest mistake doctors make with the saline sonogram is when they see no fluid from the tubes and stubbornly say that the tubes must be blocked, therefore you need IVF. Let me explain.

The saline sonogram is not the best test to check the tubes. It gives a hint as to the tubal status, but the results are not definitive enough.

Last blog we discussed one of the basic concepts of the saline sonogram: water looks black on ultrasound, polyps and fibroids look white. We put water inside the uterus and the white polyps or fibroids float in the black fluid making them easy to see.
During a saline sonogram, the saline, after it fills up the uterus, will wander through the tubes and out into the pelvis. So it makes sense that if we can see some black fluid outside the uterus, around the ovaries and intestines, the tubes must be open.

Here is a picture of an ultrasound showing some free fluid in the pelvis. The arrow points to the free fluid. Presumably this fluid stated in the uterus and got squeezed through the tubes and ended up in the pelvis.

However seeing water outside the tubes does not necessarily mean the tubes are in good shape. First of all, one can’t see much detail of the patterns of water flow; the flow can’t be seen as clearly as the dye on an x-ray. We may be able to see if there is water present but we can’t see how it got there. Let’s say, for example, that only one tube is open. This is easy to see on HSG, but on saline sonogram, you cannot tell if one or two tubes are open because you usually can’t see the water flowing from each tube.

Here is an HSG showing open tubes. In the second picture I places lines to show you the approximate place there the tubes ends and there the free flow of dye out the tubes starts. This is much better visualized on the HSG; you can see each tube and the flow of dye directly.

In the case of a hydrosalpinx, the end of the tube can fill with fluid, and although the doctor should be able to tell the difference between and hydrosalpinx and an open tube, sometimes the distinction is difficult.

Here is an HSG of a hydrosalpinx. The arrow points to the blocked tube. You probably noticed that some HSGs show the dye in white and some in black. It just depends on the preference of the physician, they can be printed with either way.

A hydrosalpinx is usually very easy to see on HSG, possible but more difficult to see on saline sonogram.
The point is that this hydro, using a saline sonogram, may have shown up as a little free fluid, and someone may have been told her tubes were indeed open. Severe tubal disease like this may be present even though there is some “free fluid” seen in the pelvis.

At the start of this blog I spoke of the biggest mistake docotrs make when interpreting the sonohysterogram. No fluid in the pelvis does not necessarily mean the tubes are blocked, and IVF may not be the next step after "failing" a saline sonogram. Do not use saline-sono tube tests to make decisions about IVF. A saline sonogram is not an adequate test to proclaim the openness of your tubes. If you want important information about your tubes, a hystersalpingogram is the only way, with very few exceptions, as in the case of a very obvious hydro. Sometimes there is no free fluid seen outside the uterus, but maybe this is because the catheter was not positioned properly, maybe the fluid just backed out the cervix instead of going upward, or maybe there was tubal spasm. In any event, if you were told no free fluid means IVF, talk to your doctor about having an HSG.

That’s it for now, thanks for reading, and don’t forget to read disclaimer 5/17/06.

Dr. Licciardi

What’s the difference between a Hysterosalpingogram (HSG) and a Sono-Hysterogram?

2010-09-17T07:10:00.016-04:00

This just happens to be one of my most frequently asked questions, and it’s a good one. Both are can be very important tests. Some women need only one, some both. In this blog you will see pictures and explanations. I enjoyed putting this blog together because I like taking things that are a little complicated and breaking them down into simple pieces to help make the readers understand every day things that were never made clear to them. Despite this I realize that there are some of you that get very intimidated when shown pictures of anything medically related, so I am sorry if some of this compounds your frustration. Give this one a shot and see how it goes.

Hysterosalpingogram, also known as the hysterogram or HSG. Hystero means uterus, salpingo means tube, so it’s a test to evaluate both the uterus and tubes. It’s a dye test that uses an x ray. As far as the patient is concerned, it starts with a speculum, like a pap smear. The doctor, through various techniques mentioned in previous blogs, squirts some dye into the uterus and it then runs out the tubes. The dye is actually as clear as water, but it’s called dye because it is white on an x ray. The dye then shows the shape of the interior of the uterus and the tubes.

Let’s start with the uterus. This is picture of a HSG x ray.

The uterus is perfect. The tubes are abnormal, but I am starting with this one because the view of the uterus is so ideal. You can see that is triangular in shape with the top being relatively straight across.
The hsg only shows us where the dye is, which is inside the uterus and inside the tubes. It does not tell us anything about the middle or outside of the uterus or tubes. The next picture is the same as above except I outlined the outside of the uterus and the approximate location of the ovaries.

You can see that the overall uterine size is greater than what is shown by the hsg, and how the outer uterus and ovaries are invisible using x rays.

The next picture shows what happens to an HSG when there are fibroids on the middle and outside of the uterus. I drew in some hypothetical fibriods in red. Fibriods like these would be invisible on hsg. As you can see, the shape of the inside of the uterus has not changed. So it is possible to have fibroids, and have a normal looking hsg. Fibriods that are closer to the cavity will make the HSG look abnormal. We will later see how certain fibroids can affect the look of the HSG, but in this case many fibroids did not change the HSG picture.

Now we will look an HSG that shows an abnormal uterus.

This hsg is abnormal. There is a black spot in the center, and this could be a number of things, all of which are abnormal. The center is dark because the dye cannot get to the center of whatever is growing in there. It is most likely a polyp, but it could be a small fibroid or even some scar tissue(less likely). The overall triangular shape of the uterus is good. This shows how an HSG can be used for diagnosing uterine problems such as polyps or fibroids that are growing in the cavity.

This is a good time to move over to salinosonohysterograms (sonohysts for short). Commonly called a saline infusion sonohysterogram (SIS). We will come back to HSGs in a bit. The sonohyst does not use an x-ray or x-ray dye. It instead is performed with a regular old ultrasound machine. Prior to performing the ultrasound, the doctor starts with a speculum and then puts a very little plastic tube inside the uterus and squirts some saline (salt water). The saline goes into the uterus and out the tubes.

Here is a normal uterine cavity on ultraound without the saline, its the regular old ultraound.

The next picture is the same, but I added white lines to show you the outline of the entire uterus.

Here is an ultrasound of a uterine polyp (could also be a fibroid). It’s that olive shape in between the arrows. No saline yet.

Here I put a circle around it to make sure you see what I am talking about.

And below is a sonohysterogram of a similar polyp. The doctor put a little saline inside the uterine cavity. Saline or any watery fluid looks black on ultrasound. The black surrounds the polyp and makes it much easier to see. The arrows are not important, they are just pointing out the stalk of the polyp.

Here I would like to end on one very important point. Performing this sonohysterogram was not necessary. We can all see that the polyp is very obviously visible in the picture without the water. There is really no reason to do the sonohysterogram. However time and time again, the doctor will say, "it looks like a polpy, lets do a sonohysterogram to be sure." Yes the picture using the sonohysterogram is prettier, but what he is doing is having you undergo one more unnecessary test, that you may have to pay for, and it’s expensive. So if you are confronted with a sonohysterogram, ask your doctor if he is sure if it really needs to be done. Ask if it will give you any more information than you already have. The sonohysterogram is a great test and I use it all of the time, but not if I know the answer before it’s started.

We will discuss both again next time. You will learn why the sonohysterogram is not a good test for showing open or closed tubes.

Thanks again for reading and please read disclaimer 5.17.06.

Dr. Licciardi

Questions about IVF, IUI, PCO and Male Factor Infertility

2010-08-28T07:44:00.002-04:00

Hello Again, I hope everyone has had a mostly enjoyable summer. The weather in the Northeast has been summer-perfect.

Here are the answers to some recent questions.

IUI and IVF

At 45 should you dismiss the idea of IVF and just do iui? Most IVF programs around the country have never had an IVF success with a 45 yo woman using her own eggs. I know it sounds harsh, but it is the reality. At NYU we have had some and I am sure that there are other programs around the country that have one or more. The odds of success with iui are always lower than IVF, so that doesn’t sound so good either, but at least with iui you can try multiple times less expensively. So at any age, IVF on a per try basis is better and may be the best first choice, but iui is more attractive to some.

31 yo, severe endometriosis, 225 units of drug and 6 follicles, cancelled to iui. Was this the right choice? Can a higher drug dose increase the egg production? I do understand the "maybe you will do better next time" philosophy, but you don;t know that next cycle will bring. You may make a few more eggs on a higher dose. The left ovary only made one, which means it could do better next time, or it is damaged from the endometriosis and there is a lower number of eggs there. For someone who is 31, not more than 4 eggs are needed to still have a good chance. There may not be much of a difference in pregnancy rate between 6 and 10 or even more eggs. So for me 6 would have been fine and if you make 6 in your next cycle you should talk to your doctor about having a retrieval.

45 years of age with multiple fertility problems and multiple failed IVF cycles. Is freezing for a carrier one option? Anything is an option, but realistically, I would discourage it. If it’s a must do for you, then find a way to get it done. This really requires a sit down discussion with you and your doctors.

Embryo Donation: I 100% endorse the process. We seem to have a problem getting embryos. We get many couples who before their cycle start, say they wish to donate their embryos. But it is extremely rare for any couple to actually make the decision to donate their frozen embryos. There are obvious advantages of embryo donation and I wish there were more couples who were comfortable with the process of donating.

High percentage of immature eggs. Remember having 10-20% immature eggs is normal. High percentages of immature eggs could be a function of a few things. First, maybe you received the hCG too early, and waiting 1-2 more days may have increased the percentage of mature eggs. Most people on average do not have an excess of immature eggs when receiving hCG once their biggest follicles reach about 18 mm. Some women however, need their biggest follicles to be 20 or 22 mm before most of their eggs are mature. There is no way to know this in advance of the first cycle. But changes should be made for subsequent cycles. There are some women, who no matter how long we wait to give the hCG, still have a large percentage of immature eggs. We can’t explain this and it’s just a case of dealing with what you have. In general we don’t want to wait too long before giving hCG because eggs can get over-mature and this could show up later as poor quality embryos.

What if you make 3 follicles on 225 units of drug, will a higher dose help next time? On average the answer is yes. I think that for most people, once you get to 300-450 units per day, adding more will not help, or will not help much. There are many cases where I do use the higher doses, as much as 600 units. However, going from 225 units to 450 units usually ups the egg number. I would not expect to go from 2 to 15, but even 4-6 would be a big improvement.

Reproductive Surgery

Will a laparoscopy help find the cause of abnormal luteal phase bleeding? Most doctors would say that at least a hysteroscopy would be indicated, which would take a look inside the uterus to be sure there are no hidden polyps or fibroids. However, if the HSG and sonohysterogram are perfectly clean, odds are the hysteroscopy will be normal and maybe could be skipped. If medicated cycles fix the problem, then you are set. A laparoscopy (surgery through your navel) will probably not find anything related to abnormal bleeding of the uterus and may not be indicated.

Are there complications of uterine surgery for a septum? Yes, but the odds of having a complication are very low. Uterine perforation, bleeding and infection are possibilities, but there are very rare. Your doctor should be able to discuss the risk of miscarriage if you do not have the surgery and the rates of surgical complications. I perform my septum surgeries using ultrasound guidance to lower the odds of complications.

Ovarian Wedge/Ovarian Drilling will not help at age 44.

Failed ivf and iui with a fibroid in the cavity? It is tough for me to comment on this without doing the ultrasound myself. In general, regardless of the surgical problem, the threshold for advising surgery changes as time goes by. If there is a fibroid you may be less interested in removal initially, but as each cycle passes unsuccessfully, the option of surgery may receive more consideration. If I were to do the scan and agree that there is a fibroid of notable size in the cavity, I would be concerned that implantation could be hampered. But you really need to get a second opinion.

PCOS

If you have PCOs and are not responding to clomid, yes FSH is one of the next options.

You are 37 and have PCOS but with regular cycles? By most definitions, you can’t have PCOs unless your cycles are irregular. There are some groups who say that you can have PCOS even if you have regular cycles, however most doctors feel part of the definition of PCOS should include menstrual abnormalities.

It is not necessary to measure the LH level in women with PCOS. Irregular cycles and many follicles on ultrasound are all that’s necessary to make the diagnosis. Other tests may be necessary to rule out diabetes or other metabolic disturbances, and sometimes we check for adrenal problems, but most of us no longer measure the LH, or the ration of LH to FSH.

PCOS, 37 years old and not getting pregnant on clomid. Should you keep trying on your own? Well if you are not getting pregnant, eventually you need to change the plan. In general, clomid is used for about 3 tries, but in the case of PCO and anovulation, more tries are acceptable. This is because clomid levels the playing field. Someone who does not ovulate, but does so with clomid, has about the same pregnancy rate as a normal ovulating woman, so why panic after 3 months? Giving clomid to a normally ovulating woman is not as successful, so switching to injections or IVF after 3 months is the typical time frame.

Next steps: if you have not become pregnant after a number of cycles of clomid and then injection cycles, IVF is the next step. Of course you can continue with iui if you wish, but you need to talk to your doctor about the options and success rates of each.

Sperm

Is there a protein in sperm that kills eggs? There is not.

If you have a testicular biopsy that shows no sperm, can clomid help? It’s a discussion you need to have with your reproductive urologist. If you are unsure about the advice, get a second opinion. If clomid were an option, I am assuming it would have been an option prior to the surgery. Homogenous means that the tissue was abnormal, without the usual network of sperm making cells.

What if the sperm has 0% morphology. This may or may not be an issue. As you have read, a very low percentage of normally looking sperm does not bother me. However, occasionally, we see a sample that is unusually abnormal and this does raise a red flag. I would repeat the semen analysis to see if there is consistently 0% normal forms. Trying another lab may give you more information.

Obesity
If you are 31 and 300 lbs you need to seriously lose weight regardless of your fertility issues. Being pregnant at 300 lbs is not safe for you or your baby. If you lose weight you may start to ovulate regularly. I know this is all easier said than done, but you need to seriously look at all of your options including medical and surgical approaches.

Thanks, enjoy the holiday, and please read the disclaimer 5/17/06.

Dr. Licciardi

The Failed HSG

2010-07-22T19:36:00.005-04:00

Today I will talk about why some women go in for an HSG and leave being told the test could not be done.

This is such a common problem, and it is usually all about the same thing. It’s about technique. The correct technique makes it easy, a different technique makes it unnecessarily difficult.

There are 2 ways to do a HSG. Remember the goal in performing a HSG is to get the dye in the uterus and then have it flow out of the tubes. To achieve this, many doctors slide a catheter through the cervix up into the uterus. This is the problem. If the cervical canal is narrow, whether naturally or as a result of some scarring after surgery, the catheter can’t get in easily. This results in pushing harder, and this causes pain, and pushing harder still may just jam the catheter against the side of the cervix. This leads to failure.

The second and easier way, for both the doctor and patient, is to put the dye in a syringe and put a soft cap on the end that snugs up against the cervix. We call this cap an acorn. The canal through the cap brings dye from the syringe to the cervical canal and up towards the uterine cavity.

Imagine trying to blow up a long skinny balloon by first shoving a straw half way in; it’s not so easy to get that straw through. But if you blow it up by just puffing into the hole (I know some of these balloons are hard to blow up but I'm just trying to illustrate the point) things go much easier.

Here are 2 pictures. Each has graphics that are a little different, but they are both drawings of HSGs, both represent a different way to do an HSG.

In the first, a catheter has been shoved through the cervical canal into the uterus. You can see the catheter inside with that little balloon at the tip. The balloon is designed to prevent the dye from backing up and coming out of the cervix. This makes sense, but there is a better way. In the second picture, the instrument is just pressed against the cervix, and that blocks the dye from coming out backwards. As you can see, nothing is shoved through the cervix. The dye finds its way into the uterus just from the pressure.

Even if the canal is very narrow, it does not matter, because the fluid dye will still have no problem following the path of the cervix. The same is true if the uterus is very ante-verted or retro-verted (tilted forward or backwards), both of which can make it very hard for the catheter to slide through the cervix and into the uterus. I’ll talk more about tilting soon in my upcoming blog about cervical stenosis.

I frequently see patients who some to see me having failed an hsg, meaning the test never got off the ground going because the catheter could not get into the uterus. The test was overly painful and there were no results to show for it.
All I do is repeat the test using the plug in the second picture and the test easily gets done. Occasionally I need to open the very end of the cervix in the place where the plug goes, but that’s much easier than needing to dilate the entire cervix to accommodate the full balloon catheter.

So if you had trouble with the HSG and live around NY, I would be happy to give it a go. Otherwise get the HSG done elsewhere, but ask first if they use the balloon. To be fair, even using my technique, rarely, rarely it still can't be done and in that case I may need to dilate the cervix in the office or operating room.

Thanks for reading and please read the disclaimer from 5/17/06.

Dr. Licciardi

Sperm Morphology: New Guidelines Announced: 4% is Normal

2010-07-01T07:25:00.001-04:00

Wow, what a relief to know that what we have been saying for years is now finally officially stated. Any sperm morphology over 3% is considered normal.

How did this change come about? The World Health Organization (WHO) determines the normal parameters for semen including volume, count, motility, forward progression and morphology. The WHO published their guidelines in 1987, with updates in 1992 and 1999. The original “normal” cutoffs were based on estimates from old data, some of it dating back to the 1950’s. There were inconsistencies in the way data was collected, ie the sperm studied was collected and analyzed in many centers, but there was little regulation of how the tests were being performed. Plus there was not clear data on the history of the men.

This time the semen tests were performed using similar protocols in all of the testing centers. Plus, some history was obtained from the men, mostly related to fertility status.

4500 men in 14 countries on 4 continents were tested. Australia, China, Denmark, Germany, Chile, Singapore, France, the UK, and the USA were some of the countries included.

Men were placed into one of 4 groups.
Fertile men. All men in this group had initiated a pregnancy sometime in the 12 months preceding testing. This was the most important group because the researchers could establish normal values based on men know to have fertile sperm.
There were 3 other groups evaluated. To save a little confusion, I’ll summarize and say 2 groups were a little more random in nature and the fertility status of the men was mostly unknown. The 4th group was also fertile, but the time since last pregnancy was unknown and may have been longer than 12 months.

The results.
The normal fertile men’s sperm had the following results.
Volume: The median (midway between the lowest and highest results) was 3.7 cc, but anything over 1.5 cc was considered normal
Concentration: the median was 73 million but anything over 15 million was considered normal
Motility: the median was 61%, anything over 40% being normal
Morphology: the median was 15%, anything over 3% was deemed normal.

Some important points.
You may have noticed that morphology is not the only parameter with a new normal value. Volume was at 2.0 cc, now it is at 1.5cc. A normal count was 20 million, this changed to 15 million. Motility was 50%, now it’s 40%. The normal morphology had the biggest change, as it went from 15% to 4%.

Keep in mind that in this group, all of these men were fertile, so even men with levels lower than the new definition of normal had working sperm. The normal values were established mathematically. If you were in the upper 95% of the fertile people you were deemed normal. The bottom 5% of the fertile people was deemed abnormal. This 95%/5% cutoff is the system used to define cut offs for other tests such as TSH, Prolactin and many others.

When comparing the different groups of men there were very slight differences in volume, count, etc, but hardly worth mentioning. Fertile men did have slightly higher volume and counts then men whose fertility status was unknown. Morphology was mostly similar in the different groups. Remember, there was no group of men who had established infertility, so in this study there is no way to compare normal fertile men to known infertile men.

And even though we have no details on the women, knowing that they became pregnant in the past year is probably all the information we need.

So now you know. Any morphology over 3% is considered normal. If your doctor tells you otherwise, ask him if he has seen the new WHO guidelines.

To take it one step farther, can there really be difference between 4% and 2%? I doubt that there is a difference between having 96% abnormally shaped sperm and 98% abnormally shaped sperm. So as I have said before, at our practice here at NYU, morphology is not considered with much respect, except in some rare cases where the sperm is unusually abnormal.

I hope this helps.

For those of you who want more details, here is the link.

www.who.int/reproductivehealth/topics/infertility/cooper_et_al_hru.pdf

Dr. Licciardi

How to Find a Good Fertility Doctor

2010-06-05T09:36:00.004-04:00

So you’ve been trying to get pregnant and it’s taking longer than you think it should. Now what? Sounds simple, you probably have a local gynecologist who you have been seeing for your checkups. Why not start there?

This may not be a bad idea at all. A general gynecologist could quite possibly be a very good fertility start. She has your history and may be conveniently located. But how can you tell she is good?

It boils down to 2 things: diagnosis and treatment.

Let’s start with diagnosis. If you have been trying 6-12 months, and you doctor says relax and try for 6-12 more months, relax your relationship with him. Of course he will occasionally be right and some people will be successful by just hanging in there, but most following his advice will still not be pregnant, and will be that much older.

Even if you want to wait, you should strongly consider at least having some basic simple testing. You can keep trying on your own as the testing proceeds, but at least you will acquire some important information. Once you get some answers, you will have the power to decide how to proceed.

Now what tests are we talking about? The gold standards are the HSG (hysterosalpingogram), semen analysis, and day 2 or 3 blood testing for FSH and estradiol (estrogen). All of these tests can be finished within a few weeks, and within that time you will have your bundle of information. Now some of this is a little simplistic because many of you have very complicated problems, but most people just starting out do not. And if the testing is systematic and is done quickly, you will all be on the right track.

You do need someone good to read your HSG. Many doctors will not look at your films; they will just read the report. This becomes less material when the report is normal, but much more significant when the report is abnormal. If you are told its normal, odds are it is. However, if you are told it’s abnormal, then you may need to take things one step further, usually by getting a second opinion, preferably with an RE. If you are told it’s normal and you continue without conceiving, you should have someone else have a look at it.

That’s the basic testing, sounds simple and it is.

What about the treatment side? For example, let’s say the HSG really is abnormal and you are told you need surgery on your uterus or tubes? Who should do your surgery? Your GYN or an RE? Many generalists are excellent surgeons, and some REs are terrible.

How do you know where to go for quality surgery? And let’s extend the question to “How do you find any good doctor?” Whether it’s a generalist or Reproductive Endocrinologist, how do you know who is good?

This is one of the most difficult questions in medicine. I would start by doing some of your own investigation.

What about those best doctors lists? This could be a good place to start because many doctors on those lists are good. However if you show a list to a good doctor who is very familiar with the people listed he will really wonder how some of them made it on. And I don’t know too many fertility doctors that are not on the “Best Doctors in America” list. That’s not a list of the super-best doctors in America, it’s a complication of all if the doctors who are on the best local doctors lists. So there is no cut to make the America list. Most of those lists give a high priority to chairmen and division directors, again most of whom are good, but holding one of those positions is not an automatic for quality. Some lists are assembled through other doctors voting, and some of that could be politically biased.

You may have local infertility organizations that could make suggestions. This is tough because although I think these groups do an excellent job, I have been involved with at least one group who referred to their biggest supporters. But it might be good to at least find out which doctors are on their list.

What if the doctor is in all the medical societies? Medical societies are very important organizations that provide education and networking, but unless you have a criminal record, almost all societies allow members in. So you will see most doctors with impressive lists of their fancily named societies, but membership is usually about paying your dues and getting your certificate. There are usually no entrance criteria that represent quality control.

What about board certification? There is no excuse not to be boarded in OBGYN. Most of us are. What if you are going to a specialist, does he need to be boarded in Reproductive Endocrinology? This is usually important but there are some excellent physicians who have good reasons for not being boarded in RE. Maybe they are young and are waiting to become eligible. Maybe they are a little older and trained before getting certified was the thing to do. I would say that if your doctor is not, you need to carefully evaluate other criteria.

Does it matter where she did her training? Again hard to say, but better programs are more likely to turn out better physicians. Some of this may have to do with recruitment. The places with the best training reputations can more easily recruit the smartest and most caring people. So just by getting the best, they will turn out the best. The problem for you is knowing which training programs are the best. There are many renowned institutions that just have bad programs. It’s not uncommon to have a hospital with a great program in one specialty and a very bad program in another. And sometimes things change quickly within a program, so the training can become worse before the reputation changes. Magazines do publish the lists of top hospitals, and I don’t think there are many bad places that make those lists. However, there are many excellent places that don’t get the nod.

Nurses can be a good referral source because they see the doctors work every day. But a referral from a nurse may not be a slam dunk. I have seen nurses refer to their better friends, or to the doctor who is popular because he frequently brings in pizza.
Nurses know who operates the most, but not about their daily functioning and this brings us to the next point.

Is a doctor who operates at high volume the best surgeon for you? Maybe. A doctor who operates frequently may be really wonderful and have a massive referral base that keeps him in the OR frequently. They can be more experienced and confident and have fewer complications. However, some busy surgeons are busy because, for whatever reason, they over-operate. And some of these doctors have not gained from their experiences and maintain a higher complication rate. They may feel their procedures are indicated, but others may not. Getting back to the nurse, he sees what’s happening in the OR but he does not know about how the patients have been worked up and how they are followed after surgery.

There is one good trick that only works in a teaching hospital: ask a resident. No one knows the skills and limitations of your doctor better than a resident. The resident is in the hospital all day long and is involved with the workups, surgeries and recoveries. They are constantly communicating with your doctor. And believe me the residents have very strong opinions about each of the doctors they work with. Now it is hard to get hold of a resident, but ask around, may be a friend of a friend knows one. Plus, many hospitals have departmental web sites that list the residents, and some may list contact information. Because they are young, tired and stressed, sometimes the residents are a little too opinionated, and they may know about some of the doctor’s personal issues that don’t affect you. If you have a doctor and want their opinion, you don’t need to hear the doctor is the best of the best. You do want to hear that she is solid, not that she is below average or worse.

What if your only source is your friend who became pregnant after seeing the doctor she recommends to you? This is not enough at all. Many questionable doctors get some of their patients pregnant. It doesn’t mean that they are good. Just like there are some of the best doctors who just can’t be successful with everyone. This is probably one of the most common ways couples find fertility doctors, but it is the least reliable. So if you are told about a doctor, use other sources to validate the person.

Check the available medical misconduct sources in your state. Your doctor should not be listed there. There is also the National Practitioner Database, but information about specific doctors is not available to the public. The database is viewed by hospitals and insurance companies. In addition to misconduct, it lists the cases where a doctor was sued. Even the most excellent doctor can have a few things listed; it’s the nature of the beast, the way of the world. Most doctors are non-malicious hard workers who can run into a bad outcome, but this should happen only very occasionally, and if they have any cases listed the list should be very short. Some of the doctors who take care of the most complicated cases are more likely to be sued. That being said your hospital or insurance company should evaulate each case and avoid the frequent fliers.

And then there’s the internet. Have you ever stayed at a nice hotel and enjoyed the experience? Go to the internet and check the reviews, you would be surprised by all the negative comments. But, the average of the reviews would at least be close. So yes, the internet chats are some of the best places to find doctors, especially if you repeatedly read similar concrete reasons why a doctor is good or bad. I have heard of administrators going undercover on the sites to steer business to their doctor, so watch for that.

More on the best doctor for you next time,

Dr. Licciardi

PCO and other Fertility Related Topics

2010-05-13T11:09:00.003-04:00

PCOS (Polycystic Ovaries) and Ovarian Drilling.

Some sort of ovarian surgery has been used to treat PCOs for the last 50 years.The surface of the ovary, also called the cortex, is where the eggs are. This is a relatively thin layer covering the ovary. Beneath this layer, in the mid portion of the ovary, is the tissue that makes the androgens. PCO women have higher levels of androgens than women without, and it is possible that these increased levels are what interfere with normal ovulation. Androgens, by the way, are the hormones that get changed into estrogens, so androgens are absolutely necessary for normal repoduction, but in PCO the androgens are in excess. Opening this layer and removing or destroying the inner tissue, either by wedging out a piece of the ovary, or putting in multiple holes using an electrical probe or a laser, changes the hormonal balance of the ovary. It lowers the androgens and and somehow allows for more frequent ovulation. These procedures are not frequently performed because they do not always work, can cause scar tissue, and there are other alternatives.

There are other ways to stimulate ovulation, including clomid and FSH injections. Clomid works to cause ovulation in women with PCO in most but not all cases. FSH works in almost all cases. With FSH injuctions there is a high risk of ovarian hyperstimulation, unless the starting dose is very low. Certainly IVF is also an option.

Now some may ask why get involved with fertility drugs and the cost of monitoring when a simple surgical procedure will do the trick. In the case where the patient cannot afford complex fertility treatments, but can get surgery, the later does make sense. In addition some women just do not want to take any form of fertility medication, so the surgery may be the best thing for them. There can be complications from the laparoscopic surgery including the usual bleeding, infection and injury to internal organs. These are increased as the size of the patient increases, and more severely PCO patient may be more obese. But more specifically, the ovarian wedging or drilling can cause scar tissue and adhesions around the ovary, decreasing the chance of conception even if ovulation normalizes. This is is more common with wedge resection (taking out a wedge) vs. ovarian drilling.

So before surgery is considered, other methods of assisting ovulation need to be employed, such as weight loss, along with medical interventions such as those listed above, with the possible addition of prednisone and or metformin.

What if there is anovulation from PCO and you are having a laparoscopy for another reason such as pelvic pain, lysis of adhesions, endometriosis, or fibroids. Should you have drilling or wedging when the doctor is in there anyway? If the other methods of inducing ovulation are available to you, I would not cut into the ovaries because of the possible scar formation. Plus, wedging or drilling removes or destroys a large number of follicles. Reducing egg number is just something I like to avoid. If, however, you decide the drilling is best for you, the ovarian surgery is an accepted method and may lead to pregnancy rather quickly.

Other PCO Topics

Cysts from Clomid. Clomid makes follicles, which are the fluid filled cysts that contain the eggs. These follicles usually dissolve away 2 weeks ovulation but sometimes, especially when there are more than one, it takes longer than 2 weeks for them to go away. It is really rare that they are there after 4 more weeks. I have not had a patient have a cyst that lasts for months as a result of taking clomid. I have heard of such things, but they must be quite rare. It’s common to use the birth control pill to help make the cysts go away. Clomid causes the follicles to grow by upping the FSH produced by the pituitary. Birth control pills lower FSH levels so the theory kind of makes sense, but no one has really shown going on the pill makes any of these cysts go away any faster.

When should you come off metfomin, at the first pregnancy test or later in the pregnancy? Every doctor has a different idea. There is a prevailing thinking that PCO increases miscarriage rates. But there is at least one good study showing there is no miscarriage difference between women with PCO and women who normally ovulate. Plus there are other OK studies calling into question an association between miscarriage and PCO. However, there are a few studies in literature from outside the US showing metfomin reduces miscarriage rates in women with PCO, plus it reduces some pregnancy complications, including diabetes. This being said, the continuation of metformin during pregnancy is not standard among REs in the US.

Will provera increase your pregnancy rate if you have irregular periods? If you have PCO and have very infrequent periods, strongly consider taking to your doctor about clomid or FSH injections. Provera, except in rare cases, will do nothing to get you to ovulate. Even if you bleed after provera, you probably did not ovulate, you just bled.

Egg quality clomid vs FSH? Probably similar.

Is a clomid cycle that makes 6 follicles any different than an FSH cycle that makes 6follicles? Probably not, providing the clomid has not thinned out the lining of the uterus.

Sperm Topics:

Sperm quality 15 years after a vasectomy? Can really vary. In most cases the sperm is fine. Now if the sperm will be extracted via a needle, even if we consider the sperm quality excellent, we can only extract enough for IVF. But in some cases the sperm quality is lower than expected, but it’s rare that you can’t get a good IVF cycle out of what you find. If there are any changes for the worse, they may be unrelated to the vasectomy.

Can a CT Scan effect sperm? There is more and more discussion about CT radiation exposure every day. However, at this point, there is no evidence that a CT scan effects sperm counts, motility, or functionality in any way.

Should you have icsi with a sperm count of 12 million with 40% motility? This depends on how many sperm are recovered from the sample after rinsing and spinning (I know, sounds like there is a washing machine joke in here somewhere). Sometimes you can recover more than 5 million motile, sometimes only 2 million. Every lab has it’s threshold and will make a decision based on the number of motile sperm recovered. In our lab, 12 million and 40% motility usually means no icsi, but I would need to reserve judgment until we process the sample.

Is frozen sperm for iui less active than fresh? It depends on 2 things. One is the numbers and motility pre thaw. The more you have to start with the more you will have in the end. The second thing is how the sperm survives the freezing. Some really good samples just can’t handle the freezing and thawing. We do not know why this is; there are just differences between men that lead to different freezability. So the talk about frozen sperm is not as good for iui as fresh would only be accurate if post thaw counts or motility are low. Donor sperm has been put to the test. Anytime we freeze sperm we do a post thaw of a very small amount. If the post thaw is bad; bad donor. A good thawed sample is good; the good living sperm have not been weakened. Maybe some dies off, but the survivors are usually good survivors.

Most fertility doctors do not believe in the sperm penetration tests, especially when doing icsi anyway.

Miscarriage

What if you have had miscarriages, then surgery for a septum, and now can’t get pregnant? Start with repeating the HSG and getting a semen analysis. You never know, the septum may still be there, or maybe you developed blocked tubes or even a male factor. Also get the day 3 bloods.

Repeat biochemical pregnancies (yes I still hate that term) require the same workup as for miscarriages.

Frozen Embryos

Re-freezing embryos. There are a few papers showing that embryos can survive being frozen, thawed and then frozen again. Logic dictates that this should not be a first option, but there are cases where it seems like the right thing to do. If you thaw more embryos than you want to transfer, which is commonly done to select the best embryos, and surprisingly all the embryos look great, then refreezing the extras may be a good option.

What if you had a baby from a frozen cycle where 10 embryos were transferred, and you want to get pregnant again but only have 5 left? Even with your 1/10 success rate, 5 is plenty. In fact 5 may be too many.

General Topics

Is an endometrium of 14-16 mm too thick? Providing there is no hidden fibroid, polyp or hyperplasia, that thickness is probably OK. And what about an estrogen level that may be too high? There has always been talk about a too high estrogen level and this goes back to studies in mice. However, I have not see women whose problems are that their estrogen levels are too high. Some women with thin linings are put on estrogen injections or vaginal pills, and it is not uncommon to see levels over 2,000 in a frozen or donor egg cycle. Some women undergoing IVF have estradiol levels 5-10,000 (not a good idea for other reasons), and they have no trouble implanting.

Do I endorse Egg Freezing? I don’t really endorse anything. I am a fan of educating to the best of my ability, and allowing my patients to make informed decisions. Egg freezing is very promising, and some early studies show that is more successful that we thought it would be. But, it is still relatively new and expensive.

Both husband and wife diagnosed with hypothyroidism. It’s possible, but get a second opinion just to be sure. Some doctors over diagnose thyroid problems in everyone.

What if you had some questions about your luteal phase, so you were placed on progesterone but are still not pregnant? Don’t wait long. Talk to your doctor about starting clomid because it too is a treatment for luteal phase defect, and it may up your odds of getting pregnant as well.

How long do you need to be on OCP’s prior to an IVF cycle? In reality, you don’t need to be on them at all. One exception is the OCP microdose (also called microflare) IVF protocol. Here the recipe calls for ocps. But for all others, ocps are not necessary. Many programs use them to time the cycle. This means the program wants you to start on a certain day to time the retrieval/transfer. Or they want you to start in a certain week because they may have lab personal coming from the outside for a specified number of days. If you are relatively young and a good responder, the length of time on the pill probably does not matter. However if you are a marginal or poor responder, pill use, especially prolonged, could lower your egg production further.

Thanks for reading and don't forget the discalimer posted 5/17/06.

Dr. Licciardi

Cancelling IVF, Converting to IUI, and a Few Other Things.

2010-04-17T08:33:00.002-04:00

What if you are on drugs for an IVF cycle and there is a low number of follicles? Should you do cancel and have an iui (provided there is sperm and at least one tube is open) or should you have the retrieval?

The number of eggs is less important the younger you are. So at age 31, 4 eggs still results in an excellent pregnancy rate. At age 41, 3 eggs is much worse than having 10. So is there a “cutoff” number? Not really, and if there is it will vary from program to program. There are no strict guidelines for who should be retrieved and who should not. In most cases, when there are 1-4 eggs developing, the doctor will say that the odds with IVF become so low that it’s not worth the cost and effort of the IVF, so the better thing to do is the iui.

There was a very interesting paper presented at the last meeting of the American Society of Reproductive Medicine. One IVF center compared the pregnancy rates for women who decided to cancel to iui vs. those who decided to have the retrieval, when 1-2 eggs were present. Those women who continued on and had their retrieval had a higher pregnancy rate than those who had the iui. Now the rates for IVF were still in the single digits, but the rates were better than the iui numbers. So IVF is better than cancelling to IVF, but the odds of getting pregnant from that retrieval is quite low. Would you have a retrieval if your odds were 2% with iui but 5% with IVF? Some patients would, some would not.

I have mentioned before that we all know or suspect that there are IVF programs who cancel the 3 eggers because they are worried about lowering their statistics. I think there is less of that going on. I see patients being informed of their odds and then be allowed to make the decision. And the threshold may be different depending on your perceived potential. If it’s your first try and the doctor really thinks that a different protocol will do you better, cancelling makes more sense. If you have been cancelled for 3 follicles, and after protocol changes you make 3 again, well you make 3 and that’s it, so retrieve away.

What about multiple egg issues at the same time?
For example there are some women who make a large percentage if immature eggs, have low fertilization rates and have low embryo quality. Others have different mixes such as high rates of polyspermy, low rates of normal fertilization and poor embryo development. Others have mature eggs that do not fertilize without ICSI despite normal sperm, and then poor embryo quality. Is there one basic problem with the eggs that is leading to a completely bad scenario? This may be, but we don’t know what it is. The reality is that most women with a large percentage of immature eggs do pretty well with the ones that are mature. And women who have polyspermy, do pretty well with the eggs that fertilized normally. But for some of you, everything seems to be wrong despite protocol changes and changes with icsi, in hcg timing and day of transfer. Yes there may be a missing link resulting in multiple problems at once. It’s a matter of trying a few times and keeping all of your options open.

Persistently elevated prolactin levels need a full workup, which usually means an MRI of the pituitary.

What if your FSH is a little high and your AMH is a little low, but you have a good number of resting follicles and make a good number of eggs for IVF?
Those hormone tests are more about predicting egg number than quality. I believe the numbers have less of an effect on egg quality. Others may disagree, ask your doctor.

What if you suffer from autoimmune disorders and are having trouble conceiving? Is there a relationship?
Overall women with autoimmune disorders seem to be as fertile as anyone else. High risk OB practices are busy dealing with pregnancy complications of Lupus, RA and others. However, there are so many unknown factors related to fertility and the immune system, it does make one think that there may be a relationship when pregnancy is not occurring. I have seen a few cases of relatively young women with autoimmune disease who are very poor responders. I think there is a relationship between their disease and antibodies to their ovaries. Unfortunately there is still no good test to measure ovarian antibodies. There are good tests for thyroid antibodies, adrenal gland antibodies, but not yet for the ovary.

Here are a couple sperm questions.
Sperm counts that go from 100 million to zero then up again? He needs to be evaluated for intermittent obstruction: a blockage somewhere that occurs some of the time. Also could be intermittent retrograde ejaculation. Send him to a reproductive endocrinologist.

What if the urologist finds low counts and motility and does a thorough workup and tells you the numbers are what they are, can’t be increased and recommends IVF. You are always welcome to get another opinion, but it sounds like this guy is honest and he is telling you what most men are told. I believe in seeing a urologist because sometimes surprises are identified, but in most cases of very low counts and or motility, nothing is found and the only answer is IVF.

Yes ovarian hyperstimulation and ovarian torsion are related.
Torsion becomes more likely as the ovaries enlarge and become heavier. This increases the chances of the ovary rolling over and twisting on its stalk. Torsion with clomid can happen, but it’s much rarer because the ovaries have fewer follies and are smaller and stay lighter.

Thanks again for reading and please read disclaimer 5/17/06.
Dr. Licciardi

A Few More Things You Should Know About Egg Freezing and Thawing

2010-03-04T18:51:00.003-05:00

Once again, some of this also applies to regular IVF.

Just as not every follicle gives up an egg, not every egg we get is usable. This mostly has to do with egg maturity. We can’t use an immature egg, it will not fertilize later. For those of you familiar with in vitro egg maturation (IVM), I don’t want to get into that whole thing here. Suffice it to say, IVM had a very limited role with very limited success.

Basically, getting an egg to mature after we retrieve it is of little value, we count on the eggs to mature in the ovary before we get them. We need tree-ripened fruit.

Most retrieved eggs are mature but 10-20% may not be. So if say you get 15 eggs, having 3/15 immature is typical. Like anything else we talk about, variations exist. Some women, no matter how we change their drugs or increase the number of days on drugs, end up with ½ or more of their eggs immature. This is an exception, as is the case when every egg is mature.

Less often we have another small problem: atretic eggs. Atretic eggs are basically just dead eggs. This is much rarer than immature eggs. Another rare problem is a cracked zona (cracked shell). These also are not very viable.

So the point here is that if your doctor sees 15 follicles it does not mean there are 15 eggs to use. By the time you account for eggs that don’t get retrieved, immature and atretic eggs and eggs with cracked shells, you should still be left with about10 that are usable. But it could be more or less depending how the chips fall.

And away they go, into the deep freeze, for months or years (decades?. You work, you live and then one day you decide the time has come to attempt pregnancy; you go to the bank and make your withdrawal. This is another spot for potential attrition.

Not every egg survives the thaw, but most do. One of the many really nice papers on egg freezing recently published by NYU’s own Drs. Grifo and Noyes ( Fertility and Sterility Volume 93, Issue 2, 15 January 2010, Pages 391-396) shows that about 92% of eggs survive the thaw. If they survive we can attempt fertilization.

There are 2 ways to fertilize eggs, one is to mix the eggs and sperm together and let the sperm swim in: this is used when the sperm counts and motility are close to normal. The other is, under the microscope, to pick up a sperm and inject it into the center of the egg: this is used when the sperm counts and/or motility is low. This is called ICSI (inter cytoplasmic sperm injection). For some reason, eggs that have been frozen require ICSI to develop into good embryos. The requirement for ICSI is not a big deal; it seems to work quite well, although it does add to the cost of the procedure. But to continue with a familiar theme, not every egg that has ICSI fertilizes. The same study above shows that 79% of eggs that get ICSI normally fertilize, which is very similar to the rate for fresh eggs.

So the 10 that were frozen are now fewer. You could have 10, but the number may be more like 9, 8, 7, 6, or even 5. And we’re not done yet.

Fertilized eggs need to grow in the lab for another 2-4 days before the transfer. I have a number of blogs that describe embryo and blastocyst development, starting on December 14, 2008. There you will see the changes that take place as things progress from egg to embryos as the the days in culture. You can see the difference between good and bad embryos. Naturally you would like to have nice good looking embryos. And as the story goes, not every fertilized egg makes it to a nice embryo.

Reading this one would think that it’s impossible to have a good outcome from egg freezing, but in reality most women have an average egg yield and enough nice embryos to have an average chance for pregnancy. But again, there is variation. The luckiest women have high egg number high fertilization rates and many really nice embryos, and even some extra embryos for freezing. In other scenarios, there are many eggs and embryos, but they do not develop well.

There is a bit of a waiting game to get your results. In fresh IVF, you know within a few days where you stand. With egg freezing, you will not know how many good embryos you have until you thaw the eggs maybe years later.

We do not yet know how many eggs we will need to thaw later. We may feel comfortable enough to thaw 4-6 and try with those. However, as we accumulate more data, we may find that you need to thaw more to have a good chance. This is important because if you have 8 eggs frozen, thawing 4 at a time can give you 2 chances, but thawing all 8 will give you only one. And then there will be a question about how many embryos to put in your uterus, the recommended number may change with time so this is just something to keep in the back of your mind.

Here’s another question. Should you do any “fertility” or “preconception” workup prior to freezing your eggs? The question here is should you have any tests that may effect you ability or decision to get your eggs/embryos back later. For example, should you have a hysterogram to look for abnormalities in your tubes or uterus before egg freezing? Should you have any genetic tests, cystic fibrosis for example, before freezing your eggs? This you should you discuss with your doctor. In actuality, there are very few things that would keep you from getting your eggs back later. If you are a carrier for cystic fibrosis, you probably will still want to become pregnant with your eggs, providing you screen your partner or donor. If you doctor is minimally good at ultrasound, she should be able to tell you if you have a major abnormality of your uterus without a hysterogram. Most women are still candidates for pregnancy even with an abnormal uterus. However, this is very important to review your history and the potential tests with your doctor. I have had women who wanted to have all the tests done before egg freezing, but not everyone does.

Costs. There are a number of cost centers associated with an egg freeze cycle. There is the cost of the egg freeze cycle. This is the fee that the IVF center charges for the ultrasounds and blood tests associated with your cycle. It includes the retrieval procedure and the egg freezing.

What does in not include? You first need to see the doctor and he usually performs an ultrasound. This is separate. There are the optional tests described above, but there are mandatory blood tests that check your thyroid, prolactin, hepatitis status and others. Your insurance may be more likely to pay for theses but you need to check.

You will most likely need anesthesia for your retrieval procedure; in many cases this this is an extra fee of $1000 or more.

There are also yearly charges to store your eggs, which usually kick in after the first year.

Plus there are real costs, in the thousands, associated with getting your eggs back. This requires the thaw, lab handling, ICSI, ultrasounds, blood tests and the embryo transfer. If you have extra nice looking embryos, you may be allowed to freeze some of them, but again there is an extra cost, and a thaw transfer cost again.

OK, I think that's almost everything you need to know about egg freezing. I hope it helps.

Thanks for reading, and read the disclaimer 5/17/06. Looks like spring may finally arrive.

Dr. Licciardi

Take a Survey to Help Fertility Research

2010-02-23T20:09:00.003-05:00

Hello Everyone,

I have been asked by a researcher to help recruit people to participate in her infertility study. I have spoken to her and she seems dedicated to a very good and important project. Please consider taking her survey. The information is below. This study was approved by the University of Texas internal review board.

Have you and your partner been undergoing treatment for primary infertility?
If so, please consider participating in an online study of the impact of an infertility diagnosis on marriage.
1. You are eligible to participate if you are a married heterosexual couple
2. You do not have any biological or adopted children living in your home
3. Either you, your spouse, or both has received an infertility diagnosis (unexplained infertility qualifies as a diagnosis)
4. You are currently receiving medical treatment for infertility, have done so in the past six months, or plan to do so in the next 6 months
5. Both you and your partner are willing to participate and have access to the internet.

Participation in the study will involve completing an online survey focused on your experience of infertility, your self-perceptions, and your feelings about your marital relationship. This is expected to take no more than 15-20 minutes per spouse.

Participants will receive a voucher good for a pair of free movie tickets upon the completion of the surveys by both partners.

To participate, please send an e mail to: morray@mail.utexas.edu
Elizabeth B. Morray, MA
Doctorial Candidate
Counseling Psychology
The University of Texas at Austin.

The Infertility Blog Wins Award: Best Infertility Blog

2010-02-10T15:43:00.002-05:00

Thanks to all of you who voted for the Infertility Blog. It was recognized as the Best Infertility Blog by you, and the people at Wellsphere. Their Logo is now on the side of this blog.
Thanks again and more to come.
Dr. Licciardi

Questions About Infertility Issues

2010-01-31T16:43:00.001-05:00

Ovulation Timing Questions
If your cycles are 55 days, are you ovulating? Most likely, probably around day 41. However, it is possible that you are not, so you must confirm through your doctor.

What if your cycles are 28-31 days but a progesterone test proves ovulation day 11? Very unusual, but it does not mean you are infertile. Check for ovulation a little earlier using the LH kit to see when it starts and to see if this is a consitant issue.

Is there a problem with 70 day cycles? Yes. You can try to track ovulation but when do you start to do so? If your cycles are always 70, check a progesterone day 60. If it shows ovulation at least you have that. It’s just harder to time things with such a long cycle, and you really don’t have many ovulations per year. If you want to get pregnant, get some help.

Miscarriage Questions
If you are having miscarriages on clomid, will IVF up your odds of going to term? Different doctors will give you different opinions. The IVF option will sit differently with different patients. We aren’t sure if IVF will reduce your miscarriage risk. So the answer is probably no, your odds will be the same with or without clomid. However there may me a play to try IVF with PGD. This option you really need to talk about with your doctor.

Does having an early miscarriage predict further pregnancy loss? Usually not. The odds are still excellent for having a baby in the next pregnancy if you had had only 1 miscarriage, or even 2-3 for that matter.

Will you ever conceive again after trying 3 iuis that resulted in one ectopic and 2 miscarriages? And suppose one of the tubes was removed? If the remaining tube is open, your odds would be excellent of conceiving again. But don't wait too long before getting help.

Is there a relationship between a long follicular phase and miscarriages? Most likely no.

IVF Questions
Is it better to transfer a fair quality embryo on day 2 or let it grow to day 3 or day 5? Does the uterus provide an advantage over the Petri dish? Unless the lab is really bad (these days there are few really bad labs), then it does not matter. Now that’s’ if there are only 1-2 embryos. If there are more, going to day 3 will help you select the better embryos for transfer. Lab differences are more of a factor when going from day 3 to day 5.

What if the sperm is normal and you are not fertilizing? Should you try donor egg? If you wish, but the problem is more likely related to the sperm. Of course, unless you try donor sperm or donor egg you would not know, but if you look at a 100 patients who are having your problem, almost always the sperm is the issue.

If you are a poor responder, will adding clomid to an IVF cycle give you more eggs? It is one of the options. I make it may last, I put Estrogen prime of microdose first, then maybe clomid. Clomid sometimes makes the uterine lining thinner.

Is there a weight limit for IVF? It depends on the program. The fact is, people are getting bigger and doctors are getting more used to dealing with the big problem. However, it may be important to meet with the anesthesiologist who would be taking care of you during your retrieval. More important than your weight is the configuration of your neck and throat. They want to be sure that if you have trouble breathing, they can get a tube down without a problem. And let’s not forget that your doctor may be less worried about the retrieval and more worried about you and your baby during and after the pregnancy. It has been clearly shown that obesity is bad for pregnant women and bad for babies to be in the short and long term.

If you’re a poor responder, will dexamethasone produce more eggs? This has not been shown to be the case.

Do frozen embryos make healthier babies than fresh? There was one article that somehow came to this conclusion. We do not think there is a difference.

What if a “dominant follicle” seems to be the problem? Dominant follicles come in a variety of forms. Some women are very poor responders and only make one follicle. I have heard this referred to as a dominant follicle. More commonly, a dominant follicle means that you have the potential to make many follicles, but for some reason, only one is big and the others remain small. There are strategies to try to reduce this phenomenon but they may or may not work. We believe that in a natural cycle, the dominant follicle may be selected before the period even comes, so by day 2 the body has already laid out its plan for that month, and stimulating the ovary with drugs may not be able to alter that plan, leaving you with a low number, or just one dominant follicle. So by using oral contraceptives or lupron to turn off the ovary system for a little while, we may be able to stop the dominant follicle pre-selection and give more than one follicle a chance at becoming dominant. However, most of the time, the difference is not extreme

25 years old and not pregnant after an IVF cycle with nice embryos? In the end you will probably be fine. As I have said many times, get to the best program possible. Even at the best programs, these things happen.

What if you have a low AMH level (a sign of poor ovarian reserve) but have many resting antral follicles as seen by ultrasound and make many eggs during stimulation. In your case, the AMH is just dead wrong. As far as we know the AMH is not predictive poor egg/embryo quality, just egg numbers. AMH is promising as a way to measure reserve, but there are a few problems, most of us are not comfortable yet using if for a definitive diagnostic tool. In many cases it does give us correct information, but we need to fine tune the testing and result interpretation.

Interesting question. If a clinic is more aggressive in bring patients to IVF early without much other treatment, will their IVF success rates be higher than clinics that get some people pregnant first with clomid or FSH? Will doing IVF on fertile people make a clinic look better? I would say in a few case yes, this makes sense. In fact overall, since IVF seems to work well enough for most people, more people are doing IVF after shorter intervals of clomid or FSH. However it depends on the IVF success rate differences between the 2 clinics. If there is a small difference, I would point to the selection. If there is a big difference, IVF quality is a big part of the discrepancy.

How do you know if the clinic does a good job with blastocyst culture? Try asking what percentage of transfers are blastocyst for your age group, then ask the delivery rates for blast vs. day 3. Of course check their SART statistics. If they have very good pregnancy rates but do much blast, that may be fine. However also check on the number of embryos they put back. If they have good rates with a higher number of embryos returned and a higher number of triplets, that’s not so good. One of the goals of blastocyst culture is to take advantage of the natural selection process so that by day 5 the best embryos will stand out. If we can see which ones are better, we can put fewer in and reduce the odds of multiples, while maintaining higher pregnancy rates.

IUI Questions
When should you do the iui after the trigger shot? Ovulation will take place 36-38 hours after the shot. There is not a specific time that has been shown to be better. The sperm may be available to fertilize for at least 2 days. The egg is good for about 1 day. So it is reasonable to have the iui performed 24 hours after the trigger.

What if it seems on FSH you are ready too early? Even though you may be ready on the early side, the egg or eggs are probably not affected. However, if it is early there is less harm in waiting an extra day or 2 to give the hcg. I have not heard this to be more effective than just giving the hcg at the usual follicle size, independent of the cycle day.

Should you see an RE or should you let your general OBGYN handle the clomid? It depends on your threshold. If it’s really that more convenient and less expensive, and you are not in a super rush, a few months with your generalist is fine. Otherwise, get to the RE.

Donor Egg Questions
One of my most difficult questions. What if you are doing donor egg with a proven donor and your embryo quality is not great, even when splitting the eggs ½ donor sperm, ½ partner sperm? Clearly all avenues have been explored. If you have not already, and wish to continue, consider another opinion. Now I have seen proven donors give disappointing results in subsequent cycles. It is true that a young donor is more likely to make a baby with embryos that don’t look as good, so maybe the proven donor made fair embryos last time and made a baby. We have been surprised when there are pregnancies from poorly looking donor embryos, but thankfully we see it now and then.

Tubal/Uterine Questions

What about a second surgery for a septum, may it be necessary? Occasionally, more likely with a larger septum. Sometimes at surgery the cavity looks fully repaired but an HSG 2 months later shows there is still a good piece remaining. In this case maybe the upper septum scars together making it appear it was never cut. Or maybe it was never cut, which could be for 2 reasons. Maybe the doctor cut and cut and cut and was really pleased and observed there was a little piece left but felt almost it was gone, and that it was ok to leave a little. He may have wanted to avoid cutting too much, which would increase his chances of perforation. And many women do just fine with a small piece left, as long as it is not too big. But leaving a small percentage may still be leaving a substantial amount. To cut more and reduce the odds of perforation, the doctor can use an ultrasound during the surgery to watch the uterus and the septum, to help cut most of the septum but not perforate.
Another reason for finding some septum after the surgery is that there may be times when the pressure of the fluid used to distend the uterus during hysteroscopy pushes the and remaining septum up towards the muscle layer, making the inside of the cavity look smooth and normal. Yet, once the pressure is relieved by removing the fluid, a bit of the septum bulges back down into the cavity of the uterus. This is theoretical on my part, but I am guessing it does happen this way.

If you have proximal occlusion and your tube is opened, will it stay open? If it was really blocked and you have a procedure to have it opened the odds are about 70% that it will stay open.

Thanks for reading and please read the disclaimer from 5/17/06.

Dr. Licciardi

Egg Freezing and IVF: How Many Eggs Do You Need?

2010-01-11T16:44:00.003-05:00

Again, this entry has many elements that apply to standard fresh IVF cycles.

Here we’re trying to close in on the real question, “If you do egg freezing, will it help you have a baby?”

Well, it will really does help if you can make some eggs. Sorry if that sounds too obvious, but the more you make the better your odds of this whole thing working years down the line. Just as with any IV F cycle, egg production is based on the number of eggs that are still in your ovaries, and how they respond to the medications.

Much of this is loosely related to a woman’s age but there are a number of other factors involved. The dose of drug can have an effect on the number of eggs produced; the more drug the more eggs, but only to a point. In other words, if your ovaries are full of eggs, a dose of 450 units per day may be way too high and lead to danger, but a dose of 225 might get you 15-20 without much of a risk. However, if your egg reserve is marginal, 225 may make 6 eggs, 450 may make 8, but going over 450-600 probably will not get you any more.

There are papers and book chapters written about how to stimulate ovaries to get the maximum response in women with limited ovarian reserve. For today let’s just say that one of the hardest things we do is try to get the ovaries to produce more eggs than they want to. There are numerous stimulation protocols that we try, and sometimes we get more eggs than expected, but sometimes we get fewer. In very many cases, it may be that it wasn’t the doctor’s choice of medications; it was just the woman’s body being more or less cooperative during that cycle.

Testing for ovarian reserve is one way to get a general guess about your response, but it’s not always helpful. A bad ovarian reserve test is not good news; a favorable result does not guarantee results. There are many of you reading this who despise ovarian reserve testing and some of you who have proved doctors wrong, having babies after being rejected for bad day 3 blood tests. I understand this. I think the testing is should at least be performed to give you a general idea about your prognosis so that the expectations can be based on all available information. Included in this is an ultrasound examining the antral follicle count. Again, not a perfect test, but it will help you get closer to answering the question, “Will this help me?”

You will not know about your egg production until after you start your cycle. Let’s say you have had your consultation and testing and things look reasonably positive, so you decide to give it a go. Fine, but you need to know a few more things. Especially if you have never been on the fertility injections before, the number of follicles that you develop will be a mystery until you are on the drugs for 5-8 days. By then your follicles will have begun to grow and your doctor can count them up and let you know how you are doing. Unfortunately, some women will be producing a low number of eggs.

Follicle number does not equal egg number. We see follicles on ultrasound; we get eggs from the follicles. We never really know how many eggs you will get until we try to take them out on the day of retrieval, but we have certain expectations. If we see 10 good sized follicles, we expect to get 8-10 eggs. There are endless examples of variations. For instance, let’s say you are ½ way through the stimulation and it looks like there are 5 follicles. But there may be others that look very small, maybe too small, but over next few days the small ones may catch up, giving you say 9-10 decent follicles on the day of retrieval. Another possibility is that you have 5 good ones and 4 tiny ones at retrieval, and even the tiny ones that never caught up in size, still give up good eggs (this is not typical).

The opposite could also happen. Your doctor may see 10 follicles and only retrieve 5 eggs. How is this possible? It’s not uncommon to have fewer eggs than follicles. Some doctors feel that there are some follicles that do not have eggs in them. I think this is possible but not very common. It may also be that the egg is in the follicle but it just does not come out through the needle. This I think is more common. Generally the egg is very loosely attached to the inside of the follicle, but if it’s stuck to the inside, it may evade the needle.

So how many eggs do you need to have a successful egg freeze (or fresh ivf cycle for that matter)? Again the too obvious answer is the more the better. However 10-15 is a good yield. More than that is a bonus. It is true 30 may be better than 15, but most women do not make 30 so that should not be your goal. Estimates in the 10-15 range usually do not prompt much patient/doctor discussion, however when the estimate is lower, the talks become more frequent and important.

Usually your doctor is close enough with the pre-retrieval estimate, so assume it will be close. If a low number is estimated you will need to make a decision, with the help of your doctor, about having the retrieval or not. Yellow flags should rise if you are told there are less than 10 follicles, and red flags should rise if you are told there are 5 or less.

Overall there is just no absolute egg number cut-off for cancellation. Some programs may have strict guidelines, but most do not. We all understand the dilemma. If there are few, your odds of success are lower, however if there are few, it means your fertility may be passing. Getting, say, 4 eggs now may be better than nothing, because as months pass, you may make fewer in the future. Stopping without the retrieval, and restarting in a short amount of time, using a different protocol, would probably be the best choice. However, even with making changes you may have the same or even fewer next time. Now I picked 4 follicles as just one example, but the discussion needs to be tailored for 3,5,6,7 etc. Your age, previous response and your desires all need to be taken into account each time.

Your doctor needs to take the information above and formulate your chances of not just getting eggs, but of getting a baby from your egg freeze cycle. This applies to all cases, good egg production or not.

You will get the most accurate information if you are using an egg freezing practice that has results, not just freezing experience. Experience and results with the thaw and transfer is very important; you need a program with a track record. You need to know their experience in going from eggs to babies. Many busy egg freezing programs have no results because they have not thawed any of their eggs yet. Others have done less than a handful of cases.

I do want to refer you to the NYU Fertility Center web site section on egg freezing.
http://www.nyufertilitycenter.org/egg_freezing.
Spend some time going through all of the pages, the information is very helpful.

Thanks to the fantastic research and efforts of the doctors listed there, NYU is known for its egg freezing practices and results. I could summarize the site here, but in the interest of accuracy, go directly there to get it from the horse’s mouth. The results are frequently updated.
The breakthrough, as mentioned on the site, is that we believe that our egg freezing success rates will remain similar to our fresh IVF success rates. Therefore, it will help if you have your eggs frozen at a program with excellent fresh IVF pregnancy rates. If their fresh IVF rates are low, their egg freezing rates will probably be low too.

Not all egg freezing programs can show good data to support good results (2 out of 4 pregnant is not enough.) There are a few who can, so if you are interested in egg freezing, you need to seek out the good ones. Details are sparse, so I really only know about NYU. Odds are there is not a quality program near where you live, so if you can swing it, it may be worth traveling.

Even the NYU rates need to be clarified. Most of the studies at NYU and elsewhere on egg freezing have been performed with good prognosis, younger women. We are not positive that older women’s eggs will freeze and thaw well. They probably will, but there is no data yet to prove the case. We don’t know how long eggs will last in the freezer. We do know there have been children born from sperm and embryos frozen for over a decade, so eggs should be able to last at least as long, but again there is no proof yet. Egg freezing is very new and still considered experimental you do need to freeze your eggs at the right place.

We and other doctors can not completely predict the landscape 5-10 years down the road. We are optimistic that our pregnancy rate estimates are correct. However there is a chance that due to unforeseen circumstances, the rates will be lower. You just need to know this going in. It may also be possible that the outcomes will be better than we had hoped.

Next time we will cover what you should know about what happens after the eggs are retrieved and how the cost structure works.

Thanks for reading and don’t forget to read the disclaimer entry 5/17/06.

Dr. Licciardi

Some Complications of IVF and Egg Freezing

2009-12-21T09:36:00.004-05:00

Hello to everyone again.

This blog is a segue into Egg Freezing. I realize that for most of the infertility community, egg freezing is not applicable, but I do get many questions about it. Plus, I suspect that many of you are the family fertility experts or the neighborhood fertility pros, unfortunately your struggles have made you experts, and you too may face questions about the topic. Some of this also applies to regular IVF, so it’s worth a read through.

If you wish you can start with the blog from 3/11/08, which goes over many of the basics and positive aspects of egg freezing.

I am writing today because a good understanding of IVF and egg freezing requires you to know the fine print. It’s not that the fine print is bad news; it’s just part of the full disclosure. This installment will deal with drug and procedure complications of IVF, which also applies to egg freezing. More specific egg freezing blogs will follow.

From a patients perspective, 95% of egg freezing is just like any other IVF cycle, which is summarized as follows. A woman takes 1-2 hormonal injections per day for about 2-3 weeks (depending on the protocol), and during that time she needs office monitoring, about every other day, where blood tests and ultrasounds are performed. We use the information from the monitoring to adjust the drug dose if necessary and to tell us when the right time is to remove the eggs. Once the time is right, a retrieval is performed. This is a procedure done usually in the office, but some programs have it done in their hospitals. It’s done under intravenous sedation, which means the woman is totally asleep, feels and remembers nothing, but is not intubated and breaths on her own. Using the ultrasound for guidance, a needle is passed through the vagina, into the ovaries and into one follicle at a time. A suction machine pulls the fluid from the follicle into a test tube, and in the fluid is one cell that’s the egg. Usually eggs are retrieved from follicles on both ovaries.

The test tube gets handed to the embryologist in the adjacent lab, who finds the egg in the fluid and then does the rest.

The retrieval procedure takes about 20 minutes, and when done you wake up right away. You are watched in the recovery room for one hour, and off you go home. The next day you would get a phone call to confirm the number of eggs that were retrieved and the number of eggs that were frozen (yes, in many cases there is a difference).

Sounds pretty simple? For most women but not all, it actually is relatively easy, but it requires time and of course money (we’ll get to that).

There are potential complications with any IVF or Egg freeze IVF cycle, but they are rare.

One is ovarian hyperstimulation. This is where the ovaries are very sensitive to the medications and become too large. Normally, the unstimulated ovaries are about the size of walnuts, and the medications may make them the size of lemons. This can be a good thing because if you are going through the trouble of the procedure, you would like to get as many eggs as you can, but within reason. Problems occur when the ovaries become too large, whereby they may leak fluid, and this fluid can spread to the abdomen and lungs and result in hospitalization. Very sick women may develop problems with their liver and kidneys and be at a high risks for blood clotting in their legs, lungs and other places.

What is happening is that as the fluid goes to places it’s not usually found, it leaves the circulatory system, making the blood thicker than usual. So there is too much fluid in the abdomen, but not enough in the bloodstream. The treatment keys are properly managing the fluid imbalances. If there is extra fluid in the abdomen or lungs, drainage is usually appropriate. If the blood becomes too dry, we need to add a little fluid there.

I realize this sounds hideous, but in fact severe ovarian hyperstimulation is very very rare in IVF and even rarer in women who freeze their eggs. Early pregnancy makes hyperstimulation worse, and since no immediate pregnancy will become of egg freezing, the odds of hyperstimulation become remote. I’m not saying it can’t happen, and mild and moderate forms of hyperstimulation are more common, but severe forms would be exceedingly rare. Plus a good infertility clinic should be able to treat this complication safely.

Still with me? What about the retrieval?

Well there’s the anesthesia. In my 20 years of being involved with 15,000 plus cycles, I have never seen a complication related to the anesthesia. Next topic.

What else? Well, we do push a needle into the abdomen, so there is a potential for bleeding and infection. The odds of needing a transfusion are less than 1 per thousand. The odds of getting a significant pelvic infection requiring hospitalization and IV antibiotics are similarly low. Women with a history of pelvic infection should receive prophylactic antibiotics at the retrieval to reduce their risk, because women with a past infection are more likely to get a second.

And then there’s torsion. The ovaries are inside your pelvis hanging by their blood vessels, not too different from the way testicle hangings on the outside. As the drugs increase the size of your ovaries, they get heavier and may make them more prone to spinning around, twisting the vessels and choking off the blood supply. You would know this is happening because it causes severe pain and nausea. Torsion can happen before the retrieval or after. It can even happen 1-2 months into the pregnancy (the ovaries of pregnant women may remain large for a couple of months after the drugs are stopped. This is because the hCG from the pregnancy stimulates the ovaries to retain their cysts to make more progesterone until the placenta takes over).

Of course for egg freezing, there is not an increased risk of torsion during a pregnancy because the pregnany will get started with the ovaries normal sized. Ovary-enlarging fertiltiy drugs are not used for the thaw cycle.

Torsion is rare event, occurring in less than 1 in 1000 cases. The ovary can be untwisted via an emergency laparoscopy. If it is untreated, the ovary can die from lack of circulation. However, we have not had this happen to anyone. The key is to call your doctor if you have pain. Losing an ovary does happen with torsion, but the usual scenario here is pain in a woman who is not undergoing fertility treatment, but develops any type of ovarian cyst that enlarges the ovary. Typically, she has pain for a while and is told to wait and see, and then she finally is told to go to the busy emergency room where she is given pain medications. Then many more hours go by waiting for the GYN consult, and by the time they get her to the operating room it’s too late. In the infertility world, your first phone call sets off the alarms and you are evaluated and treated in plenty of time.

And then there is the potential for the ectopic pregnancy. Check out the the ectopic bogs starting 5/31/07.

So that’s the yucky drugs and needles part.

Next time we talk about the pitfalls of egg freezing will try to answer the question, “Will egg freezing help me?”

Thank you, and please read disclaimer 5/17/06.

Happy Holidays!
Dr. Licciardi

Infertility Q and A

2009-11-29T19:21:00.002-05:00

Hello again. Here is the latest entry.

Can a small hydrosalpinx prevent pregnancy? Yes it can and it can prevent pregnancy when trying on your own or with iui (assuming the other tube is normal) , or with IVF. Now a small one is less likely to be problematic, but the studies showing hydros are a problem do not differentiate between small and large. It is not mandatory that hydros be removed, but the pros and cons of removal should be discussed with your doctor.

Does a 44 yo a woman who makes 14 eggs have a higher pregnancy rates than most women in her age bracket? Absolutely. For women in their 40’s, egg number is strongly related to odds of conception. It may be that bigger the reserve the healthier the eggs are in general, or it may be that the more you have, the high the chances of finding at least one good one. This is less important in younger women, whose odds are good even with a lower egg number.

Should you have a second laparoscopy soon after a first in order to do more fixing and cleaning up? These are options but there are others. Back in the day before IVF worked well, this scenario was common, but today if the first laparoscopy looks that bad we recommend IVF. Now this does not mean surgery should be out of the question, it’s just that odds are if the pelvis is so bad, a second surgery will not help much. You really have to try to get a sense of what the doctor feels the improvement will be after a second surgery vs. IVF. If IVF is not an option for you, then the surgery may make sense. It’s a little strange that all of the fixing up was not performed at the first surgery, but there may have been very good reasons for stopping the first time.

Why give 5,000 units of hcg instead of 10,000, and are there any problems with this? It has to do with hyperstimulation. You cannot have significant hyperstimulation without the hcg injection. The hcg stays in your system for at least 10 days, stimulating and stimulating the ovaries to make progesterone, but the stimulation keeps the ovaries big and can push them to hyperstimulate. So it makes sense to maybe give less if we are worried about hyperstimulation. If we give half the dose we may be lowering your risks. Again, makes sense, however, I have not seen much written showing that ½ the dose is any safer. It is possible that if you try to take less you will not get enough. Now if you have a good vial that really has 10,000 units, and you are a good mixer, then ½ the dose should be enough. But it may be that some vials do not contain the full 10,000 units. Sometimes the extra mixing instructions are just too confusing and for one of a number of reasons 5,000 units do not make it into the syringe and into your body. This is why we measure the hcg level the day after the hcg injection. A few times per year someone in our practice has a blood level of the zero the day after the injection. The most common reason for this is the injection of air, which occurs by not putting the needle into the liquid before withdrawing. The second most common problem is the injuction of water only, which happens if you forget to mix in the powder. Believe me, both of these happen mopre than we would like. The water only problem can't happen when using the premixed. Sometimes the there is some hcg in the blood, but the level is really low. If we get numbers under 50, we give another shot but go with the original retrieval time. If the level is zero, we give the hcg that evening and make the retrieval one day after the original day.

Can you exercise while trying to conceive? Sure. However you cannot if your ovaries are enlarged from fertility drugs. If you are unsure when the stopping time is, ask your doctor every time you have a scan.

I am reposting this question because it’s really well written and it applies to a large number of fertility patients who are starting out. My comments are in bold:
So my hubby and I have been doing infertility testing for a year. I had a miscarriage at about 7 weeks about 2.5 years ago and have been unable to get pregnant since. I did a 6 month study through the national institute of health where they gave me either a placebo or low-dose aspirin and a fertility monitor, all with no success of pregnancy. My hubby's done 3 semenalyses, (which have proved to be normal. . . he had an abnormal count of about 30% on one, but the rest were fine and the counts were fine), we both did the antisperm/antibody test most of us to not do this test, it just has not been shown to be helpful which turned out normal, he did the hamster test and got 100% penetration never done anymore, an ultrasound which proved to be normal good, as well as blood tests for both of us that have proved to be normal.
My cycle varies between 25-33 days, but always falls within that window, just varying lengths within that window no problem. I recently did an HSG test and it showed no blockages excellent.
Our next step in the process is a post coital test antiquated, a blood draw at a certain point in the cycle, and a sample of my uterine lining antiquated to see if it's thick enough at that point in the cycle to be viable for a baby.
My dr. said that at that point, if everything's normal, we can proceed with IUI. However, he did say that we should consider doing a laparoscopy to check for possible endometriosis. He said that even though my HSG test was normal that if I had endometriosis it could possibly flare up and die down. I've always experienced mild cramps for 1-2 days on my cycle but isn't that normal? He said cramps could be indicative of endometriosis. I have no problems with doing a laparoscopy if it weren't for the cost. . . $2500. I'm just wondering if with everything else positive if mild cramps being my only symptom are enough to warrant the cost of checking it out, or if it's something that won't affect my fertility too much. This is acceptable medical practice, however you need to ask about the payoff. If the hsg, exam and ultrasound are normal, the odds of having endometriosis are very very low. Actually the odds of finding a little endometriosis are about 10% because that’s the baseline rate in all women, but the odds of meaningful endometrioses that has grown to the point of interfering with you getting pregnant are very low. Now that’s not to say that the laparoscopy is not an option, but I would get a second opinion if you wish.
As far as my comments on the antiquated tests, again acceptable medical practice, but a little out of date. It does seem that your doctor is organized and at least has a plan.

If you are a little older and had a chromosomal miscarriage, should you be discouraged from trying again? I don’t think so. Yes the odds of miscarriage increase with increasing age. Most pregnancies, even in women in their early 40’s go to term. The miscarriage rate is high, but there are more babies than miscarriages.

Should you take any steps to shorten the follicular phase? If your cycles are far apart, it just makes it harder to conceive because you get fewer chances per year than most people. Another problem is that it’s hard to know when ovulation is taking place, so timing can be an issue. However, I am not aware that the egg quality is compromised in a long cycle. If you can time it well, the odds are the same as in a more normal cycle, and I have not heard that the miscarriage rate is any higher. So most do correct a long cycle to make it shorter, but it’s not because we are trying to control embryo quality.

How are polpys diagnosed? Ultrasound or HSG or sono-hysterogram (this last one is where the doctor uses a speculum and squirts a little water inside the uterus while doing the ultrasound. This really helps see small defects in the uterine lining, like polyps). I have found through the years, especially as the quality of the ultrasound machines have improved, that a careful vaginal ultrasound works quite well. HSG has been OK, but it misses small polyps. The sono-hysterogram is probably the best test because it finds the smaller ones, but if the uterus looks perfect on regular ultrasound there is only a small benefit to having the sono-hysterogram.

Day 7 blastocyst? If day 6 works why wouldn’t at least some day 7s?. I have not had any patients use day 7 embryos. It’s suboptimal. Maybe as we get more experienceday 7 will become useful. One problem may be that a good embryo will be hatched out of it’s shell by day 7, which may or may not be a problem. .

IVF during breastfeeding? It can work but I don’t know if the breastfeeding affects your chances of success. Yes most fertility drugs are the same hormones that are already circulating, but taking the drugs will increase their concentration in breast milk.

After chemo, if the sperm counts are ok, is the sperm ok? This is tough to answer. My feeling is that it is, but it’s just a feeling. You will certainly get different opinions from different doctors. I have not met any doctors who do not want the husband to use the sperm, but there could be some out there. The doctors may inform the husband that there may be unknown issues.

Translocations: is IVF the only way to have a healthy child? No. Pregnancy and delivery on your own is possible. The stats on this are tricky because most embryos that are created from a couple where one partner is a translocation carrier are abnormal. However, most abnormal embryos do not implant, so if there is implantation, odds are its normal (not 100% and the odds depend on if the translocation is maternal or paternal). You really need a genetic counselor to give you more specific numbers and more of an explanation. IVF with PGD will help, however, it’s expensive and tedious, and does not guarantee a pregnancy, or even a transfer. That being said, there are patients with translocations who are only interested in IVF with PGD.

If I am not crazy about PGD for genetic screening (for Down’s syndrome and the like) , how do I feel about PGD when you know when you have a specific disease (such as CF or hemophilia)? I feel much better. PGD works better in such cases.

Cervical stenosis: good idea for a blog, but yes it can be a cause of infertility.

If the semen analysis is abnormal, always repeat it. Sometimes the minor abnormalities just go away.

What if you go for the hsg and the cervix is closed? If you get a period, your cervix is not closed. There are different ways to do the hsg and one involves putting a tube through the cervix and into the uterus. This is at times difficult or impossible to do because the cervix may not be completely closed, but narrow. The better way is not to put the tube in and just squirt the fluid up the cervix. The cervical canal acts as the tube and brings the dye up into the uterus. In this case, there is a much lower chance of running into "stenosis" issues.

Thanks again and please read the disclaimer 5/17/06.
Dr. Licciardi

Frequent Fertility Questions

2009-11-06T08:25:00.002-05:00

Hello to all,
Here is your latest entry.

What if I have had miscarriages but my HSG and clotting tests are normal? Make sure you get the karyotype test, the blood test to check your chromosomes.

What if your partner recently had a vasectomy reversal and the motility is only 20% with poor morphology. Will these numbers improve with time? Hard to say. If there is not much improvement in 6 months, there will probably not be much change after that.

Are there any tests to explain poor embryo quality? At this time there are none. We don’t know why within a batch of embryos, some look good and others do not. We don’t know why some women make nicer embryos than other women.

What about shared risk IVF programs? They have their pluses and minuses. The name is deceiving. It sounds like your doctor is somehow contributing to and sharing your financial burden, but this is not the case. Shared risk means the other patients in the program are all sharing the risk. The price of shared risk in many cases does not include all of your costs. It’s all figured out mathematically. Some patients will end up pay less, some pay more, but what the average a person pays in most shared risk programs is the same the average person would pay without the program.

Are there options other than IVF ICSI with 6% motility? Realistically; no. Miracles can happen. We don’t know why but to get pregnant on your own, your need millions of moving sperm. Even IVF without icsi requires millions, although not as many as you need for a natural pregnancy.

What if you are young and have had 4 unexplained miscarriages and your workup is normal? Facing another pregnancy and miscarriage sounds impossible to you, and your doctor says there are no other tests? The unemotional cold hard fact is that trying again is the only real option and the odds are that the next pregnancy will be successful. Your miscarriage risk is higher than others without your history. I’m not saying trying again is the best thing for you, I understand why you may not want to.

Mini IVF. It has its place. Things to watch out for are any hidden costs, which could be high. There is a higher chance that there will be no egg retrieved. You really need to know what the deliver rate is for people your age. The “pregnancy rate” is not the delivery rate. There are different versions of mini IVF. Most involve clomid, but sometimes low doses of injections are added. Also be careful about the freezing option. Many times the doctor will say the lining is not right and he wants to freeze the embryos, so they can be transferred when the lining is more favorable. This gets a mini Arghh. Mini IVF has a lower pregnancy rate and freezing embryos probably makes the rates lower still. Plus if the goal of mini IVF is to save money, it seems that the costs will add up between the cycle, the freeze and the frozen transfer.

What if you have been offered frozen donor eggs (not embryos). This could be a good option. Ask for details (not an estimate) about success at your clinic. If they do not have good results from at least 10-15 thaws, you may want to reconsider. People in the field feel all of donor egg will be using frozen eggs in the near future, although today the science is still new.

Should you consider a surrogate if you have had 2 failed fresh DE cycles, one with a proven donor? If you have no uterine issues i.e. a nice lining and no scaring/previous surgery, the added benefit from a carrier will be minimal. However, if you have access to a good carrier and are open to the idea it is not unreasonable to at least explore the option.

What if you only have access to insemination M-F? Not great. Most of the time there is room for getting inseminated a little early or late, but having weekend services available to you is much better.

Does natural cycle insemination increase your odds of twins? No. Twins come from 2 or more eggs and in the natural cycle, usually only one is produced.

What if you have pain and your doctor is not listening? Maybe your doctor does not feel that you have a pelvic problem that requires further evaluation because your exam and ultrasound are normal, and she does not feel a laparoscopy is right for you. If that’s the case your doctor needs to at least give you another complete exam and a repeat the ultrasound, and then needs to discuss your options. She needs to let you know what she is thinking and visa versa. If you can’t get this with her, try someone else.

What if you are 41, and have gotten pregnant easily twice. Is there an advantage to going to IVF? Theoretically yes because if you have more than one embryo to transfer you will increase your odds of success. The dilemma is that you are getting pregnant on your own easily, which does not necessarily mean you will get pregnant easily with IVF. If you decide to try on your own again, get help quickly if you don’t get pregnant soon.

What if you have stage 3 endometriosis and have not become pregnant with a few iuis? You should consider moving to IVF sooner than average. Pregnancy even without drugs is certainly possible, but the odds are lower because of potential tubal issues related to the endometriosis.

What about stress management programs to increase the odds of conception? I think these programs are extremely helpful. I started the NYU Fertility Center Wellness Program, which incorporates acupuncture, mind-body and yoga into our practice. I don’t like selling these things as ways to get you pregnant, because more research needs to be done. But they are very beneficial for stress management and treatment tolerance.

What’s better for low sperm counts, IVF/ICSI or donor sperm? Donor sperm is a lot easier and cheaper and may lead to a quicker pregnancy. That being said, most people prefer partner’s sperm, IVF and ICSI.

Could a hydrosalpinx prevent pregnancy? The answer is yes. A publication of the American Society of Reproductive Medicine states that a hydrosalpinx can lower pregnancy rates by as much as 50%. I think it’s closer to 30%. Many years ago I would remove a hydrosalpinx in any woman wishing to attempt IVF. More recently I let people know that a hydro will lower the odds in some women but not all, and with the hydro the odds are still good. So I let them decide if they want the surgery prior to IVF. Having a hydro will increase the chances of an ectopic pregnancy with IVF. Hydros can be a problem even if you are not yet a candidate for IVF. In other words if one tube is normal and the other a hydro, removing the hydro may help you get pregnant on your own.

What if you are 44 and were told the chances of IVF are 5%, but you make 14 eggs and have nice embryos? Are your odds higher? Yes they are. Most, but not all, women who get pregnant in their mid 40’s are lucky enough to make a high egg number. The more the better.

What if you were just diagnosed with terrible endometriosis and are offered Lupron? There are no good studies showing Lupron will take away any of the endometriosis or improve scarring. The story is different for pain; Lupron can help tremendously with that.

How to find the best IVF clinic? Start with SART.org and look up the pregnancy rates for your age group. The tables are a little hard to read, go to the line that says live births per retrieval. After that it’s about chatting it up in person and on line.

What if you are obese and the doctor is worried about doing IVF in the office safely? Different doctors will have different thresholds for maximum weight. Some are more relaxed when dealing with very obese patients. So get more opinions. Some IVF centers do their retrievals in the hospital, and they may be more eager to treat you. At 26 you do have time to lose weight before you start, which would be better for the baby. There is new data every day on the detrimental effects of obesity on the fetus. The old saying"you are what you eat" has been replaced by "you are what your mom eats."

What if you have a 2 cm endometrioma on your ovary? As long as they are sure that’s what it is, and it’s not another type of tumor, a 2 cm endometrioma will not hurt your chances of conceiving with IVF.

What next? You are young and have had a baby then 3 miscarriages, the workup doesn’t show much. Too many women have been hit with similar issues. It’s all about the tough decision to continue. If you get pregnant again, odds are that you will have the baby. However the thought of facing another loss sometimes overwhelms us. I try to encourage more attempts, but it’s your decision in the end.

Thanks for reading and read the disclaimer 5.17.06.

Dr. Licciardi

Please Vote for the InfertilityBlog

2009-10-17T08:35:00.003-04:00

Dear All,

Congratulations to all of you who read this blog, it has been nominated for the People's HealthBlogger Award. See the yellow blue and orange box to the right? Clicking it would be a great help. Winning would be very helpful because the blog would get more publicity, which will bring us more readers. This in turn could help us get the blog to even more health-related web sites. The voting ends December 15Th.

Thanks for everything through the years.

Dr. Licciardi
PS The company encourages you to ask your contacts to vote too. I guess they want some publicity too, which is fine with me.

Question and Answer Time

2009-10-16T19:43:00.002-04:00

Hello Again. I will spend the next few blogs catching up on questions. It’s been a while and I see that many were time sensitive, so I am sorry if missed your immediate problem. I’ll try to keep more up to date. One problem is that not all readers like the questions, but I like doing them, and if I make the answers relevant to a group of people, I think they work for a larger group of people. I got caught up in a bunch of topics that I wanted to cover, but for now, back to the questions.

What if you are young, make many eggs and embryos, have very nice quality, a normal uterus and are not getting pregnant? Could it be an implantation issue related to the uterus? Chances are this is not the case. Your doctor may be right, it could be bad luck. It could also be that you need to try another IVF clinic. It could also be there is some unknown genetic problem with your eggs or sperm, but the answer here is years away. Some would consider PGD in this case, but it is questionable if it would help.

If you do clomid, do you need to wait 2 weeks and provera to start? No. Your doctor wants 2 things. He wants you to bleed before the clomid, and he wants you not to be pregnant when you take the povera or clomid. There are ways around this. If you have not bled in many many months, it’s not a bad idea to get a period to start, so provera is not a bad idea. If you have had a period in the past few months, provera is probably not necessary. To be sure you are not pregnant; you can just do a progesterone blood test. You can’t be pregnant if you never ovulated, so if your progesterone is very low, it’s ok to start the clomid (if your doctor says it’s ok). If it’s high, you did ovulate, and you will need to wait less than 2 weeks for your period. If your period does not come, do a pregnancy test.

What if you were diagnosed with stage one enodmetriosis and were told to take Lupron for 3 months. Here is today’s ARGHHHHHHHHHH!!!!!
No one has ever shown that being on Lupron after surgery does anything to reduce endometriosis or improve pregnancy rates. It works like this. Endometriosis grows from estrogen; when Lupron takes away the estrogen the endometriosis stops growing. But Lupron does not kill the endo, it just suppresses it. So once the lupron is stopped, the endometriosis goes right back to where it was. Yes staying on the lupron will take away pain, but once the lupron is stopped, the pain comes right back. So the 3-6 moths of lupron will not help you become pregnant, it just makes you older and more frustrated. A new endometrioma should not appear on Lupron. If the cyst was not well removed at surgery, it can reappear, even if on lupron.

Is a large clot during the period a problem? Probably not. A very large clot is probably not coming from the uterus. It’s from fresh blood that flows from the uterus into the vagina, then sits there and clots. If you think overall the amount you are bleeding is excessive, there could be issues related to fibroids, polyps, etc.

Do we know more about Unexplained Infertility? The problem with writing about unexplained infertility (UI) is that patients are put in the category of UI only after the things we know about have been excluded. It is true that in the past many years, no new meaningful tests have been developed to get people out of the UI group and into one of the groups that are explained.

What if you have severe endometriosis and are not getting pregnant with IVF. Women with endometriosis do make few eggs than average, but 16 is plenty. Should you go to another IVF center? Look up their stats at SART.org. If the numbers look good, stay, if not, get another opinion. Genetic testing is always an option. With a mostly normal family history, the odds of a chromosomal problem are 1-3%.

What if you are 37-38 and your FSH is very normal buy you only make 4 eggs? Well FSH is not the whole story. It’s a good guide but if your number is low, it doesn’t mean you will definitely make many eggs. If you are starting on 2 Follistim and one Menopur, there is definitely room to increase your dose, which could make a difference.

What about a poor responder with normal FSH levels and antral follicle counts? Our pre cycle predictions don’t always match what we get during the cycle. Estrogen prime is probably as good as day 2 start. But if you have tried one, it makes sense to try the other next time.

What if you spot for 51 days straight? You need a pregnancy test and an ultrasound. Things may be just fine but there could be problems with ovulation (or non-ovulation) or uterine issues.

Are frozen embryos any worse because of ICSI? If they were frozen on day 3, is it ok to they and transfer day 5? Yes it is. ICSI will not negatively affect the embryo’s ability to grow from day 3 to day 5 after the thaw, depending on the labs experience with day 5 culture.

If you have regular cycles can you have mild PCO? No, because by definition, PCO women have irregular or lengthy cycles. Now this does not mean you can’t have ovaries that have a high number of eggs and follicles. So your ovaries can look like they are pco, but you don’t have a disease or syndrome. It also means that clomid could still be indicated, even if you do not have PCO.

Someone actually had a conversation with her doctor and he paid attention, and now she is pregnant. One of the most important things I learned in medical school was, “If all else fails, listen to the patient”. “When all else fails examine the patient” is another good one.

Should you have the laparoscopy or do the IVF? It would be easy to answer of either could get you pregnant right away. With a family history of endometriosis and severe cramps, and infertility, a laparoscopy is very reasonable. On the other hand, if you are a good candidate for IVF, the pregnancy will do a good job in suppressing your endometriosis, and some women have a permanent reduction in endometriosis pain after a pregnancy. If your tubes are open on HSG, and there are no endometromas of your ovary (ultrasound visible cysts of endometriosis), the odds of meaningful endometriosis (endometriosis severe enough to be preventing pregnancy) are low.

What about the third biochemical pregnancy in a row? The testing is normal so far. Here are just a couple of suggestions. If you and your husband did not have the blood karyotype test, that should be done. Even though you had a laparoscopy, consider a hysterogram.

After testicular surgery, will a sperm count of 18 million and 20% motility improve with time? It could go either way. At 31 you have few more months to see. Getting pregnant on your own with these numbers is not unheard of, but it may take longer.

I think I should have more frozen embryos. It is very disappointing to have 17 eggs, 12 embryos , 2 for transfer and none to freeze. There could be a few reasons related to the lab for this. If they transfer on day 3 and wait till day 5 or 6 to freeze, they may not have enough experience going to day 5, if they did they would do more fresh transfers on day 5. It’s also possible that the embryos look fair on day 5 and they just do not want to freeze them. There are 2 elements to this. One is a cycle using frozen embryos has a lower pregnancy rate than a cycle using fresh embryos, and that’s when using embryos that look very nice when they are frozen. So if you freeze embryos that are marginal looking, the pregnancy rates will be even lower, and many times not worth the freeze. The other element is that some programs are too restrictive on the quality of the embryos they freeze. I other words, they want their frozen rates to be high. One easy way to do this is to just freeze the really nice embryos and not the ones that look ok or worse. Lastly, it is possible you have some average or good embryos to transfer and all of the others are not really that nice. It may have nothing to do with the lab. Modifying your protocol may possible improve the quality of the lot.

We do not recommend amnio based on just ICSI. However, every case is different. For some, amnio may be indicated.

We have never dealt with a day 7 embryo.

Progesterone orally or vaginally? For IVF we use IM because we had some bad experiences with vaginal. However that was years ago, and maybe the preparations are better now (that’s what’s claimed). The oral is too unreliable to be used alone. If we use oral, it’s in combination with vaginal. Oral progesterone may make you very tired or dizzy.

What if you ovulate every month and on clomid, nothing, no ovulation? Yes indeed, this can happen. Why, we do not know, but it is pretty rare. If you are taking estrogen with the clomid, the estrogen may stop your cycle (like the birth control pill ) . But otherwise, we really don’t know why. If you take clomid another month, odds are you will ovulate. These types of problems usually do not recur.

Is it bad to switch doctors because the first doctor has your history? No not at all. We can all tell exactly what’s going on with you by listening to you in person and studying the paper work. IVF is about the stimulation and embryos, both of which should be clear in the documents.

It seems that there are doctors who tell patients that IVF is the way to go because in their case FSH iui is too risky. It is a little risky but it can be handled correctly. Start on a low dose, get monitored and stop the cycle you are on track to make too many eggs. If a low dose causes a big response, use even less drug next time. Yes, it’s easier to do IVF but if you chose to do FSH iui, talk to your doctor about trying.

If you hyperstimulated during an IVF cycle, and have frozens, generally it does not make sense to do another fresh. The point about saving young embryos for later is valid, although I do not push for that much. Saying you can get kids from a frozen cycle is not appropriate. You really don’t know if you will get pregnant from any embryos, fresh or frozen. If your plan is to have 3-4 kids, doing another fresh and saving the frozen is reasonable. Clearly you need a much lower dose of drug for the next fresh cycle.

OK that’s it for now, more to come.
Thanks and see disclaimer 5/17/06.
Dr. Licciardi

Dr. Licciardi on TV

2009-09-27T08:43:00.002-04:00

I was invited to the MSNBC show "Dr. Nancy". Here's what I had to say.

http://www.msnbc.msn.com/id/31388323/#33006217

When is the Right Time for hCG?

2009-09-27T08:09:00.003-04:00

The time between the hCG and retrieval
For an FSH injection cycle leading to insemination, it’s ok if the ovulation naturally occurs a little early (via a premature LH surge) because we can just do the insemination early. Rarely it’s too early, before the follicle is big enough, and we cancel the cycle. However, for an IVF cycle we have to cancel the cycle if there is an early natural LH surge, even if it’s only a little early, because the timing of the retrieval is very dependent on when the surge starts. The retrieval needs to be about 34-36 hours past the start of the surge (which would also be the time if the hCG shot).

Because we are not taking blood every hour, if the blood test shows a rise in the LH level, we don’t really know when the rise started so we don’t know the right time for retrieval. Lupron, Antagon and Cetrotide prevent the natural rise of the LH, so the premature surge usually cannot occur. However, these drugs do not interfere with the effects of an hCG injection. So there is no natural surge, but there is an artificial surge which starts the moment the hCG goes in.

Final Maturation
There is a second very important job of the LH Surge/hCG injection:
it causes the egg to mature. As the days of stimulation progress the eggs are slowly maturing, but more is needed for the final maturation. Necessary last minute changes occur inside the egg from the LH/ hCG.

Why is this important? An immature egg will not fertilize. If the retrieval is before about 33 hours after the hCG, the result will be immature eggs. Sometimes they are all immature, or just some.

If the retrieval is 38-39 hours after the hCG, the eggs will be mature but they will already have ovulated. We would retrieve none; they would be floating in the pelvis around the ovaries waiting to get picked up by the tubes. So we need to grab the eggs just after they mature but just before they ovulate, which is at about 34-37 hours after the hCG injection.

What day should you get your hCG?
hCG can only mature eggs that have been growing for enough time for the follicle to become large. The sizes of all of the follicles need to be taken into consideration before giving hCG in IVF cycle.

Not all of the follicles grow at the same rate. For example, if there are 10 follicles, and the biggest is 18mm, they will not all be 18 mm. Some will be mid-sized and some will be much smaller. Each follicle does not need to be 18 mm to produce an egg that is mature. As long as the biggest (the lead follicle) is 17-18mm, the mid-sized (13-16) should also have mature eggs. The small follicles (10-12) may or not be mature. But if the lead follicle is 14 mm, none of the eggs have yet reached maturity. Giving hCG would not be enough to achieve maturity.

How Important are Estrogen Levels?
Not very. When you are monitored for your IVF cycle, the follicle size is much more important that the estrogen (estradiol) levels. We need the estrogen to rise, but if midway through your cycle we see 10 follicles, with the biggest being 13 mm, we don’t really care if the estrogen level is 500 or 900. Estrogen is more important when we are monitoring someone who may be on track for hyperstimulation.

Therefore, we use mostly the size of the follicles, with not much emphasis on the estradiol levels, to determine when to give the hCG. At NYU we feel the best time to get the hCG is when the lead follicle reaches 18 mm. Now because there are many variations from cycle to cycle and from patient to patient, it’s not easy to say that 18 mm is the rule.

For example, let’s say there is one follicle 18 mm, three that are 15 mm and others that are smaller. Here we may worry that some of the small ones may be too immature, so we may wait another day before giving the hCG. Let’s say there are 20 follicles, with the biggest 17mm and an estrogen level of 2900. Here we are aware that the smaller follicles may be immature, but we also are concerned about the estradiol getting much higher because the woman would be increasing her risk of hyperstimulation. So we give the hCG at 17 mm, which may yield some immature eggs, but should give us enough mature eggs to work with.

And there are many more variations. Some women have gotten their hCG a little on the early side and have all mature eggs. Some women in their first cycle get the hCG at 18 mm with lots of good size follicles, and have ½ their eggs be immature. So next cycle we wait till the follicles are 20-22 mm before giving hCG. This sometimes gets more mature eggs but sometimes no matter what we do, that woman’s ovaries make more immature eggs than expected.

So why not wait and give hCG later? Because eggs can get over-mature. This over-maturity can lead to lower embryo quality and lower pregnancy rates.

When we see the records of women who have failed IVF elsewhere, many times we see that he hCG was given with large sized follicles. The first and easiest “fix” we can do is to give the hCG earlier in her next cycle, more inline with our standard procedures.

Why do some doctors wait longer to give the hCG?
Some may feel that the higher the estradiol level the better, so by waiting estrogen levels will go up. This is probably not important. Others may feel that it is necessary to wait so there will be no immature eggs. Well this sounds good, but it may not be worth sacrificing the quality of the eggs form larger follicles, which are probably the best eggs anyway.

And back to the original question.
What if instead of the average 11-12 days it takes to grow the follicles, they are of the right size after only 6 days or 8 days?
If the size is good, but it seems early, we usually go at least one more day that we normally would, maybe 2. If it’s day 9 and the follicles are 19-20 mm, it really sounds ok to give hCG. If it’s day 7 (so 5-6 days of FSH injections), and the follicles are 17-18 mm, more time would probably be a good idea.

Thanks for reading and don’t forget the disclaimer 5/17/06.

Dr. Licciardi

The Natural LH Surge vs. the HCG Injection

2009-09-13T10:10:00.003-04:00

We are still working towards the timing of the hCG shot, but we first need a little more background. We need to go over difference between the natural LH surge and the hCG injection.

After LH leaves the pituitary during the surge, it causes the ovulation by landing on specialized spots on the ovarian cells, the LH receptors. All hormones act by landing on (binding to) their specific receptor, and usually one hormone does nothing if it lands on the receptor of a different hormone. There has to be a match.

This is usually dictated by shape. It’s like a lock that recognizes the shape of the key. FSH and LH are similar hormones, but their shapes are a little different. So if LH comes across a FSH receptor, it would not bind.

There is a notable exception. Because hCG and LH are chemically very similar, with very similar shapes, hCG can bind to the LH receptor, and can do it well. Since hCG can land on the LH receptor, hCG can do the same job as LH.

This is actually very important to pregnancy. Pregnancy needs progesterone, which comes from ovarian cells with LH receptors. So LH causes the ovary to make progesterone after ovulation. Good: the progesterone allows the embryo to implant. Then the embryo makes hCG. Better: this causes the ovary to make even more and more progesterone which keeps the implantation going strong. Both occur via the LH receptor.

That hCG can behave like LH is good for treating fertility patients because we can cause ovulation with an injection of hCG instead of an injection of LH. This is good because hCG is easier to get than LH.

So why not just give LH? Up until very recently, LH was not available. Years ago the only way to get FSH for our fertility drugs was to extract it from the urine of menopausal women.

(This is a whole story by itself. Initially, starting in the 1970’s, the urine was obtained from menopausal Italian nuns who would leave jugs of pee for the drug company Serono to pick up in the mornings. Menopausal women have really high amounts of FSH in their blood, and most of it comes out in the urine. The pee would be taken to a factory with a swimming pool-sized pee vat, and they would somehow get the FSH from the pee. Serono went on to be the most profitable company in the world. The Catholic Church was rewarded for its cooperation. Even today, pee swimming pools exist for companies who make fertility drugs from urine.)

Because FSH and LH are similar molecules, the methods used to pull out the FSH grabbed LH too. Once we got the FSH/LH mix, we didn’t have the science to separate the two. So we could not get enough pure LH to cause ovulation. Today we can get pure LH made in a lab, but still in small amounts, not enough to get a good ovulation going.

How do we get the hCG? That is piece of cake, we get it from placentas. There are tons hCG in placentas and it’s easy to extract. Today hCG is also made in a lab, that’s the Ovidrel. It’s pure stuff, and that’s why it can be given in the skin. The placental hCG is given IM because it’s contaminated. hCG is also a protein, and the system for extracting the hCG protein from placentas is pretty crude, so tons of other placental proteins get caught in the net too. These extra proteins can cause a local allergic reaction when given in the skin, but not when given in the muscle.

When we used to get fertility drugs from urine, same thing, they had protein contaminants and needed to be given into the muscle. Recent exceptions are Menopur and Bravelle. These are from urine but using new systems that are better at cleaning out most of the unwanted contaminating proteins. Gonal-F and Follistim are both made in the lab and do not have the contaminants. They are given into the skin.

Today there are 2 products, placental hCG given in the muscle, and the lab-made hCG given in the skin. The placental is still cheaper and words great.

In a cycle stimulated with injected FSH (for IUI or IVF), most of the time the natural LH surge does not occur at all, so we need to give the hCG. In some cases the LH surge does occur, but it happens too soon, before the eggs are mature. This is probably due to the fact that estrogen levels are higher earlier in a medicated cycle, so the LH rises earlier. We don’t know why a premature LH surge only happens in about 20% of cases.

The bottom line is that we cannot count on the natural surge to occur at all, or at the right time, when we are using FSH injections. We need to use the hCG injection for proper timing of ovulation and proper timing of the egg retrieval.

That’s it for now. Next time we finish up by talking about the right time to give the hCG shot.

Thanks for reading,

Dr. Licciardi

A Little More About Normal Ovulation

2009-09-03T08:04:00.005-04:00

Here is a question someone asked about the timing of hCG. It’s a good starting point for this blog.

“I am 40 and just had a failed first IVF cycle that resulted in all immature eggs (7 retrieved) after only 5 days of stims (follistim/menopur + ganirelix days 4 & 5) before the hCG shot.
The doctors were very surprised that by day 5 I had 7 follies 12 - 19 (more <10) and they said I had to trigger, my final E2 was only around 700. I had a good hCG level after the trigger.

I have never heard of anyone only stimming for 5 days. I am curious what your experience has been with people who are fast responders and what you recommend in terms of changing protocols? Do you believe that follicle size alone determines egg maturity or can a short follicular phase be a problem even with larger follicles?”

Figuring out the right time is not that difficult, but there are a few important factors that must be taken into consideration. We need to first start with a brief review of what happens in the natural menstrual cycle, then it will be easier to understand how the IVF cycle works. There are 3 important elements: the growing follicle’s schedule, estrogen levels, and the size of the follicle at ovulation.

Just a reminder: the follicle is the fluid-filled cyst that houses the egg. Each follicle has one egg. We can't see the egg on ultrasound because it's microscopic. But we can see the follicle.

The Growing Follicle’s Schedule: By the 2-3rd day of bleeding, the previous month’s follicle has disappeared and the new one, which has already been chosen, has not started to grow much. On ultrasound you may see it, but you may also see other small ones that look the same. It’s the FSH coming from the pituitary gland (the pituitary will be a blog to come) which causes the little follicle to start and continue to grow.

As the next week goes by, the chosen (or dominant) follicle gets bigger and bigger, until it ovulates somewhere usually between days 11 and 20, most often close to day 14. It’s pretty rare to ovulate before day 11, but not so rare to ovulate later. The day of ovulation is related when the follicle starts to grow, and the cycle length gives us a hint as to when this was. It takes about 2 weeks for the follicle to grow from tiny to big. That means for a 28 day cycle, the follicle grows till ovulation, usually day 14.

What if the cycles are, say, 35 days? Well it still takes the 2 weeks to grow, it just starts later. So for a 35 day cycle the early follicle sleeps for about a week, then wakes up and starts growing day 7 and ovulates day 21. We don’t know what causes these differences.

What if the cycle is 24 days? In this case the follicle probably takes less than 2 weeks to grow, so 2 weeks is not mandatory. Again, the reason for these differences are unknown.

Estrogen Levels: As the follicle grows, it makes more and more estrogen, so the blood levels of estrogen rise each day. The estrogen is not coming from the egg, it comes from the tons of little ovarian cells (the granulosa cells) that surround the egg. The estrogen is probably not important for the egg, but one of estrogen’s very important jobs is to thicken up the lining of the uterus.

Estrogen’s second job is to cause the ovulation. The pituitary gland is constantly monitoring the estrogen levels, and when they get high enough, the pituitary dumps out LH (this is what your home ovulation kit reads) and this is what causes the egg to pop out.

There is not an exact estrogen level that causes the ovulation. Most of the time it’s anywhere from 150 to 350. Why there is a difference we do not know, it may be that there are other unknown hormones that work with the estrogen to get the job done.

Follicle Size: The size of the follicle is important too. Most ovulations occur with a follicle that is 20-25 mm(about one inch), but 16 mm is close to the bare minimum and 30 mm is close to the top size.

Next time we will talk about the timing of ovulation in an IVF cycle.

Thanks for reading,

Dr. Licciardi

This Time Even I Got a Little Mad

2009-08-14T08:00:00.000-04:00

It wasn’t supposed to end this way. We all knew going in that nothing was guarantied, but we felt good and optimistic about starting. Together, we believed that if we just obeyed the rules and had faith, that good things can happen to good people. We anticipated sacrificing time, emotion and money, for a process that was logically the most reliable way to go. We figured it was the best option, and we were “all in” to work towards success.

Shari was 41 when we first met and she was already at it for more than a year. She was very smart and informed. Shari understood the small details of each treatment, but didn’t dwell on the negativity. She was super practical. The plan, which she started at 39, was to start with iui, and move to IVF if nothing happened. She eagerly and compliantly stuck to the plan, and had 2 IVFs under her belt by the time she first saw me.

At our consultation I definitely saw hopeful signs from her previous cycles. She made 15 eggs the second time. Plus her embryo quality was very nice. I explained that 3 things really help when you are trying to get pregnant with IVF at 41; a high egg number, good looking embryos and chromosomally normal embryos. We knew off the bat that she at least had 2/3. More eggs means more selection. We all know that a large percentage of embryos have bad chromosomes, so if you have more embryos, you are increasing your odds of at least one of them being normal. And if they look nice, all the better.

Wow, she called to tell me she got pregnant on her own. Sweet. But there was no heartbeat at 7 weeks, and she needed a D and C. This caused her to pause, and logically concluded that maybe FSH iui could work. So she tried to no avail.

Doing more IVF cycles was not an easy decision. She had some infertility insurance coverage, but that was all gone, so she had to pay for anything else, including the medications. But she weighed the options and decided to proceed with more IVF based on her good response, recent pregnancy and advancing age.

So off she went into her 3rd and 4th IVF cycle with me. Each time producing eggs and very good embryos. We changed the protocol a bit, but in the end she had cycles that most other women could not achieve.

Except for the two negative pregnancy tests.

And that’s the end of the story.

When we last spoke she was again very practical. She just didn’t see the value in going into a 5th IVF cycle. She could not afford donor egg. She was very kind, expressing her gratitude for the treatment she received. But this was it; she was done. She had ended her quest for a baby. Stated differently, she was probably not going to have a baby.

So why am I bringing this story to you, as this is not the first tale of woe in the infertility world.

I think this one was tough for me because she had to stop, but I still had some hope in the chest. For many, stopping becomes the best option because multiple attempts have given me information saying that it really may not be worth continuing. Few eggs, very poor embryo quality, advanced age etc. When younger women have to throw it in, I can at least feel that with time their situation will change, and although it looks like the end now, they may get another shot later on. It’s also easier when the best option is donor egg, and donor egg is agreeable and affordable to the patient.

Now every doctor does get very disappointed every time a patient has a negative pregnancy test. But the story about Shari just left me hanging a little more than usual. Many eggs, nice embryos, and my sense that if she could just do more cycles her time would come. Maybe. The thing was, I couldn’t tell her it would happen, and that always makes it tough. And I couldn’t lay on the optimism thing, even though had some. After 4 cycles, the energy and drive to continue has to come from the patient.

But I will continue to have hope for her. Maybe she will fall into an insurance program that will get her at least one more cycle. She doesn’t have much time for that. May be her financial situation will change and she will get to donor egg. This she has a little time for. And maybe, she will get pregnant on her own, which is not out of the realm of possibilities.

Thanks for reading, and Shari is a substitute name.

Dr. Licciardi

Dr. Licciardi’s “Infertility Blog” named as one of the top 50 Pregnancy Blogs

2009-07-09T07:12:00.000-04:00

The list can be found at http://onlineultrasoundschool.com/2009/top-50-pregnancy-blogs-required-reading/.

Back to Frequently Asked Questions

2009-07-01T06:57:00.000-04:00

Before getting to FAQ’s here is a little vignette.

Last week I saw a woman who has been trying for 3 years. 3 years ago she told her doctor she had an extremely heavy period, and during her other periods she was losing more blood than she did in the past. No ultrasound was performed. Well 3 years later another doctor got a scan right away and she was found to have a huge fibroid in the middle of the uterine cavity. There is no way she could have become pregnant in the past few years with this fibroid in place. She lost 3 years. Take home message: abnormal uterine bleeding requires an ultrasound. In fact all infertility patients need an ultrasound right off the bat.

Can you travel by plane after IUI and IVF? There is no evidence that plane travel hurts anything. However, you need to have a very flexible schedule. There are a few things that could force you to stay home after a cycle. One is hyperstimulation. The other is an abnormal pregnancy. If you’re pregnant, the worse time to plan travel is about 2 weeks after your transfer. This is a bad time because often enough we don’t the location of the pregnancy. So if the day 35 blood test does not show a doubling every other day, your doctor may order you to stay put. No one wants you to rupture a tubal pregnancy, especially on a plane. The condition and location of the pregnany will mostly be determined as the next 1-2 weeks progress, so after that travel becomes more of a possibility.

Prolactin: Will get its own blog

MTHFR: Methlyenetetrahydrofolate reductase (yes, I had to cut and paste): This is an enzyme (a protein that is involved in a chemical reaction in the body) that is involved with the metabolism of folic acid. Folic acid can’t be properly utilized if there are problems with this enzyme. We have 2 copies of the DNA for this enzyme. It’s more common to have on abnormal copy, but 2 abnormal copies are more rare. If there are one or 2 bad copies, the next step is to measure the homocystine level. If the homocystine is normal, this indicates that even of the copies are abnormal; folic acid is still doing its job. If the homocystine is high, there is an interference of folic acid’s function. In this case, treatment may be necessary, with folic acid and other vitamins. Some doctors will recommend Lovenox (a heparin blood thinner). Some doctors recommend these therapies when the homcystine level is normal, but this is very controversial.

Late Onset Congenital Hyperplasia(CAH). Testing is via hormone levels, however there is a DNA test. If you have CAH, you shuold have the DNA test and your partner needs to be tested too. Just like above, you have one copy. He may have one copy too. The bigger problem is that your offspring may inherit one from you and one from him, and have 2, which is a much more serious disease. As far as treatment and pregnancy attempts, if you have a mild form of CAH, DEX may be overkill. Ask your doctor about other options such as just going to clomid.

Is IVF the only option for 1% sperm morphology? No, you also have the option trying on your own or iui.

What if you did 3 FSH iui cycles and can’t afford IVF? Practicality will dictate your path. You can get pregnant with FSH iui in the 4th 5th or 6th try. The odds become lower in the later cycles, but it’s still better than on your own or with clomid.

A 29 year old who made 10 eggs and had 2 average quality embryos is being told she needs donor egg. ARRGHHHHHHHH!!!. Give me a break. Can I guarantee you will get pregnant with your own eggs? No. Keep at it. Keep tweaking it, and get to the best program you can.

One tube and Clomid. If you have one tube clomid can work, but it does help to have the follicle on the same side as the tube. You may not need IVF right away. Usually with FSH iui you can make eggs on both sides at the same time giving you a better chance each month.

What IVF protocol is best? No one knows. I prefer the day 2 start with pure FSH. Why? Because no one has ever shown that one protocol is better than another. This is especially true when comparing pure FSH with FSH combined with LH. So if they are the same, why not make it simple. With the day 2 start there are no pre-cycle medications, and with FSH only there is just one drug to worry about. If that does not work, I can use all of the other protocols out there. I do feel that day 21 lupron is not the best for women we expect to be low responders.

How long after having a baby should you try before seeing your RE? It depends on your fertility problem. Obviously there is no waiting for severe tubal or sperm issues. If ovulation was the problem, you can wait a little to see if your cycles straighten out, but if even early on you see that things are as they were, get back to the RE.

What about a short luteal phase when taking clomid or FSH? Studies have shown that the luteal phase in a clomid or FSH cycle is better than a luteal phase from a natural cycle, probably because the progesterone levels are higher. I routinely do not prescribe progesterone for clomid or FSH. However, occasionally a patient will let me know that the luteal phase after a drug cycle was unusually short, maybe 8-11 days. I don’t know why it happened but I agree it sounds too short. Now maybe it’s ok, and if there were a conception, early bleeding would not have happened, but here I make sure we give progesterone in any subsequent cycles.

What should my progesterone level be? It needs to be over 8. No one has shown that 11 is worse than 40. When using clomid we sometimes get levels to be sure ovulation took place, but I don’t worry about the level.

Female anti-sperm antibodies. I would definitely believe in them if there were quality papers showing they play a role in infertility.

What if you have a short cycle but home ovulation testing shows a color change late? Well either the kit is off or there is a short luteal phase. In this case, office monitoring is the way to go. There are a few people who do well growing the follicle, but it just sits there a few days before deciding to ovulate.

Should you take progesterone with normal levels and a normal luteal phase? Data does not support its use.

Is DE the only option if the FSH level is 16. You have to ask your doctor what the odds of having a baby are using your eggs with an FSH of 16. I am sure the odds are very very low. So you have to decide if the numbers make it worth it to you.

Should husbands with male factor get genetic testing? It depends on the counts. The lower the counts, the greater the chances of a genetic abnormality, although even in cases where the sperm counts are less than 2 million, the genetic testing usually comes back normal. So I suppose it’s up to you and the urologist. There’s always a small chance that the genetics will be abnormal.

What about clomid in the case of severe endmetriosis and and at least one blocked tube. You can try clomid, but with the enod and only 1 tube, your odds with clomid are low. Remember, for women with normal tubes and sperm and FSH levels, the odds with clomid are only 8%. So with a problem pelvis, the odds will only be lower.

What if you became pregnant naturally with a sperm count of 3.8 million, and you want to now try again? Yes miracles do happen, but not often enough. Start with repeating the semen analysis. Maybe the counts are higher now. It’s also possible that they are lower, so you should check. If they are still 3.8, you can try for a little while, but I would get help if you are not pregnant quickly.

This is for relatively young women who don’t make many eggs. Get off the lupron. Many times, but not every time, more eggs are produced without lupron. If the egg number remains the same, then you are stuck and you will have do decide if its worth going through with the retrieval.

How often do you need to monitor progesterone levels after IVF? Usually progesterone levels are very high the first week after retrieval, but after the ovaries decrease their progesterone production in the second week. If the levels are high enough 1 week after, they will probably be fine as the second week progresses. The hcg produced by the early pregnancy will increase the ovaries output of progesterone. The point is is that if the progesterone levels are low on the day of the pregnancy test, it’s probably because there is no pregnancy, not because there is not enough progesterone being given to the woman. If a person is getting more than the usual amount of progesterone(IM plus vaginal and or oral), measuring levels will be less helpful.

If you have a family history of miscarriage, genetic counseling is indicated.

That's it for now, thanks again. Please see disclaimer 5/17/06.

Dr. Licciardi

Spotting and other Variations in Bleeding

2009-06-06T07:59:00.000-04:00

Spotting.

Really frustrating. Where does it come from? We first look for an anatomical reason (a problem due to some sort of growth that we can see usually with the ultrasound). The most common reason is that there is a polyp inside the uterus. A polyp is a benign growth inside the uterus, kind of like a skin tag on the inside. They are easily removed via hysteroscopy. If you have had polyps removed and still have spotting, you need to have a sono hysterogram to be sure that the polyps were completely removed. Or maybe they grew back. If the lining is pristine, you we have to look for other causes. Adenomyosis is another reason for spotting. Usually there is evidence of adenomyosis on ultrasound. If not, an MRI will make the diagnosis.

Women with endometriosis are more likely to have spotting, and this may be may be due to a few causes. With endometriosis, the glands of the uterus grow in areas they shouldn’t. The most common abnormal areas are around the ovary and tubes, but there can also be spots of endometriosis on the surface of the cervix. Because the glands don’t always behave as the normal endometrium, they can bleed anytime, causing spotting.

Another source of spotting in women with endometriosis is a hydrosalpinx. A hydroslapinx is a big scarred fallopian tube that is blocked on the part away from the uterus, near the ovary. If the hydro is caused by the chronic inflammation of endometriosis, blood can slowly built up inside the tube. This blood can sometimes back up from the tube into the uterus and then out the cervix, causing spotting. It’s usually not red, but more of a chocolate brown.

Occasionally no reason for the spotting is discovered. So we blame in on being “hormonal”, but we really don’t know what the specific hormonal abnormality is. Could spotting a few days before the period be due to a luteal phase defect and low progesterone levels? There may be one rare woman who has this issue, but for most women with pre-period spotting, their hormones are just fine. I have found that persistent spotting stops when moving to injectables, which do increase both of those hormones.

Post ovulation spotting can in many cases be controlled with progesterone and estradiol in the luteal phase. I remember one patient from years past who had the spotting mid cycle, had a negative hysteroscopy, and got pregnant on her own a few months later. So even though she had monthly spotting it had little effect on her ability to conceive. Maybe the spotting was normal for her and it stopped once she became pregnant.

If you are anovulatory due to PCO and you have frequent spotting, you may need to have a biopsy of the endometrium. PCO women who rarely get a period are at higher risk for endometrial hyperplasia or even cancer. This usually causes heavy irregular periods, but sometimes it’s just spotting. An office biopsy can usually make that diagnosis.

Other Variations in Bleeding

“I don’t bleed for a long as I used to”. I hear this a lot. Typically someone will say they used to bleed for 4-5 days and now they are finished after 3. There is no evidence that this means anything bad. Certainly after a delivery such changes are more common. But even without pregnancy, some women have changes that are hard to explain. I don’t think this means there is a change in fertility.

Heavier bleeding is more of a problem because it is more likely to signify a change that may be important. Remember that fibroid the doctor told you you had, but said it’s not a problem because it’s small? Unfortunately they can grow and become a problem with time. Increased estrogen levels associated with repeated drug cycles can accelerate their growth. Adenomyosis can also progress, leading to increased bleeding.

Consistent heavy bleeding in the setting of normal anatomy may require a consultation with a hematologist. Many of us are born with blood abnormalities that don’t’ allow for proper blood clotting. These issues are usually discovered in adolescence after the first periods are found to be abnormally heavy.

And of course, unexplained heavy bleeding may also require an office biopsy or hysteroscopy to rule out pre-cancerous or cancerous cells.

Thanks for reading and please see disclaimer 5/17/06.

Dr. Licciardi

2009-05-15T08:57:00.000-04:00

In February 2009, “The Infertility Blog” celebrated 3 years of production. I have been very pleased with the response. At least once per week someone tells me how valuable they find the information and how much they appreciate the effort.

Not only is it an effort to produce, I am finding it’s a lot of work for patients to read the 121 entries to date. Sometimes patients ask me to write on a certain topic, and I have to say, “I already did, go back and check.”

So to make it easier, here is the table of contents of Blogs so far. These are the “topic blogs”. They are not all of the blogs as there are many “Answers to Questions” sprinkled in between. Hopefully this will give you easier access to the information from earlier chapters. You can also print it to keep as a reference.

In addition, you can search the blog. In the upper left next to the orange e sign, is a box for you to type in your search words. If you type in a word such as FSH or SART, blogs containing those words will be listed.

Here you have it. Feel free to share it with others needing help.

2/05/06: A Woman Who Thought Her Hysterogram was normal. A classic story of a woman being surprised when I told her the radiologist read her hysterogram incorrectly.

2/07/06: From No Sperm, to a Few Sperm, to Twins. A classic story about a couple who was told by one doctor they had no sperm, but who saw another who said they had sperm.

2/15/06: No More Happy Birthdays. Birthdays and infertility can mix.

2/22/06: The Dreaded Biochemical Pregnancy. Explains the diagnosis and meaning of a biochemical pregnancy.

3/05/06: The First of a Few about FSH levels. Day 3 FSH levels explained.

3/09/06: FSH Levels: An Excuse to Send Patients Away. In some cases pregnancy is possible with elevated FSH levels.

3/12/06: FSH and Estradiol (Estrogen). Discusses day 2/3 estrogen levels and their relationship to FSH levels and pregnancy rates.

3/21/06: But Doc, What Went Wrong? Maybe Nothing. Your doctor can’t always explain why cycles are not successful.

3/27/06: Endometriosis: It’s Everywhere, but in Small Amounts. An introduction to endometriosis and its effect on fertility.

4/02/06: Endometriosis: What Are you Waiting For. Endometriosis is both over-diagnosed and under-diagnosed.

4/07/06: Why Do We Do IUI? Insemination can be more successful than intercourse.

4/12/06: Is There Enough Sperm for IUI? IUI can help with low, but not very low counts.

4/18/06: What are Your Odds? Don’t start treatments until you know your odds with each procedure.

4/22/06: This is Your Brain, This is Your Brain on Clomid. Clomid had some unique side effects.

4/27/06: The Clomid Death Sentence: Too many months on Clomid can kill your chances.

5/4/06: Sperm Morphology Mythology. Morphology may not be that important.

5/11/06: Abnormal Sperm Can Fertilize Eggs and Make Babies. More on morphology.

5/17/06The Disclaimer: Medical advice must come from your doctor.

5/19/06: Hysterograms: Let’s Not Forget the Uterus. Focusing on the tubes can miss important information about the uterus.

5/31/06: Who is Reading Your HSG? Reading the report without looking at the films doesn’t cut it.

6/04/06: Pregnancy Rates Matter. The pregnancy rates from each program are published by SART and the CDC. You should read the reports.

6/16/09: Your Doctor’s IVF Pregnancy Rates are Available to You. More of the same.

6/22/06: Ovarian Cysts Part One: Normal Ovulation. The term “Ovarian Cyst” can have many meanings.

7/01/06: The doctor said I can’t start because I have a cyst. What it means to have a cyst on day 2/3.

7/06/06: PCO: Pretty Cute Ovaries? What is PCO?

7/13/06: You Can't Have a Baby Unless you are Pregnant. The positive pregnancy test can be the start of a good thing.

7/20/06: How to subscribe to this blog. Get the blog sent to you.

7/21/06: Uterine Scar Tissue After a D&C. D &C, and the potential for scarring.

8/03/06: Abnormal Bleeding? Don’t have a D and C without a Hysteroscopy (and have an ultrasound first). “Blind” scraping doesn’t help much.

8/20/06: The Boxes of Pregnancy and Miscarriage. Especially when infertile, miscarriage really hits home.

8/28/06: Diagnostic Laparoscopy. Becoming a less-important infertility treatment.

9/11/06: Psychologists are Available: Consider Using Them. Why go it alone.

9/19/06: Hysteroscopy 101. An explanation of Hysteroscopy.

9/25/06: Is LH Important for IVF Success? There is little controversy; LH is not so magic.

10/05/06: Blocked Tubes: 2 Cases of Proximal Tubal Occlusion. Blocked tubes can mean different things.

10/17/06: I called and an embryo picked up the phone. Embryos do grow up.

10/27/06: What About Tubes that are Blocked at the Other End, Near the Ovary? More discussion about tubal blockage.

11/09/06: How Many Embryos are You Putting Back? Fewer is usually better.

11/20/06: How Can the Pregnancy be Bad But Still Growing? A few details about early pregnancy loss.

11/30/06 What’s a Hormone? Definition and examples of reproductive hormones.

12/09/06: What is Lupron and Why Are Only Some People Using It? Insight into different stimulation protocols.

12/12/06: More On Lupron and Why We Don’t use it as Much. More of the same.

1/08/07L Microdose or Microflare or Flare Lupron. More of the same.

1/20/07: Sperm Deficient Females Can Be Quite Fertile. Many donor sperm patients get pregnant quickly.

1/28/07: So Your Uterus is Bicornuate? Check Again, and Again. It may really be a septum, and it’s very important to know.

2/06/07: Bicornuate or Septate? What’s difference and why it matters.

2/26/07: Last One About Septums. How and why they are corrected.

3/10/07: When and How to time the IUI. Home and office monitoring.

3/16/07: A Little More about IUI. Inseminate one day or 2?

3/15/07: More on PCO. The basics workup, cysts and treatment.

4/02/07: Polycystic Ovaries and Insulin Resistance. What PCO can mean for your health.

4/04/07: Even More about Polycystic Ovaries. Is Metformin useful?

4/23/07: The Last Word on PCO, For Now. Modifying fertility the work-up for PCO patients.

5/06/07: The PGD Paradox: On paper, PGD for aneuploidy sounds great, but so far it has not lived up to expectations.

5/15/07: 3 Good Stories About 2 Opinions. Why wouldn’t you get a second opinion?

5/23/07: More About PGD. The pros and cons of PGD for aneupliody.

5/31/07: Ectopic Pregnancy. One woman’s story of a tubal pregnancy.

6/09/07: Ectopic Pregnancy FAQ’s. Some basics about ectopic pregnancies.

6/19/07: More questions About Ectopic Pregnancies. Treatment with Methotrexate.

6/29/07: Miscarriage and the Immune System (antibodies). Testing of the immune system.

7/12/07: Miscarriage, Infertility, Antibodies and the Immune System. More evidence would be helpful.

7/22/07: Meeting Your Doctor: What are You Thinking, What is the Doctor Thinking? Your doctor should make your first visit a positive experience.

7/30/07: A Bit More on Seeing Your New Doctor. Don’t let pre-conceived notions keep you from seeing a fertility doctor.

8/17/07: The Follicular Phase and the Luteal Phase. A basic understanding of the menstrual cycle.

8/25/07: Luteal Phase Defect. What are we looking for in the biopsy?

9/05/07: Luteal Phase Defect 3. More about how we make the diagnosis.

9/11/07: Four Simple Clicks Will Help You Have a Baby. You owe it to yourself to check the pregnancy rates of your clinic. It’s all at SART.org.

9/28/07: More About Pregnancy Rates: How to decipher the pregnancy statistics.

10/06/07: Why is Progesterone Used for IVF? The sources and actions of progesterone.

11/06/07: Are You Sure You Need Donor Eggs? Some women are pushed into Donor Egg.

11/19/07: What’s a Fibroid? What they are, how they start and the problems they cause.

12/01/07: Myomectomy. How it’s done.

12/06/07: Fertility and Diet. Mostly involves losing excess weight to improve ovulation.

12/17/07: Exercise. Please exercise.

1/03/08: Your Fibroid: Should it Stay or Should it Go? Which fibroids require removal.

1/12/08: More About Fibroid Surgery. Complications of the myomectomy procedure.

1/21/08: Minimal Stimulation. Less may not be more.

2/01/08: If You Live in the State of New York, the Government May Help Pay for Your IVF. It’s called the New York State Demonstration Project.

2/19/08: Fertility Questions: SCSA. Sperm DNA tests are unproven.

3/11/08: Fertility Preservation. Authoritative information about egg freezing.

4/13/08: Varicocele. A controversial operation.

6/10/08: The Endometrium. The essentials about the uterine lining.

6/22/08: The Endometrium Part II. The thin lining and scar tissue.

7/21/08: Improving Endometrial Thickness. Tricks of the trade to make the lining thicker; limited success.

8/02/08: The Endometrium Part III. Less conventional therapies.

9/01/08: Polyps. The significance of these benign growths inside the uterus.

11/26/08: Stories of Persistence. Women who succeeded by not listening to the doctor.

12/14/08: The Road to Blastocyst: Eggs and Embryos. Understanding the embryology part one.

1/12/09: More About Embryos. Developing embryos and embryo morphology.

1/27/09: Just Before Blastocyst: The Morlula. Day 4 embryos.

4/08/09: Meet the Blastocyst: Photos and descriptions of blastocysts.

4/27/09: What Can Blastocyst Do For You? A good blastocyst program can help you get pregnant with fewer embryos.

What Can Blastocyst Do For You?

2009-04-27T10:31:00.000-04:00

The advantage of a day 5 blastocyst transfer has to do with selection. These days most reputable programs are putting 2 embryos back in youngish women (I know what you’re thinking, but we’ll skip the octo discussion). Anyway, let’s say you’re lucky and have 5 nice embryos on day 3. Even though some may look a litter nicer than others, we really may not be able to tell which embryos are the best ones. So, we can wait 2 more days. In that time, some embryos may not grow well, but probably those embryos would not have survived in the uterus anyway.

The advantage here is that the embryos that do survive are probably stronger, and these can give you a better chance of pregnancy. It’s like a stress test, those that pass are probably better. One of my partners puts it nicely: just because a horse is leading ½ way around the track doesn’t mean it’s going to win the race.

But not all programs use the day 5 transfers, and some do it selectively i.e. only in some patients. Why is that? Some of it has to do with initial experience. At NYU, our initial experience was excellent, in fact better than expected, so we felt very comfortable continuing with it and this led to more and more cases and more expertise with time. Other programs had a bad experience initially. They were therefore less eager to increase their blast cases. Once something does not go well, especially in medicine, it’s really hard to go back to it.

Why would there be different experiences in different programs? Hard to say. I am prejudice in favor of the NYU lab, the people are all excellent, but there are other good labs around.

It may have something to do with the media. Media is the nutrient juice we grow your embryos in. We used to make it from scratch (what a pain), but now we buy it. An important factor making blast possible is the media. The old types of media could only support an embryo in culture for 3 days, and some very important changes in media composition were necessary to allow the embryos to grow 2 more days in the lab.

Initially, there was some variation in the new blastocyst media composition and quality, and there were batches that did not grow blastoctys well. So if you were an IVF lab who just happened to start out with an inadequate media batch, your outcomes would be lower, and you would be reluctant to explore blast culture further. Thanks to your lab directors and staff, we had a very careful process of testing media and analyzing which worked best. This allowed up to keep up the embryos quality in the face of variable conditions.

Among the programs that go to day 5, there is considerable variation in their criteria for going to blast. Some IVF centers need you to have 10 nice embryos on day 3 before they will consider growing the embryos longer. Others need you to have 6 day 3s, some 5, etc etc. Programs also put age in the mix; in other words less likely to go to day 5 the older you are. The more comfortable a program is with blastocyst, the softer their criteria will be.

Our criterion is that if you have more embryos than we want to transfer, you go to day 5. We transfer 2 embryos in most women which means if you only have 2 viable embryos on day 3 we do the day 3 transfer. If you have 3 or more, as is usually the case, you go to day 5.

Naturally, the obvious by-product of a good blast program is a lower multiple rate. Getting you better selected embryos, will help you become pregnant with fewer embryos. We started with blastocyst transfer in 1999. At the time we had a 20% of women under 38 had 3 embryos implant and now the rate is 1.9%. And many of those women had 2 embryos transferred, but had one of them split into identical s.

We went from putting in an average of 3 embryos per patient to two. Our pregnant rates would not be as high as they are if we put 2 embryos in on day 3. It’s just too hard to tell which are the best ones on day 3. Besides we have numbers to support our work. The implantation rate per embryo (this is a number that is used a lot. It’s the odds of each embryo sticking) was 34.5% in women under 35 and now its 43.4%.

So if your program is not doing a lot of blastocyst, does this hurt your chances? It really depends on the published pregnancy rates from your clinic. If they have great rates, but don’t do much blastocyst, that’s not so bad. Unless of course they are putting in more embryos per transfer to maintain the higher pregnancy rates. It’s not always easy to predict who will not get pregnant and who will get pregnant with triplets or quads. If you want to avoid 3s and 4s, your best bet is to not take the risk.

Sometimes there can be a diagnostic advantage to blastocyst transfer. If you are not getting pregnant with day 3 transfers, it may be time to try blastocyst. Occasionally, the embryos look much worse on day 5 than they did on day 3. This would not be not good news but at least you would know where you stand. It is also possible that they look just ok on day 3, but perk up very nicely by day 5, and this information might be of help to you.

Thanks for reading, and please see disclaimer 5/17/06.

Dr. Licciardi

Meet the Blastocyst

2009-04-08T17:54:00.000-04:00

Hello everyone, this blog will describe the blastocyst. I will show you some pictures and tell you what is good and what is less good. Next time I will tell you a little about our blastocyst experience at NYU.
Let’s start with an easy one, a nice one. This is a very nice blasotocyst.

This is the type of embryo you may see on doctor’s web sites.

So what are we looking for? In no particular order, one is the thickness of the zona. This is the thin membrane around the embryo; it looks like a clear plastic shell. The thinner the better. As the embryo grows, gets larger, and becomes ready to pop out of the zona. The zona gets thinner, and this is a good sign. We don’t measure the thickness; we just look at it and make a judgment. The bigger embryo in the picture below has a really thin zona, almost impossible to see, which is a good thing.

This embryo has a much thicker zona, not as good.

What else are we looking for? We look inside the embryo. You may not be able to tell by looking right away, but the inside is hollow. Thus the name blastocyst: the inside is like a fluid filled cyst. That’s a good thing. So the next embryos have a lot of space on the inside, the cavity (the space inside) is large, another good thing.

This familiar embryo has a smaller cavity, not as good, but not a terrible embryo overall.

What about the cells of the embryo? There are 2 types. There is the inner cell mass and the trophectoderm. The inner cell mass goes on to become the fetus/baby, the trophectoderm cells go on to become the placenta. Many more cells are designated for the placenta than are for the fetus. Ideally, the inner cell mass (ICM) is easy to see as a clump of tightly bound cells more towards the center of the embryo. Here is the nice embryo we saw before with a nub of cells at about 8 o’clock. This is a good-very good inner cell mass.

These embryos have ICMs that are smaller; in fact it’s hard to see the ICM in the bigger embryo.

Next we move on to the other cells of the blastocyst, the cells that make up the outer area. These are the trophectoderm cells, troph cells for short (really sorry about all the terminology, it just goes with the territory). Cells that are more plentiful and smaller make a better embryo. The larger embryo below has very nice troph cells (and the ICM is really nice too).

This embryo has troph cells that are not quite as good: they are larger and fewer in number.

The embryo on the left below has just a few troph cells and they are really spread out, not so good.

The next embryos are not very good looking. The top left does have a cavity, and the cells are not very good. The top right has a very small cavity. The bottom embryo looks like there is no cavity.

The next embryos have cavities, but not the nice ICM cells and troph cells we have previously seen.

These embryos have thick zonas, the lower left has no cavity, and the upper right has a small cavity and few large cells inside.

This poor embryo has a nice thin zona, but just a few cells inside. The troph cell at 4:00 o’clock is just spread so thin, across almost half the embryo. The ICM at 11 o’clock is tiny.

So now you know more about blastocysts than the average person undergoing infertility. I realize that some of you are not as interested in the details, and others really use the details to get through the infertility day.
Next time I will talk a little about the numbers we assign and a little about the NYU blastocyst experience.

Thanks and see you sooner next time,

Dr. Licciardi

Infertility FAQs

2009-03-07T15:19:00.000-05:00

Hello Everyone, catching up on the questions again. I know the topics are popular and I owe you one for next time.

I changed the format a bit for this time. I have the answers in more of a FAQ format with a little less verbage. I go through the question and try to distill out the major point. Hopefully this will be more efficient and informative, plus it allows for me to get to more issues more quickly. Let's see how it goes. Next entry will be a topic.

Do you need to remove Hydros? I am assuming your RE made the tubal surgery an option; some people can get pregnant with hydros in place. I make it an option with most of my patients. Of course you need to discuss this with your doctor, he knows your case better than I. It’s too early to tell about the Essure.

Is a high estrogen bad for implantation? I have not seen this to be the case. It is very true in mice, but mice are very different.

Why would someone who is 33 have 2 kids then 4 miscarriages in 15 months? If your workup is negative, we don’t know. It is important to have a hysterogram. I have had women with 4 miscarriages go on to have more than one child.

Is the estrogen prime good for low responders? It is no worse than anything else. If other stimulations have failed, give it a try.

If you make a lot of eggs does that mean you have PCO? It does not. It could mean you just make a lot of eggs. We see this all of the time.

If you are discouraged because you failed you fresh DE cycles, should you bother with your frozen? Believe it or not, we have some women who did not get pregnant with their fresh de embryos and have not returned for their frozen. Now there may be many reasons for this. If you would like to be pregnant, get up the nerve for the frozen cycle.

If you do not ovulate with clomid, should you add metformin? Consider the other option of very low dose injections. Metformin an option, but it may take months to get results, and in many cases ovulation dose not occur even with metformin.

Will acupuncture help? We don’t know, but I have many women doing it. In fact, in our office we provide acupuncture services, and the patients are very happy we do. We also provide Yoga and Mind body and psychological services. It’s all under the NYU Fertility Center Wellness Program.

FSH on day 2: should you wait for a lower number? Not sure. We prefer if our patients start with a number less than 13.4.

Can coasting have a negative effect on egg quality. Absolutely. Probably less so if the coasting is 1-2 days, but longer coasting is at times very bad for egg quality.

Can someone be prone to chromosomal miscarriages? Yes, there are some women who have a high proportion of chromosomally abnormal embryos.

Septum and PCO, which to fix first? Yes there are women with a septum who have had normal fertility and pregnancies, although I would be hesitant to leave a septum in because of the potential problems. It’s between you and your doctor. PCO is always fixable.

Is obesity a problem? No hard data, probably leads lower IVF rates. It’ more of a problem for pregnancy because of harm to the fetus. 11 eggs is ok, a few more may be better, ask your doctor about increasing your dose.

Should infertile women have a laparoscopy? Very few of my patients get a laparoscopy. If the only thing your insurance will cover is laparoscopy, then it’s a more reasonable approach. However, if there is no pain, no cysts and open tubes, the odds of a laparoscopy helping anything are low. Yes there are some women who everyone thought were fine who were found to have bad endo, but these cases are rare and usually there is a sign of the problem pre op.

Low sperm morphology: Usually not a factor. Some exceptions exist.

PCOS-like. I am happy that your doctor put it that way. Too many women are labeled with PCOS.

Temperature charting was good for the cave people. Please use a predictor kit.

What are the chances of conceiving with Clomid at age 40? Probably around 3-5 % per try.

Sperm clumping is probably not a problem. If anything, it should be solved with iui.

Stay with Clomid? Getting pregnant with clomid, but 2 miscarraiges. If you are getting pregnant, there is more of a reason to stick with it. I don’t think the clomid is causing the miscarriages, so getting pregnant with the injections amy be no different. See what your doctor thinks.

BPA leaching from cans an interfering with implantation? I wouldn’t worry about it.

Can a 34 yo with a poor response to the drugs become pregnant with IVF? Yes. At your age you only need a few eggs. Now more eggs would be better, but the odds are still very good with few eggs.

How to deal with antisperm antibodies? IUI or IVF.

Polar bodies are different than pronuclei. They both contain chromosomes. The polar bodies are the cells garbage. The pronuclei stay inside the egg and fuse the day after the fertilization. They come together to become the complete genetic material.

Is going for more than 9 eggs at 34 greedy. No , if your doctor thinks adding more drug will safely get you a few more eggs, that’s not so bad.

Is a lining of 16 mm too thick? It is if there is a reason it is thick. That is to say, if there are polyps making it thick, that’s not so good. If the lining is perfectly normal, and it’s thick, that’s ok.

Nuclear transfer and cytoplasmic transfer are not allowed in the USA. Just like many things in medicine, some preliminary results looked ok, but no one ever proved any benefit.

Does thyroid disease, like Hashimoto’s, cause miscarriages? This has been debated for the last 20 years, and there is no good evidence that it does. We are trying to do yet another study to look at the problem.

Does age matter for frozen embryos? No it’s the age you were when they were frozen, not the age you are now.

How come I became pregnant easily at age 23 and am having trouble now that I am 39? This is not uncommon, 16 years is a long time. A lot can happen.

Can you have regular cycle and not ovulate? I don’t think so. Ask what your progesterone levels are, even if they are over 3, you are probably ovulating. If you are not, well then it’s time for induction of ovulation.

Will DHEA help? It might, and if you are making a very low number of eggs, it may be worth a shot. I have had mixed results.

If you have frozen embryos, should you use them or jump into a fresh cycle? It is easier to use the frozens, but if you want the higher pregnancy rate, do the IVF again. If you only have 1-2 frozens, it may be better to do another fresh because not all embryos survive the thaw well.

Can a chromosomally abnormal embryo look beautiful? Absolutely, we see this every day.

What is the optimal TSH level? It depends who you talk to. The endocrinologists are going crazy trying to get everyone’s under 2. There is no real conclusive science showing this is important. Probably ½ the population has a TSH over 2, and ½ the population can’t be abnormal.

Can antidepressants interfere with FSH levels? Probably not.

Will assisted hatching reduce miscarriage? No it will not.

Can you have too much progesterone? No.

Does everyone with endometriosis need IVF? No. It depends on the status of your tubes. If the endo is causing scar tissue around the tubes and ovaries, than yes, IVF may be the best option.

Is a 12 cell embryo on day 3 a bad thing? The embryologists seem to think so. You cannot say you have a serious egg problem after 1 cycle.

Are fragments removed? They are typically removed f you are having hatching because the same little tool used to hatch can be used to suck out some fragments (unless you are having laser hatching). However, no one has ever showed that fragment removal makes a difference. Same goes for assisted hatching.

How do you define poor egg quality? I would say embryos that look less good than average. Embryos that are fragmented more than 20% are poor, even 20% is not great. Slow embryos are poor. However if you just did one cycle, you cannot be given the label until another cycle is performed.

What’s better, a frozen cycle with estrogen, or a natural frozen cycle? They are about the same. I find that sometimes the natural cycle gets a little confusing with the timing, and a small number of people ovulate earlier than expected, so if you do a medicated cycle, less is left to chance. However a natural cycle FET is a very acceptable practice.

See next time. Please read disclaimer 5/17/06. Dr. Licciardi

Back to More Fertility Questions

2009-02-16T18:29:00.000-05:00

There will be 1-2 more for the blastocyst, but I will answer a few questions first.

Sorry, some of these questions were asked a while ago and my responses may be a little late if immediate action was necessary. I will still answer many of them hoping the answers will help others. If I skip your question, it does not mean it’s a bad one, it just means I cannot comment, or I just don’t have anything additional that will help.

There are a number of women who have tough stories about failing many IVF cycles and being faced with the donor egg decision. I always feel I want to recognize the problem by commenting, but my responses have been similar. Usually, it’s just up to you. The boring answer is get tot the best clinic possible and weigh your options. If I see anyone who I think is getting pushed to donor egg too soon I’ll comment.

Jennifer was discouraged because on clomid she found it difficult to time her intercourse because the cervical mucus remained thicker.
You should use a different method of checking for ovulation, namely the ovulation predictor kits. Clomid does make the mucus thicker, but not in some and partially in others. You can get pregnant if the mucus is thicker, but it depends how thick. This is another reason to consider insemination in order to remove the mucus from the equation.

Muriah had septum surgery but the HSG post op showed some septum remained. Why?
This is more common when the septum is very large. With a large septum, there is quite a bit of cutting. Of course we don’t want to cut too much, so at the top it may look like a dramatic improvement, but in reality, a little more should have been cut away. It is also possible that the doctor saw that there was a little left, but felt he had cut enough, but did not. It is also possible that as the uterus healed, it scarred a little at the top, making it look like the septum remained, when in fact it was cut properly but did not heal well. In any event, when I have a patient with a large septum, I do say that a second procedure may be necessary, although it has not been necessary in years.
It is also possible that there is a little left, but it’s not clinically significant. This is very common. I sometimes see a bit left and I say it’s not enough to worry about.

Jamie has spotting being treated with progesterone.
Just make sure your uterus is normal. Make sure you have a thorough ultrasound and HSG, and maybe a sonohysterogram, to be sure there are no polyps or fibroids. Some women need a biopsy. Otherwise, some women spot for unknown reasons and progesterone, sometimes with estrogen, fixes the problem.

Ruby’s husband has anti-sperm antibodies. I do not think this means anything.

KSNYC makes a few follicles but only makes 2 eggs Why? We do not know. If you had only done 1 cycle, we could say it’s just one of those things, try again. But after 4 cycles with varying protocols, and consistent results, well, that’s how you behave. I would say that at age 34, you should not give up yet.

Ronni is 40, makes nice eggs and embryos, has severe male factor, and is being told to do DE after 3 failed cycles. She is being told it’s an “egg issue”.
It’s up to you. Of course your problem is an egg issue, but you eggs can still give you a chance. I am going to guess that your odds are 15-25% with your eggs. You may want to consider traveling farther for a better clinic.

Amanda was on clomid, and injections are being suggested but is worried about multiples/hyperstimulation. Yes minimal stimulation is the way to go. We use anywhere from 37.5 -75 units.

Katrina’s husband has zero morphology. There is not much that can improve morphology. Spotting may or may not be a problem. See the post above.

Flycat is Catholic and does not want IVF or IUI. My suggestion is for you to speak to your priest/pastor. You never know, they may be more permissive and sympathetic than you think.

Helen has a bleeding cervix. You are right, cautery or freezing may scar the cervix. Get another opinion.

Lazarus is 41 and has failed a few cycles. Her doctor does not want to use the estrogen pirme. I say why not? It may or may not help, you just need to see.

Mina is 33 and was told she is in premature ovarian failure. You need to repeat the FSH and estrogen levels every 6 months, and least for a while. Sometimes things get better. However odds are the numbers are accurate and your doctor is correct.

Tracylayne’s husband has a translocation and 6 sperm. It seems that your advice is accurate. We do not know with certainty about odds of pregnancy and miscarriage.

Rehab nurse is considering reversing her tubal ligation. You are right in that you need to get to the right doctor, but it is hard to know who that person is. Some states have insurance companies that cover the procedure so doctors there have more experience because they do more. It’s the balance between reversing the tubes and just doing IVF. Some women prefer the IVF because they can still have contraception after the baby is born. The operation may cost more than one IVF cycle, however it may take more than one IVF cycle to get pregnant.

Chris has severe endometriosis. She has done 2 retrievals , makes a good egg number and has nice embryos. She has also done frozens.
Make sure you don’t have a hydrosalpinx (blocked swollen tube). Assuming you do not, it may just be a matter of trying again. Your history does sound like there are many positives that can work in your favor.

Karen has triplets and the new fertility clinic is criticizing her for wanting another baby. Go elsewhere, their attitude is not appropriate.

Heather wants to know if she should do back to back iuis. It probably is not necessary, providing the timing of the one iui is proper. If there is a question about the timing, use the 2.

The Kinsleys had a nice fresh cycle that failed and are worried that their frozen cycle will fail too.
There is not much to worry about. If they thought the embryos were good enough to freeze, they are probably more than good enough. This is one of the main reasons we freeze, if the fresh fails, you have the backup. It can work.

Curley wants to know if poor sperm can cause embryo quality issues. This is tough one. Usually not. However, I have seen a few cases along the way. The big problem is how to find out. If you make 20 eggs, you can feel better about splitting the eggs and using 2 sperm sources. If you have make 4 mature eggs, the experiment may not give you the answers you need. Most of my patients will try a few IVF cycles first, and then be forced to make a decision. May do not opt for the husband/donor split.

Just Before Blastocyst: The Morlula

2009-01-27T17:40:00.000-05:00

So what happens after day 3? Two days later we would like it to be a blastocyst. The day before it becomes a blastocyst, it should be a morula. A morula forms when the 8 cell embryo divides further, and at the same time the cells become very close to each other. Here it’s difficult to see the borders of the cells, so the morula looks like one big blob. It ‘s solid in the middle. It’s still inside the shell. There are about 12-30 cells in a morula.
Here are some pictures:

Here is a nice looking morula.

Here are a few others . The top right looks nice, the others look OK, the bottom right looks the worst.

Most morulas (some write the pleural morulae, but most write it morulas) look about the same, so we don’t give them a number or a grade. We may say “nice” for a good one, but that’s about it.

Is it ok to transfer a morula? If your doctor wants to transfer your embryos on day 4, you will probably have morulas, but it will be hard for you to get a handle on quality. Most programs transfer day 3 or day 5. Day 4 transfer is ok, but most of us would say if you are waiting till day 4, just wait till day 5 so that the embryos have more time to grow, and quality can be better assessed.

What if on day 5 you are told the best embryos are morulas, not blastocysts? Not so good. I have had patients get back 2 morulas and become pregnant with twins. However the chances of pregnancy are much higher if you have blastocysts.

If there are morulas on day 5, isn’t it better to wait another day until they are blastocysts? No, because even if they become blasts on day 6 they are still a day behind. Rarely, we transfer on day 6. This may happen if , for example, there are 4 morulas and we want to give them, one more day to see which ones, if any, develop a little more.

Can we do anything to make the embryos grow faster? The same answer as last time. We try to change things up a bit next cycle, but there is no special drug protocol for slow embryos. Its just a matter of trying again and hoping for a better outcome.

Thanks again,

Dr. Licciardi

More About Embryos

2009-01-12T10:35:00.000-05:00

The questions: at the time of this writing there were 84 questions to answer. I will read through them and get to most, but probably not all. I am sure this is most difficult for those who write about the here and now, i.e. questions about a cycle in progress. Many of you have commented that the topics are more helpful than the questions, so I want to continue with the embryo blogs, and then go to more questions. I do like answering the questions.

The egg is one cell, the fertilized egg is one cell, and then the egg divides, becoming 2 cells. The 2 cells are smaller than the one big one, and with each division, the cells become smaller. After 2 they become 4. Actually many times they become 3. Both the 2 cells may not divide at the same time. That’s why an embryo can be a 3, 4, 5, 6, 7, 8 or other cell number. It does not need to be an even number.

So here are pictures of 2 cell, cell 4 cell and 8 cell embryos.

The overall size of the embryo does not change. The zonna pellucida stays the same size, so the cells need to fit inside. Just like a developing chick can’t be bigger than the egg, till the end.

These are pictures of perfect looking embryos. Most embryos do not look like these, and that’s ok. These are the typical embryos you see on web sites.

Most of the questions about embryo development we cannot answer. Why do some embryos look prettier than others? Why are some embryos slower than others? Why are some embryos fragmented? We are not close to understanding these questions. We prefer if an embryo looks “better”, meaning the cells are dividing at the right rate and there is minimal fragmentation.

How quickly should an embryo grow? 1 day after the retrieval, they are still one cell, but the next day division should take place. A 4 cell may be the best, but a 2 or 3 may be ok. And of course, they have to keep growing, so that the next day, day 3, they should be 5-8 cells. A 4 cell on day 3 is really slow. Certainly, as with many other slow embryos, a baby is possible with a 4 cell on day 3, but it’s better to have an embryo that is more advanced. The closer you get to 8 the better, 6 is the minimum “good” number”.

Most clinics have their own classification system for grading embryos. Some labs call their best embryos A’s. Some 1’s, some 5’s. There is a reason for this. IVF is a relatively new science and many of the lab directors who started 10-20 years ago had little human IVF experience. There just were not a large group of scientists who previously worked in IVF labs. They had backgrounds in brain science, animal science and all sorts of other areas. Some of them turned into great lab directors (hats off to our lab director, Dr. Krey), but there was not grading system that the whole country followed. Each program just made up its own system for grading day 3 embryos. We could all get on the same page, but now it’s too hard to go back.

It would be really difficult for each program to go back through 20 years of charts and change the numbers assigned to each embryo. Plus if we all change now to a new system, it’s hard have some embryos graded one way and some another, especially for research purposes. So things will stay as they are. It just makes it a little difficult when you talk to your friends to compare embryos. To jump ahead a little, there is a system most of us follow for day 5 embryos.

What is fragmentation? Fragments are little pieces of the cell that break off as the embryo divides. A little bit of fragmentation is normal. As the degree of fragmentation increase, the odds of implantation go down.

Let’s look at some day 3 embryos to see varying amounts of fragmentation.
This close up shows the normal larger cells, and some smaller round “fragments”.

Here is a group of embryos from the same woman. The embryo far right is the best. It has very few fragments. The top embryo looks good too. The bottom middle looks ok, but is a bit more fragmented.

This embryo has a high degree of fragmentation (compare to the nice embryos at the begining).

In this picture, the far right embryo is full of fragments.

We frequently assign a fragmentation score by estimating the percentage of the embryo volume that is replaced by fragments. 0% is actually rare, some fragments are expected. 0% is ok, but it does not happen much. We consider up to about 10% to still be very good. 10-20% is still OK, not quite as good. More than 20% is more abnormal, we consider the embryo to be of poorer quality. Pregnancy can occur with a fragmented embryo, but the odds are lower.

Sometimes fragments are removed from an embryo in the lab, by making a small hole in the shell and sucking out the fragments on day 3. This is done at the time of hatching since the hole is the same. The embryo can look much better, but we do not know if it means the embryo is really in better shape.

Can we reduce a woman’s chance of producing fragmented embryos? We try, but we never know if our efforts helped, or things improved as a result of chance. We add lupron, remove lupron, add LH, remove LH, lower doses, increase doses, give few days or more days of stimulation, etc etc.

So what’s worse, a slow embryo or a fragmented embryo? Of course it depends on how slow or how fragmented, but basically, it’s a tie

An important issue here is that if you have done 1-2 cycles of IVF, and you make eggs and embryos and have fragmented embryos, donor eggs may still not be necessary. Get a second opinion at the best program possible. Maybe DE is the best thing for you, but maybe another try under different conditions will do the trick.

Thanks for reading, and please read disclaimer 5/17/06.
Dr. Licciardi

The Road to Blastocyst: Eggs and Embryos

2008-12-14T08:54:00.000-05:00

This is the first installment of blastocyst blog; but it's a bit of a pre-requisite. To give you a feel of where we are going, I will start with pictures of eggs and embryos and then blastocysts.

This is an egg. I doesn't really look like an egg. Part of the reason for this is that in this picture there are hundreds of cells, but just one that is an egg. The dark circle in the center is the egg. You can see how big eggs are compared to the rest of our cells. The surrounding specs are granulosa cells. These are the ovarian cells that line the inside of the follicle. Prior to ovulation, the egg's position in the follicle is along the edge, so the granulosa cells that are growing along the inside of the follicle surround the egg. When the egg ovulates, it carries some of these cells along. When an egg is retrieved during IVF, it is also surrounded by granulosa cells.

The granulosa cells make the estrogen (estradiol). So as the follicle grows, more granulosa cells form, and estrogen rises. In an IVF cycle, the more eggs there are, usually the higher the estrogen levels.

This is a picture of an egg a few hours after retrieval, after the granulosa cells have been removed.
In the case of IVF using ICSI, the embryologist needs to remove the granulosa cells a few hours after retrieval. This is necessary so she can see the egg and to properly inject the sperm. If ICSI is not necessary, we can mix the eggs and sperm together, and the sperm will swim through the granulosa cells to get to the egg.

The little round object on the top is the first polar body, and this is an indication that the egg is mature. The first polar body contains chromosomes, as does the larger egg cell. For the egg to accept the DNA of the sperm, it needs to dump some of its own DNA, otherwise there will be too much. So the egg unloads some of the DNA into the polar body, which just withers away. Sometimes testing the DNA of the polar body can tell us about genetic diseases in the egg. For the most part, we can not use an egg that is not mature. There is some encouraging research looking at maturing eggs in the lab, but so far the process of maturing eggs in culture has not been widely accepted.

This is what we call a 2 pn zygote (or 2 pn embryo). The picture was taken one day after the retrieval. You can see a few granulosa cells still hanging around.
The halo around the embryo is the zona pellucida. It's the shell of the egg. It has the consistency of a thin vitamin E capsule. Inside is the egg (or oocyte). In the middle of the egg, you can see 2 little round objects, and these are the pronuclei (pn). One contains the genetic material from the egg, the other from the sperm. In some animals we can tell which came from where, but not in the human, although as our microscopes improve, I suspect we will very soon be able to tell. So if we expose eggs to sperm, and look the next day, and do not see 2 polar bodies, fertilization has not occurred. Sometimes we see one, and this means fertilization possibly occurred. In this case we may or may not see 2 later in the day. The 2 pn will combine to complete the fertilization process.

Dr. Licciardi

Stories of Persistence

2008-11-26T15:46:00.000-05:00

I know you are waiting for the blastocyst blog. I am just getting some photos together and will have it ready for next time.

Like it or not, the holidays are here. Maybe it’s a good time to spread a little message of hope. Now hope isn’t for everyone, but let’s face it, it’s probably the number one thing that keeps us going. It’s an emotion than can be applied rather universally, applicable to mostly all of our basic functioning.

Anything we need or want, we hope for.

As stories from the internet have shown, some women with low chances can become pregnant.
Here are a few of my own. And these are only a few out of many others, these just came to mind.

Ms. A was 38 when we met. Her FSH was 22. She was “dismissed” from another program. 2 years earlier she delivered, but this was after trying for 18 months. The sperm motility was a little low, but the sample was close enough to normal, ICSI was not needed.
She first tried a day 2 start, her FSH was 13,4, and was cancelled and converted to IUI because there were only 3 follicles. The plan: keep trying. Her second cycle never got off the ground because of a day 2 FSH of 17.7.
Her FSH was 11.9 on her 3rd attempt and she went on to make 4 eggs, 4 fertilized . On day 3 one looked good, the other fair. This ended in an early biochemical loss.
Her next cycle we changed up the protocol a bit. She had 4 eggs, and 2 embryos transferred, both looked good. This worked, and she just delivered.
So here we have a woman who most doctors would tell there is no chance, but she persisted.

Ms. B was 35 when we met. Her FSH was 14. Her resting follicle count was less than 5. She started a cycle with an FSH of 12, got 6 eggs, poor fert and a cancelled transfer for arrested embryo growth.
Her second cycle was cancelled for no response (not one follicle).
She got pregnant on her own. This theme is an internet favorite. Buy the way, she did not use DHEA.

Mrs C. was 36 and suffered from severe edometriosis. She did 2 IVF cycles before we met.
She did 3 more retrievals with me, always making a good egg number and having good embryo quality. She travelled long distance to get to NYU. On her 3rd cycle (5th total) she became pregnant.

The next one goes under the dumb doctor category (that would be me). Mrs D, a 38 year old from overseas, e-mailed me and told me about her FSH of 25. Realizing she was from far away, I tried to save her some travel time and money and told her IVF was out, but donor egg was in. The couple came to see me, heard the donor egg schpeal and as I finished the husband looked up and said that his wife was going to be day 2 in a few days, could they try IVF while they were still in the States? Without boring him with the low odds speech, I just said, “sure why not.”
Sure enough the FSH was 12, she made 9 eggs and delivered twins. I think they are happy with me, but I am sure they have their reservations.

How can we put these all together?
1) They about women under 40. I don’t mean to exclude the 40 and over crowd from the hope discussion, as there are plenty similar stories about women in their 40’s, but the facts support that it’s easier to beat the odds when you are younger.
2) FSH may not be as important as we once thought. Again, a bad FSH is better under 40. Every so often there is a paper or abstract reminding us that pregnancy rates shoot down with increasing age and FSH levels. Which leads us to the next point:
3) Some infertile women can at times become pregnant on their own. We do use this fact when recommending that some women cancel their cycle or give up on IVF. We say yes you can get pregnant with IVF, but your odds are low, about the same as getting pregnant on your own. Of course this is much more difficult concept to accept when there is a severe male factor.

So for Mrs. A, C, and D, their persistence is what lead to their success. They did not accept the advice of a doctor; they did what they felt they needed to do. Of course we have to keep in mind that it is also true that there are women who try and try unsuccessfully.

Sometimes the fertility establishment is criticized for giving a bit too much hope, while profiting nicely from tons of women who are needlessly spending tons of dough. And sometimes we are criticized for not giving an infertile woman the chance she deserves.

But it will always be true that for most women with low odds, there is a small chance, and sometimes their only chance, using IVF. So it all goes back to getting to the right clinic and getting informed about your odds. After that it’s between you and your doctor, sometimes with a little tug of war.

Dr. Licciardi

A Marathon of Infertility Questions

2008-11-06T16:16:00.000-05:00

As this Sunday was the New York City Marathon, I figured I would have my own little marathon and answer all of the outstanding questions. Here it is.
It took me a few days to cross the finish line, but I was able to eat and sleep along the way, possibly experience some weight loss, and I seem to be injury free.

From October 4th

Niki has had a very tough time trying to have a child. She has had a number of bio-chemicals and worse (see her post). Her basic questions are 1) is a thinish lining the reason, or is it an immune problem, or some other problem we just don’t know about?
I also do not buy into the immune issues. These have been studied now for many many years and never has anyone produced a quality study showing they mean anything. However, you have few choices, so it may be reasonable to consider getting tested and treated, if something shows up. I am not recommending one way or the other. You should give equal consideration to a carrier.

Esther had open tubes on hsg and a few weeks later had both tubes blocked at laparoscopy. She is being told she needs IVF.
I am not so sure. When I have open tubes on HSG, I don’t even check at laparoscopy. Why? Because it is common for tubes to be open on hsg and closed at laparoscopy. It’s a mechanical issue. Sometimes the doctor just has trouble getting dye out the tubes at laparoscopy. Now it depends on where the blockage is. If you have proximal occlusion (blocked at the uterus), this may be a false finding. If he says you have bilateral hydrosalpinx (blocked near the ovaries) that’s different and real. If there is any question, the answer is simple, just repeat your hsg. If the tubes are open on your next hsg, there were not blocked at your laparoscopy.

Mosche and his wife need IVF with ICSI due to male factor, however even with ICSI, there was no fertilization.
I have only had one young patient make many eggs and not fertilize with icsi. So it can happen, but it is rare. It’s a little more common when there are also issues with advanced maternal age and low egg number.

Ruby asked about sperm antibodies.
I do not believe in them because no good recent scientific paper written showing me that sperm antibodies are relevant.

Angie did a clomid IUI cycle, and the sperm count was 18 million with 56% motility.
The count sounds reasonable for iui. Although you should still ask for the total motile count, and look for that to at least be over 5 million, preferably over 10.

Tabi did 4 IVF cycles, 3 with lupron, one without. The non-lupron was her worst.
We don’t know if it was the no lupron, or was it just going to be a bad cycle for you that month, independent of your stimulation protocol. It may be that in your case lupron is better. For most women who make few eggs, this is not the case, but not all women are the same. I don’t think you are declining.

Ali did IUI. The sperm count was 143 million with 48% motility. However for the iui, only 3 million were recovered.
This is strange and does not make much sense; unless the initial volume was very low (2cc is normal). I am not worried about his morphology. “Abnormal” sperm are not removed when preparing for iui.

Manny and his wife are trying to conceive. He is asking if the lining could be an issue, especially because she takes anti-migraine medication that theoretically could restrict blood flow to the uterus.
The question is interesting, but unknown. One option is to measure the lining on and off the medications. Or, try to conceive off the medication. Another option is to look elsewhere for a potential problem. Do the basic workup i.e. semen analysis, HSG, day 3, to see if there are not bigger problems with more known quantities.

Anonymous has PCO and 2 weeks of bleeding after clomid.
This is not normal. Actually, the first cycle sometimes the bleeding can be unusual, but once you get into a pattern of periods, they should not be 2 weeks long. You need a good exam and ultrasound and maybe an endometrial biopsy.

Anonymous is 42 yo with 3 failed IVF cycles. Some borderline FSH levels and 1, 1 and 3 embryos available for transfer. Should she stop?
Your odds are what they are, low. It depends on your clinic, but your chances are probably about 5-10% per try. Many women, probably most, would stop here. But some persist, and a few get pregnant. As you know there are emotional, physical and financial issues to wade through. You can’t say you didn’t try. I hope it works out.

Mark is asking if he and his wife should consider natural cycle or minimal stimulation IVF vs. the standard IVF using more drugs.
You will need to decide. My only comment on your post is that it is not true that fertility drugs for regular IVF will ruin the eggs forever. But the opposite is also true. If you do a natural cycle, you can always do a regular cycle later. Regular IVF may not be for everyone, however, for most people, it has a higher pregnancy rate, which means a better chance of having a baby. The cost is less for natural, but with its lower pregnancy rate, it is common (not in every case) to spend at least as much money because the cost of multiple cycles really adds up fast. If you get pregnant early, great, you were the lucky one.

Erika has had 9 pregnancy losses and IVF is now recommended.
I understand the theory; if you put more than one embryo in, maybe if one fails another one will stick and you can have a normal pregnancy. Certainly, your odds of loss will be higher than the average person, even with IVF. I don’t think we can tell you that your odds of loss will be lower than from a natural pregnancy. However, your options are limited, so it may be worth a try.

Dizzy has totally unexplained infertility. All tests are very normal and she is 31. She has done 6 FSH iuis and is considering IVF, but insurance does not cover.
IVF is the next step. No one will be able to tell you why you are not getting pregnant, but IVF has an excellent pregnancy rate, even if you have failed FSH iui. You odds with FSH iui are now going down, because it has not worked. Of course you could do more FSH iui, and it may work, but it may be more of the same.

Purple Mocha has a 3 mm lining on clomid.
Sounds a little too thin. You can try again, or change to FSH. You could also check you lining in a no drug cycle to see what your baseline is. Of if you want to get going, just go to the FSH.

Mtroth has some endo and failed one IVF cycle, which was complicated by hyperstimulation. She has frozens. Did an undiagnosed biochemical pregnancy lead to her hyperstimulation?
You may have had a biochemical, but probably had plain old hyperstimulation. Your estradiol was high and you needed to be coasted. I do not think the endo was an issue. You can’t prepare for the FET. The good news is you seem to have nice embryos and should do well.

Athena has 8 months of infertility, short luteal phases of about 10-11 days, and serious pelvic pain. Her doctor will not see her until she has a year of infertility.
Maybe you have insurance that will not pay your doctor until there is a year of infertility, or maybe he is not a nice person. See which it is. If you think your timing has been good, it would be better if you saw him or another doctor soon. In general I do not believe in luteal phase problems, but you may be an exception because your luteal phase is so short. But do not only get that treated; work on other things at the same time. Get the hsg and ultrasound to look for cysts and endometriosis. Get the sperm checked.

Anonymous is an over-exerciser and because of this does not get her period on her own and does not bleed after provera. Because clomid starts after the period she does not know that do about starting the clomid.
You can start the clomid without a period, providing you get a pregnancy test. I am fine with you trying the clomid, but may women like you do not ovulate on clomid because, due to the exercise, your pituitary does not have much FSH or LH, and clomid works by releasing FSH and LH from the pituitary. Most of time, injected FSH is necessary to get you to ovulate. But you can try, sometimes it works.

Milka is 37 and her doctor told her her IVF failure was age related. He also wants to repeat her sonohyst and cultrures
I do not repeat those tests unless there is a good reason. Failing IVF is not a good reason. Your failure was not age related, you are young compared to many fertility patients.

From October 15th

Niki wrote back and did her IVF cycle, froze all due to lining issues. She is considering a carrier and does not want pgd.
It all sounds reasonable to me. It will have to be your choice.

Anonymous has pco and endometriosis. She did 8 clomid cycles and is in her last FSH iui cycle. Should she do IVF?
If you have done 2-3 FSH iui cycles, IVF is the next step. I like the way your doctor is doing the FSH iui. I am very optimistic. You are 28 and have eggs, that’s all it takes (in most cases). I expect you to do well and get pregnant quickly.

Anonymous is 33 and has had 3 miscarriages.
You odds are still excellent of having a baby in your nest pregnancy. Your doctor needs to do a miscarriage workup.

Anonymous has a normal pap with some cells missing and burning and numbness in her vagina.
As long as your doctor and the report say the pap is normal, it’s normal. I do not think the burning is related to antibodies, and it’s not due to the pap.

Diana was diagnosed with a septum and that was corrected. She then had to delay fertility treatment for treatment of thyroid cancer. New she is trying again without success. She is 35.
Give it the 3th month, but start making plans if things do not work. As far as your next steps, you know the drill. Get the options, get the pregnancy rates, and then decide which treatment sounds best for you. Be sure all of the septum is gone. I see many patients who have had septum surgery, only for me to tell them their doctor left a lot of septum still in place.

Anonymous does not get her period and is starting with a SIS.
I does not matter if you see her or a RE, but you need assistance ovulating ASAP. I don’t get the SIS, unless she sees something suspicious on ultrasound. You need to ovulate and this will probably require medication. Ask the doctor about getting the HSG before you try, or trying a little while (with ovulation) and then getting the HSG.

April did an IVF cycle with some immature eggs and late icsi. The embryos did not look good.
It sounds like there were a few issues with your cycle, but they seem correctable in the next try. It’s hard to tell if there was a problem with your IVF clinic, or things just want bad on their own. If you think you are at a very good place, give them another try. If you have reason to believe there is a better clinic near you, make the switch.

Shari in Chicago has endometriosis. She was treated with lupron and is waiting a long time for her period to return.
It works like this. The lupron is given every month (unless you have the 3 month version), and that lasts about 5-6 weeks in your system. Then you need to start your cycle again, and most women ovulate 2 weeks after that, and get a period 2 weeks later. That means you get your period about 8 to 10 weeks after you last shot.

Christine asked if IVF babies were born earlier and or smaller than non-IVF babies.
The answer is maybe. Some data suggests this is the case. However not all studies break out singletons from multiples, which usually deliver early. If there is an association, it may be due to the fact that some women with infertility may have uterine abnormalities that cause premature delivery. It is also possible that infertile people are more likely to have subtle genetic issues interfering with the length of pregnancy or the size of their babies. Or it may be that there is no difference at all and the right studies have not yet been done. Or maybe the IVF process is flawed and babies are smaller and deliver early. At this point, if there is a difference it does not seem to be great.

Alesha is trying to have her second IVF baby. Her first was at age 32, she will be 35 in January; her FSH is normal. Because she is a teacher, she wants to wait till summer to try. Her doctor says try now; her ovaries may change in the next 7 months.
It will be a little harder then, but if you are very fertile now, you will be very fertile then. Although there is a small chance he is right. Don’t forget you will be 3 years older than you were at your first try. I think it’s up to you, but consider this. Many women become very sad when they get pregnant on their first try, but not on their second, because it seemed so easy the first try. This could happen, and your following cycle will need to be during school, which is what you were trying to avoid. Therefore, why not just do one during school now. The logic is a bit of a stretch but I hope you get the point.

Leila has endometriosis and a fair response to meds. Her first 2 cycles yielded few eggs, and she did much better with a day 2 start than with lupron or microdose. If this fails, should she try again?
This cycle was very encouraging. You are only 36 and make 11 eggs, not bad at all. Question for your doctor: do you really need icsi? It sounds like you are on the right track. Consider the same protocol or estrogen priming.

Anonymous asked why go to FSH iui after 6 failed clomid cycles? Why not go to natural iui?
For younger patients, natural iui has a 5% pregnancy rate and FSH iui has a 20% rate. You can do whatever treatment you are comfortable with, just know the odds.

Anonymous is 42 years of age and has a FSH of 18. She failed a response using 14 days of lupron and 750 units of FSH. Should she stop?
It really does not sound encouraging. If you really wanted another try, ask your doctor about the estrogen priming protocol. Lupron is not the best for poor responders.

Anonymous has irregular cycles and is trying with clomid. She is using cervical mucus to time things.
Use an ovulation predictor kit instead. You can get pregnant with mucus that is thicker, but, if the clomid does not work after 3-6 times, ask your doctor about FSH. You may get pregnant before you get to the FSH.

Anonymous did 2 clomids, 3 FSH iuis and one IVF. She made 9 eggs but had slow embryos.
Get yourself to the best IVF clinic available. It may be where you are, or you may need to switch. Check rates at SART.ORG. Use a different protocol. I hope it works out.

Beth was diagnosed with endometriosis and is not ready to conceive. Should she go on Lupron for 9 months?
9 months sounds like a long time to me. The pill is definitely an alternative to lupron. Ask your doctor or get a second opinion.

Amila had an iui, had intercourse that evening and then had an iui the next day. The second iui had a lower count.
Probably too much. Stick to the iui’s.

Jesse b: Wife 30 he is 34. They just started the workup and were found to have one blocked tube and a low morphology. Their doctor is already talking about IVF.
Wow, they are going fast! First of all, if the tubal blockage is “proximal occlusion” a laparoscopy is aggressive. It is an option, so is repeating the hsg. It may have been spasm. If it shows distal occlusion, maybe surgery is more indicated. The morphology is probably not an issue. I don’t why they don’t just consider clomid first. Even if one tube is blocked and one is normal, it may be worth a shot with clomid. Of course, ask your doctor or get a second opinion.

Anonymous is 37, has a bicornuate uterus and a poor response. 4 failed ivf cycles, 0-6 eggs each. Her husband had a vasectomy.
Since your last protocol seemed to work best you could try one more cycle. You could also consider stopping. If you do another, consider the same protocol you just used. The reversal is not a bad idea, because at least you can try every month. But, they don’t always work, or they work but the counts are low.

Lisa tried many natural donor sperm cycles then used low dose FSH and got only 1 egg. She is worried that if she made only one on FSH, maybe she made none on her own or on clomid.
I believe you made one on your own and one or more on clomid. Your doctor did the right thing trying to control your dose, but now it seems you need a little more. It can work with the one. If not you may need a little more drug.

Anonymous has a doctor who wants to do an endometrial biopsy the month before the IVF cycle to promote a better lining.
Most of us do not do this. If your doctor can do a study, or maybe he has seen such a study proving it works, fine with me. But I am not aware that this method is of any value.

Kate is 31 yo and she did 2 IVF cycles. Her response is fair, 5-6 eggs, and after her first cycle her embryos did not look good. They got rid of the lupron and in her second cycle she had nice embryos. A pregnancy ended in a miscarriage at 6 weeks. She was told she has bad eggs.
I do not see that you have bad eggs. Your last cycle gave you nice embryos, and it almost worked. I think your chances are still very good. You could change to a microdose, or you can stick with your last stimulation, or you can consider an estrogen prime protocol. They will all be similar, it’s hard to say which one will be the best for you. Check pregnancy rates, if their results are good stick with them.

Murgdon’s husband has very low counts and her RE and urologist feel there is nothing practical that will raise counts, leaving them with IVF as their only option.
It’s hard for me to give specific advice about your husband’s condition, but in most cases, the advice you have received is correct.

Indigirl is 40 with a couple of cancelled ivf cycles for poor response. She switched to the estrogen prime and had 10 eggs. Her FSH is 10-12 and she has a bad AMH level. Is 10 a bad count?
10 is a very nice number, definitely enough to work with. We do not know enough about AMH to know if a bad level means pregnancy is not possible. Right know it’s a guide. The technology of PGD changes for the better every day, but ask your doctor what he thinks about not doing PGD. There is an element of embryo damage that can occur. PGD may be the best thing for you, but double check.

EAS is considering IVF with PGD because she has had a biochemical, 6 week misc at 6 weeks, and now a beta that does not look promising.
As long as you are informed about the pros and cons of PGD, then the choice to use PGD is reasonable. I just get upset when patients are led to believe that PGD is a perfect science.

Anonymous is 27 and does not ovulate or get her period, even with provera and clomid. What should she do? Her doctor is suggesting metformin.
Some women go great with metformin, but they are a mininority. The down side to metformin is that you need to wait another 3-6 months to see if it works. Certainly, it’s less expensive than getting FSH injections and monitoring, and you don’t need the doctor’s visits. It is a less aggressive way to go. Weigh your options.

Kahla’s husband has a low count. They got pregnant and had a baby on their first IVF try. The next 2 cycles failed and she had a 6 week miscarriage on her 4th try. She has had it and is considering iui.
It depends on the sperm counts, and you need to know your odds with iui and IVF. Most people find it really hard to go back to iui after doing IVF. But, if the counts are at least adequate for iui, you could do iui, and IVF later if necessary.

Jennifer’s mom has the BRCA gene discovered after being diagnosed with breast cancer twice. Should Jen take clomid?
Maybe you should get another opinion. Clomid is not that different than tamoxifen, a drug used to treat breast cancer. However, breast cancer is not my area, so I will defer. You could use letrazol to stimulate ovulation. This can cause ovulation, but is also used a breast cancer drug. Make sure you are not pregnant if you take it. Make sure you are fully screened for cancers before you try.

Elize has had enough history for 5 women. Check her entry for details. Now she is left with multiple major surgeries, miscarriages, and a uterine scar.
Much depends on how much scar there is. If it’s a little area, and most of your uterus looks good, and your normal endometrium looks thick enough, you may be ok, even if the scar comes back. If scarring returns after the first surgery, the odds of a second of third operation permanently removing the scar are much lower, especially if the scar takes up a large amount of the enodmetrium. We are not sure why you had the miscarriages, so I can’t say that you are at high risk for another miscarriage. Rupture is really rare, more common if you needed to have a large uterine incision for your myomectomy. A scar will incresase your odds of miscarriage and premature labor, but again it depends on the size of the scar. Scar will increase your odds of placental problems such as increta (where the placenta grows too deeply into the uterus)

Jesus my best friend has a unicornuate uterus with an open tube, and was encouraged to try on her own.
It sounds like a good plan to me.

OK, see you next time with a topic, probably blastocyst.
And please see disclaimer 5/17/06.
Dr. Licciardi

Infertility Questions and Answers: Almost Caught Up

2008-10-15T19:38:00.000-04:00

Anonymous asked about really trying to nail down the best progesterone for her IVF attempts. She failed one fresh cycle and 2 frozen cycles. She tried the injections and cream and Crinone. Her latest problem is she bled on Crinone, and had a thin lining in the luteal phase, and now is scheduled for a biopsy on Crinone.
Why? Crinone may be a good drug for some, but in your case it does not work. Why do a biopsy when you already know this drug gives you problems? I have never done an ultrasound in the luteal phase to check the lining. Maybe your doctor is on to something, but for most of us it’s all about the lining before your progesterone(ie we check in the follicular phase). Your problem highlights the reality that progesterone in oil, as difficult as it is, gives consistent results. If vaginal progesterone is your only option, and Crinone does not work out, you can consider old fashioned progesterone suppositories.

Anonymous asked about not getting her period after lupron.
This commonly happens. You odds of pregnancy will be based on your clinic’s success rates. Remember it’s the age you were when the embryos were frozen, not your age now.

Wannabmomma has PCO and has tried 5 clomid cycles with intercourse, no luck yet. She is 26 yo.
It is almost time to move to the injections. Most of us make your limit 6 cycles, fewer if you have regular cycles on your own. But, you are only 26, so you could consider a couple more with insemination. I really think this can be up to you.

Big Childwish has a significant miscarriage problem. She has had 4 consecutive miscarriages at about 7 weeks, all with a sac but no fetal pole. All of her testing is normal. She tried the blood thinner.
I am assuming you had a hysterogram, if not you need it. I am not sure if you have had a d and c with any of the pregnancies? This would tell you about the chromosomes of the fetus, possible giving you more information about the causes of your problems. Otherwise it may depend on your age. If you are younger, your chance of a baby in your next pregnany is still over 50%. If you are older, your odds are much lower.

Katie has PCO, did an IVF cycle with 7 eggs, 5 fertilized and 2 embryos for transfer on day 3, one 4 cell and one 5 cell.
OK, there are some positive things here. I like the way your doctor was cautious stimulation, and you do make eggs and embryos. You can use the information to improve your next try. First a little more drug will be OK. You don’t need to make 30 eggs, but 15 may be better than 7. If you are at a clinic with a 26% pregnancy rate, but can travel to a clinic with a 49% pregnancy rate, I say travel. If your clinic treats 100 patients, 74 will not get pregnant. If the other clinic treats 100 patients, 51 will not get pregnant. That’s a big difference.

Alibee has a complicated history. She has a unicornuate uterus with a normal tube and 2 ovaries. She has a fairly large fibroid. She has done 5 FSH iui cycles and 1 fresh IVF cycle and 3 FETs, and maybe more more fresh IVFs?
It sounds like your fresh IVF cycles were excellent because you had so many frozen embryos. It’s hard to prognosticate your future after failing frozen cycles. They just do not work as well as the fresh. They are worth doing, but if they don’t work, it’s hard to say things are bad. Your last fresh IVF cycle yielded very nice embryos. So why no pregnancy? Can it be your uterus? Possibly. Most women with a unicornuate uterus are not infertile, but there are a few who have trouble implanting, we don’t know why. Is it just bad luck with IVF? Possibly, but why are you not getting pregnant on your own? This is going to be a case of trying again, if you wish. Should you consider a carrier? It should be a consideration, but of course even that is not a guarantee.

Emily has unexplained infertility and has started clomid. Her first try did not work. She asked about some recent press concerning a terrible article about clomid not working for unexplained infertility.
That will be another blog, but they are wrong. There have been many many studies showing clomid does work. Just remember the odds, which are 8% per try in women with regular cycles. So you are on the right track, I hope it works out.

Jen seems to be hanging in there with her endometriosis progression and pain. Keep us posted.

Anonymous is concerned because her first IVF cycle worked and her second did not. She is worried about the 8% morphology.
This is not the issue. Morphology will not lower IVF pregnancy rates. It’s common that success in the first cycle causes fear when the second cycle does not work. Stick with it. Even in the best clinics, odds are 50% for young women, meaning it’s a 50% failure rate.

Amelia’s husband has an inversion in chromosome 1, causing low sperm counts. She asked about IVF with PGD.
This all depends on what your needs are, and the advice of a counselor. Of course you need to ask about the problems associated with this inversion. Is it just a low sperm count, or are you at risk for a miscarriage or even an abnormal child? You also need to be informed about the costs and success and failure rates of doing the IVF with PGD. In addition, you need to ask about the error rate of your PGD procedure.

Singh did 2 IVF cycles. The first resulted in 10 eggs, but 8 fertilized with more than 1 sperm (polyspermy). Her second cycle she did ICSI and did not have polyspermy. She is wondering if the polyspermy means her overall egg quality is bad, leading to a failure in her second IVF cycle.
We do not know if your problem is egg related, or related to a lab issue. Since you say you had nice embryos in your second cycle, your eggs are probably fine.

EMLU has severe endometriosis. Had Twins with her first IVF cycle, but has since had 2 fresh cycles, and then a frozen cycle revealed fluid in the uterus so the cycle was cancelled. She still has fluid in her uterus and a biopsy revealed endometritis.
Fluid in the uterus is a very difficult problem. I have a few patients with this and it’s tough. In your case you may want to a have a hysterogram (after the endometritis is cured) to be sure you do not have a hydrosalpinx, as this is the most common cause for fluid. You have another possible cause: endometriosis. Some women with advanced endometriosis also have adenomyosis (endometriosis of the uteris) and this can cause fluid. Definitely get treatment for your endometritis. However, most cases on biopsy are not really endometritis, it depends how quick your pathologists are to make the diagnosis. Some overdo it.

Anonymous has unexplained infertility and failed 6 months of clomid.
I would say that’s enough clomid, and you should consider FSH iui or IVF.

I agree with Christine

Beth asked about clomid for raising sperm counts.
It depends why the sperm counts are low. If his FSH is present but low, clomid may help, but that’s a really rare cause for low sperm counts. If his hormones are normal, clomid probably will not help. In fact some doctors think clomid lowers sperm counts by raising men’s estrogen levels. In any event, it’s ok to try some of these things, but don’t waste time waiting for results. Move on with your plan of action in the meantime.

Anonymous had a low progesterone and was put on clomid. So far so good. Then her luteal phase was only 10 days on clomid, and now she thinks she has not ovulated on clomid.
OK, see if you can get office monitoring on the clomid. Ask about getting an hCG shot once your follicle has reached 18-20 mm. This should straighten everything out. If monitoring shows that your cycle is not behaving properly, switch from clomid.

Anonymous is 27, but only got 3 eggs at her IVF cycle. Her doctor was overly cautious with the dose of drug.
OK, so now you know, you need more drug. It sounds like you had at least one nice embryo, so with more eggs you will get more nice embryos and have a much better chance of pregnant. I am optimistic.

Anonymous had infertility, tried clomid, and got pregnant with FSH iui. She miscarried twins at 6 weeks. She is a carrier for factor V.
It sounds like you are doing all of the right things. You just have to wait for the results of all of your tests. I hope it works out.

Mrs C was told she needed IVF because her husband had 1% morphology.
He was wrong, she was right. She got pregnant on her own.

Pam is 40, and failed 2 fresh donor cycles, with 2 good donors and nice embryos. She failed the frozen cycle and has 3 frozens left.
This could be bad luck or fair medical care. I can’t tell. You want to be sure you have had a hysterosalpingogram after your myomectomy. Make sure your doctor reads the films. After that it’s too hard to say form the blog what’s going on with you. Check the delivery rates form your clinic for DE. Most good centers are at least 50-60%.

I can’t comment on one article showing success with a strange therapy in a small number of patients. Let’s give it more time.

MiraclesdDHappen: 26 yo, trying for 7 years, 6 failed clomid.
We are all sorry to hear your still are not pregnant, but it’s time to move on. It’s either FSH iui or IVF. It can happen, it’s just going to take more work.

See you next time, and please read disclaimer 5/17/06/.

Dr. Licciardi

Answers to Infertility Questions

2008-10-04T09:12:00.000-04:00

Mas asked about Rogaine and low sperm motility. My urologists tell me Rogaine has no effect on sperm production or motility. However, just like everything else, maybe he is the one out of hundreds whose system is very sensitive. See if stopping the drug changes anything.

QVC has had elevated FSH levels but recently had a 1.9. Make sure there was an estrogen level done at the same time. Once the estrogen (or estradiol- same thing) goes over 50, it will artificially make your FSH lower. Once the estrogen is over 100, levels like 1.9 are common. You should still be on a protocol designed for women with high FSH levels.

Stephanie had a low egg number using a long lupron protocol. I suggest removing the lupron. I rarely use lupron anymore. I have also started using the estrogen priming protocol. So far I can’t say it’s better, but it seems to be at least as good.

The infertility acupuncturist asked about progesterone after IVF. There is a theory that you need more progesterone for IVF because the follicles, which become the progesterone producing corpus lutea(CL), become disrupted by the needle at retrieval. This may not be the case, but we are not sure. I would think that even in this is true, there are so many CL with IVF, progesterone production should be just fine. However there is more to the story. IVF drugs, especially lupron, but possibly antagon or cetrotide, may lower progesterone production. This is because lupron stops your pituitary from making LH, and LH drives progesterone production. Once you stop lupron, LH function returns, but it takes a few days and by then it may be too late. There are many studies showing if you use lupron, pregnancy rates are higher with progesterone. I don’t believe such studies have been done with antagon. Most studies show no improvement in pregnany rates with fertility drugs and iui. This may be because Lupron or antagon are usually not used for iui.

Melinda asked about ectopic pregnancy. She had one and is worried about another with IVF. Yes you are at increased risk, however the odds are still low, even lower if they took out the tube with the ectopic. I do not know the status of the remaining tube. Your odds could be anywhere from about 2-8% for having another ectopic. It’s good that they told you about potentially having an ectopic, but ask them to check their numbers.

Hopeful in Arkansas asked about clomid iui with male factor. It depends on the total motile count. This number is arrived at after the wash. It’s the total number of sperm you are getting back. The higher the better. Less than 5 is bad, 5-10 is ok, 10 or more is good. If you are getting low number back, consider IVF. If you are getting good numbers, then it’s up to you.

M asked about embryos that were frozen when her husband was drinking excessively. There is just not enough information out there to answer your question. Sorry, I wish I could help you with this one.

Helen asked about taking estrogen pills during her cycle. It is not a good idea to take estrogen pills as part of a natural cycle. It will interfere with ovulation, making it come early, late, or not at all.

Michelle asked about her iui cycle # 12. I am sorry you cannot afford IVF right now, I hope you can find a way. I hope this iui works.

Aimee asked about the necessity of an HSG. I skip it in only a few patients. I have to be really comfortable with their age, history and ultrasound to let it slide. If your doctor is even hinting at it, get it done. You will know soon if your first doctor was wrong. Odd are he was right, but you will see.

Nina asked about extra fertility testing before getting further treatment. I can’t really know what you specifically may need; however for most people the testing is pretty basic. It’s a HSG, SA and day 3 bloods. After that it’s all about your history and the philosophy of your doctor. You can waste a lot of time and money on tests that are not mainstream. Progesterone problems are rarely the cause of infertility. Remember, they go up and down throughout the day. Ask your doctor, taking some extra may not hurt, but don’t go on progesterone for 6 months without doing something else at the same time.

Della hit the jackpot! Very nice.

Julie has immature eggs. DO NOT GIVE UP!! Get a second opinion. I am not sure if you had the same problem both cycles. Taking more HCG may be the answer, but not if your levels were high enough. Let another doctor look at your records. Some women make a huge percentage of immature eggs no matter what we do, but even they can be successful with persistence.

Jen-Jen is 42, PCOS, considering IVF. Well, the good news is that you have PCOS. So many women think this is a bad thing for IVF, but it is a good thing, and as you get into your 40’s it’s a great thing. If the diagnosis is correct, you will make many eggs. IVF success in your 40’s is increased but getting high egg numbers. On the other hand, iui should make many eggs and your odds may be higher than expected. But, IVF rates are always 2-3 times higher than iui. So if you are considering IVF, do it soon, because you will never be younger.

Stacey came to see me and has 3 year old twins. Thanks for writing; let’s hope for good luck to all who need it.

Dove has a very high estrogen from IVF drugs. I am sure you had to make a decision before today. I hope it worked out.

So there it is. See you soon. Read the disclamer 5/17/06.

Dr. Licciardi

Infertility Blog

Clomid vs Letrozole: The Last Words

Clomid and Letrozole Part 2

Dr. Licciardi Performing Surgery to Repair Uterine Septum

Clomid vs Letrozol

Back to School, Back to Questions

Tension

Being Positive

Update on a Past Story

Infertility Questions from Readers

Preventing Ovarian Hyperstimulation: The Lupron Trigger

Preventing Ovarian Hyperstimulation

Ovarian Hyperstimulation

Answering Some Infertility Questions

Cervical Stenosis from a Cone or LEEP

Cervical Stenosis

Checking Tubes: The HSG is better than the Saline Sonogram

What’s the difference between a Hysterosalpingogram (HSG) and a Sono-Hysterogram?

Questions about IVF, IUI, PCO and Male Factor Infertility

The Failed HSG

Sperm Morphology: New Guidelines Announced: 4% is Normal

How to Find a Good Fertility Doctor

PCO and other Fertility Related Topics

Cancelling IVF, Converting to IUI, and a Few Other Things.

More Questions, More Answers

A Few More Things You Should Know About Egg Freezing and Thawing

Take a Survey to Help Fertility Research

The Infertility Blog Wins Award: Best Infertility Blog

Questions About Infertility Issues

Egg Freezing and IVF: How Many Eggs Do You Need?

Some Complications of IVF and Egg Freezing

Infertility Q and A

Frequent Fertility Questions

Please Vote for the InfertilityBlog

Question and Answer Time

Dr. Licciardi on TV

When is the Right Time for hCG?

The Natural LH Surge vs. the HCG Injection

A Little More About Normal Ovulation

This Time Even I Got a Little Mad

More Answers to Great Infertility Questions

Dr. Licciardi’s “Infertility Blog” named as one of the top 50 Pregnancy Blogs

Back to Frequently Asked Questions

Spotting and other Variations in Bleeding

Table of Contents

What Can Blastocyst Do For You?

Meet the Blastocyst

Infertility FAQs

Back to More Fertility Questions

Just Before Blastocyst: The Morlula

More About Embryos

The Road to Blastocyst: Eggs and Embryos

Stories of Persistence

A Marathon of Infertility Questions

Infertility Questions and Answers: Almost Caught Up

Answers to Infertility Questions

More Fertility Questions Answered