Clomid vs Letrozole: The Last Words

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

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

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

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

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

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

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

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

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

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

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

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

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