More Questions, More Answers

Good day to all of you. As you have seen, the last few entries were on egg freezing. If you are not interested in egg freezing, but want to know more about IVF, I think you will learn a fair amount about regular IVF from the egg freezing entries.
I am in the “catch up” phase, so you will see a few more FAQs answered. I’ll start with a little case from my recent day in the office.

The question leading to the topic was, “Can you be a poor responder and get pregnant on your own? “ So al little story about a couple I saw this week. She was a poor responder with borderline FSH levels, normal tubes and a favorable age. He had low sperm counts. They had been through IVF. I suggested that he see a urologist because there maybe something that can be done to improve his counts. She still ovulates every month, so by upping the odds on the sperm side, maybe they could get lucky and get pregnant on their own. My statements were very surprising to them. They were told that because of her “fertility status”, meaning her FSH was a little high, pregnancy could not occur naturally, so why bother with the sperm. This may be close to accurate but it is not completely true. Unfortunately, many couples with significant fertility problems never get pregnant, but for some the pregnancy rate per month is not zero. Even if its ½ percent per month, after a year, a few women with normal tubes, borderline FSH levels and good sperm will get pregnant (age helps). Can you count on it? No, but if there is something fixable, you might as well explore the options. I do hope they do take the advice. This is also the reason that some doctors suggest a laparoscopy after many failed IVF cycles. Even if the odds of tubal disease are low, correcting a small problem may improve the odds of a spontaneous pregnancy down the road.

Here are some surgery questions.
If you have severe endometriosis and pain with a history of multiple laparoscopies, and you are at the end of your rope, is a hysterectomy the answer? This is too complicated for me to give any hard advice here. The options are to get another opinion from a doctor is an established endometriosis laparoscopy doctor, who can maybe improve your pain without a hystersctomy. Maybe even someone who is not in your area. On the other hand, there are some women who say the hysterectomy was the best decision they ever made, and some who are neutral and some who are not happy with the results.

Is a laparoscopy through 3 incisions better than a laparoscopy where the doctor only used 2 incisions? Impossible to say. Some surgeons are really crafty using only 2, some need 4. Sometimes a doctor who usually uses 2, will need to use 3-4 in the really tough cases. But redoing a laparoscopy just because only 2 incisions were used does not make sense.

What if there is a hydro on hsg and at laparoscopy the tube does not fill with dye? Should the doctor assume the tube developed proximal occlusion and just leave it? I think not. For some reason, sometime tubes just to not fill with dye at the laparoscopy. Even normal tubes sometimes do not fill, but a post op hsg shows normal tubes. So if they are hydros at hsg, but closed at laparoscopy, your doctor should consider removal.

Is it normal to have a myomectomy and have some fibroids left behind at surgery? This does happen, but I do not leave any behind. I could see rare cases of fibroids left behind for a couple of reasons. Fibroids on the cervix are more dangerous to remove because the cervix is where the uterine arteries bring blood to the uterus, so around the cervix there is more blood flow and more chance for heavy bleeding during the operation. Also, if there are very thick intestinal adhesions attached to a fibroid, separating the intestine from the fibroid may cause excessive bleeding or damage to the intestines. That being said, leaving fibroids behind should be reserved for the most extreme cases. I have not left a fibroid in 15 years. The doctors I work with do not leave in fibroids. However I am aware of doctors who routinely leave in some of the smaller or difficult to reach fibroids, and I do not know if this is the best thing. A myomectomy is not minor surgery. In many cases, smaller fibroids get bigger. So if your problems are bad enough that you need the myomectomy, getting them all is the best thing. It is also true that the doctor may do a great job getting them all out, and sure enough, 3 months later a scan shows another fibroid. This is harder to explain, but probably there was a very small one that could not be seen, and it that grew after the initial surgery.


Clomid, IUI and PCO
Do you need to get a period before starting clomid? If you have either post pill amenorrhea or hypothalamic amenorrhea, it will be hard for you to get a period anyway. You probably will not bleed after provera. So in my patients, I do not require that they bleed. Also, you may not respond to clomid. Clomid causes the pituitary to release its stores of FSH and LH. Women with hypothalamic amenorrhea, because their brain makes no GnRH, do not have FSH stored in the pituitary. That being said, it may be worth trying because sometimes it does work and it’s much easier and less expensive than the injections. I have been pleasantly surprised by some nice responses and pregnancies in women who should not have responded.

Can you have polycystic ovaries and have low ovarian reserve? No they are the opposite. Women with PCO have many many eggs and are not close to menopause. Now women with PCO eventually lose their eggs to and get to menopause, but if you are told now that your ovaries are PCO on ultrasound, you do not have low ovarian reserve.

If IVF is not in your future, does it matter if you do iui with Menporur or FSH? It probably does not matter.


Are progesterone levels important to measure in the luteal phase during a natural cycle. Very few infertility doctors feel this is important. It has not been shown well that levels matter, plus they change throughout the day.

What if your follicle size looks good, but it’s Friday and your doctor wants to try to get you to Monday for the iui? Not so good. In some cases it may be fine, but in others it’s not the right thing to do. The fertility doctor you work with really needs to provide services 7 days a week. Many say they will, frequently resort to doing things a little late or early because they are not as staffed as they say. It’s probably true that a little late or early here and there actually may not make a difference, but more than a little is a problem.

Miscarriage
Does having a miscarriage after iui mean IVF should be your next step? As hard as it is to lose the pregnancy, the delay is sometimes the worst part. It took you a while to get pregnant, then you may have waited a few weeks to confirm the status of the pregnancy, then there is waiting 1-2 months after the miscarriage. There are tons of factors that will go into your decision of how to proceed, but the frustration of the miscarriage process does push many people into IVF.

If you are in the process of an early miscarriage, should you have a D and C? There are pros and cons of the d and c vs. waiting for a natural bleed. A d and c should not be automatic. Go over your questions with your doctor and you will both come up with the best course of action.

4 biochemicals in a row with a normal uterus? Your age is important, along with any miscarriage tests your doctor feels is necessary, especially the karyotype. This is a tough one. It is true that implantation is at least starting, and this is a positive. But finding cause may not be possible. I hope it works out.


IVF and Stimulation Questions
Should you avoid pregnancy if you are starting an IVF cycle with day 21 Lupron or Synarel or Buserelin? The stock answer is yes. However there are many women who have become pregnant while on those meds. If you do become pregnant, make sure you get luteal support with progesterone and maybe estrogen. Ask your doctor.

Does it help to take estrogen for luteal support in an IVF cycle? Probably not. There have been studies showing no improvement. There is even scientific evidence that estrogen may be unnecessary in the luteal phase. Some clinics routinely prescribe the estrogen; I tried it for a while in select cases with no improvement. I have had a little success using estrogen in women who have luteal bleeding despite progesterone. It’s used in medicated frozen cycles and DE cycles because the ovaries in those cases make no hormones (no estrogen or progesterone) so we add both hormones during their cycles.

Should you try IVF again if you are 29, have an FSH of 12 and make 8 eggs with 2 fertilized? Yes. I have been getting many comments from young women, some with high FSH levels, who are failing first cycles. Get to the best clinic possible and have your doctors come up with possible improvements for your cycle. Age is key. A high FSH in a 27 year old woman, or even a 36 year old, is not as telling as it may be with a woman in her 40’s.

What can I suggest to up your odds for the FET? Most FETs are pretty routine. Sometimes we suggest thawing more than you need and picking the best for transfer. Not everyone wants to do this. Some would rather thaw few so they can get more cycles out of what they have frozen. Either way is ok; see what your doctor says.

Hopeless after failed iuis, 2 fresh IVFs and one FET cycle? You do have to take into consideration age and FSH levels and embryo quality. It’s rarely hopeless. Maybe less hope, but not none. Know your stats, get another opinion and take it from there.

Can a para-ovarian cyst interfere with IVF or implantation? Probably not.

What if you are an established young poor responder who has had multiple failed IVFs. In addition there is a question about your uterus, meaning the was a scar but hysteroscopies and hsgs are now normal? This depends somewhat on the thickness of your lining on ultrasound. I have said before, and still believe, the lining thickness may be less important than we once thought, but of course everyone’s story and uterus are a little different. If you want to carry and our uterus is “acceptable” then donor egg without carrier is what most women would do, and probably with a very acceptable pregnancy rate. If you feel strongly that carrying is not important, just getting that baby asap, consider a carrier. However, donor egg, carrier is not guaranteed either.

I am hearing from women who have premature surges during antagonist cycles. I have not had this so I don’t know why people are having this problem. Antagonist should start at a follicle size of 13 mm (some clinics use 12 mm). Sometimes the estrogen levels do fall a little when the antagonist is started, but this fall does not mean there has been premature ovulation. So if the estrogen falls (but not by too much), but the follicles still grow, and the estrogen level goes up the next day, that’s all ok. There has not been a surge.

How long after the last depot lupron shot do you need to wait for IVF? The depot shot is supposed to stay in your body 4 weeks, but may be in a little more. Ask your doctor about this one but probably if you start 4 weeks after your last shot, but the time you are retrieved it will be 6 weeks after the shot.

What’s the doctor doing at my transfer, and why is there a delay? You can’t see what’s going on at the transfer, but any of your questions at the time should be answered. Doctors have certain catheters they like to start with. If they have trouble getting the catheter through the cervix, they may ask for another type. They should keep you informed.

Breastfeeding during IVF. FSH levels in breast milk will be higher than during a natural cycle. I really can’t comment more than that. There are some women who do IVF while breastfeeding.

Can a varicocele repair correct azospermia? I am not a urologist, but I have not had an azospermic patient develop sperm in is ejaculate after a varicocele. I’m not saying it can’t happen. It is also possible that the counts could go up without surgery.

What about a period that lasts for months with a completely negative workup? Make sure you do not have a bleeding disorder. Some women have vascular abnormalities if the uterus that cause constant bleeding. Maybe an MRI will help.

Thanks for reading, read disclaimer 5/17/06, and talk to you soon.
Dr. Licciardi

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

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