You are currently browsing the archives for the Eggs category.

Embryo Banking

award winning fertility doctor new york city

 

Good Day to All,

Today I’d like to talk about embryo banking, which means storing as many embryos as you can for later use. It’s a topic that comes up every day in my practice and on the surface it makes sense, just as egg freezing makes sense for the young and unattached.   The typical scenario is of a woman who is committed to a partner or has identified a donor, who wants to become pregnant now, but is concerned, due to her age, that she will not be able to become pregnant again when she wishes a second or even a third. She may be also concerned that if she does become pregnant and has a miscarriage, she will be similarly be placed at a disadvantage due to the loss of time and the advancement of age.   She therefore packs away as many embryos as she can, possibly after preimplantation genetic screening, and is limited only by her tolerance to the IVF process and, of course, finances.

Does this sound like a good idea? Yes, it’s an outstanding idea; it’s proactive, realistic and optimistic. But, it comes with a number of down sides. Is it really worth the trouble? All of us fertility doctors have charts and graphs blaring out the chances of pregnancy based on age, but those are just averages. We can’t know for sure who will and will not have a baby now or 2 years down the road. And what about all women over 35 who are thinking of becoming pregnant on their own, should I seek them out on First Avenue and scream, “Wait, you’re making a big mistake, come in and bank your embryos!”?

While I consider IVF to be one of the true miracles of modern medicine, its effects on a patients psyche is one of medicine’s scourges. On average, things seem to work out wonderfully for most involved, but individually it can be frustrating, disappointing, exhausting; the list goes on. Some who intend to bank are confronted with low egg production or poor embryo development or genetically abnormal embryos or a combination of these all leaving nothing to save. Granted, some would rather know these things sooner rather than later, and are strong enough to consider other options and move on, but some do not appreciate being thrust into a hole, left with uncertainty in their ability to even naturally conceive.

And then there is the cost; embarking on such a process without insurance coverage is a considerable commitment; having coverage is an enviable luxury.

Summarizing, banking could be a smart play. However for many, the negatives may outweigh the positives.  

Dr. Licciardi

 

AMH (Anti-Mullerian Hormone)

 

award winning fertility doctor new york city

 

Hello to all.

In this blog I will review the usefulness of Anti-Mullerian Hormone, otherwise referred to as AMH. AMH is one of the hormones, along with estrogen and a few others, produced by the ovary.

Like estrogen, AMH is produced by the granulosa cells. The granulosa cells are the small cells that surround each egg.  These small cells are tightly attached to egg surface whereby they help to vitalize and, when the time is right, mature the egg.   This egg-granulosa cell unit is called the follicle.

No one yet knows what the function of ovarian AMH in females.  AMH is present in males, and we know that it has a very important role in the development of normal male sexual anatomy.  What we do know about AMH in females is that the more healthy follicles one has, the higher the AMH levels.

Measurement of AMH levels can help us predict a woman’s fertility, in a very general way.  We already said that estrogen is also produced by the granulosa cells, so why wouldn’t we just need to measure estrogen levels to find out about ovarian health?  Because estrogen only comes from follicle at a time; the one that is in the process of ovulation. A woman may have 100,000 follicles, but on most cases only one per month gets involved in ovulation and becomes an estrogen producer.   Follicles may make different amount of estrogen each month, so judging fertility based on an estrogen test is not helpful.

Many follicles at one time, however, are producing AMH. Now it’s not every follicle, but it is a large number.  It works like this. The ovary contains different follicles in different stages of maturity.  Here is a microscopic view of the ovary.

 

Some follicles are very immature and have few granulosa cells; just one layer surrounding the egg.   Some follicles are more mature and their granulosa cells have multiplied into more cells in multiple layers.  These are the ones producing the most AMH.  In general, if you have a lot of eggs, you have plenty of follicles in all of the stages of development, giving you higher AMH levels.  Lower AMH levels mean fewer follicles of all types.

Follicles are always making AMH therefore levels can be measured any day in the cycle. In fact, it does not matter if a woman is on oral contraceptives, AMH is still produced and can be measured.

AMH may turn out to be and excellent way to measure a woman’s fertility potential, but we are not quite there yet. We do know that a high AMH is good and a low AMH is bad. What’s a good high level? We are still not sure. We know a little.  Any level over 2 is really not bad at all. Certainly, higher than 2 is better still. We know that undetectable levels, less than 0.16, are bad.  But, we have had women with these low levels become pregnant.  The odds of pregnancy are much worse for women with low levels, but people frequently get pregnant with low odds.  Some women have asked me if the level can be too high.  High levels may indicate the presence of polycystic ovaries (ovaries with an above average number of follicles).  While it is true that some women with polycystic ovaries have trouble conceiving, a high AMH level is not the issue.

Recent studies (one was in the headlines a few weeks ago) have used AMH levels to predict IVF outcome.  But again, really high levels were shown to be good and really low levels bad, but overall, not predictive enough to tell someone they can or can not get pregnant.

What we typically do is to put all of the information we have together to estimate ovarian health.  If we use age, FSH levels, AMH, antral follicle counts, the prognosis becomes a bit more clear, but the system is still not perfect.

AMH testing will become more useful sometime soon. More and more women need to have the test done do we can compare levels to outcomes on a large scale. In addition the laboratories need to get better at the testing.  But once we get better with AMH levels, we may be able to do some very important things.

For instance, some studies have been done comparing AMH levels to the time of menopause. Again, not ready for prime time, but the concept may be very important.  What if we could measure AMH in a young woman and determine at what age she will start losing her fertility? Or at what age will she lose half her fertility? What if we could measure AMH levels in a woman destined for chemotherapy and determine if she should freeze her eggs first?

These would all be wonderful uses of this test and it may be that in the future we could reach these goals.

It’s more likely that newer tests will be developed to improve ability to predict.  As alluded to before, combination tests may be more accurate. For example labs are starting to market “fertility profiles” based on AMH, FSH, inhibin and other hormones.

But in the end, like in all of medicine, the genetic tests will dominate.  Scientists are looking for a gene or groups of genes that control the fertile lifespan of women.  As genetic testing becomes less expensive and as we increase our ability to look at more and more genes at one time, the goal of accurately determining a woman’s ovarian age and potential will be reached.

 

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

 

Dr. Licciardi

 

Trends in Pre-implantation Genetic Diagnosis

award winning fertility doctor new york city

Welcome,

So what are the new developments increasing interest in PGD?

The first is that there is more laboratory expertise on growing the embryos to blastocysts (see blog on blastocyst). These are embryos that have grown not 3, but 5 days in the lab.  As the embryo grows with time, the total number of cells increases from 6-8 to 30-60. Because the cell number is much higher, we can more safely remove more than on cell, maybe 3-5 cells. All of that extra DNA helps us reach much more accurate results.

 

The second has to do with the way we test the DNA.  The DNA amplification techniques have improved, as have the techniques for identifying important areas in the DNA.

 

An advantage of blastocyst biopsy is that in a good blastocyst, we can tell by looking which cells will be the embryo (the inner cell mass) and which will be the placenta (the trophectoderm- thus the term trophectoderm biopsy, also called TE biopsy for short).  Naturally, at the time of the biopsy, it is the placental cells we take as not to interfere with the fetal cells. Taking a few extra cells from the placenta is much less harmful than taking cells needed for the fetus.

 

Another advantage of performing the biopsy on day 5 is that mosaicism is much less of a problem in a blastocyst. (The last blog explains mosacism), The cells we get on day 5 more accurately reflect the DNA status of the embryo as a whole.   We are not sure why mosacisism is less of a problem on day 5, it may be that it’s common for an embryo to start off with some abnormal cells, but with time the normal cells outgrow the bad ones.

 

One downside to TE biopsy is that in most cases, the results of the biopsy take 1-3 days to process. We do not want a day 5 embryo growing extra days in the lab waiting for the results. Therefore, we usually freeze the blastocysts just after the biopsy, get the results a few days later, and then have the patient come back the next month for a thaw cycle.  This gives the patient a one month delay, which may or not be an important factor, depending on the expectations of the patient.  There are some programs that offer same cycle PGD biopsy and transfer, but usually those women with only the fastest growing and best looking are candidates for the same cycle process.

 

Patients are naturally concerned about embryo freezing, as is it is mostly true that embryos in a frozen cycle have lower pregnancy rates than when the embryos are transferred when fresh.  However, there may be some very explainable reasons why freezing normal blastocysts may not be problematic.  In a standard fresh cycle, the best embryos are transferred. While the extra embryos may look very good, the best ones go back originally, leaving the left overs for the frozen cycle, and this could explain the lower rates.  In a PGD cycle, even the best embryos are frozen, upping the odds for a successful cycle after the thaw.  Also, at least from what I have seen, normal embryos seem to thaw and freeze very well. So if you know you have a good one in the freezer odds are good that it will survive the freeze and thaw and have good potential for success.

 

In addition, freezing techniques have really blossomed in the past few years.  Most programs have moved to vitrification (the fast freezing method), and embryos do have better outcomes when preserved this way.

 

On top of all of this, there are some doctors who believe that all embryos, even without biopsy, should be frozen. There is the revival of an old theory that the endometrium of an IVF cycle is not ideal for implantation, possibly due to excessive estrogen levels caused by the fertility drugs. Others feel that the relationship between the timing of ovulation and embryo transfer is altered with IVF, lowering the ability of the embryo to implant.  I’m not so sure about theses theories, but I am raising the point here to say that a frozen embryo cycle is not necessarily a bad thing.

 

There are still a few more points about PGD that I will go over next time.

 

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

 

Dr. Licciardi

 

References:

  • Braude P. Preimplantation diagnosis for genetic susceptibility. N Engl J Med 2006; 355(6):541-3.
  • Gutiérrez-Mateo C., Colls P., Sánchez-García J., Escudero T., Prates R., Wells D., Munné S. Validation of microarray comparative genomic hybridization for comprehensive chromosome analysis of embryos. Fertil Steril. 2011; 95: 953-958.
  • Twisk M, Mastenbroek S, van Wely M, Heineman MJ, Van der Veen F, Repping S. Preimplantation genetic screening for abnormal number of chromosomes (aneuploidies) in in vitro fertilization or intracytoplasmic sperm injection. Cochrane Database Syst Rev 2006; 25(1):CD005291.
  • Munne S, Fischer J, Warner A, Chen S, Zouves C, Cohen J, Referring Centers PGD Group. Preimplantation genetic diagnosis significantly reduces pregnancy loss in infertile couples: a multicenter study. Fertil Steril. 2006; 85(2):326-32.

 

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

award winning fertility doctor new york city

 

Once again, some of what applies to Egg Freezing  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

References:

  • Noyes N, Knopman J, Labella P, McCaffrey C, Clark-Williams M, Grifo J. Oocyte cryopreservation outcomes including pre-cryopreservation and post-thaw meiotic spindle evaluation following slow cooling and vitrification of human oocytes. Fertil Steril. 2010 Nov;94(6):2078-82.
  • Rudick B, Opper N, Paulson R, Bendikson K, Chung K. The status of oocyte cryopreservation in the United States. Fertil Steril. 2010 Dec; 94(7): 2642-2646.
  • Rybak EA & Lieman H. Egg freezing, procreative liberty and ICSI: the double standards confronting elective self-donation of oocytes. Fert Steril. 2009 Nov; 92(5): 1509-12.
  • Liu KE, Greenblatt EM. Oocyte cryopreservation in Canada: a survey of Canadian ART clinics. J Obstet Gynaecol Can. 2012 Mar; 34(3): 250-6.
  • Werner M, Reh A, Labella PA, Noyes N. Laboratory evaluation in oocyte cryopreservation suggests retrieved oocytes are comparable whether frozen for medical indications, deferred reproduction or oocyte donation. J Assist Reprod Genet. 2010 Nov;27(11):613-7.

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

award winning fertility doctor new york city

 

Again, this entry has many elements that apply to standard fresh IVF cycles. Here we’re trying to close in on the real question, “If you do egg freezing, will it help you have a baby?”  Well, it will really does help if you can make some eggs. Sorry if that sounds too obvious, but the more you make the better your odds of this whole thing working years down the line. Just as with any IV F cycle, egg production is based on the number of eggs that are still in your ovaries, and how they respond to the medications.  Much of this is loosely related to a woman’s age but there are a number of other factors involved. The dose of drug can have an effect on the number of eggs produced; the more drug the more eggs, but only to a point. In other words, if your ovaries are full of eggs, a dose of 450 units per day may be way too high and lead to danger, but a dose of 225 might get you 15-20 without much of a risk. However, if your egg reserve is marginal, 225 may make 6 eggs, 450 may make 8, but going over 450-600 probably will not get you any more.

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

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

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

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

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

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

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

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

Your doctor needs to take the information above and formulate your chances of not just getting eggs, but of getting a baby from your egg freeze cycle. This applies to all cases, good egg production or not.  You will get the most accurate information if you are using an egg freezing practice that has results, not just freezing experience. Experience and results with the thaw and transfer is very important; you need a program with a track record. You need to know their experience in going from eggs to babies. Many busy egg freezing programs have no results because they have not thawed any of their eggs yet. Others have done less than a handful of cases.

I do want to refer you to the NYU Fertility Center web site section on egg freezing.br /a href=”http://www.nyufertilitycenter.org/egg_freezing”http://www.nyufertilitycenter.org/egg_freezing/a.  Spend some time going through all of the pages, the information is very helpful. Thanks to the fantastic research and efforts of the doctors listed there, NYU is known for its egg freezing practices and results. I could summarize the site here, but in the interest of accuracy, go directly there to get it from the horse’s mouth. The results are frequently updated.

The breakthrough, as mentioned on the site, is that we believe that our egg freezing success rates will remain similar to our fresh IVF success rates. Therefore, it will help if you have your eggs frozen at a program with excellent fresh IVF pregnancy rates. If their fresh IVF rates are low, their egg freezing rates will probably be low too. Not all egg freezing programs can show good data to support good results (2 out of 4 pregnant is not enough.) There are a few who can, so if you are interested in egg freezing, you need to seek out the good ones. Details are sparse, so I really only know about NYU. Odds are there is not a quality program near where you live, so if you can swing it, it may be worth traveling. Even the NYU rates need to be clarified. Most of the studies at NYU and elsewhere on egg freezing have been performed with good prognosis, younger women. We are not positive that older women’s eggs will freeze and thaw well. They probably will, but there is no data yet to prove the case. We don’t know how long eggs will last in the freezer. We do know there have been children born from sperm and embryos frozen for over a decade, so eggs should be able to last at least as long, but again there is no proof yet. Egg freezing is very new and still considered experimental you do need to freeze your eggs at the right place.br /br /We and other doctors can not completely predict the landscape 5-10 years down the road. We are optimistic that our pregnancy rate estimates are correct. However there is a chance that due to unforeseen circumstances, the rates will be lower. You just need to know this going in. It may also be possible that the outcomes will be better than we had hoped.

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

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

Dr. Licciardi

References:

  • Noyes N, Knopman J, Labella P, McCaffrey C, Clark-Williams M, Grifo J. Oocyte cryopreservation outcomes including pre-cryopreservation and post-thaw meiotic spindle evaluation following slow cooling and vitrification of human oocytes. Fertil Steril. 2010 Nov;94(6):2078-82.
  • Rudick B, Opper N, Paulson R, Bendikson K, Chung K. The status of oocyte cryopreservation in the United States. Fertil Steril. 2010 Dec; 94(7): 2642-2646.
  • Rybak EA & Lieman H. Egg freezing, procreative liberty and ICSI: the double standards confronting elective self-donation of oocytes. Fert Steril. 2009 Nov; 92(5): 1509-12.
  • Liu KE, Greenblatt EM. Oocyte cryopreservation in Canada: a survey of Canadian ART clinics. J Obstet Gynaecol Can. 2012 Mar; 34(3): 250-6.
  • Werner M, Reh A, Labella PA, Noyes N. Laboratory evaluation in oocyte cryopreservation suggests retrieved oocytes are comparable whether frozen for medical indications, deferred reproduction or oocyte donation. J Assist Reprod Genet. 2010 Nov;27(11):613-7.

Some Complications of IVF and Egg Freezing

award winning fertility doctor new york city

 

Hello to everyone again.

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

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

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

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

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

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

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

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

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

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

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

Still with me? What about the retrieval?

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

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

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

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

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

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

So that’s the yucky drugs and needles part.

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

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

Happy Holidays!
Dr. Licciardi

References:

  • Noyes N, Knopman J, Labella P, McCaffrey C, Clark-Williams M, Grifo J. Oocyte cryopreservation outcomes including pre-cryopreservation and post-thaw meiotic spindle evaluation following slow cooling and vitrification of human oocytes. Fertil Steril. 2010 Nov;94(6):2078-82.
  • Rudick B, Opper N, Paulson R, Bendikson K, Chung K. The status of oocyte cryopreservation in the United States. Fertil Steril. 2010 Dec; 94(7): 2642-2646.
  • Rybak EA & Lieman H. Egg freezing, procreative liberty and ICSI: the double standards confronting elective self-donation of oocytes. Fert Steril. 2009 Nov; 92(5): 1509-12.
  • Liu KE, Greenblatt EM. Oocyte cryopreservation in Canada: a survey of Canadian ART clinics. J Obstet Gynaecol Can. 2012 Mar; 34(3): 250-6.
  • Werner M, Reh A, Labella PA, Noyes N. Laboratory evaluation in oocyte cryopreservation suggests retrieved oocytes are comparable whether frozen for medical indications, deferred reproduction or oocyte donation. J Assist Reprod Genet. 2010 Nov;27(11):613-7.

The Road to Blastocyst: Eggs and Embryos

This is the first installment of blastocyst blog; but it’s a bit of a pre-requisite. To give you a feel of where we are going, I will start with pictures of eggs and embryos and then blastocysts.

This is an egg. I doesn’t really look like an egg. Part of the reason for this is that in this picture there are hundreds of cells, but just one that is an egg. The dark circle in the center is the egg. You can see how big eggs are compared to the rest of our cells. The surrounding specs are granulosa cells. These are the ovarian cells that line the inside of the follicle. Prior to ovulation, the egg’s position in the follicle is along the edge, so the granulosa cells that are growing along the inside of the follicle surround the egg. When the egg ovulates, it carries some of these cells along. When an egg is retrieved during IVF, it is also surrounded by granulosa cells.

The granulosa cells make the estrogen (estradiol). So as the follicle grows, more granulosa cells form, and estrogen rises. In an IVF cycle, the more eggs there are, usually the higher the estrogen levels.

This is a picture of an egg a few hours after retrieval, after the granulosa cells have been removed.
In the case of IVF using ICSI, the embryologist needs to remove the granulosa cells a few hours after retrieval. This is necessary so she can see the egg and to properly inject the sperm. If ICSI is not necessary, we can mix the eggs and sperm together, and the sperm will swim through the granulosa cells to get to the egg.

The little round object on the top is the first polar body, and this is an indication that the egg is mature. The first polar body contains chromosomes, as does the larger egg cell. For the egg to accept the DNA of the sperm, it needs to dump some of its own DNA, otherwise there will be too much. So the egg unloads some of the DNA into the polar body, which just withers away. Sometimes testing the DNA of the polar body can tell us about genetic diseases in the egg. For the most part, we can not use an egg that is not mature. There is some encouraging research looking at maturing eggs in the lab, but so far the process of maturing eggs in culture has not been widely accepted.
 

This is what we call a 2 pn zygote (or 2 pn embryo). The picture was taken one day after the retrieval. You can see a few granulosa cells still hanging around.
The halo around the embryo is the zona pellucida. It’s the shell of the egg. It has the consistency of a thin vitamin E capsule. Inside is the egg (or oocyte). In the middle of the egg, you can see 2 little round objects, and these are the pronuclei (pn). One contains the genetic material from the egg, the other from the sperm. In some animals we can tell which came from where, but not in the human, although as our microscopes improve, I suspect we will very soon be able to tell. So if we expose eggs to sperm, and look the next day, and do not see 2 polar bodies, fertilization has not occurred. Sometimes we see one, and this means fertilization possibly occurred. In this case we may or may not see 2 later in the day. The 2 pn will combine to complete the fertilization process.
Dr. Licciardi
References:
  • Papale L, Fiorentino A, Montag M, Tomasi G. The zygote. Human Reproduction, Vol.27, No.S1 pp. i22–i49, 2012.
  • Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod 2011; 26:1270–1283.

A Guide to Eggs and Embryos Part I

This is the first installment of blastocyst blog; it’s a bit of a pre-requisite. To give you a feel of where we are going, I will start with pictures of eggs and embryos and then blastocysts.
This is an egg. I doesn’t really look like an egg. Part of the reason for this is that in this picture there are hundreds of cells, but just one that is an egg. The dark circle in the center is the egg. The surrounding specs are granulosa cells. These are the ovarian cells that line the inside of the follicle. The egg’s position in the follicle is along the edge, so the granulosa cells that are growing along the inside of the follicle surround the egg. When the egg ovulates, it carries some of these cells along. Same for when the egg is retrieved.
Sperm swims through the granulosa cells and then into the egg. Again , same process for natural or IVF.
References:
  • Papale L, Fiorentino A, Montag M, Tomasi G. The zygote. Human Reproduction, Vol.27, No.S1 pp. i22–i49, 2012.
  • Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod 2011; 26:1270–1283.

 

Are You Sure You Need Donor Eggs?

This is going to be a tough blog to write. Many have asked, when should I say goodbye to using my eggs and switch to a donor’s eggs? This of course assumes that you would consider using a donor’s eggs. Donor egg: It’s not for everyone. But for those who are interested it can be a very real way to become pregnant and have a child.

Every woman and man has a different threshold for getting to donor egg (DE). If you are in menopause and would consider donor egg, your decision is made for you. For everyone else, choices need to be made. For some people, decision-making in general is very easy, for others it is almost impossible, and most fall in between.

No one else knows what’s best for you. No doctor, lawyer, friend can tell you which direction to turn. A little advice from any available source you feel comfortable tapping into may not be a bad idea. But no one really knows how you feel; no one has had your unique life experiences that you go back to as you make your choices.

Before you even face the decision, you need to feel good that you are at the crossroads. You need to understand the advice of your doctor and you need to feel that you have received correct the information about your ability to produce eggs of reasonable quality.

Stories of the average woman going to donor egg did not inspire me to write this blog. Rather, it was the stories of a smaller group of women who were told they needed to go to donor egg, maybe a little prematurely. Over the years I have seen a few too many women who were told they needed donor egg when in fact they would have been better served using their own eggs.

To be clear, I am not talking about most of the women going to DE, including women who we would say have a “very reduced” chance of becoming pregnant with their own eggs. All of these cases can be debated, but in the end DE may be the better option mostof the time.

What I am talking about here is the woman who is 39, makes 11 eggs, gets 2 fair embryos back, no frozens, and at her post cycle visit the doctor brings up donor egg. The doctor may talk about doing another IVF cycle, but for some reason he/she has a real need to start planting the seeds of egg donation. This happens way too often, and I don’t really know why.

One failed cycle of IVF is not completely predictive of future cycles. Yes many women are consistent in their response to meds and embryo quality, and not every woman at 39 will become pregnant with IVF even with multiple attempts. However, women get pregnant with marginal quality embryos every day. Women get pregnant on their 2nd or 3rd IVF cycle every day, and 39 year olds get pregnant every day.

I said this would be a hard blog to write. The reason is that I am trying to avoid upsetting any of you (especially my own patients). Every case is different so it is impossible for me to say who needs what. I do want to state for the record, however, that there are too many women with reasonable chances at getting pregnant using their own eggs being offered donor egg.

So if you cant really understand why your doctor is bringing up donor egg after one failed IVF cycle, you need to entertain the option of getting another opinion. Who knows, maybe your doctor is absolutely correct. Or maybe you would much rather go with 50% using donor vs. 25% with your eggs. If that’s ok with you, it’s ok with me.

What I don’t like is when the doctor almost shames you into donor egg by stabbing you with the bad embryo quality speech. Embryo quality cannot be accurately assessed after 1 IVF cycle. If you have done more than one cycle and you are being told your embryos grow poorly, show the pictures to someone else. If you are of a reasonable age and you make nice looking embryos, but are told they are not good, get another opinion.

Donor egg is a great way to get a family started, or expand the family you may already have. Just be as sure as you can that DE is really the next step for you.
Thank you and please read disclaimer 5/17/06.

Dr. Licciardi

References:

  • Reh A, Amarosa A, Licciardi F, Krey L, Berkeley AS, Kump L. Evaluating the necessity for universal screening of prospective oocyte donors using enhanced genetic and psychological testing. Hum Reprod. 2010 Sep; 25(9):2298-304.
  • Mullin CM, Fino ME, Talebian S, Keegan D, Grifo JA, Licciardi F. Comparison of pregnancy outcomes in anonymous shared versus exclusive donor oocyte in vitro fertilization cycles. Fertil Steril. 2010 Feb; 93(2):574-8.
  • Noyes N, Hampton BS, Berkeley A, Licciardi F, Grifo J, Krey L. Factors useful in predicting the success of oocyte donation: a 3-year retrospective analysis. Fertil Steril. 2001 Jul; 76(1):92-7.