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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

 

Important Final Words on Pre-Implantation Genetic Diagnosis

award winning fertility doctor new york city

 

Good Day to All,

These past few blogs covering PGD raise a few important issues. There are some well-know fertility centers that are really pushing TE biopsy. The feeling is that the technology has finally become accurate and safe enough.  It may be that doing IVF with PGD leads to a higher pregnancy rate and a lower miscarriage rate.  Plus, if you know you are getting a normal embryo, we can transfer fewer embryos, lowering the rates of twins and triplets.

This all sounds good, however, I think we need just a little more time, but maybe not much more.  In a good center, the pregnancy rate for a woman under 37 years of age is 40-50% without PGD.  PGD adds an invasive procedure. The shell of then embryo has to be opened, usually by a laser beam, then some of the embryo, even if it’s a small piece, has to be chopped away.  We make it sound simple, and so far it seems safe, but no one should promise you all of the safety data is in.  Not to mention the additional costs, which could vary from program to program, but $6,000 is a safe estimate.

In theory, ideally, PGD will be the way to go and everyone doing IVF will have their embryos tested, the pregnancy rates will go up, miscarriage rates will go down and we will say goodbye to IVF twins.   And if the system works really well, in the end this will save money because people will need fewer IVF cycles for success (not to mention the drug cost savings if fewer cycles are needed).

Encouraging news concerning PGD is coming out of the data on miscarriage. Good PGD does decrease the rate of miscarriage. A very high percentage of miscarriages are caused by aneuploidy, which means an abnormality in the number of chromosomes present in the embryo. Just one example of aneuploidy is Down’s syndrome, which is the result of an extra chromosome 21 (also called trisomy 21).  The bulk of PGD is performed looking for aneuploidy.

The reduction of miscarriage rates after PGD has 2 important implications. One is that preventing a woman from having a miscarriage is obviously a welcome idea, as the emotional toll of pregnancy loss is significant. The second is that miscarriage takes time.  While many miscarriages occur early, many women do not suffer their loss until 7-10 weeks, later if the fetus survives to the CVS (10 weeks) or amnio (17 weeks).  When you add in the recovery time of 1-2 months before a woman can try again post-miscarriage, the total time lost could be 2-4 months. This is especially difficult in an older woman whose reproductive time is already limited.

One shortcoming of this technology is that this new method of testing requires a blastocyst. Many IVF programs are still not comfortable growing their embryos to blastocyst; they prefer transferring their embryos on day 3.  These programs will not be able to provide these new services until they become very good a growing embryos out to day 5, which for some clinics could take a very long time.

Lastly, not everyone who wants PGD is a candidate for PGD.  The group that may benefit the best from a PGD cycle is those who are above the average age for reproduction. However in this group, egg production is lower, as is the rate of good (biopsyable) blastocyst formation. So there may be the intention for PGD at cycle start, but if the egg number or embryos quality is low, the option for PGD in that cycle may be lost. Straight IVF may or may not still be a viable option, but at times even those are not possible.  I try to be positive to the end, but it is always necessary to cover all eventualities.

 

Well, that’s quite a bit about PGD. Thanks very much for reading.

Don’t forget to read the disclaimer from 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.

 

 

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.

 

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.

 

How Many Embryos are You Putting Back?

Consider fewer.
Women under 35 and egg recipients should at least entertain the idea of a one-embryo transfer. Over the past few years there have been abstracts and papers (some of my own) written showing that in selected cases, a one-embryo transfer has an excellent pregnancy rate. The best candidates are women who are in their first try with excellent embryos. Many women who elect 1 embryo have at least 1 child at home. In these cases, the uterus is “proven” and this may increase their odds of getting pregnant with IVF or DE. In a small study here at NYU we showed that in good prognosis patients, the pregnancy rate with 1 embryo was the same as with 2. Once we do more cases we can update these results. I do believe that overall, the pregnancy rate with 1 will be lower than with 2, but I don’t think the difference is very big. One reason is that when we put in 1, we put in the best one, and that is the one with the highest chance of making a baby.
Why consider 1 when 2 can give you twins? A twin pregnancy is a complicated pregnancy. The idea of twins in not foreign because twins occur naturally. We all have friends or family members who are healthy twins. The problem is we may not know about the twins that delivered early, suffered early death, or are surviving with long term disability. The number one issue with twins is early delivery. We say twins deliver about a month earlier than singletons, bringing the gestation to about 36 weeks, no big deal. Delivery at 24-30 weeks is a very big deal. And yes it’s true even singletons can deliver early, but the odds are lower.
All this being said, almost all women still prefer to get at least 2 embryos back, which is fine. People are surprised to hear they have the option of requesting 1.
And again, please see disclaimer 5/17/06

References:

  • Jain T, Missmer SA, Hornstein MD. Trends in embryo-transfer practice and in outcomes of the use of assisted reproductive technology in the United States. N Engl J Med. 2004 Apr 15; 350(16):1639-45.
  • Mullin CM, Fino ME, Talebian S, Krey LC, Licciardi F, Grifo JA. Comparison of pregnancy outcomes in elective single blastocyst transfer versus double blastocyst transfer stratified by age. Fertil Steril. 2010 Apr; 93(6):1837-43.
  • The Practice Committee of the American Society for Reproductive Medicine and the Practice Committee of the Society for Assisted Reproductive Technology. Criteria for number of embryos to transfer: a committee opinion. Fertil Steril. 2012 Oct 22.
  • Niinimäki M, Suikkari AM, Mäkinen S, Söderström-Anttila V, Martikainen H. Elective single-embryo transfer in women aged 40-44 years. Hum Reprod. 2012 Nov 22.

I Called and an Embryo Picked Up the Phone

This is the truth.
Everyone’s job is at times difficult, including mine. We are overworked, don’t get enough sleep and basically tired. As interested as we are with the task at hand, we have to worry about the ongoing tasks and the upcoming tasks. It is rare that we can really think and reflect about the purpose of our labor, and the long-term permanent effects that may follow.
So my job is to help people get pregnant. Sounds great, and it is. With all of the demands of a busy medical practice it’s sometimes hard to appreciate that we in infertility are not just helping people get embryos, or heartbeats, or even deliveries and c sections. It’s obvious that it goes well beyond that, but for us, once we are happy about your heartbeat, we need to get happy about the next patient’s heartbeat etc.
Well, the other day I needed to call one of my past patients. Who picked up the phone, and said “hello, this is …..” ? Yes, it was the embryo. First it was a spec of an embryo, then a heartbeat. It then went on to be a 2 dimensional cute photo.
This is all wonderful and miraculous, but it took the phone call to really drive home the meaning. I was now interacting with the embryo. There was cause and effect. My task, the phone call to her mom, was dependent on the decision making of the embryo turned little girl. What a great day for me.
I hope that all of you reading this can someday have these types of experiences with your own families.