Chat Transcript: Jacques Cohen, Ph.D.: World Famous Embryologist


[INCIID Moderator] : Good Evening, Dr. Cohen.
Sammie : I had my retrieval last week. We were able to get 12 eggs, 10 mature, 6 fertilized with ICSI. I had a 3 day transfer of two 8 cell grade A+ and A- embryos. Two of the remaining embryos made it to blastocyst and were frozen. Does the fact that those two made it to blastocyst stage in any way correlate to the 'hope' the two that were transferred might have made it to to blastocyst stage as well? 

Jacques Cohen, Ph.D.: There may be a positive correlation, but it differs from case to case. Anyhow - things look good thus far 
Ted : Do you recommend ICSI when using donor sperm?

Jacques Cohen, Ph.D.: Yes, although with some footnotes. Donor sperm is freeze-thawed and many sperm will be lost in the process. Sperm purification techniques can resolve that problem and only yield motile ones at the end of the process. IVF is not really a problem here, yet I would still opt for ICSI.
Mary: At 8:15 the morning of my 3 day transfer, I had two 8 cell embryos that were ready to go. By the time transfer rolled around at 1:30 pm, they had multiplied to 12 and 14 cells respectively. Is that growth too fast for day three embryos?
Jacques Cohen, Ph.D.: The embryos proceeded to the next division and that in itself is not so bad. It would have been possibly a different situation if your embryos were that fast at 8:15 AM;  Had it been  observed then it would have lowered the chance of conception by just a fraction.
Jerry : Is a 60% fertilization rate w/icsi and donor sperm normal? I'm 34. I was hoping for a higher fertilization rate.
Jacques Cohen, Ph.D.: Fertilization rate should be calculated for mature eggs only. I presume you knew the TOTAL number of eggs and calculated the fertilization rate from that. Yet, only 50-100% of the eggs are usually mature and these are used for ICSI. In other words 60% is really not so bad.
Janie: Hello, and thank you for this opportunity. I have undergone 3 IVF cycles to date, I made it to the retrieval stage on two of the three cycles. On both, I did ICSI with donor sperm. Of the 7 mature eggs over both cycles, none would fertilize. The embryologist said my eggs looked great, and she did not have a good reason for no fertilization. One suggestion was research showing there could be DNA problems with the sperm which causes it to break down in the egg. Have you heard of this? 

Jacques Cohen, Ph.D.: Yes I have heard of this, but it is an obscure situation. It is possible that your eggs lack factors that deondense sperm and make it ready for conception. There are experimental ways to overcome this. Also was the sperm donor the same? It may be better to have a more lengthy discussion regarding this. Please email me.
Susan : Dr. Cohen... could you comment on the opinion by some medical professionals that the eggs of women over 40 are 'too fragile' for IVF.
Jacques Cohen, Ph.D.: Yes I can. Provided the eggs and embryos are checked for an anomaly called aneuploidy. This anomaly is related to the number of chromosomes in the eggs and the anomaly occurs much more frequently in eggs from reproductively advanced women. The technique is called PGD for aneuploidy.
Pat : Is there a way to tell if a normal-looking egg is under or over-mature?
Jacques Cohen, Ph.D.: I think that I already hinted at this in my previous answer, yet there are many factors to consider. The rate of success in nature and after ART is entirely dependent on maternal age, but 'fragility' sounds like the issue is permanent and may be reflected in children. There is no evidence that it is. The only problem is obtaining an 'embryo that will take' and in many cases finding the right one for transfer. These are the two challenges. Yes - there are some tools that embryologists have available. Immature eggs lack a little cell called the polar body whereas over-mature eggs have light membranes, thin zona and so-called luteinized corona cells. There are other markers as well. 

Jacques Cohen, Ph.D.: Yes - there are some tools that embryologists have available. Immature eggs lack a little cell called the polar body whereas over-mature eggs have light membranes, thin zona and so-called luteinized corona cells. There are other markers as well.

Linda : I think that I've seen references on the INCIID Forums to something where research has found that IVF isn't any more effective than IUI in women over 40. Is that correct?

Jacques Cohen, Ph.D.: There have been no randomized trials to suggest this just sporadic experiences of practitioners. It is also dependent on success rates of both technologies in hands of individual practitioners. Overall, when reviewing all data, there is no evidence to support the contention that IUI is 'better' in any age group.
Carrie : I think I've seen something about maturing eggs in-vitro. Could this offer more hope for pinpointing exactly when an egg is mature enough for fertilization?
Jacques Cohen, Ph.D.: Well, they can probably do it but their results 'probably' have indicated that it is not as good as transferring them earlier. This issue is rather common, that is, clinics have different experiences depending on the patients they see and the techniques they use. ART is called ART for a good reason. Some of the technologies are quite exact and one can adhere to protocol, other technologies are 'soft' and depending on a myriad of factors. I would feel comfortable with their suggestions, because they base these on experience.
Mary Anne : My wife had surgery for endometriosis two years ago, since then we have had several IUI's with our endocrinologist with no successful pregnancies, he has now recommended IVF. My endometriosis was found to be moderate. What is your experience as far as IVF and success with endometriosis?

Jacques Cohen, Ph.D.: Many patients with endometriosis have undergone IVF with great success. The severity of endometriosis may determine the chance of IVF outcome, but things do not seem too bad in your case as far as prognosis is concerned.
Michelle:  I am going to have my first IVF in February using an Antagonist (Cetrocide). I had three children before having my tubes tied. I am 34 years old. I never had any problems conceiving my children. What do you think my chances are? I also would like your opinion because I heard he transferred a 2-cell embryo after 36 hours. Is that normal (he rated the embryo excellent)?

Jacques Cohen, Ph.D.: Your chances of success should be considerable. Comparing your own success with that of other patients or their experiences is not always a good idea. 

Delly:  I am 41 yr, have miscarried 5 times up to 9wks (3 natural & 2 IVF NYC); D&C tissue test 1X - genetically normal male Would PGD be useful? What is the PGD risk/reward? What would you recommend?  two vs. one cell - PGD? Are there risks sending samples from NYC to a PGD lab in California? Is a 5-day transfer better than a 3-day transfer?
Jacques Cohen, Ph.D.:  PGD is the way to go. One blastomere should suffice. Why Cailfornia? There are excellent PGD labs nearby! 

Jackie :  What are the benefits of going to 5 day blasts instead of 3 day? Is it possible embroys that were good at 3 day may not make it to 5 days, but could've made it if it was transferred on day 3 instead of 5? 

Jacques Cohen, Ph.D.: Good question! The answer is 'yes'. But it is not the norm. Excellent looking embryos on day 3 have a higher chance to become blastocysts, yet some fail. What is important also is how many good embryos there were on day 3.

Janice:  Dr. Cohen, I want to thank you for your decades of work in the field! I hope you know what a tremendous difference you have made - what changes you have wrought. Thank you!
Jacques Cohen, Ph.D.: My pleasure and thank you really so much for your comment.

Cecliia: What is the average rate of damage to the egg when ICSI is performed with IVF? How does the embryologist decide which sperm to choose for purposes of ICSI?

Jacques Cohen, Ph.D.: The average of damage should be lower than 5%. The spermatozoa in the final preparation for injection have come there after a long road of passages and hurdles both before sperm retrieval and afterwards. Usually this preparation contains motile sperm only and these are slowed down to visualize individual cell. Even if the embryologist would be pressed by time, he/she will 'automatically' opt for the one that is relatively fast, moves well and has the best morphology 'looks'. 

Shari:  I am planning to do a FET this spring - I have 8 day 5 blasts in the freezer. What is your opinion on nursing during a FET? I am currently nursing my 10month old.

Jacques Cohen, Ph.D.: This is a question for your RE. It is related to prolactin, oxytocin and E2 levels. I presume that it is not a good iea but I am not sure.

Maria : Hello, and thank you for being with us tonight. I am 32, no children, and after 5 years of infertility with recently diagnosed endometriosis (moderate), my endocrinologist has recommended IVF. Do you suggest any particular vitamins or therapies in preparation for this? I have read about acupuncture and massage. Thank you,

Jacques Cohen, Ph.D.: There are preparations already available regarding this that can be obtained over the counter. If you are interested I can obtain the names. Email me 

Jessie:  I am 41 yrs old, have had 5 miscarriages up to 9wks (3 natural & 2 IVF NYC). D&C tissue tested 1X - genetically normal male. 2nd IVF cycle in NYCI had 6 transferred (cells were 9,8,8,8,8,8) on day 3 & used 40 g. IVIg; Progesterone. and 30 mg Lovenox. I had a chemical pregnancy. Do you think it was an embryo issue or an implantation & environment issue?

Jacques Cohen, Ph.D.: All of the above. You may be frustrated by my answer, but so am I. This is so complex that it is rather rare that specialists can diagnose failure. An important aspect is your age: 41.... That is usually suggestive of an 'egg' problem but failure can be multi-factorial; with many causes.
Annie: At what size, does a follicle normally produce an over-mature egg?
Jacques Cohen, Ph.D.: It is not just size related but dependent on number of follicles as well. It is also dependent on days and types of stimulation. I would think that anything over 22mm has a good chance of over-maturity of some kind, but even this size does not mean that the egg would be always affected. Obviously we must exclude 'natural' eggs from these comparisons since these can be normal even from very large follicles.

mia : In general when using blastocyst in a thaw cycle how much information is known about the embryo prior to transfer if the embryo was frozen at the blast stage? Does transfer occur before the blast has a chance to expand?

Hopper : If cells are dividing too fast, what might that indicate?

Jacques Cohen, Ph.D.: Good question! There are too many aspiring scientists in this chat room! Answer: One can only speculate, after all the government does not allow any federal funds for embryological research, so what we know is quite little. It must be the cell cycle that is gone haywire. The cell cycle is a very complex mechanism studied by scientists mostly in somatic - non-embryonic cells. This can lead to loss of function. There are also genes that 'time' these events and these may not control the situation when embryos go to fast. Anyhow, all of it is speculative.

Laurie:  Can high STIM doses reduce significantly embryo quality ?

Jacques Cohen, Ph.D.: A loaded question! Overall, the dose is negatively related with INDIVIDUAL embryo quality, yet the high dose produces more embryos for selection and when this is done properly (and that is often a big if), the loss in quality should be made up for.  

Leslie : Can ICSI damage eggs?

Jacques Cohen, Ph.D.: Sure. Eggs can be damaged immediately and this can be seen microscopically. What is more relevant is whether ICSI could damage eggs in such a way that the children could be affected. Well, there is no evidence of this, although I am sure we will learn more with time. The same can be argued for embryo culture, IVF and freezing. Things look good thus far, but the true extent of the technology we will only know in generations to come.

Zippy:  Dr.Cohen, If embryos pass the PGD test (which I know only tests for about half the chromosomes), how likely is it that they still have some abnormality?

Jacques Cohen, Ph.D.: It is possible that some of the chromosomes are still affected but the percentage is much smaller than the chromosomes that are already tested. These chromosomes were selected based on their high incidence of abnormality in early embryos. In other words they account for the vast majority of problems.

Linda:  What is the expected rate of chromosomal aneuploidy for a 34-year-old woman ?

Jacques Cohen, Ph.D.: Do you mean in the embryo or after establishment of pregnancy? In the embryo the rate is higher than one would think; about 30-40% on average. After establishment of pregnancy (when most abnormal embryos are already lost in the reproductive tract often without leaving a trace of evidence) the rate is only a few percent for this age.

Lidia:  Is there actually a condition called 'empty follicle syndrome' or is this simply a mistimed retrieval? If empty follicle syndrome is valid are there any resolutions for it?

Jacques Cohen, Ph.D.: Empty follicle syndrome is one of these doubtful topics. We can only know if it exists if the follicles were excised and removed from the ovary rather than sucked empty. It can be very frustrating to obtain eggs from certain follicles and from certain women. Such findings should probably be characterized as problematic retrievals and not 'empty'.
Nora:  Can PGD biopsy be done to embryos with fewer than 8 cells on day 3?
Jacques Cohen, Ph.D.: Yes. The lowest number is usually 5, but sometimes 4. It depends on the experience of individual programs.
Veronica : How unusual is it for embryos to still be in morulas stage at five days then continue to blast on day six? How big of a concern is this slow development?

Jacques Cohen, Ph.D.: It is only a minor issue in most cases. The first blastocyst pregnancy was one of my patients in 1984. This was exactly such a case. The embryo was frozen on day six and replaced in a cycle after one more day (that is day 7) and she is now a happy 20 year old.

Another interesting question. You guys are good! It is all a matter of give and take. The longer one cultures embryos the more likely it is that even good ones stop growing. The earlier one transfers an embryo, the more likely it is that the selection process has not picked up the 'best' one. Those that defend the 'zygote' approach maybe would be in disagreement with me, but events such as mosiacism and development rate, are better observed later. Yet, in a perfect world, if we could find a better way of selecting zygotes and eggs, the earlier the transfer the better (and that would of course offend the 'blastocyst' proponents, so whatever the truth is - I can't win).

Brenda : Can PGD damage the embryo and cause to stop developing, even though it was healthy before PGD ?
Jacques Cohen, Ph.D.: It probably can, but I have little evidence for this. The scenario is plausible though for certain rare embryos. In general, embryos catch up pretty quickly after biopsy.
Betty:  How "portable" are frozen blastocysts from one lab to another. A friend is willing to donate her frozen blastocysts to me, but my RE's embryologist seems reluctant to work with "another embryologist's blastocysts." Is there such a wide variance in lab technique? Or just a matter of personal preference?

Jacques Cohen, Ph.D.: well, it is a matter of how and in what the embryos were frozen. In my opinion it is always better to have embryos thawed in the laboratory that performed the freezing process.
Jacques Cohen, Ph.D.: I like to say good night to my kids and to you all. Any further questions can be emailed to me at: Good luck to you all. Jacques Cohen


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