FET

[bows&ribbons]

The center (NYU) where i am considering doing PGD will only do acgh, 5 day biopsy with fet. I am very concerned about doing FET because NYU has only had 46 cases of FET leading to pregnancies and there have only been 1000 cases of FET done in the world. Those numbers just seem so small. Do I have any reason to be concerned. How do we know that the the process of freezing and thawing embryos doesn't hurt the embryos..or that ice crystals that form doesn't lead to damage in the resulting babies.

[Carole]

Dear bows&ribbons,
When you say NYU has only 46 cases of FET leading to pregnancy, are you just speaking about PGD cases? Their regular FET pregnancy rates are relevant because the freezing process used is likely the same- but you should check this- and most IVF centers have done hundreds, if not thousands of FET cases over the years. Their PGD cases may only be 10% of all their cases so the FETs associated with these cycles will be fewer. Also, are the 46 cases out of 100 attempts or out of 1000 attempts? That makes a difference as well because one represents a 46% success rate, the other a 4.6% success rate. Finally, if they are doing vitrification and not slow freezing (the older technology) ice crystal formation is not an issue. Vitrification is a kind of flash freezing that completely bypasses the ice crystal phase with water entering directly into a "glass-like" state. Lots of patients are concerned that partial embryo damage will result in a child with missing parts. This doesn't happen. If the embryo is too damaged, it dies. It is an all or none phenomenon. We don't have a generation of outcome data from FET births but of all the IVF technology, there have been fewest worries about effects on babies from this one. The problem with FET has always been dismal pregnancy rates because too many embryonic cells didn't survive the freeze-thaw process but vitrification, done properly, has achieved pregnancy rates equivalent to fresh rates. Since you still have concerns, I would definitely try to get some more face time with your doctor so that your specific concerns and their specific experience can be discussed in more detail. Then it will probably become more clear what you should do. Best Wishes, Carole

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[bows&ribbons]

Thank you so much> I met with the dr. Today. He says that he really prefers the FET method with 5 day biopsy/ac-gh bc you are able to get results back from all of the embryos and put back the best ones. He said that if i was insistent, i could do the 5 day biopsy with acgh and fresh transfer (assuming that there are embryos to transfer back at that point and freeze the rest) but that may lead to the fact that not the best embryos are transfered back. What does that mean? Do better grade embryos lead to healthier babies or pregnancies? He has had a lot of success with FET and the 5 day/acgh -- everyone who has done it that way is pregnant (except for one patient with lining issues). he prefers to test everything (bc some embryos wont be ready for the biopsy on day 5 and they will have to biopsy those on day 6 and freeze those anyhow) and then put back in a different cycle the best embryos...and he also believes that having your body in an unstimulated state results in better pregnancy rates in fet. I was thinking that maybe i'd just see what happens and continue with the progesterone shots just in case and if i have an embryo to put back fresh i'd go that route and if not, i'd freeze the rest and transfer back in a different cycle. He thinks this is not the best route since i'd be tampering with some of the benefit of the 5 day biopsy/acgh in transfering back the "best" embryos. What does that mean -- how do they determine which embryos are the best and what does that mean clinically in terms of the babies that result from those embryos?
THanks!!

[Carole]

I am not sure from your description what he means by "best" embryos. In a fresh cycle on day 5, you will get a report on how they look on day 5 from the embryologist (one estimation of "bestness") , so maybe that is what he means by putting back progressive good looking embryos but these may not yet have all the genetic testing results back (another estimation of "bestness"). Sometimes lovely looking embryos are genetically abnormal so there can be a disconnect between these two estimates of embryo quality. Honestly, if he has good results with the day 5 biopsy and transfer in a later FET, it makes sense to go with his program's experience rather than trying to go a "third" way which is not proven. If he has a good freezing lab, then there is no downside to waiting for a FET cycle to transfer the embryos in which your uterine lining can be hormonally prepared for implantation. In the fresh stim cycle, the uterus gets exposed to way more hormone than is optimal for implantation because the primary goal is to stimulate the ovaries to get lots of eggs and (hopefully) not disadvantage the uterine environment--but there is evidence to suggest that implantation rates are better in non-stimulated cycles even if embryo quality is equal in each cycle. Anyway, whatever you decide, I wish you all the best !! :) Carole

[bows&ribbons]

I would think it would be a no- loss situation -- put back any embryos that have gone through testing and freeze the rest. WHat is the risk that one not yet tested on day 5 and frozen would be "better" than those tested on day 5 adn what does that mean -- does that mean it has a greater chance of implanting or suriving or developing into a healthier baby? The RE is at NYU so im sure its flash freezing.

[Carole]

Dear bows&ribbons,
I don't know why your RE feels strongly about doing this one way over another. You should probably ask him explicitly. Perhaps he wants all the information on each one before proceeding. Perhaps he's a strong proponent of better implantation in a non-stimulated cycle so why risk "wasting" embryos in a day 5 transfer when your body is less primed than it could be for implantation? Perhaps he knows that his team doesn't handle departures from routine very well and something is more likely to go wrong if you are a patient with a "special" protocol. I am sure he will let you do whatever you want to do. The "customer" is always "right". Carole

[bows&ribbons]

That is exactly what he wants -- all the information before proceeding -- knowing which embryos are best for putting back in and when your body is in the best condition for the transfer.

[Carole]

Seems like a reasonable approach. Good Luck!! Carole

[bows&ribbons]

What does he mean by the "best embryos to put back." how does one determine which are the best and how does that assesment relate to the actual babies or pregnancies ensuing from those transfers?

[Carole]

Dear Bows & Ribbons,
When I hear the word "best" in the context of embryos, it usually refers to the things that we can measure about embryos. There are only two types of assessments we make. The first is a morphological and progression assessment that the embryologist makes during the case- usually at fertilization, day 3 and day 5. Some programs may do more or less evaluation. The embryologist uses one of several embryological scoring systems to come up with an embryo score (a number) that gives embryos the highest score if they have the appearance expected for their stage of development and if they look like they are reaching developmental stages at the expected time. My post http://fertilitylabinsider.com/2010/11/embryo-stages-progression/ shows pictures of what ideal embryos look like at each step as well as some comments about pregnancy outcomes. The second type of assessment that can be made is genetic testing looking for the presence of either abnormal disease genes or a trait (like gender). The genetic assessment is done on a small cellular sample from the embryo which is shipped to a genetic testing lab. The morphological scoring systems or "embryo beauty pageants" are as old as embryology. Genetic assessments are relatively newer. We have found that the combination of these assessments is a pretty good indicator of the most likely to implant embryos. However, our current assessment methods are far from fool proof because perfect looking embryos can harbor genetic abnormalities and scruffy looking embryos can lead to healthy babies. Genetic tests are not fool proof either because false results can occur (as with any lab test), so clinicians rely on both types of assessments (if available) when making recommendations of which embryo to transfer. Hope this helps, Carole

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[bows&ribbons]

Part of me feels like i should listen to my doc who is a head re in this field and just do a fet since that is what is working for him..but part of me feels like i should try fresh if i can and freeze the rest (if i am so lucky to have more than one embryo to transfer). Are there any studies suggesting that babies resulting from frozen embryos are at an increased risk for abnormalities etc? Thanks! Do you know of any links to the safety of FET?
Thanks!

[Carole]

Dear bows&ribbons,
Here is a nice summary of concerns that have been raised about FET safety, almost all of which have been shown to be unwarranted. http://www.ivf.net/ivf/embryo-freezing-is-it-safe-o335.html However, since embryo freezing in humans is only as old as IVF- about 20+ years- we simply don't have life-long outcome data. But there have been tens of thousands, maybe hundreds of thousands of births using FET worldwide that don't demonstrate any obvious ill effects from starting life as a frozen embryo. If freezing is done poorly, the most likely effect is that too few embryonic cells survive the process and the embryo dies or is too damaged to implant or grow to it's full potential and the pregnancy fails before it ever gets started. With vitrification, damage from freezing is much much less common. The power of vitrification-done correctly- is that usually, post-warming, the embryo looks as good as before freezing. With traditional methods, we expected up to 50% cell death as "normal". IMO, FET, especially with vitrification is safe and effective. Carole

[bows&ribbons]

That article sounds a little scary. Seems like the embryos goes through so much stress to be frozen and then to be thawed! that is why i'd rather try fresh and freeze what i can for future transfer if the fresh doesnt take. We just dont know what the long term ramifications of this is...biopsying the embryo in of and itself is already complicating the already complicated iVF process.

[Carole]

Once you leave sex behind and enter the world of IVF, you have only about 30 years of human experience to draw upon. Ironically, freezing technology is what we have the most experience with because we have been freezing sperm and then embryos in the animal industry for decades longer than we have been doing IVF. I have the least concern that we will discover long-term problems from FET than from anything else we do.

Somewhere in this thread, you asked about biopsy and stage of embryo. Biopsy can be performed on the embryo on either day 3 or day 5. The morula stage embryo on day 4 is disorganized and it is not possible to recover a single cell cleanly and the trophectoderm layer is not developed at this day 4 stage so trophectoderm biopsy must wait for day 5 or day 6.

[bows&ribbons]

are there any articles discussing the safety of vitrification technology? The article you referred to me was written in 2004 and i am wondering if there have been any follow up studies. THanks!!
Also, the day 5 biopsy is done on what will become the placenta and other fetal membranes. Is there any way that these structures could be damaged and the embryo harmed in any way because of this biopsy? I believe Australia has been doing the day 5 biopsy for more time than we have -- have they had any negative experiences resulting fromt the day 5 biopsy e.g., more preterm labor, damaged placentas after babies are born etc? Thanks again for all of your help!

[Carole]

There are tons of articles in vitrification technology. You can simply google "embryo vitrification .gov" and find tons of articles to read. The ".gov" weeds out some of the weak opinion pieces. Some articles are written by IVF clinics, some are primary research articles. There is no shortage of articles to read about vitrification. Every year at the annual ASRM meeting, new evidence is accumulating to show that vitrification is an improved technology over slow freezing. If I were doing IVF to create a child, I would want my embryos to be vitrified and would only go to a lab that shows excellence with vitrification because IMO that demonstrates both technical proficiency and a commitment to improving outcomes for patients. Slow freezing is old technology that simply hasn't yielded the results possible with vitrification. Some researchers have shown better implantation for vitrified embryos than fresh embryos, probably because the uterus can be more receptive to implantation in a non-stimulated FET cycle. See a review of this here http://therotundaramblings.wordpress.com/2008/11/20/vitrified-embryos-seem-to-produce-healthier-ivf-babies/

Biopsy at any stage does not result in partial harm to embryos. IF the biopsy damages the embryo, it dies and implantation does not occur. There is no midway point with a organism of 10-100 cells where there is enough damage to cause partial damage but still allow implantation. Removal of a small number of cells for biopsy does not result in missing limbs in the fetus. Limbs won't develop until thousands of cell divisions later. The embryo on day 3 has less than a dozen cells, by day 5, it has about 100 cells. If you take a few cells away in the biopsy, especially when it is less than 10% of the cells, there are still plenty of cells left to get the job done. A loss of less than 10 cells at the earliest stage will not affect the function of the future placenta.

Best Wishes, Carole

Like my blog? Check out the ebook, Fertility Lab Insider,
now available through Amazon (Kindle) and Barnes & Noble Booksellers (Nook)
Fertility Lab Insider | http://www.amazon.com/dp/B004QOB7Z8

[bows&ribbons]

Does cryopreservation mean vitrification or slow freezing? how do i find out what type of freezing NYU practices? Thanks!

[Carole]

Dear bows&ribbons,
Cryopreservation is a general term that means preserving living cells by taking them to a temperature that is so low that metabolic processes don't take place and so the cells are in a state of suspended animation which is reversible. Under that umbrella term, there are two methods to get the cells to that ultra low temperature. Traditional slow freezing is one procedure to accomplish cryopreservation and vitrification is another procedure. Here's an eHow article I wrote that goes into more explanation http://www.ehow.com/how-does_5932899_cryopreservation-procedures.html. If NYU doesn't mention it on their website, you'll have to call their office and speak with someone in the lab. Hope this helps, Carole