Every last baby out of every last egg The appropriate goal for fertility treatment in women older than 40 years

Authors:
Richard J. Paulson, M.D.

Volume 105, Issue 6, Pages 1443-1444

Abstract:

Another patient in her 40s came to see me for a second opinion last week. Her story is quite typical, and it is easy to summarize in general terms. The patient is aged 42 years and has undergone three IVF cycles without success. More accurately, she has undergone three IVF retrievals but did not have an ET. This is because she was told that all of her embryos were found to be chromosomally abnormal. She was further advised that she seems to only be producing abnormal embryos and that she should now pursue oocyte donation.

  • This inklings piece with the theme “no embryo left behind” addresses one of the most important topics in contemporary ART- namely the best strategy to achieve IVF success in women with advanced reproductive age. As the lively discussion in this forum already demonstrates, this is a controversial topic and the jury is still out as to what the right answer is.
    As one of the program directors for the next “Pacific Coast Reproductive Society” (PCRS) meeting in Palm Springs in March 2017, I would like to point out that we will have a debate on this topic at the meeting, featuring Dr Richard Paulson, the author of this article, and Dr Richard Scott from RMA New Jersey. It should be a good discussion!

  • Rose Rose

    I would like to share my viewpoint as an “older woman” undergoing IVF. I went about it the “standard way” which meant fresh Day 3 transfer, had a miscarriage at 3-months and a D & C that damaged somewhat my uterine lining. This is not surprising given the high rate of miscarriage in older women and the fact that D & C often thins the lining. I think this risk (risk of miscarriage & potential consequences) is large. The risk of discarding an otherwise good embryo by doing genetic testing is small in comparison (although I fully recognize the rarity of a good embryo at an old age). “First do no harm” needs to carefully balance the two risks, and I feel that those who warn against genetic testing tend to not fully give the risk of miscarriage the weight that it deserves. When it is mentioned, it is often about the emotional aspect and not the physical one, which is very real (thin lining like in my case, but also Asherman’s, etc). I am now doing cycles every month and we are freezing the embryos to accumulate a bunch and do genetic testing – a strategy that I feel comfortable with. My uterine lining looks ok some months and not others, but at least I know that I have a fair chance of giving birth with either my own egg or donor egg. My goal in writing this message is to share my personal opinion that 1) The risk of miscarriage in older women is very high and this should be in the forefront when thinking about “risk” (“first do no harm”). and 2) There may not be a “good” or “bad” strategy. It may depend on the couple. If the goal is to take home a baby (own egg or donor egg), one should be more conservative using genetic testing to minimize the risk of miscarriage. If the goal is to get pregnant with one’s own eggs in the most efficient manner (i.e., quickly and at low cost; at the high risk of a miscarriage), transfer after each cycle makes sense. Thanks for your hard work and for caring about women of “advanced age” like me!

    • Richard Paulson

      Dear Rose Rose, thank you so much for your comment. Your point is very valid, and of course, you have lived it. I must tell you that I’m so very afraid that genetic testing will tell me that an embryo is no good, and that the test will be wrong and I will throw away the patient’s one good embryo. Depending on how far beyond 40 the patient is, there may only be one embryo capable of producing a baby in one out of every 4 or 5 egg retrievals! I’m also afraid of transferring a “good” embryo that tests normal, but then the transfer fails because of the damage the embryo suffered from the trophectoderm biopsy. And I wonder if that could have been a baby if we hadn’t done the genetic testing. And as you know, there are lots of miscarriages after the transfer of “genetically normal’ embryos. Those patients ask, if the embryo was genetically normal, why did I miscarry? Was it the embryo biopsy? It’s not yet a perfect system, the testing is not harmless and it is not always correct, but I know it will get better. I look forward to the day when when we have 100% accurate genetic testing with 0% damage to the embryo! Then we really will test every embryo prior to embryo transfer. I sincerely hope your treatment is successful! All the best!

      • Rose Rose

        Thank you so much Dr. Paulson for having taken the time to respond! I share your concerns and also look forward, for other couples, to that day when genetic testing is less risky. For now, it is very much like being stuck between a rock and a hard place. I have 11 frozen blastocysts “banked” and in terms of odds, one of these may be genetically normal (if I am lucky). If I had it my way, we would just transfer them all, but LOL, I realize this would not pass any ethics board (although frankly I don’t understand why given that almost everyone agrees on the odds – I am a recent 44 year-old). The choice that I have is to transfer based on morphology (a maximum of 2 is allowed by law in Quebec, Canada), but run the risk that I miscarry and damage my lining further (quite likely preventing a future pregnancy), when maybe there is a “good” embryo in the cohort (it just was not one of those 2 best-looking ones!); or send a bunch (all or most) for genetic testing which brings down the risk of miscarriage from 60% to 10% (this is my understanding)….if there is an embryo to transfer in the first place (i.e., there is no error in calling the “euploid” one “aneuploid”, and it is not damaged by the biopsy or even just the extra thaw-freeze). It’s really a tough decision! I really liked your point about the “genetically normal” embryos that end up in a miscarriage and the why. Too bad there is by definition no way to compare the outcome of “genetically normal” embryos that underwent genetic testing with those that didn’t :)! I will not be writing again as I don’t want to be a bother – this is actually my first time participating in a “forum”. I just felt that your article was very pertinent for me and you tone very compassionate. Thank you so much again, for caring and for your reply. And all the best to you as well, in terms of your research and your work.

        • Richard Paulson

          Thanks again, Rose Rose, it is a very good sign that you have 11 frozen blasts, and yes, you’re right, it is not evidence-based to limit the transfer to 2 blastocysts if they come from 43 or 44 year old eggs. But that is another imperfect part of our world. Thank you for taking the time to write and I sincerely wish you the best in your upcoming transfers, I hope there is more than jut one!

        • Dear Rose Rose,
          As one of the “Interactive Associates” for Fertility and Sterility who care about this forum, I would like to point out that you are not a “bother”- quite the opposite! I read your well written comments with great interest, thank you for sharing. This is what the forum is for.
          Good luck with your future treatments,
          Alex Quaas

  • Richard Paulson

    Prof Pandiyan, thank you for your kind words. As Mark Twain said, “It ain’t what you don’t know that gets you into trouble. It’s what you know for sure that just ain’t so.”

  • Prof Dr N Pandiyan

    Prof Paulson, you have given a wonderful perspective to an overrated technology. There are no simple solutions to age related decline in fertility.

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