ASRM Today: Genetics - Episode Seven

We're diving deeper into our season long exploration of genetics in reproductive medicine, and this one's a must-listen.

Joining us is the brilliant Dr. Elizabeth Ginsburg - President of ASRM, Professor at Harvard Medical School, and Program Director at Brigham & Women's Hospital - to unpack the science and the controversy around PGT-A (Preimplantation Genetic Testing for Aneuploidy)

When is PGT-A actually helpful?

Should women under 35 consider it or avoid it?

What are the most common myths and misunderstandings?

Don't miss this thoughtful, expert-led discussion on a topic that's shaping the future of fertility care.

Welcome to ASRM Today, a podcast that takes a deeper dive into the current topics in reproductive medicine. I'm Jeffrey Hayes, and today on the show, we are continuing our season long look at genetics and genetics in reproductive medicine. Joining me to discuss the topic of PGTA is Dr. Elizabeth Ginsburg, who is the current president of ASRM, Professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School, and Program Director, Reproductive Endocrinology and Infertility Fellowship, Brigham and Women's Hospital.

Dr. Ginsburg, thank you for being on ASRM Today. Thank you for having me, Jeff. So I'll just jump in, big question, like right off the bat.

Who is PGTA appropriate for? I think it's a really good question. PGTA is yet another way we have of differentiating embryos that are more likely to result in a live birth from those that are less likely to result in a live birth. One of the things that people really need to keep in mind is that PGTA doesn't make embryos better.

It's a way of sifting through a cohort of embryos to find those which we think have the highest reproductive potential, because as far as we can tell, that embryo has normal chromosomes. There are now several randomized trials looking at PGTA, all of them showing no benefit in terms of the likelihood of that stimulated cycle resulting in live birth. So in my opinion, the appropriate use of PGTA to help sort through embryos when there are a large quantity of high-quality blastocysts.

So women who have excellent ovarian reserve or perhaps in their later 30s or early 40s who develop many high-quality blastocysts, it's a very nice way of differentiating those that are most likely to result in live birth and also to avoid the complications of multiple pregnancies that would occur if you were transferring more than one embryo. So I think it does optimize the live birth rate per single embryo transfer, but you have to keep in mind that the overall likelihood that that cohort of embryos creating a baby is not improved. So you would say that that's a misperception? I think it's a misperception, and many times patients think it's going to help them get pregnant, and that is absolutely just not the case.

Yeah. Yeah. I want to jump back to what you were saying a moment ago about age.

Is there any controversy that PGTA would be appropriate in women under 35, over 35? None of the studies show any benefit in PGTA, mostly even per embryo transfer in patients, for example, using donor egg. Donors typically are women in their 20s. The vast majority of their embryos are going to be normal chromosomally, and there's no benefit in any study of doing PGTA in women using donor egg embryos.

For women over 35, one of the randomized trials did show a reduction in miscarriage rates, and that makes some sense because as women age, the percentage of chromosomally abnormal embryos increases. So if you weed these out doing PGTA, one would think that per embryo transfer, the risk of miscarriage would be lower. That actually has not been found in all the trials, surprisingly.

For women who are less than 35, there again is no evidence of benefit in terms of the likelihood of live birth per stimulation, and also no benefit's been found from the standpoint of reducing miscarriage risks. There is a cohort of patients who have chromosomally abnormal miscarriages, and those patients do find it sometimes reassuring if at least they know that as far as we can tell, the embryo being transferred has normal chromosomes. So I do think there's a role for it in women who are less than 35, as long as they're counseled that again, the technology doesn't make it more likely that that cohort of embryos is going to get them a baby, but perhaps it can give them more information about the embryo being transferred.

I'll go ahead and double down. What is the likely outcome in women with decreased ovarian reserve? That is the million-dollar question, and I think from the standpoint of decreased ovarian reserve, one of the tricky things is we don't even know whether blastocyst transfer is optimal in women with decreased ovarian reserve. All of the randomized trials comparing day three to day five embryo transfer, there's only one randomized trial of day three versus day five embryo transfer using vitrification freezing technology in the literature, and that study only included women who had four embryos that had normally fertilized, so four 2PN embryos were required in order for those patients to be randomized.

So we have no data about whether even blastocyst transfer is the optimal way to go for women with significantly decreased ovarian reserve. And if you think about statistics, so for example, when we get a cohort of eggs out of the ovaries, we expect about 70% to be mature. Of those mature eggs, typically about 70% fertilized, so you expect about 49% of the eggs that you retrieve to fertilize, right? So if you have four eggs, if you have a patient with significantly decreased ovarian reserve, that typically means she has less than six eggs retrieved.

If you get four eggs, you're going to probably get two embryos. And again, there's no evidence that blastocyst transfer is any better than day three or whether it may be harmful. So we don't even know about the first stage of embryo selection, which is blastocyst development.

That's a way of selecting out from a large cohort of embryos too, because not all embryos will divide between day three and five. So if you add in another selection criteria, which is ability to create an embryo that as far as we can tell on biopsy is chromosomally normal, are you helping patients with decreased ovarian reserve have a baby? No. No patient cohort has a higher chance of having a baby per stimulation with PGTA testing.

The question is, in patients with decreased ovarian reserve who may not get any blastocyst at all, are they harmed even by blastocyst culture? So we don't have an answer in that cohort specifically. Well, I know your time is very valuable. I really appreciate you being able to come on the show and talk to us a little bit about PGTA today.

My guest has been Dr. Elizabeth Ginsburg. Thank you so much for being able to come on. My pleasure and see you soon.

All right. Thank you so much. This concludes this episode of ASRM Today.

For show notes, author information and discussions, go to ASRMtoday.org. This material is copyrighted by the American Society for Reproductive Medicine and may not be reproduced or used without express consent from ASRM. ASRM Today series podcasts are supported in part by the ASRM Corporate Member Council. The information and opinions expressed in this podcast do not necessarily reflect those of ASRM and its affiliates.

These are provided as a source of general information and are not a substitute for consultation with a physician.