To PGT-a or not to PGT-a: Diving into the Science
Have you ever gone back and forth about whether to do PGT-a testing?
This podcast goes over what is known in 2025 about when PGT-a testing might add benefit to your treatment planning, and also when it might be best to leave it out.
We will discuss:
evolving science
factors in your history
future planning considerations
how to make the best choice for you and your situation
Join me as we discuss the science in detail.
As always, please keep in mind that this is my perspective and nothing in this podcast is medical advice.
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Please don’t let infertility have the final word. We are here to take the burden from you so that you can achieve your goal of building your family with confidence and compassion. I’m rooting for you always.
In Gratitude,
Dr. Erica Bove
Transcript:
Hello, my loves, and welcome back to the Love and Science podcast.
Today, we're gonna talk about a very sciency topic, which is genetic testing of embryos, and when does it actually help? I've been doing this long enough that I can think back to when PGTA technology, which is pre-implantation genetic testing for aneuploidy, when this was first introduced, because before we actually used to test a three-day embryo, which only had eight cells, and to extrapolate data from one of the eight cells to the entire embryo, pretty wild that now we can take a very small sampling of the part that becomes the placenta.
But I think that as this technology has sort of gone on and on, and we're getting more data and understanding more about mosaicism, I think that the pendulum is swinging a little bit back in the direction of being, I wouldn't say like anti-PGTA, but maybe like this is not the thing that's gonna fix everything, and maybe we need to be a little bit more cautious about it, and maybe we need to think about like each specific person as we always do, but what is their exact situation, and is this somebody for whom PGTA is actually gonna help them, or is it somebody for whom PGTA might actually make things muddier, or maybe even potentially lower their success rates, right?
So let's talk about PGTA, and I'm not talking about sort of sex selection and family planning, that's a whole other topic, but what I'm really talking about is when does it really help somebody's clinical situation in a way that is gonna help them build their family in a safer way, in a way that maybe is going to be with lower risk to the mom, or the baby, or babies, all those things, right? So I figured out we have five ways that I can think of at least where PGTA may be beneficial.
So the first is when we really want to do a single embryo transfer. If you haven't seen it yet, the ASRM has a guideline of how many embryos to transfer, and interestingly, if you are under the age of 38, pretty much you're going to be transferring one embryo under any circumstance. Once you hit 38 to 40 and over 40, there's sort of different categories in terms of numbers of embryos to transfer. And of course, this depends on whether these embryos are tested or untested, whether people are good prognosis or not so good prognosis.
Obviously, if not so good prognosis, it's a little bit more lenient to transfer more than one. Anytime it's a PGTA-tested embryo, it's going to be one embryo, because we know that those embryos in general have higher success rates compared to untested embryos.
So say somebody has a unicorn or a uterus, and you really, really, really do not want them to get pregnant with twins. Say they have a history of preterm delivery, and you really don't want to put two embryos into a 39-year-old. Say somebody already has a couple of kids, and they would rather not build their family than have twins, and I do hear that sometimes, right?
Everyone's situation is different. When somebody, or maybe it's a single parent who says, "Listen, I could handle one, but I don't think I could handle two," it's really important to many people to try as hard as possible to get pregnant with one healthy baby. And like I say to most of my patients, most things I do in my fertility clinic, for the most part, are going to increase the risk of twins.
And so I think we have to be very cautious that we are honoring that Hippocratic Oath, which is first do no harm. So the point is, any time we really want to put in one high-quality embryo and only one embryo, we don't want to risk it by putting in two or three and hoping only one takes. That's a great time to think about PGTA testing, because if you look at it for most women, embryo or embryo, if it's a genetically tested embryo, you're going to have a higher chance versus if it's not tested, then you just don't know, right?
And in young women with good prognosis, those numbers do approximate each other. And there's some data that even suggests that PGTA might be a little bit worse in terms of outcomes. So the point is, the older you are, and depending on the clinical history, you're going to see more benefit from PGTA tested embryos.
But if you're a little bit on the older side and you really want only one embryo put in, PGTA very well may help you in a setting where you might have otherwise put in two or more embryos, if that makes sense. So that's really the first scenario, is really, really hoping for a single embryo transfer. The second scenario is when genetic testing is already being done for other reasons.
And so classic example is PGTM technology. So when we, say, have a monogenetic disease like cystic fibrosis or spinal muscular atrophy, or maybe something even that's X-linked, we can actually test the embryos for that monogene, that genetic mutation, that allele, and identify embryos which are affected, and also identify embryos which are not affected.
And the ideal situation for people, especially whose families have been dealing with genetic issues or BRCA even, when people really want to weed something out of their genetic line, and they don't want the risk of having a child with a disease, and oftentimes, even like an autosomal dominant disease as well, we actually can do that same process of growing the embryos out to day five, day six, taking a small sampling from the part that becomes the placenta, and then sending that tissue off for genetic analysis takes about two weeks to come back. Most labs are doing next-gen sequencing.
And then, like I said, we can identify affected and non-affected embryos, with pretty good accuracy, actually. Now, the thing is that, you know, say you're 38 and you're doing PGTM, right, for your embryos, maybe you don't even have a history of infertility, but if I told you that, you know, 30 to 40 percent of your embryos were going to be chromosomally normal, and the rest were going to be chromosomally abnormal, it really wouldn't make sense to put in an unaffected embryo that was aneuploid, right? So that would not make any sense. And we're already going through the process of genetically testing those same cells for the gene mutation.
So most people who are doing PGTM technology, which is for monogenetic diseases, they are going to also think about doing PGTa testing so that they know that they're, you know, with at least pretty good certainty based on the limitations of the testing, that they're putting in an unaffected euploid embryo, right? And we could get into the weeds about mosaicism and the imperfectness of PGTa technology, but I would say all things considered, it probably makes sense for most people to consider that, you know, especially when going through all the other things of IVF.
All right, so that's the second thing is when you're also doing PGTM.
The third thing, and, you know, it's really sad thing to talk about, but, you know, I see a lot of patients with loss in my practice. And, you know, a lot of the times we don't really know why the loss has happened. Probably the number one reason for losses is genetic abnormalities of the embryo, where the pregnancy stops growing, or sometimes, you know, the pregnancy has ended, if that information comes a different way. But really, when we look at sort of things that can happen in a pregnancy, and why do people suffer from losses, most of the time it's related to chromosomal issues of the embryo itself, right?
And I've seen this, I mean, it's devastating when it happens in the first trimester. It's also extremely devastating when it happens, even later on. I've seen many, many second trimester losses, or like I said, determinations because of people had these sort of genetic issues of the fetus. And it's really, really tough to know what to do in those situations. Certainly, if somebody has a loss, you know, and we counsel them about their risk of recurrence, maybe they're even on the older side, like 40, 41, 42, most people absolutely do not want to think about having to go through this again.
Similarly, even, you know, even if somebody has gotten the information in a medical context and said, like, this is not a pregnancy I want to continue, you know, it's really like, I just can see it in the office. Like, it's a feeling of like, I do not ever want to go there ever again, right? It's very traumatic to go through these things.
And so when people have those histories, the ability to genetically test an embryo and say, you know, with reasonable certainty, this is at least a chromosomally normal embryo, and that risk of loss or that risk of needing to make a tough decision, that that's reduced substantially. That is seen as a benefit for a lot of people. Now, I will say it's not perfect because as we know, it takes a long time to go through IVF.
It takes a long time to generate uploid embryos. Sometimes the uploid embryos don't take. I've seen many people with actually recurrent implantation failure or lots of treatment cycles that haven't worked. And I think then the question is like, well, would I just have had a live birth on my own if I hadn't gone through all this? And, you know, we'll never know. But I think that if a loss has been particularly traumatic or somebody really wants to avoid going through that again, then I think PGT may offer a way forward.
We do know that it increases time to pregnancy. We do know that the miscarriage rates when you look at PGT tested embryos are lower. I mean, you know, it's not zero though, I will say, you know, if we say that based on somebody's age, they have about a 20% chance of loss, you know, in the 30s.
And then that starts in the late 30s, that gets to be a little bit higher, about 25%. You know, and even in the early 40s to mid 40s, that can approach 40 to 50%. So, you know, losses are pretty common, unfortunately, in untested embryos. But even when we know the genetic testing of those embryos, some studies show about a 10% chance of loss, even with PGT tested embryos. And recently, I even saw some data that it might even be closer to 20 to 25% in some populations. I also recently saw a study when I was reading for my MOC, maintenance of certification, that women over 35 might have a lower rate of implantation when they're over 35 and put in a euploid embryo.
And so that's also something to consider is like, you know, what is that? Does that also apply to cycles outside of IVF? You know, there's a lot to consider, I think. But, you know, thinking about the history of loss, I think it's important to honor that, especially for people who really don't want to go through that, again, and they want to decrease the chances as much as possible.
Okay, so the fourth situation where it may make sense to consider PGT is in, you know, sort of older women, which is it's always hard to know where to put that line. Anything above 35 is considered advanced reproductive age. If you look at the PGT data, anything that is actually 38 or above, anybody who's in that age range is thought to have, you know, maybe a slight advantage in terms of checking the chromosomes prior to doing a transfer.
Now, I will say if somebody doesn't make blastocysts, then perhaps a day three transfer is better. Of course, there's all these different nuances. Certainly in the 40 and above population, it does seem like PGT may be helpful, especially if people are making blastocysts. But it's estimated that about 80% of embryos may be abnormal at that point. And gosh, if it were me, and I knew that I had, say, I even made five embryos, and one of them was normal, I would not want to go through so many transfers to get to my good one. You know, I'd want to know what the good one was and discard the rest and put in that good embryo under controlled circumstances.
So, you know, that's really the fourth situation is kind of older women going back and sort of nerding out for a second. When we think about the test characteristics of sensitivity, specificity, positive predictive value, negative predictive value, we know that sort of the test is going to have the highest positive predictive value in a patient population where that thing that you're looking for is the most prevalent. So, if you think about a woman who's 32 years old, she probably, I mean, because the miscarriage, the aneuploidy rates are so much lower in people under 35, that test is going to perform more poorly than somebody, say, who's 42 years old, who has a much higher chance of aneuploidy.
And that's just how, you know, test probabilities work. But that's why we really do recommend, well, recommends a strong word, I mean, offer, and I do, I mean, it depends on my patient, I think, you know, it depends on our history, but I do often recommend PGTA for people who have, you know, a high chance of so many of their embryos being aneuploid. I remember one woman I took care of, she generated, she was only 42, and she generated 15 blastocysts and had one euploid.
And so, I think we just have to take this into consideration. That would have been a lot of transfers and a lot of time spent on embryos that never even had a chance, would have potentially yielded a miscarriage, or possibly even a pregnancy where decisions had to be made, compared to knowingly putting in a euploid embryo that just, you know, sort of reduces a lot of those other variables. So that's the fourth reason. The fifth reason is, you know, future planning. And, you know, I am all about reproductive rights. I'm all about having children when we want them and not when we don't. And, you know, we know that training is like a bajillion years long. And so, we are doing more and more fertility preservation.
I would say both, you know, egg cryopreservation, o-site cryopreservation, but also embryo cryopreservation. You know, say somebody has their partner and they know that embryos are a little further down the road. Like those same eggs, quote unquote, should perform the same, whether we freeze them as eggs or if we sort of freeze them as embryos later. But, you know, 10 eggs, for instance, I mean, that could be five embryos, that could be one or two embryos.
And if it were me, and I had my sperm source already sorted out, I would, I would, and if I knew that that, if I really trusted that that was my person, right, we do see relationships end and such. But, you know, if I was in a solid relationship and really trusted that this was my relationship with the future and really wanted to freeze embryos, in that situation, you know, adding that layer of PGT can sometimes give a little bit more insight into what's actually frozen versus how many blasts there are, if that makes sense. And so, you know, maybe somebody's going through cancer or maybe somebody has a very long training program and they really want as much information as possible, you know, rather than like freezing eggs or freezing embryos at the 2 p.m. stage, sometimes it's nice to grow those embryos out and to figure out the chromosomal data of that and, you know, and make a call. I will also say, you know, there's a lot of single women who I take care of who are like 39, 40, and they're like, I want to freeze my eggs and, but I really want to hold out the possibility of meeting a male partner in the future and having, you know, a child with, you know, my eggs and his sperm.
And so sometimes, you know, what I've done for some women actually is like basically retrieve eggs and we actually fertilize with donor sperm and just kind of see how those eggs and embryos perform. I've had people with very low blast conversion rates. I've had people with very high blast conversion rates. If somebody has a high blast conversion rate, which means that, you know, of the eggs that fertilize, they have a high number that get to the blast stage, then that's somebody I may think, okay, well, maybe we could freeze another group of eggs and have those frozen because those eggs are likely to perform well based on the first test cycle with the donor sperm.
And they may want to use, you know, those embryos later, right? The donor sperm embryos, but that's somebody, especially since, you know, we don't have a ton of data for 40 and beyond in terms of egg freezing, you know, that sort of a nuance can sometimes help me counsel somebody about how, you know, I hate having false hope in the freezer, right? Kind of helps me counsel people about what could we expect from this group of eggs and not just like patting ourselves on the back because we have 15 eggs in the freezer when we don't really know how they might grow and develop over time. I think that there are also situations like regarding reciprocal IVF where people are going through an awful lot to, you know, retrieve eggs from one partner and then fertilize them with donor sperm and, you know, sort of minimizing numbers of transfers in that situation can be helpful. I have seen people do PGT and those circumstances, I don't truly feel strongly about it, you know, because I think if you're 32 and have no infertility, then untested embryos, you know, less is more sometimes, but that's sort of the tailored conversation that I have, especially if there might be a delay from when somebody generates the embryos to when they're planning to use them.
And I also think if somebody is using a gestational carrier, that's, you know, obviously a big financial investment. There's a lot that goes into it.
Coordinating to women's bodies can be, you know, tricky sometimes. And so that's a situation where I often do think it may be a good idea to get that extra testing just to understand more about the embryos. Now, even in the last couple of years, we have now looked a little bit differently at mosaic embryos. We now treat low level mosaic embryos similarly as we do to euploids because the sort of they perform pretty much equivalently. So I think that's important to think about is how that science is changing over time. But I think, you know, there are these situations in which PGT A may be preferred compared to not doing it. It does add cost. It does add time for waiting for the data, of course. And so you can't just have a fresh transfer.
You know, usually you have the retrieval biopsy, the embryos freeze them, send the cells off. You're waiting two to three months. Sometimes the period even starts in the meantime. So I have my patients go on pills so that, you know, once their data comes in, they can move into another cycle if, if our clinic can accommodate that.
But I think, you know, if we think about broad pictures, what did we talk about today?
When could PGT A, you know, beyond sex selection really have, you know, add an edge to somebody's treatment planning? The first is when you really want to do an elective single embryo transfer.
The second is when you're already doing PGT M. The third is when somebody has a history of loss or maybe a medical termination and does not want to ever go through that ever again, and wants to minimize those chances of having to go through that. The fourth is for women, older women, which I would say is, you know, definitely 40 and above, but probably 38 and above 35 to 38 is that gray zone. I don't feel strongly. I think we probably throw away good embryos if we do PGT A testing. And so that's a very nuanced and individual conversation. And then the fit is really for planning for the future, just to try to have as much information on the embryos as possible, but understanding it is an imperfect technology. And there are some benefits, but also some risks.
And so that's where that individualized care really comes in. So I hope this clarified your questions about PGT A. We can absolutely talk more. You know, it's been interesting. Like I said, when I first started and we were doing fish on day three embryos now to be able to test day five, day six embryos, even day seven embryos, you know, to see the different technology platforms change.
I do anticipate that there will be even like, I mean, we, you know, we've sort of even seen like the PGT sort of ranking of embryos is sort of up and coming and maybe like looking at disease risk and not even just like disease itself. And so that's why the conferences are so interesting.
I'm looking forward to going to ASRM in October, because hopefully there'll be even more about this, you know, coming out and what's up and coming. But I think it's a really fascinating field.
And, you know, thinking about how even, you know, 35, 40 years ago, the success rates were in the single digit percentages. And now with the, with a U-plate embryo, you know, you can have a 65, 70% chance of pregnancy with an embryo, sometimes even 80% based on some, you know, labs data.
I think that's absolutely phenomenal. So we continue learning, we continue striving, but at this moment in time in 2025, this is what we have to work with. So like I said, if you have questions, send me a DM. I love talking to science. And you know, I love you.
Talk to you soon. Bye.
