Ep 151: Revolutionizing Reproductive Medicine: The Future of Genetic Testing and Single Euploid Embryo Transfers
Fertility Forward Episode 151:
Imagine a world where parents have the power to protect their future children from inherited genetic disorders before they even take their first breath. In this episode, we dive into the groundbreaking science of single euploid embryo transfers and Preimplantation Genetic Testing (PGT) with returning guest, Dr. Rachel Danis, a reproductive endocrinologist, infertility specialist, and board-certified obstetrician and gynecologist at RMA of New York. Join us as we discuss Dr. Danis’ research on this topic, how this technology is revolutionizing fertility treatments, and what it means for parents hoping to eliminate the risk of passing on genetic diseases. You’ll also learn more about the ASRM 2024 Scientific Congress and Expo, where Dr. Danis will present her findings. Tune in as we uncover the science, the stories, and the ethical debates shaping the next generation of reproductive medicine!
Rena: Hi everyone. We are Rena and Dara and welcome to Fertility Forward. We are part of the wellness team at RMA of New York, a fertility clinic affiliated with Mount Sinai Hospital in New York City. Our Fertility Forward podcast brings together advice from medical professionals, mental health specialists, wellness experts, and patients because knowledge is power and you are your own best advocate.
Dara: Today we have back on our podcast Dr. Danis. She's one of our, RMA’s fabulous reproductive endocrinologists. And today she's actually coming on to discuss something a little bit different. Every year we have our annual big conference, the ASRM conference, which we are recording this a little bit early before the conference, but we can't wait! By the time this comes out, you will all be privy to this fabulous abstract that she was a part of that is titled Single Euploid Embryo Transfers in Patients Utilizing PGT-M is Parity Associated with Outcomes. So Dr. Danis, thank you so much for being here and thrilled that you're part of it this year. There's always such great research and this one sounds really interesting.
Dr. Danis: Yeah! I actually thought of this study idea - we usually start constructing research studies like a year in advance. So probably a year ago it was because I was just reading our regular monthly journal called Fertility and Sterility and I also just anecdotally, I think have had patients who have had previous births before come to us for an embryo transfer after completing an IVF cycle. And they'll ask me if their prior fertility history and obstetrical history helps predict their success for their future embryo transfer. I'm like, you know, logically I would think a person who's gotten pregnant, had a full term delivery, does have better odds for their embryo transfer, for their first time embryo transfer. So, but we don't have that information out there. My guess is because, well, a few reasons. One is maybe just in the last 10 years or so, have more practices like RMA routinely been growing embryos until the blastocyst stage instead of culturing to the cleavage stage. For listeners out there, blastocyst is a day five to sevenfold embryo versus a cleavage stage embryo is a day three embryo. And we actually naturally always have a blastocyst or a blast, as we colloquially say, implant into our uterus. But back in the day when we were not as good in the lab at culturing embryos that long, we would hurry and wanna put a cleavage stage embryo in. And it works. It's not, it doesn't not work. But we have a few benefits of putting a blastocyst embryo inside these days. One of the big ones, and this is another reason for why maybe this hasn't been studied yet, is because we're starting to biopsy blastocysts more and more to see if they're genetically healthy or not since we assume that a genetically healthy embryo has better opportunity for successful implantation, less chance of miscarriage, than an embryo that could be genetically abnormal. Now, we initially, were trying to look at RMA data since RMA of New York, we're a high volume center. We have a strong lab and we fortunately can culture patients of all different ages to the blastocyst stage and often will recommend a biopsy for pre-implantation genetic testing or PGT. Now, there's many reasons for why someone would want to do PGT. So one of the biggest things is to test to see if there's aneuploid and aneuploidy is what we call an embryo that's genetically not healthy or not normal. And we want embryos to be euploid or genetically healthy, having 23 pairs of chromosomes. So fast forward now, we have all this data, we have a high volume center, a lot of patients to work with, and I wanted to know, do patients who have proven fertility and delivery, so it's not just enough to have a pregnancy 'cause you could have had an ectopic pregnancy, a miscarriage. So we wanted to look specifically at people who have had live births before. And then do those people who then need IVF who then move forward with a frozen embryo transfer, do they bode better than someone who is nulliparous meaning they've never had a live birth before. They're basically virginal to a programmed embryo transfer. And I say programmed specifically because a programmed embryo transfer is more common, but people do undergo natural embryo transfer cycles. And I realize maybe now I'm opening up a can of worms to, you know, compare the two. But I think a problem with research is that if you have too many variables and too much diversity, it's hard to look at a single endpoint. So we tried to clean data very concisely where we only wanted to look at people doing a programmed embryo transfer, meaning we're giving them hormones to program their uterine lining to get the uterine lining ready for that embryo transfer. So, and then how do we kind of counter other components of fertility because there could be so many reasons why people come here for fertility treatment - it could be a male factor, it could be an egg quality issue, it could be an ovulation factor, a tubal factor. So we wanted to, again, to clean the data. We specifically focused on people who weren't necessarily infertile for any of those reasons. We looked at people who were coming here because they were a known carrier of a genetic disease and wanted to use IVF and genetic testing to screen out embryos that could carry this specific genetic disease. So in that situation, we're not doing a biopsy of this blastocyst to screen the embryos specifically for, not just do they have 23 pairs of chromosomes, is aneuploidy, which is abnormal, or euploidy, which is normal. We wanna take our biopsy one step further and to see if that embryo had components related to a monogenic disease. So we abbreviate that as PGT-M. So you're doing pre-implantation genetic testing for a monogenic disorder. An example could be, let's say one person is a carrier for BRCA, B-R-C-A, which is an autosomal dominant disease that can cause ovarian cancer, breast cancer, as well as prostate cancer, a conglomerate of cancers actually. So in that situation, couples come here and they're like, hi, we have this family history of breast cancer, or we already know that we're carriers of this mutation and we want to prevent this from being passed on to our children. Now we wanna do IVF and screen the embryo for this disease so we can screen out the affected ones and only have healthy embryos in the future. The other type of diseases are autosomal recessive ones where let's say you have each parent is a carrier for one of the mutations. So it's not autosomal dominant like B-R-C-A or BRCA, but let's say it's like cystic fibrosis where you really need two hits to be sick and be affected with that disease. So if each sperm and egg source has one hit, there's a 25% chance of your embryo having two hits and being affected. So if people come here and they get their genetic screening results back, or they've already had them done, had counseling and now they're coming to do IVF because they wanna do PGT-M for cystic fibrosis, an autosomal recessive disease. So when we look at those people, we assume the egg is fine quality, the sperm is fine quality, there was no infertile factor to identify until we got these genetic results back. And it's important that we highlight this because there's so many other variables that can play into a couple's reasoning for infertility such as endometriosis or adenomyosis. And we're just not smart enough to like identify a marker necessarily, or even a tool to fix the endometriosis. But we do find that those people do have subfertility. So we wanna weed all those people out and really just focus on if your uterus has had a live birth, held a pregnancy, does that bode better for your next implantation cycle? And we looked at also not just programmed embryo transfers, we specifically looked at euploid embryo transfers. So in, we assume every embryo has the same equal opportunity for implantation when isolated in a dish. We equate or we designate a euploid embryo, a genetically healthy embryo, as having a 65% chance of implanting even up to 70% depending on your lab. We're really fortunate at RMA, we have a great lab. So with my study I said, well, let's pull all of our people who did PGT-M for a certain disease and now they're moving forward with their first single euploid embryo transfer. So they're moving forward with their first embryo transfer where they thaw an embryo and they're getting their hormone therapy in preparation for this embryo transfer. And now let's see if the people who have had a previous baby, let's see if their ongoing pregnancy and live birth rates are higher. And it's important that we had to record data that could still affect your chance of success, like BMI. We know that people have a lower BMI or underweight or have a higher BMI or are overweight, their chance of conception is lower than if someone had a healthy average BMI. We need to look at smoking history, for example. So we also wanted to look at pregnancies that maybe didn't result in a live birth but resulted in a miscarriage or a biochemical pregnancy. So we had to monitor our data and make sure we were keeping track of these variables. So what we did was we looked at the past seven years of data and granted we haven't been doing PGT for 20 years yet. So hopefully in the future we'll get more data, more years worth of data, to analyze. But in that seven year time period, when we looked at people who did PGT-M, sorry, I have to go through our numbers here for a second….we had about 40, so 39 people in one group, PGT-, and had a prior live birth. In group two, those were people who did PGT-M and did not have a prior live birth. So we had over four times the number in that group. So 179 people didn't have a prior live birth, which kind of makes sense because they're coming here and maybe they got preconception counseling and now they wanna start their family and screen embryos versus the other group who have had a live birth before. It makes sense that they are smaller in number because you would've thought like they would've screened their embryos before trying to conceive the first time. So 39 and 179 are the number of people in each respective group. The demographics were similar as far as age of the woman, BMI of the person. And then when they looked at the two groups as far as their ongoing pregnancy rate and life birth rate, they actually found no differences between the two. So in other words, we could tell someone, even though you have not had a live birth yet, your chance of success in your given situation being a couple who needs genetic testing before conception, there's not a tubal factor, male factor, egg factor going on. Even though you have not had a live birth. I would say your chance is similar compared to someone who has. So I think that gives patients hope that they can have also a, a high potential and positive outcome even though they have not proven to have a live birth yet. So granted our data, our numbers are small sample size that are small, but this is the first step, and I haven't seen this in the literature yet, which is why I think it got accepted for an oral presentation at ASRM, which stands for the American Society of Reproductive Medicine, just because, yeah, this is all new. PGT is becoming more popular, single embryo transfer fortunately is more popular. It's safer for both the parent and the baby and future babies. So I think there's just more room now to grow. Yes. We need more people, more samples in each group. The people who have had live births to not, I think other aspects to this research and I don't know, am I talking too much, Dara?
Dara: No, this is great. I I'm, I'm so interested. I have so many questions, but I,
Dr. Danis: I'll keep going!
Dara: I would love to hear more. No, I, no, no, I want you to keep going. I think it's great.
Dr. Danis: Okay.
Dara: I know our listeners are gonna be so fascinated with this.
Dr. Danis: Yeah. So I think we actually have another project ongoing where we're looking at mode of delivery and if it's mode of delivery that matters. And in our small sample sizes that we looked at thus far, we find that the people who have a proven vaginal delivery, and this is all people, not just people doing PGT-M. So it's a bit messier of data. Okay. We did see a higher chance of ongoing pregnancy to live birth and people who had a vaginal delivery versus a c-section. Which makes me wonder, people who need a c-section, is it a infertility variable that's making you more at risk of c-section? Is it that maybe you're older, you're more likely to have hypertensive disorders in pregnancy and then get induced and which fails. And then c-section, like there are so many variables that could be in play here for why someone needs a c-section. But then that C-section may be hurting your chance of future success. I'm not saying C-sections hurt your chance of future success at all. I'm just trying to understand why we see an improvement in your second pregnancy outcome in someone who's had a vaginal delivery versus someone who's had a C-section. Why are the live birth rates a little higher for someone with secondary infertility? There could be so many things like endometriosis, adenomyosis, we have to look at why these people had c-sections. So before I, you know, open Pandora's box and make this so complex, I think first step would be increasing our data sets. So finding, having more patients who have done PGT-M because those people don't have an inherent infertile diagnosis yet. But then looking at their modes of delivery when in that group too, in that cohort of 179 plus people - who had a vaginal delivery, who had a C-section? And then let's take this one step further - did the mode of delivery change your chance of live birth? Because if so, well then I wanna know why they have the C-section. Also, were these full-term deliveries? Were these preterm deliveries? There could be uterine issues in addition to their genetic issues for why their not just mode of delivery was different. But also their chance of live birth would be different.
Dara: Or even I would think if they're generally high risk pregnancy, if they find that their high risk pregnancy, if they have gestational diabetes, if they have preeclampsia, if it's a planned C-section, if it's an emergency C-section…
Dr. Danis: Yeah. And we know things like diabetes, pregestational diabetes hurt your fertility. Pregestational obesity can hurt your fertility, which does put you at risk of gestational diabetes and gestational hypertension and needing a C-section. So I mean there's so many variables that you could look at in just people who are doing IVF for a monogenic disease or PGT-M. And then also, I mean, adenomyosis and endometriosis are so tricky because we see that 25 to 50% of these women do have infertility, but there's also the other 50% or so of people who don't have infertility. So we're still just understanding those gynecologic disorders and why they're related to infertility, how they could impact your live birth. So you also, I think moving forward, it would be nice if we had large enough data sets and then coding for people who had these gynecologic conditions and then you could include or exclude them and see if there's a difference just based on their next life or just based on that variable.
Dara: Yeah. I find also interesting to see if it would be, you said it was a fairly similar sample set in terms of weight. I would also find that interesting.
Dr. Danis: Yeah, well I mean I guess you're thinking these people, again, they're not obese. Your weight, I shouldn't say obesity 'cause If you are having a BMI less than 18.5, your natural for, and you compare natural fertility, the time interval from trying to conceive to pregnancy is four times longer than someone with a healthy BMI. And if you're overweight, it's two times longer. So actually being underweight can hurt your natural fertility even more. But granted our groups, they're small. So we had 39 people with the prior delivery, 179 without. But I think that's nice that their demographics were similar, their BMIs are similar. Yeah, it was nice. I would imagine it would still, usually you would think that they're not similar when you have small data sets, small numbers in each cohort. So, I would imagine it would, that part would stay consistent with larger data.
Dara: Yeah, I think this is great. I, I feel like now that you have this, these seven years and since you mentioned that PGT is still somewhat new, it would be interesting to see another 2, 3, 4, 7, you know, seven years down the road and take a, a larger group and see if that still would remain the same. It's, I just find it so fascinating. I mean, I remember when I first started at RMA 14 years ago, PGT was not even something that I had heard about.
Dr. Danis: And now the rage is talking about mosaicism. So
Dara: There's always new things on the horizon, new things to learn. But this is great. I love that you found a topic that of interest or something that you saw with your patients, didn't see it in the research and then, you know, created this. So there's, I think there's a lot to go from here and I do feel like people will be very interested in this and hopefully it's reassuring to…
Dr. Danis: Yeah, even for people who haven't had that live worth, I hope they're reassured that it can still happen. And it's like not unfair just because you haven't, I think unfortunately a lot of times people come to this fertility space and there's a lot of resentment and regret. But I hope that data like this can reassure people that even if you haven't proven to have a live birth, I would say your chance of live birth is similar to someone who has like, there's still hope.
Dara: Definitely. So you said you kind of wanted to, to continue this down the road. Is there anything else that you would wanna change in terms of…
Dr. Danis: I would wanna record delivery outcome, prior delivery outcome, and break that down why someone had a C-section. Also, was it a low transfer C-section? Was it a classical C-section for a preterm delivery? Was it a preterm vaginal delivery? So I'd wanna look more closely at delivery outcomes. Because I would, my sense would be that if you've had a C-section, there's potential for scarring. There's a potential future risk of an isthmocele, which is a fluid pocket from where the C-section scar would be. Maybe the person had a section because they failed an induction and they needed that induction for pregnancy complication like gestational diabetes or hypertension. And so I would think that those variables would not bode as well for your future success because it could hurt your uterine cavity. Also makes me think overall maybe health status isn't optimal, but I'm just theorizing, you know, who knows?
Dara: Yeah. You're interested also in the delivery outcome of the previous, oh, I thought you meant for the future. That's so interesting!
Dr. Danis: I, I wanna know if your past delivery outcome, like if you're comparing people who have never had a live birth to people who have, I then wanna break down that latter cohort into vaginal delivery and c-section. And if ideally, like preterm vaginal delivery term vaginal delivery, preterm c-section, term c-section. More to come now that PGT-M and single embryo transfers are normalizing.
Dara: It's interesting, the blastocyst and the cleavage, again, that's, it's amazing how in, in just a number of years how that has become like the… I remember for me, blastocyst weren't, like, were very hard to reach. So cleavage was typically what was used. So it's, again, I love, it's great that we're doing this research because it really is helping for, for things down the road.
Dr. Danis: Yeah. Hopefully that's why ASRM is such a great conference and it's such a big deal in our field. I mean, that's why we start thinking about, we'll start thinking about 2025 ASRM probably November of 20 of this year. Exactly. 24, like the month after, weeks after, two weeks after we come back from ASRM. Because you also get to like, hear other people's research presentations and then it gets the wheels turning.
Dara: Yeah. It definitely inspires you. And I'm super proud of RMA in terms of what we've presented over the years. I feel like the number keeps growing.
Dr. Danis: Yeah, voluminous. It's really amazing.
Dara: And it, it says a lot about what, you know, the interest and what we're able to do at the clinic. It's, it's pretty remarkable. Well, this is great. I'm thrilled that our listeners got to hear this. Tune in for a lot more to come. And definitely from you, we're gonna be having you back, I'm sure, a number of times again this year.
Dr. Danis: Yeah. I love this. This is really great. I hope listeners, if you're like, this podcast is really wonderful with so many resources and I’ve done fertility treatment myself, I obviously, I practice it. I would much prefer patients using resources like this versus like the doom scrolling. It's so in our field is so anxiety provoking. It's so nice, Dara, that you're putting this together for listeners.
Dara: We actually are interested also in what our listeners are interested in. So if there's any topics that you haven't heard of or what you'd like, you know, us to cover and guests to have on, we're always interested in what you're interested in. But what I'm so impressed is we've had this podcast, what, for four years now, I wanna say almost? And there's still so much new information out there. New stories to be told, different topics to share and I'm constantly learning. And this is a big reason why I love doing this, is because I'm also, you know, I'm in my own little nutrition bubble. So this is a great opportunity to really see what's going on and what's new. Especially for those of you who can't make it to ASRM this year in Denver. At least still get little tastes here and there of, of the highlights from RMA.
Dr. Danis: Which is great. Yeah. Well, thanks for having me.
Dara: Of course. And as you probably know by now, how we like to end our sessions is with words of gratitude. So what are you grateful for?
Dr. Danis: Well I guess a spirit of research. I am grateful to have these resources. I'm grateful to have a fellowship program and a residency program to help with the data collection and the design process. I am grateful for the statisticians and research admin help. I think, you know, in order to grow our field and help people, we need to do research. So I'm grateful for the resources here at RMA.
Dara: I'm with you. I, I really am so amazed at what we've created at RMA and what's been coming out and the interests and, you know, the doctors, the team, this all, you know, the embryologists, the nurses, the whole team, you know, it, it takes a group to really make things come together. And it's so nice to see how everyone comes up with some great ideas and work together. I'm excited to also, this is my first podcast recording in quite some time, so I'm just happy to be back in the game. I miss Rena! Rena is gonna be back on for, you know, the next couple weeks we'll be doing more recordings, but I'm just thrilled to be back at it and thrilled to have you on and really, you know, hearing the title of this, I was like, what does this fully mean? And so I am super excited to see you guys present and also the, to be continued on this study down the road. Yeah. Thank you so much for, for being on again, and we really appreciate you.
Dr. Danis: Thanks. Thanks, Dara. I appreciate you guys.
Dara: Thank you so much for listening today and always remember: practice gratitude, give a little love to someone else and yourself, and remember - you are not alone. Find us on Instagram @fertility_forward. And if you're looking for more support, visit us at www.rmany.com and tune in next week for more Fertility Forward.