Ep 153: ASRM Abstract: The Effect of Trophectoderm Rebiopsy on Serum B-Human Chronic Gonadotropin Levels in Pregnancies Resulting in Live Births with Dr. Erkan Buyuk
Fertility Forward Episode 153:
Joining Rena and Dara on the Fertility Forward podcast today is Dr. Erkan Buyuk, who is a board-certified reproductive endocrinologist, infertility specialist, and OB-GYN practicing at RMA of New York’s Eastside office. He currently serves as the Director of the Reproductive Endocrinology and Infertility (REI) Fellowship Program and as an examiner for the REI Division of the American Board of Obstetrics and Gynecology. Before joining RMA of New York in 2019, Dr. Buyuk was the Director of the Fertility Preservation Program and Reproductive Tissue Bank and the Director of the REI Fellowship Program at Einstein/Montefiore Medical Center. We are very excited to have Dr. Buyuk share a fascinating abstract presented at the most recent American Society for Reproductive Medicine Conference in Denver. Join the conversation to hear from Dr. Buyuk about why their research topic is important, why they chose to do this study, how they completed it, the results, and much more. Be sure not to miss out on this very insightful episode!
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 Ford 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: Dr. Erkan Buyuk is a board reproductive endocrinologist and infertility specialist, and obstetrician and gynecologist who practices at RMA of New York's East Side office. He's currently the Director of the Reproductive Endocrinology and Infertility Fellowship program and examiner for the REI division of the American Board of Obstetrics and Gynecology. Prior to joining RMA of New York in 2019, Dr. Buch served as the Director of Fertility Preservation Program and Reproductive Tissue Bank and the Director of the REI Fellowship program at Einstein Montefiore Medical Center. And today we are thrilled to have Dr. Buyuk sharing with us very interesting abstract that was presented at the most recent American Society for Reproductive Medicine Conference in Denver, which I believe we just wrapped up a couple of days ago. So thanks for being on here and sharing with us this really interesting abstract and the title of it, which I'm sure Dr. Buyuk will explain to everyone what this means is The effect of Trophectoderm Rebiopsy on serum beta, human chorionic gonadotropin levels in pregnancies resulting in live births. So a very heady topic, but something very interesting for I'm sure many patients. So thanks again for being on here today.
Dr. Buyuk: Thank you very much Dara, for having me. You know, it's a great pleasure and honor for me to be here. So, like you said, we are gonna talk about our abstract presented at ASRM three days ago actually as an oral abstract, and it was Monday, early Monday morning. So what is the abstract about? It is about early pregnancy, like you said, human chronic gonadotropin levels, how they change during early pregnancy from embryos that are not tested, so not biopsied, and also embryos that are biopsied once or twice. So why is this important? So in order to make the diagnosis of pregnancy as well as possible, the main tools that we have is HCG, human chorionic gonadotropin levels that are tested in the blood, in the serum. Okay? And the earliest that we can find this in the serum in normal pregnancies is roughly a week after ovulation. In IVF pregnancies after the transfer, we check that level nine days later. Why is it important to check this first? To give the good news, right? So that's, that's the main thing. We wanna find out if our patient is pregnant. If it's pregnant, it's a celebration but what's important is we are gonna ask our patient to continue their medications that are supporting that pregnancy. So that's why it is important. If it is negative, we are gonna tell them to stop the medication so that they don't get, take the medications for, for no reasons, you know, unnecessary. Okay. The second important thing is we see other than just being positive or negative, when we test in the serum, we know what the level is. And that level is very important in predicting the outcome of that pregnancy. The high levels, let's say nine days later we tested it, is around 100 to 200. That's the next level that tell us that most likely it's gonna be a normal pregnancy, it'll continue normally. If the levels are very low, then we are afraid that it is not a normal pregnancy, but being not a normal pregnancy is not enough. It may be an abnormal pregnancy that ends up with what we call a biochemical pregnancy meaning the levels are increasing and then before we see anything inside the uterus, they start to decrease on their own. That's a biochemical pregnancy. It may be an pregnancy of unknown location. That means there's a pregnancy, the levels are increasing, but we cannot see anything in the uterus and the levels are either plateauing or continue to increase, but we can never see a pregnancy. Okay. So this is important and serious. Why? Because we don't know where the pregnancy is. Majority of the time, these are abnormal pregnancies inside the uterus, but there may, they may be also pregnancies in the tube. That's what we are afraid of, an ectopic pregnancy in the tube. Why? Because if we cannot find it, if we don't treat it, it may rupture, cause internal hemorrhage, internal bleeding, and may threaten the life of the woman. Okay? So that's why it is very important to have and to diagnose the pregnancy as early as possible, again, to see if there is pregnancy and then what the levels are. So why did we do our study? We did it because we do biopsies from the embryos when we do IVF, that's called PGT, Preimplantation genetic testing. Often we do this for what we call aneuploidy to check the number of the chromosomes, if that particular embryo has the right number of chromosomes or not humans. As humans species we have 46 chromosomes. Not every human embryo has that. Some of them are missing chromosomes, some of them have extra chromosomes. Even at young ages, roughly one third of less than 35-year-old, roughly one third of the embryos that are created are abnormal genetically. Okay. So that's why we are doing those tests, preimplantation genetic testing, to see if that embryo has the right number of chromosomes. Okay? In order to do that, we have to do a biopsy. So when the embryo is ready to implant to attach to the uterus, that stage is called blastocyst. And at that stage, the embryo has two discernible parts and inner parts that will form the baby and then outer parts that will form the placenta. This is what we call the trophectoderm. Trophectoderm are the cells that will form the placenta itself. Of course we don't wanna take a biopsy from the part that from the baby. So indirectly we have an idea about the chromosome complement of that embryo with the biopsy from the placenta. And then when we do this biopsy, we take roughly four to seven cells. And keep in mind at that stage, the embryo has roughly 50 to 100 cells. Okay? So doing that testing as to our knowledge does not damage the embryo. That's one of the most common questions that the patient says. So, however, when you do that biopsy, you take cells from the part that will form the placenta. And the HCG, the test that will be diagnosed with pregnancy, is coming from the placenta itself. So when we do this test, when we take couple of cells, will this affect the level of HCG that we are gonna test nine days later? That's the main question. And then our main question in this particular abstract is, sometimes when we do the test, roughly 1 to 2% of the time, the results come back as indeterminate. So there's no results. The laboratory could not determine if the chromosome numbers are correct or not. If it is 46 or not 46. So in those cases, sometimes we do a second biopsy from the same embryo. And then as you can think of it, we will take more cells from the same placenta. So then in theory, it should affect the number, the level of the HCG that we will eventually test. It may or it may not affect the hypo- our hypothesis when we started was that patients who got pregnant with embryos biopsied twice may have lower HCG levels when they are first tested for pregnancy test and when they are retested during that pregnancy. So that was our hypothesis. How did we do our study? We looked at the HCG levels from patients who got pregnant and have baby eventually, because we wanna know what is the lowest levels, you know, if the levels are low, what is the lowest level that can end up in a pregnancy? And are they really low in patients who had two biopsies who had more tissue taken out from their blood center? So we looked at the HCG levels from patients who ended up with a baby, but who never had biopsy. So this is unbiopsied embryos. Okay. But we know that these embryos are normal because they have a healthy live births. The second group was the patients who had only one biopsy. And the last one is patients who had two biopsies performed because in the first one is, was indeterminate. Okay? So in the literature before we did the study, there were reports on one biopsy compared to no biopsy, the HCG levels from those patients. And it was mixed. There were studies that said there's no difference in HCG levels, but there was one study that said when you do one biopsy, HCG levels may be lower. So for two biopsies, that was no study done until now. So when we looked at, we collected our groups, our study group again is the two biopsy group. We had four patients that ended up with a live birth after two biopsies of the, of their embryos. And then we had control groups, no biopsy, and one biopsy at a 3:2:1 ratio. So we had 132 groups in each and we did propensity match scoring. That's a way to match the study group to the control group in order the main aim is to diminish the biases. So to make the groups as equal as possible to each other. So, and as a result, at the end of the study, we found out that the HCG levels were at the beginning of the pregnancy were very similar between no biopsy and single biopsy groups. But they were significantly lower in the two biopsy groups in embryos that were retested. Okay. However, although they were lower, these groups still ended up with a baby. Again, all patients in the world controlled and study groups ended up with a live birth. Why is it important to know that? It is important because when we see a low level, we then, like I said at the beginning, it may be associated with an abnormal pregnancy. It may be a biochemical pregnancy. It may be a pregnancy of unknown location, an ectopic pregnancy or a miscarriage, abnormal pregnancy inside the uterus. However, we should also know and counsel our patients that if there are two biopsies, the level may be low at the beginning of the pregnancy, but it may still end up with the live birth. This is the nature of the embryos that are biopsied twice. So the patients may be reassured that yes, we are starting with a low level, but this may still end up with a healthy light baby live birth.
Dara: That's reassuring. I mean that's what I was hoping to see. I mean, I appreciate you giving us the whole story. And of course in my mind I was thinking, oh no, this is not gonna be good. But that's actually reassuring. I think a lot of times we look at numbers and to see low numbers doesn't necessarily mean that that's not gonna lead to success. And, and I wanted to ask you, so you said that nine days later you check your HEG. Typically it's between, we wanna see it between 102 hundred. When you say low, what approximately would that that number be? I'm sure there's a range.
Dr. Buyuk: So not necessarily when it is less than 50, we are not very happy because you know that pregnancy, you know, may end up, like I said, with an abnormal pregnancy. However, there is really no range because the lowest HCG level that ended up with the libs in our center was 3.7.
Dara: That low!?
Dr. Buyuk: That's mind boggling. Yes. From that low, it ended up with a live birth. How is that possible? It is possible that the implantation, although we think that once we do the transfer within the next 24, 48 hours, the implantation should happen but maybe the embryo stayed a little bit longer. So implantation happened a little bit longer and the level was that low before at the time of test. But yes, the lower the level, the less likely that is gonna end up with a live birth. If it is less than 50, generally in our center we are not happy with the results, although it may still end up with the live birth. So we have to look at everything in context. If that embryo had two biopsies, we have a low level, that's fine. You know, it may still end up with a healthy live births.
Dara: And also I, I think it's important to note prior to working at RMA and when I was going through my own fertility struggles and, and coming to RMA as a patient for those patients who have not started a treatment, you know, with HCG, when you get your HCG level, it's a moment in time also the importance of getting tested a number of days after to see how the numbers rise. So I think a lot of times we focus on the initial number and it's also reassuring to hear that there are situations where implantation happens a little bit later. So there may be a lag time in terms of the numbers increasing the way they need to.
Dr. Buyuk: That's correct. That's absolutely correct. So that's why, you know, every time we have a positive pregnancy test, we retest it in two days. Why in two days? Because on average we should expect roughly 100% increase in two days. However, there is a threshold for that. For example, minimum increase that is needed is around roughly 50%. So as long as there is,
Dara: That's good to know.
Dr. Buyuk: 50% increase we are comfortable, we can hope that it's gonna be a, it's gonna end up with a normal pregnancy and live birth. Can it increase more than that? Yes. Sometimes it increased 200% so that these are all normal. One more thing that I wanna mention because we are talking about lowlevels always and it's concerning when it is high level, very high level. Then we talk, think about twin pregnancies.
Dara: Yes.
Dr. Buyuk: So that's twin pregnancies are also concerning. Honestly, we are not very happy when we see that one embryo that we put in is split and ended up with twins. Why? Because there are more complications in those pregnancies.
Dara: Higher risk.
Dr. Buyuk: However, very high level. Let's say if I see on day nine, a level of 400, 500, I suspect that it's gonna be a multiple pregnancy. Of course it's not always, but more likely
Dara: That's good for, for our listeners to hear. And I think it's not only a reassuring when you see those numbers, the initial numbers of an HGG, but I think also when you're speaking to patients about having to potentially re-biopsy at that moment in time, that's a great opportunity also to say, of course with each potential biopsy there could be risk. But at least from what we've seen from this study, that it is not something to be as nervous about as I'm sure the reason why you initially did this study is you really wanted to see is this something that we should be concerned about? Maybe is there a different way that we can biopsy? Are we taking maybe too many of the cells? But that's interesting to note. And I think, again, I I wanna reiterate, you said there's approximately a hundred or so cells and you take with each biopsy anywhere from five to eight or five to seven?
Dr. Buyuk: Correct. It is around, you know, five to seven, four to seven cells. Embryologists really cannot count each cell because they are not taken one by one. But it is a rough estimate of how many cells are taken. And also in our lab, the embryologist, if they're doing the re-biopsy, generally they tend to take a little bit lower number of cells. So if they took five to seven cells in the first one, maybe it's gonna be three to five in the second.
Dara: Okay. So that's good to know too. I think, you know, knowledge is power and especially when people are going through fertility treatments and they feel like there's so many things out of their control, gaining this knowledge can really give people a little more confidence and reassurance in a time where there's a lot of potential unknowns.
Dr. Buyuk: Absolutely.
Dara: And so from this study, is there anything else you would like to see being done in this realm of research down the road?
Dr. Buyuk: So the first thing that we are gonna look at, we have not looked at this yet, like we talked about it, the rate of increase. Is it gonna be, what we are seeing now is that the rate of increase in double biopsied embryos in pregnancies that come from double biopsied, the embryos seems to be a little bit higher. It seems like the embryo is trying to catch up, the pregnancy is trying to catch up. So that's what we are going, we are looking at now to see if the rate of increase is higher in those double biopsied embryos.
Dara: Great. There's a lot to look forward to every year when it comes time to this conference, the ASRM conference, I love learning and there's, there's so many new things coming out, new possibilities, new ideas, new discoveries. And this is just one of them. So I'm really excited for our listeners in the coming weeks and months really to hear some of the fabulous research that comes out of RMA from our fabulous REIs like yourself. And really, you explained it in such a clear and interesting way that really can be more understood for the lay person. There's a lot of interesting words and interesting concepts, but it all, it's all for the good. It's so nice that we're a really a research based clinic and I appreciate the work that you do. So thank you very much.
Dr. Buyuk: Thank you very much.
Dara: And how, of course! And how we end our podcast is always with words of gratitude. So Dr. Buyuk, what are you grateful for at this very moment?
Dr. Buyuk: So I'm grateful to my patients who are providing, you know, all this data to us that we can use and make life better for our patients that are actually gonna come up.
Dara: That's beautiful.
Dr. Buyuk: You know, of course I'm grateful for my family. Why am I doing this job? I am doing it because my family is the most important thing in my life and I want my patients to have the same feelings, to be able to live the same experience that I'm living.
Dara: That's beautiful. Well, I guess I'm gonna piggyback on you, Dr. Buyuk, and, and say that I am, I'm also really grateful for the patients that I come across every day. It's been 14 years at the clinic and you know, it all started from my own personal experience. I had such a phenomenal time in my fertility journey with Dr. Sandler, giving a shout out to Dr. Sandler, who was my doctor. And Dr. Flisser at the time was there as well. Helping out and having such a great staff and community a made me want to be part of the community. And also I have two RMA IVF babies. And so my hope is to help every patient that I come across to give them some hope and support in that. And it's so nice to see that we really, we have a such a fabulous team at RMA. You're definitely such an asset to the team, so thank you so much.
Dr. Buyuk: Thank you very much, Dara.
Dara: And hopefully we get to have you back on for more research down the road.
Dr. Buyuk: I'm looking forward to it. Thank you.
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 [email protected] and tune in next week for more Fertility Forward.