Fertility Forward
Fertility Forward
Ep 179: Mosaic Turner Syndrome and IVF Outcomes with Dr. Emily Clarke
Discoveries made during fertility testing can sometimes reveal more than patients expect. In this episode of Fertility Forward, Dr. Emily Clarke, a third-year fellow in Reproductive Endocrinology and Infertility at RMA of New York, shares new research on Mosaic Turner syndrome and what it can mean for patients undergoing IVF. She explains how many people discover this chromosomal condition incidentally, why it can vary so widely in presentation, and how understanding it helps improve counseling and care. We explore the emotional impact of unexpected genetic results, the reassurance that information from these types of studies can bring, and how compassionate counseling empowers patients to move forward. Tune in to learn how clearer data and compassionate communication can empower patients on their path to parenthood.
Hi everyone, we are Rena and Dara, and welcome to Fertility Ford. 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. I am so excited to welcome to Fertility for today, Dr. Emily Clark, who is a third-year fellow REI at RMA of New York. And she is here today to share her research with us in a study titled Mosaic Turner Syndrome: Pre-implantation genetic testing for annuploidy outcomes. And she is about to present that paper at the upcoming ASRM conference. So we are so excited to learn about your study and what you found.
SPEAKER_01:Great.
SPEAKER_02:Thank you so much for having me today, Rena. Thank you so much for coming on. So tell us about your study and what you found. Sure.
SPEAKER_01:So kind of to start, we're noticing that a few of our patients were coming, their karyotype reports were coming back showing mosaic Turner syndrome. And we went to the literature to kind of understand more what this means for their general health, their fertility, their IBF outcome specifically. And we realized that there is very, very little on this topic and very limited mostly to just small case series.
unknown:Okay.
SPEAKER_02:Well, sorry to interrupt, but to just to clarify, one, so were these patients coming in, they don't know they don't have Turner syndrome themselves.
SPEAKER_01:Yeah. So most of these patients were infertility patients who were having various workups for causes of infertility, whether it was recurrent pregnancy loss or if they had multiple failed cycles, and they would have a karyotype scent. So for the most part, they it's an incidental finding. But the what kind of piqued our interest was the ones that kind of were more incidentally found.
SPEAKER_02:Okay. And then just to our listeners so they can understand context. What is Mosaic Turner syndrome?
SPEAKER_01:So Turner syndrome, to take a step back, this is a sex chromosome disorder that's characterized by the complete loss of one of our two X chromosomes. So having one X chromosome leads to various different anomalies, including short stature, cardiac defects, renal defects, and then specific to us as REIs, gonatal dysgenesis or failure to form functioning ovaries. So most of these patients have premature ovarian insufficiency and infertility. So mosaic Turner syndrome, this is when some of the cells in your body have the normal 46XX chromosomes, but some other cells have 45x. And it's a very kind of there's a large variety of different phenotypes that you can have, and it really depends on the percentage of cells in your body that are mosaic. So the percentage of 45x versus 46xx, and then where the cells are located, what types of tissues are affected. So you could have very little symptoms or very little Turner phenotype, or you could have more symptoms and more of the classic Turner phenotype.
SPEAKER_02:Okay, thank you for clarifying. So okay, so with your study, what did you find?
SPEAKER_01:So with our study, we basically, you know, we figured with our huge RMA network and US fertility network as well, we we would be able to find enough patients to make a kind of stronger, newer case report or case series looking at these patients. And specifically, we were interested in looking at PGTA outcomes. Because Mosaic Turner syndrome is a chromosomal disorder. We thought perhaps do these patients have higher incidence of chromosom of embryonic aneuploides? And there was really no information about PGTA outcomes in these patients. Okay. So with that finding, what do you do with that? So our hope was really to gain more understanding of these patients and how their mosaic Turner status might affect both fertility and IVF outcomes. And we can use this information to better counsel these patients who are diagnosed with mosaic Turner syndrome. And you know, previously we might not have really been able to counsel them on expected PGTA outcomes, IVF outcomes. And now with this study, we have a little bit more information that can describe how they might do in an IVF cycle.
SPEAKER_02:Got it. Yeah, so it's it says here your impact statement that patients with greater than 10% of mosaicism for Turner syndrome exhibit higher rates of embryonic anepoidy compared to those a normal karyotype of less than 10% 45x mosaicism, suggesting that PGTA outcomes are influenced by the degree of chromosomal mosaicism.
SPEAKER_01:Yes. So what we did is after we identified these patients who had mosaic Turner syndrome, we divided them into two groups essentially. We looked at patients who had more than 10% mosaicism versus those with 10% or less mosaicism. We figured our hypothesis was that the more mosaic cells we have, the more likely there is to be higher rates of embryonic aneuploidies. So those were our two study groups, and then we matched them to patients with normal karyotypes as our kind of control patients. And that's exactly right. We found that the patients who had higher rates of mosaicism, so more than 10%, did have significantly higher rates of chromosome of embryonic aneuploidy in their in their IBF outcomes compared to those who had lower rates of mosaicism and of course comp compared to the normal karyotype controls.
SPEAKER_02:So that sounds like it's super helpful to help with patient expectation.
SPEAKER_01:I think so. I mean I think one strength of the study is that right now there's really no data on this. So when we have patients with Mosaic Turner syndrome, our counseling is more based on the speculation and our understanding of chromosomal, you know, abnormalities. And you know, we know that these patients in general have higher rates of miscarriage. So the thought is that it's due to higher rates of aneuploidy. But now we actually have data that suggests that the more, the higher percentage of mosaic cells that you have, it's more likely that you'll have slightly higher rates of aneuploidy.
SPEAKER_02:Got it. So a patient could hear that and then understand, I think, perhaps of their right likelihood to get a normal genetically tested embryo versus not, and then sort of take from there itself.
SPEAKER_01:Right. And it's it's not like these patients have extremely high rates of aneuploidy. There were still, there was still a high proportion of euploid embryos that were produced. So it's not like a detrimental diagnosis by any means whatsoever. It is just helpful for counseling purposes. And I also think it's helpful for those patients who have 10% or less mosaicism, which is a much, much more common karyotype report that we do receive when we send out these tests for our patients, that these patients don't really appear to have any worse outcomes than if your karyotype was normal. So I think it's reassuring for those who come back with 3% mosaicism, 5% mosaicism, where we can say, hey, look, based on the studies that exist, we we don't think this is going to have any negative impact on your IVF cycle on your PGT outcome. So I do think that's a reassuring piece that comes out of our study. And then for the ones that do have higher grade mosaicism, I I think it's helpful to be able to set expectations. But again, it's not like we're seeing, you know, major major changes in annual employee. It's just a little bit higher.
SPEAKER_02:Got it. Okay, that sounds really encouraging.
SPEAKER_01:Yeah, I think it is encouraging, and I think that this is you know, it's still a very small study, but I think it's a step in the right direction to help patients who are diagnosed with this to better understand their fertility potential and their IVF potential as well.
SPEAKER_02:Mm-hmm. Yeah. I mean, we always say on this podcast knowledge is power. So this sounds like a really tangible piece of information you can give patients to help them understand um, you know, exactly more about themselves.
SPEAKER_01:Absolutely.
SPEAKER_02:So, what about any future implications for this study?
SPEAKER_01:So I I think our you know, next steps would really be to continue to try to pull together a larger database of these patients because right now we only have uh 21 patients in this study. It's very small, with there was about 40 or 50 IBF cycles in total. So next steps would really be to you know encourage other large fertility networks that have large numbers of patients, just like ourselves, to start to report these findings for a more comprehensive understanding. Yeah, that would be my my next step.
SPEAKER_02:Yeah, okay. Well, I know you're presenting this at the conference soon. Are you looking forward to that?
SPEAKER_01:I am very excited. I think it's a very kind of niche topic that I think more fertility doctors might say, like, hey, you know what? I actually had a patient with this too, and I you know never really thought about this exact question. So I think it does come up time to time, and it's nice to kind of see all these patients brought together into this project.
SPEAKER_02:Yeah, absolutely. Anything else that you think would be important to share with our listeners about this?
SPEAKER_01:I think one other thing to um take note of is that a lot of I mentioned in the beginning, but a lot of these patients don't have anything close to your classic Turner phenotype. So most of them don't have cardiac defects or renal defects. Most don't even know they have a chromosomal abnormality until they get this report, this test sent. So, and this, you know, this is what an incidental finding is something we never would have known about unless we sent the test. So I think that we're probably under-reporting the amount of mosaic Turner syndrome in the general population, and this could be, you know, more prevalent than we than we think. And, you know, if we're if we sent a karyotype on every single patient, maybe we would pick that up a little bit more commonly. But I think the specific patient population where we are sending a karyotype tends to be those who might have recurrent pregnancy loss or you know, multiple IVF cycles where there was no fertilization or poor outcome. So it's a little bit of a specific population that we're studying here where most of these patients are infertile and have, you know, a reason to be here.
SPEAKER_02:Well, I think you touched upon something that's really important that I I deal with in a lot of my patients, which is that trying to conceive and going through sort of all the testing that that comes up right when you start working with a reproductive endocrinologist, it there's a lot of incidental findings, right? And so I think that's something really important to touch upon because I think it's those incidental findings, right? And you're saying a lot of these patients they don't present with any signs or symptoms of Turner syndrome. And so what is very difficult for patients emotionally is like, wait a second, you know, I've been existing my whole life and I had no idea that I had Turner syndrome or was a carrier for that, you know, or that I had endometriosis or PCOS or fibroids or any of the things that might come up when you start this process. And I think that can be really tough for people to grapple with because it makes them feel very uncomfortable in their bodies, like, wait a second, how did I live 30, 35, 40 years without knowing that that I have that this was a part of me? And so I think that when you have your research, right, and someone finds out, say they're a carrier, they have Turner syndrome, and then you can present this data, it can help make it a more manageable pill to swallow because you're, you know, going back to the idea that knowledge is power. You're giving somebody information, you're empowering them, right? Okay, I'm giving you this diagnosis or I'm giving you this information about yourself, which I understand feels really scary and daunting and is making you really uncomfortable. But here's even more information about it, right? Here's even more data, here's even more facts to help you process that.
SPEAKER_01:Absolutely. Hit the nail on the head.
SPEAKER_02:You know, and so I think that's what a real gift is for patients. You know, again, that this process, it it brings up all these things which you might not even know that you had if you hadn't gone down this road. And that can be really jarring for people. And so the more you can tell them about it, the better it is.
SPEAKER_01:Absolutely.
SPEAKER_02:Well, thank you so much for your research and this study. And we wish you all the best at the conference.
SPEAKER_01:Thank you so much. I'm so happy that you're interested in hearing about this.
SPEAKER_02:Yeah. And so the way we like to end our podcast is by saying something that we are grateful for.
SPEAKER_01:In general.
SPEAKER_02:I know to put you on the spot. Yeah, it could be anything.
SPEAKER_01:Well, I'm very grateful for my amazing training at RMA and all my mentors here, my family for all the support through these years of medical training.
SPEAKER_02:That's beautiful. I love that. Well, I will say that I'm grateful for you. And, you know, we say that so much on here, but really the work that you do, you know, makes my job easier in terms of the mental health counseling, right? Because now I can help patients even more, you know, process when they have these sort of incidental findings and give them more information and better empower them. So thank you so much for the work that you do. Thank you, Magic. Thank you so much.
SPEAKER_00: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 at fertility underscore forward. And if you're looking for more support, visit us at www.rmany.com and tune in next week for more fertility forward.