Ep 125: Severe Male Factor Infertility and Embryonic Mosaicism with Dr. Tamar Alkon
Fertility Forward Episode 125:
Today, we are joined by Dr. Tamar Alkon from RMA's Mexico City office to discuss her groundbreaking research on embryonic mosaicism and its correlation with spermatozoa recovery in severe male factor infertility patients. Dr. Alkon begins by explaining embryonic mosaicism and shares insights into her research process and findings. The research will be presented at the ASRM (American Society for Reproductive Medicine) conference in October, which signifies a tremendous step in fertility knowledge and understanding! Tune in to hear Dr. Alkon’s conclusions firsthand.
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.
We're so excited to welcome to Fertility Forward today, Dr. Tamar Alkon who is a physician and coming to us all the way from the RMA of New York office in Mexico City. We are so excited to have her on today to talk about her paper that she wrote for ASRM and the long title is Method of Spermatozoa Recovery Does Not Correlate with Embryonic Mosaicism in Patients with Severe Male Factor Infertility. So that was a mouthful and let's just dive right in because that right there, that title, I mean that's so much to unpack. So we're super excited to have you on and to tell us what you found in this really fascinating study.
Dr. Alkon: Well, thank you so much for having me. Well essentially we started with this idea because embryonic mosaicism, it's something that is not really well understood still and there are many questions as to how, how or to what it's related. Also many articles and published work has related embryonic mosaicism to severe male factor infertility. So to our knowledge we didn't know or we couldn't find any, any literature that could relate the source of the sperm with our relation with embryonic mosaicism. So we decided to look into couples who had severe male factor infertility and to look into their embryo outcomes. So we divided them into two groups. One group in which the partner ejaculated and in the other group they underwent a testicular biopsy. And then we decided to compare in particular mosaicism rates to see if there was a difference or not because it's established that the sperm that it sourced from the testis instead of ejaculating, it should be less prone to DNH damage. So based on that, we thought that maybe there would be a difference in the rates of mosaicism. But essentially after comparing both groups, we found that it was practically the same, the rate of the mosaic embryos.
Dara: So what exactly is embryo mosaicism for those people who aren't really familiar with that term?
Dr. Alkon: Okay, so when you do IVF, there's the option to biopsy the embryos. And when you biopsy the embryos, you can have what is known an euploid embryo, which is a chromosomally normal embryo. Then you can have an aneuploid embryo, which is an abnormal embryo, which it doesn't have the 46 chromosomes. And then there's a new term that it's called embryonic mosaicism, which is defined of the, as the presence of two more chromosomal different cell lines within an embryo. So you have normal cells and then you have abnormal cells. And then is the question of whether the entire embryo would be abnormal or the embryo is gonna be normal? So based on the mosaic range, some embryos have been transferred and even have a successful life birth. So basically those embryos are in question whether you can use them or not.
Dara: So somewhere in between perhaps. So not necessarily not usable and not necessarily in the perfect, you know, development, but somewhere potentially in between that you know, potentially could have some use.
Dr. Alkon: So yeah, exactly. So when you biopsy an embryo, you only take a couple of cells, I mean like 5, 6, 7 cells and then the rest of the embryo stays frozen. So what you're analyzing are only those cells in particular. So you don't know if they're representative of the entire embryo or just those cells in particular. So when you have a euploid embryo, it's they analyze those cells and all of the cells come up normally. So then give a call that the embryo is gonna be normal. If all of the cells are abnormal, then they give a call that the embryo is abnormal. And the mosaic embryos, they have a few that are normal and then a few that maybe are abnormal. So they're what known high mosaic, which most of the cells are abnormal, but there are a few normal and then low mosaic that it's the other way around. So with those embryos it comes in question, what do you do? And specifically with patients that only have a mosaic embryo for transfer. So that is why mosaicism is starting to be more common every time. And also more clinics are feeling more comfortable transferring mosaic embryos, obviously with the appropriate counseling to the patient.
Rena: Sure. And I think, and so that's super new because you know, I've been in this field for quite a long time now and you know, there was in the past mosaics were so controversial and many clinics wouldn't transfer them. You know, they were deemed unusable and then, you know, as science progressed, it's now, it's different. And so I think that's super important to talk about 'cause I think so many people, they hear the word mosaic and they think that's like a big, you know, red flag. And just to understand it is, sounds like the research is still developing, but there's much more understanding now about mosaics.
Dr. Alkon: Yeah, for sure. I mean obviously if you have a euploid embryo and then a mosaic, you're gonna go first for the euploid. But there are cases in which the couple undergo several IVF cycles and they only have mosaic embryos and, and comes in question, what do you do with them? It's, and also depends on what the report is saying. Obviously if there's something, compare a mosaic embryo that has cells like for example, trisomy 21 or something that it's compatible with life and we know that those embryos can implant and even develop a, a live birth, then it comes in question whether you transfer them or not. But when the embryo is mosaic for something that it's probably not gonna implant, if it it is actually aneuploid, then maybe you can transfer them obviously with the the right counseling to the patient.
Dara: So there's options, which is great. I think that's, I feel like a step in a more hopeful direction.
Dr. Alkon: Yeah, definitely. So I mean at least you're giving a possibility to a patient that maybe it wouldn't have any embryos for transfer.
Rena: Yeah, that's huge. I think that's amazing. And so what are the main, would you say takeaways from your study that you know, patients should look to in terms of hope or you know, new information?
Dr. Alkon: So mosaicism actually it's something a little bit different or something that’s different from what we know 'cause we know that embryonic aneuploidy, it's related basically to maternal age. So as the mother gets older, the probability of having a healthy embryo is gonna decrease. But with mosaic embryos, we've seen that even they're more likely in younger patients. And as I mentioned previously, previous studies have related them to males than have severe male factor infertility. So I mean, if you compare them to the rest of the population, probably they're gonna have more mosaic embryos, but they don't necessarily have to undergo a testicular biopsy to have a euploid embryo have less mosaic embryos. No. At the end of the day, if they ejaculate, if they're able to ejaculate, or if they undergo a testicular biopsy, their mosaicism rates are gonna be the same. So essentially it's something that as a physician you can recommend to the patient that they can feel comfortable if they ejaculate, they don't have to undergo a testicular biopsy in order to improve their outcomes if they're able to ejaculate and produce usable sperm.
Dara: I'm assuming that the testicular biopsy is a more invasive procedure and so the fact that there's options that it doesn't…In the past, was this something that was more recommended prior to…
Dr. Alkon: Well, not necessarily related to mosaicism, but there are many studies that relate embryonic aneuploidy in general to severe male factor infertility. So it's thought that the testicular sperm has less DNH damage, so essentially it could produce better embryos. So many physicians or practices recommend for males that have severe male factor infertility a testicular biopsy in order to improve their embryonic quality. But we've demonstrated not only with this paper, but with previous studies by Dr. Hernandez, that it's not necessarily true that embryonic and euploidy, it's the same even if you ejaculate or you do a testicular biopsy. And now here we are doing the same with embryonic mosaicism, which at the end of the day, the outcome should be the same. And the patient does not necessarily have to go a more invasive procedure like you mentioned previously. Their outcome should be the same. Obviously the patient is able to ejaculate because we have a lot of patients with severe male factor infertility who don't have sperm or are not, we're not able to find sperm within the ejaculate and they do have to undergo testicular biopsy. But these are cases in which the patient could ejaculate and then you can just go ahead and recommend that instead of a more invasive procedure, their, their outcome should be the same.
Rena: Wow. This is incredible. And so this we'll say, we'll tell everyone we're recording this now August 1st actually, but this is not going to be released, I guess, or made public until it's presented at the ASRM conference in October. Correct?
Dr. Alkon: Yeah, correct.
Dara: Super exciting.
Rena: Yeah. What about anything else you know, you kind of have in the pipeline or, or would this study lead to any, you know, future studies or implications for practice? Kind of like where you going or…
Dara: Or follow up even?
Dr. Alkon: Yeah. Well, definitely. We are also presenting a poster related to this, in which we selected couples with male factor infertility who had DNA fragmentation, sperm DNA fragmentation, more elevated than the average people. And we compare them also to see if males that have elevated sperm DNA would be more prone to have also mosaic embryos compared to the ones who have a normal a DNA fragmentation. And we also found no difference. So essentially what both of these works are showing is that although a lot of papers have related embryonic mosaicism to severe male factor infertility, we didn't find a specific relation to DNA damage or the source of the sperm in particular. So if there is a relationship, it's not related to the DNA damage that it thought that it could be a, something that could cause the…[inaudible]
Dara: It's amazing. A lot of advancement. I feel like both Rena and I, you know, from the many years that we've been in this field, it's nice to see that it's ongoing and that, you know, we're really at the forefront of, you know, finding and discovering things that can, you know, provide better treatment and care for for patients.
Dr. Alkon: Yeah, definitely. And I think every time we're gonna see more and more advances and less invasive procedures.
Rena: Yeah. Which is amazing for the patients, obviously. Right? You know, it's debilitating to go under anesthesia or surgery or, you know, it's just such a life disruptor. So the more non-invasive things we can do, the better. So this is so hopeful and we're so lucky to work at, you know, an institution that supports this and with wonderful smart physicians like yourself. So thank you so much for your hard work and sharing with us.
Dr. Alkon: Oh, thank you. It's actually an effort team, all of the research team that is involved and obviously being part of an institution like RMA, that gives us the opportunity to have a lot of patients and a lot of data.
Dara: A bright woman and humble too. So hopefully by this time the research will be available online for people to see, especially after the conference. And I'm excited to see what's in the future in terms of research down in Mexico and, and back here too.
Dr. Alkon: Thank you. Thank you. Me too.
Rena: Well thank you so much for taking the time to come on and share with us. The way we like to end our episodes is by sharing a gratitude or something that we're grateful for. So not to put you on the spot, but nothing that you are grateful for today.
Dr. Alkon: I'm really grateful for being able to work in a place like RMA actually. I really appreciate the institution and all of the physicians and the team and being able to practice what, what I love to do. It's, it's something amazing.
Rena: Oh, love that. How
Dara: How nice. Rena, what about you? I'm sure you have gratitude also for, for your job.
Rena: Of course. Yeah, I can totally hop on that train and you know, just gratitude working with, I mean, smart women, I just think it's amazing. You know, the three of us have such different backgrounds, but, you know, to work with smart men too, but you know, particularly smart women in science, I think is really, really awesome and really cool. And, you know, just reflecting on the ability that, you know, that we have to work and learn and yeah, I mean, I think the way this field moves is so fast, so it's amazing to get to be a, a part of it. So I'm super grateful for that. Dara, what about you?
Dara: Yeah, I'll piggyback on that. I often reflect on work and what I do and just, I learn so much from, you know, my area of nutrition and wellness. But I love working with this podcast, learning about other people in this field, hearing stories from people and their experiences with their fertility story and their fertility journey. Working with doctors and researchers, especially researchers 'cause that's not something that, you know, I do myself. But I'm proud of, of seeing that we're at the forefront of such change in evolution in this field. And I can't wait to see what's ahead. I know there's a lot of exciting things, I'm sure down the road, but great to hear this wonderful research study that I know people will be interested in. So thank you so much again for being on and can't wait to see what's down the road.
Dr. Alkon: Thank you so much.
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.