Ep 152: Understanding Egg Maturation with Dr. Keri Bergin
Fertility Forward Episode 152:
Knowledge is power and understanding the nuances of egg maturation is incredibly helpful in any fertility journey. Based on her abstract on Assessing the Reproductive Potential of Late Mature Oocytes and Egg-Freezing Cycles, Reproductive Endocrinologist Dr. Keri Bergin shares her knowledge on this episode. We begin with background information on the study: when you do egg freezing, you want to stimulate the ovaries to grow as many eggs as possible; at the time of retrieval, the embryologist will determine which are mature and which are immature. At her lab at RMA of New York, Dr. Bergin keeps the immature eggs in culture in the hope that they will mature. If they do, she will freeze them. This study looks at the potential of mature and late-to-mature eggs, and how they fare down the line, and this conversation covers what that means for your fertility journey. Join us as we unpack this important aspect of the egg-freezing cycle.
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.
Rena: I am so excited to welcome to Fertility Forward today, Dr. Keri Bergin, who is going to talk to us about her abstract that she is presenting at ASRM next week titled, Assessing the Reproductive Potential of Late Mature Oocytes in Egg Freezing Cycles. Thank you so much for coming on board. Dr. Bergin is a reproductive endocrinologist at RMA and we are so, so happy to have her on. Thank you so much for coming on and sharing your knowledge about this study.
Dr. Bergin: Thank you for having me. I'm excited to get to talk about some of our outcomes and results.
Rena: So tell us, so tell us, dive right in, what were you studying?
Dr. Bergin: Yeah, sure. Let me give a little bit of background information on it. So we looked specifically at egg freezing cycles and when you do egg freezing, you know you wanna stimulate the ovaries to grow as many eggs as possible. And when you take them out at the time of retrieval and the embryologist looks at them under the microscope, some of them are already mature and ready to be frozen and some of them may still be immature, so they might not have gone through that final maturation process. And in our lab we keep those immature oocytes in culture in the lab for an additional four to six hours to see if they can eventually get to that mature egg stage. And if they do, we freeze them. So the ones that are ready right after retrieval, we just call M2s and the ones that are ready four to six hours later we call late mature M2s. So they matured later. And what we wanted to look at was how the outcomes of these M2s versus late mature M2s differed when patients came back to use them down the line.
Rena: Does that have anything to do with follicle size? So if you have a follicle, let's say it's above 16, right versus below, would, could you look at that and say okay, one of those would be late mature and one would be M2?
Dr. Bergin: So it’s definitely related so that's why we do try and get the follicles to grow and sink the best we can and to get them to one of those large sizes like you mentioned, because those have the best chance of having a mature egg in them. But at the time of retrieval we're going to suction out all of the follicles so even if they're smaller, we'll go for them because when we take them out and look under the microscope, even if they came they were a smaller follicle, they may already have a mature egg in it. It may respond to that final trigger and be mature when we remove it. But it could be likely that those smaller follicles might have an immature egg in them and those are the, those immature eggs are the ones that we culture for longer.
Rena: Okay. Yeah, I'm just wondering because patients so often say, oh you know I have four 18s on one side and three 16s on one and then the rest are really small. So would your study then sort of help a patient that maybe is, oh I'm feeling super disappointed, I only have one 18 and then the rest are really small to say, well actually this new study could help eggs mature outside of your body so let's just be stoked that you have follicles at all?
Dr. Bergin: Yeah, it definitely means we can get either mature eggs directly out of the small follicles or even if yeah we got an immature egg out of the smaller follicle, it still has potential because yeah, like you said, we can still culture it in the lab and see if it gets to that mature status.
Rena: Okay.
Dr. Bergin: Now we didn't really know well before this study is the ones that do come out immature and mature in the lab - how do those do compared to the ones that are ready at the time of retrieval?
Rena: Okay, yeah, so tell us more about what you found.
Dr. Bergin: So we found that the oocytes thought at similar rates, so they both have really high thaw rates. So we, we take the frozen eggs and we thaw them out, that they survive the thaw at similar rates. But when we fertilize them it seems like they have lower fertilization rates than the ones that are ready right at the time of retrieval. So in other words, late mature M2s have lower fertilization rates than these on-time M2s. And then when we took it a step further to see how they then grow into a blastocyst or an embryo for transfer, they also tend to do a little poorer than the mature M2s do in the lab. So they have lower blastulation rates and then when tested using PGT-A, they have lower rates of being chromosomally normal or euploid. So in all, in all it is to say that these late M2s tend to have a little poorer prognosis down the line, but they still have potential, they still make high quality euploid embryos and for some people in our study the only euploid embryos they got were from these late mature eggs. So I think there's still a really meaningful contribution to the egg freezing cycle.
Rena: Okay. That sounds positive that this is some semblance of hope for people.
Dr. Bergin: Yeah, I think that it helps us understand the prognosis after an egg freezing cycle. So for a patient who had 10 eggs retrieved and maybe half of them ended up being late mature, like they had to culture in the lab, you know, we could take those numbers into account and kind of think, well those might not make as many embryos as we thought they were going to, like if they were all on time, like mature right away. And so that, that might, you know, encourage people to, depending on their family building goals, freeze more eggs overall just to have a backup. But also it, they all still have potential in the long run.
Rena: Well it sounds like that even is a super valuable piece of information because as we know, our listeners may or may not know when you freeze embryos you have a, you have more data to go off of because you can grade the embryos. When you're freezing eggs, we can't know egg quality but it, we usually say 8 frozen eggs equates to one live birth. And it sounds like from this data it's sort of proving it's, it's like well there is, there is some more hope there is the potential that these later mature ones could be growing and and could end up being a viable embryo. But also yes, looking at that in the data and if your family building plan is multiple children, then we would recommend that you do another egg freezing cycle because if the eggs you're freezing are these later maturing ones, we wanna make sure that you if possible can get…
Dr. Bergin: Yeah, yeah. Like you said, it really is insight into oocyte quality in a way 'cause Like you said, we can't test oocyte quality 'cause the eggs are just one cell. We can't have like quality of the embryo until it's developed to a certain stage where we can actually grade the different parts and test it to see if it's chromosomally normal. And so when we're looking at eggs, you know, we just have the one cell and we just know as it mature or not mature. But this kind of adds another layer to that by seeing okay all the ones we're freezing are mature, but some of them seem to be better quality 'cause they were mature right away and some of them took a little longer to get mature. And so it's, it's almost a way of like, yeah, prioritizing or seeing a quality thing in the eggs that you have frozen.
Rena: And that in itself is huge because we didn't have that before. It was really a guessing game. You know, generalizing okay, maybe eight for one live birth, but…
Dr. Bergin: It's kind of right. It's kind of another factor that ultimately would be great if we can put into a predictor model to eventually counsel patients on down the line. So like when looking at, like you said, how many eggs equals a live birth, we probably have to add in okay, how many of those were on time eggs, how many were late eggs in addition to someone's age and all these different kind of factors that can affect the embryo development and you know, live birth potential is sort of is another factor to add in there now.
Rena: Yeah, that's huge.
Dr. Bergin: Yeah. Yeah. And right instead of not using these late matures, so I don't want, even though they have a little lower reproductive potential than the early or on time M2s, mature eggs, they're still worth keeping. Like, they're still worth buying out and worth seeing what you can get from them because they definitely have the potential just slightly lower.
Rena: Yeah. So obviously we're doing this in the RMA lab and sounds like this is really new, groundbreaking technology and and something to do. Is this something then that's being done across the board or if you're a patient at another clinic, can you feel confident that they're also doing this or how is that working?
Dr. Bergin: So some labs will culture the immature oocytes overnight, so even up to 24 hours in the lab, before making a decision about if they've reached maturity or not. And that's where there is some data out there on fresh IVF and maturing these oocytes overnight and those that are not ready until the next day we already knew have poorer outcomes actually and we've looked at our data as well. And so since those outcomes for the ones that aren't ready until the next day are lower, we stopped doing that routinely and that's why we just kind of look at the ones that are gonna be ready later that same day. So once that still have really good potential and are ready the same day rather than waiting overnight. But most labs do some kind of in vitro maturation and culture process.
Rena: Okay. So is this something that you should ask about at a clinic or just assume that they're doing it?
Dr. Bergin: You could definitely ask. You can ask your clinic and doctor to see if their embryology lab cultures out immature eggs. In vitro maturation used to be done in the past without doing any simulation, any medications, any trigger shot, like it was just done to purposefully retrieve immature eggs and we have definitely seen in the old data that that's not a really efficient way of, of getting eggs. Definitely the stimulation and the trigger help with the egg maturation process and so we're not advocating for just in vitro maturation of like purposefully retrieving immature eggs but still doing stimulation and just if you happen to get immature ones, you know, they can ask does does the lab culture those either for a few hours or until the next day to see if they reach that maturity level?
Rena: Okay. And what about any implications for future from this study? Where might you go next?
Dr. Bergin: So we, we actually in another study that's going to be presented as well did look at embryo quality. So like you mentioned, we can't really grade the embryos on quality until we have them grown out in the lab. And so we looked at the late mature embryos and saw that they do tend to be a little poorer quality than the on-time mature ones as well. So again, just really another prognostic factor, but we haven't seen a lot of transfers from these embryos yet. So that's really the next step is as patients come back to use their cryopreserved embryos that were created from these frozen eggs, we wanna see what the pregnancy and life birth rates end up being.
Rena: Oh wow. Fascinating.
Dr. Bergin: Yeah. So even though they might have lower potential of getting to the blasts stage and their grading might be lower, you take two embryos with the same grade, but one came from an late mature M2 and one came from a regular M2, do they have the same implantation potential and live birth rate? That'll really be the next question as patients come back and use them.
Rena: Sure. Oh wow. Well I'm so fascinated to hear those results. Maybe we'll interview this time next year to see!
Dr. Bergin: Exactly, yeah, as we have more patients hopefully. And then really, like, we were mentioning the predictor model. So once we have that data from patients actually coming back and using their late mature M2 embryos, then hopefully that can be an added layer into some kind of predictive model that we can help counsel patients on when trying to guide them on how many eggs they should have frozen.
Rena: Yeah, this is amazing. You know, I think knowledge is power. I always say that on the podcast and I think patients are really gonna find this fascinating and a really, really strong data point and information for themselves when you're nuancing this even further.
Dr. Bergin: Exactly. Yeah. You know, we, we call and we tell patients how many mature eggs they have frozen and that's, that's true. This is how many mature eggs they have frozen. But yeah, it raises that next question, you know, were any of the mature eggs I had frozen late mature M2s and how does that affect what I should do next?
Rena: I love this. I mean, I know we're so lucky, especially at RMA, I think our patients are such smart, strong women and, and so I think this is really gonna be fantastic for them to have as a tool in their pocket to ask the physicians and get this data and information to feel more empowered and informed.
Dr. Bergin: Exactly, exactly. And from the physician side as well, you know, I think we didn't have the answers to necessarily say yet what that means. What does it mean that they had some late mature M2s as part of their whole cohort? You know, we didn't really have the information before and now this study will hopefully give more counseling tools for us.
Rena: Yeah, it's amazing. You know, I, I know as healthcare providers, I'm sure you, you know, myself, I find myself getting frustrated when I can't give a patient an answer. And so the more we can know and explain to them about care data, I I think the better for us too. So, you know, we feel more competent.
Dr. Bergin: Exactly. Exactly. Like we're freezing them because we know they can make embryos, but we don't know how they compare and now we, you know, now we have some data to, to help back us up
Rena: This is fantastic. I guess the final question I would have too, if, if you went through a retrieval, right? And you saw, okay, I have some late mature eggs and then some not, with that data, would a physician then say, okay, this might call for a protocol change if they notice like, okay, yeah all of your, you have so many late mature eggs, okay I can make this change to a protocol to try and…
Dr. Bergin: Yeah, there are some changes that can be made for patients that have a lot of immature eggs that are recovered at the time of retrieval and you know, whether they do mature in the lab or not. But yeah, if they have immature eggs that became late mature, it might be a reason to try and push the cycle a little bit longer. So maybe to try and get those follicles like we're talking about a little bit bigger before doing the trigger shot or to try medications before someone's period comes to try and synchronize the growth of the eggs the best we can so that they're all kind of growing in sync at the same size together so that some aren't much bigger than the other ones to try and get as many on-time, mature eggs as possible.
Rena: That's amazing. So there really is so much to be done with this data to really help a patient get the results that they want.
Dr. Bergin: Yeah, I think so. I think it will be really valuable.
Rena: Well this is wonderful. Thank you so much for coming on and sharing your wisdom. Is there anything else that you think our listeners would wanna know?
Dr. Bergin: I think we pretty much covered it. I think if you have eggs frozen, it's a great question to start asking your doctor about, you know, are they, were any of them late mature M2s and based on this new data, do they recommend anything differently for your next steps?
Rena: Okay, amazing. Well the way we like to wrap up our podcast is by saying something that we are grateful for. So something that you are grateful for today.
Dr. Bergin: I am grateful for all of the mentors that I've had in this project and all of the people that have met with me every day, probably, for the last many weeks to talk through some of this data and prepare the presentation for ASRM. And you know, really grateful to be working with a lab that collaborates so closely with the physicians and fellows to get this data and put it out there.
Rena: That's beautiful. And I would say that I'm grateful for you and our lab and physicians and fellows and everyone at RMA that works so tirelessly to keep moving this field forward. You know, I've been in this field now for quite a while and the more information I have the better and it's, it's amazing to see, you know, kind of how it started and how it's going with patients and what information I can give them now thanks to the work that people like you are doing.
Dr. Bergin: Thank you. It makes all the hard work worth it.
Rena: Well, we wish you the best at your ASRM presentation. We will not be the podcast until after, but we are confident and will go very well. And we're looking forward to having you on for the next round of data to let us know what happens with the
Dr. Bergin: Can't wait.
Rena: Thank you so much. Good to see 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 us at www.rmany.com and tune in next week for more Fertility Forward.