Journal Club Global: The number of autologous, vitrified mature oocytes needed to obtain three euploid blastocysts increases with age

This episode of the Fertility and Sterility Global Journal Club explores new research on elective egg freezing and how age affects the number of frozen eggs needed to achieve future live births. An international panel of reproductive medicine experts discusses a large study evaluating age-specific probabilities of obtaining euploid embryos and successful pregnancies from frozen oocytes. The conversation covers patient counseling, realistic expectations, fertility preservation strategies, healthcare policy, ethical considerations, and the challenges of balancing optimism with evidence-based guidance. The discussion offers practical insights for clinicians counseling patients about fertility preservation and family planning.

Discussants

Nikolaos P. Polyzos, MD

Barbara Lawrenz, MD, PhD

Alexandra Izquierdo, MD, PhD

Jim Toner, MD


Author

Amalia Namath, MD


Fertility and Sterility Moderators

Paul Pirtea, MD

Specialty Editor, Fertility and Sterility

Yannick Hurni, MD

Interactive Associate, Fertility and Sterility

Hello everyone, my name is Paul Kertéa. I'm hosting today the Global Journal Club for Fertility and Sterility and we have a great topic and even greater discussions today with us and also we have a new co-host which is Yannick Hurny who will actually co-host me today this journal club. Yannick is a new member joining us from Spain.

He's Swiss so he does it all. The topics we're going to talk today about it's about egg freezing and which is I think it's you all agree it's a very hot topic, very debated, touching many associations for patients and so forth and not to mention social media etc. And why we believe, Yannick and myself, believe that this is important is because this paper which is called the number of autologous vitrified mature oocyte needed to obtain 3U per blastocyst increases with age.

It was a paper that was actually designed to try to counsel patients that are looking to freeze eggs and try to tell them the length of the journey and how much eggs they should require to actually have a good insurance if that's possible to be mentioned. So today we are very lucky to have Amal Enemath who is actually a third year REA fellow in AHH. Her research is focused on third-party reproduction and of course oocyte cryopreservation outcomes and she actually done the most part of this work in this paper.

So I think she's the best person to present to you the outcomes and implications, the limitations and therefore afterwards we're going to have our discussions, magnificent discussions with us to try to squeeze out the best messages to take home and to our patients. So Amalia please let us know what you think about this paper and what you have found. Thank you.

Okay I'm going to share my slides. All right. So hi everyone.

I'm going to present my paper, part of our paper for this Global Journal Club and I'm excited to share the highlights of this article and then open this up for a clinical discussion. So recurrent implantation failure is one of the many difficult situations in our field. With the advent of PGTA technology and the increase in single euploid transfers, there's a question of how often true RRF occurs.

And then separately in a more of a theoretical sense, how can we counsel our patients about what to bank in oocyte cryocycles to give them a high likelihood of a live birth down the road? So we know from Dr. Portea's landmark 2021 study, they showed a 93% chance of a live birth after three cumulative euploid FETs with the graph shown here. So we took that study and thought what would it take to get patients there to three euploids to as close a chance of live birth as we could predict, particularly a patient who's doing an oocyte cryocycle. Though there are calculators and some data that's been published on oocyte thought patients, it's limited particularly in what's known about live birth outcomes.

So because of this, we counsel patients that we cannot look into a crystal ball once they freeze oocytes. And so it's hard to say how many oocytes they should bank with the goal of one, two, or three children for their family plan. So we thought, what if we did a study that looked at patients who had used their frozen oocytes to see how many it takes to get to three euploids based on age? The primary objective of our study was to analyze the mean number of M2 oocytes required to bank three or more euploid blasts for eventual transfer stratified by age and separately by indication for oocyte cryo.

And then our secondary objective was to demonstrate the probabilities of live birth of one or more children based on known outcome data from thought oocytes with the goal of providing a counseling tool for our patients based on raw data to illuminate future chances of live birth based on what they bank. Our hypothesis was very straightforward. There's more M2s that will be needed as age increases at time of oocyte cryo.

So for materials and methods, we included all oocyte warming cycles from 2011 to 2023 at a large ART practice in the United States. We excluded cancel cycles, oocytes used for donor cycles, patients who continued to store, they didn't warm their oocytes, or slow freeze. Our primary outcome was the mean number of M2s to get to three euploid blasts.

And then our secondary outcomes were the total number of M2s for one, two, or three live births. So these are our results from over 8,000 vitrification cycles, we analyzed 1,041 thaw cycles. So here in graph form, we demonstrated the probability of obtaining at least three euploid blasts based on the number of M2 oocytes banked by age.

For example, to achieve at least a 70% chance of obtaining three or more euploids for patients less than age 35, they need 15 M2s. And this nearly doubles to 28 M2s for patients age 38 to 40. And then off the graph, it's over 50 M2s for patients age older than 42.

So this data is pretty consistent with what has been previously published in US literature with much smaller sample sizes. And it's important to note here as well that you can see a plateau. As younger patients bank 25 or more M2s, their probability stays around 95%, which is about the highest it can go.

And this is something to keep in mind as well when people, patients think about is there a maximum. So now looking at both real and potential live birth outcomes from thaw cycles, we calculated the expected live birth per thawed M2 oocyte, which was 0.13 if less than 35, and then all the way down to 0.04 if older than 40. We converted this into the graphs you see here separated by age at the time of oocyte cryo.

Where for one child in the blue, for example, patients age less than 35 need to bank at least 10 M2s for a 75% chance of one child, which increases to 23 at age 38. These graphs also show the probabilities for at least two children in the red, and then three children in the green. And we thought it was important to include this because many of our oocyte cryo patients come to us wanting at least two or three children as their family plan.

Because our study did include a lower number of patients who are older than 42, you see that the data really spreads in that last graph. This is another way to look at our data, which is less colorful, where we established probabilities based on the minimum number of M2s and separated it by age. As you can see, there's still a high probability for 20 M2s to get to three or more euploids all the way up until age 38, which is where there is a shift of a much slower probability of 50% or less if you bank 20 M2s, which continues to decrease all the way to 20% at older than 42, which is almost equal to 10% probability.

So overall, given our results, patients should undergo oocyte cryo before age 38, if possible, because they will likely need to bank less to get to their desired outcome, if they need to use their oocytes down the line. The goal of banking 15 to 20 M2s puts most patients at a high probability of at least three euploids, and therefore a high probability of achieving at least one live birth from them. Patients should be counseled that multiple oocyte cryo cycles will be needed to bank these numbers, particularly if they're age 38 or older.

Most patients average at least two cycles, even if under the age of 35. For a brief overview of strengths and limitations of the study, which will likely be covered more in depth in our lively discussion, this is a very large sample size. We updated Doyle's previous study from 2016 of 128 cycles with 10 times as many cycles.

We also included a very similar study population. We focus on euploidy as the primary endpoint, which bypasses social variables like patients only wanting one child or patients who do not return to use their embryos. And there is standardization across a single practice with that laboratory protocols.

Limitations include that this is a retrospective study with data from patients who were returning to use their eggs, which may be patients who are more subfertile than those who never end up using their eggs. We were limited in the number of patients with advanced ages, which is also due partially to practice limitations where we only had 37 patients who were age 43 or older. And then only 13 of those patients use PGT.

So it is harder to generalize our findings for that patient population. And then for our secondary analysis, we mathematically assumed that frozen embryos had the same reproductive potential as those already transferred actual live data that we had. Which we may not know to always be the case, but allowed us to calculate these probabilities beyond just one live birth for this paper.

So with that, thank you for allowing me to introduce this study that I'm personally very passionate about and highlight its key points. And I look forward to the discussion with this wonderful group of international experts. And I'm going to stop sharing.

Great. Well, thank you very much, Amelia. It's a great study, great presentation.

So before we start discussing this great paper, I would like to introduce our guests. So first joining us today is Dr. Barbara Lorenz, Scientific Director of ART Fertility Clinics in the United Arab Emirates and guest professor at Ghent University in Belgium. Barbara, welcome and thank you for and discussing this interesting paper.

So joining us as well is Dr. Alexandra Izquierdo, Medical Director of Vida Recoletas Madrid in Spain and coordinator of the master's program in Human Reproduction and Competency University of Madrid. Alexandra, we are delighted to have you with us today. Thank you.

It's a pleasure for me to be here too. Next panelist is Dr. Nikos Politsos, head of the Department of Reproductive Medicine at the University Hospital in Barcelona in Spain and visiting professor at Ghent University in Belgium. Nikos, thank you very much for being with us today.

Great pleasure to be in such a great panel. And finally, we are delighted to welcome Dr. James Stoner, Reproductive Endocrinologist at Atlanta Center for Reproductive Medicine, Georgia and vice president of the American Society for Reproductive Medicine and co-author of the paper we are discussing today. Jim, thank you very much for joining us today.

You are mute, Jim. Sorry, we can't hear you. Yeah.

OK, sorry. Thanks for the invitation and the opportunity to offer some comments. Well, after this magnificent introduction and politeness, let's dive in and let's start the discussion.

So first of all, what do you think about it? So Barbara, what do you think about this? Well, first, my congratulations to the team, to Amalia and the team for this beautiful paper. And what I really like is that it gives like numbers at hand, because often we are sitting opposite of our patient and we are just wondering how do we counsel them. And especially for us in the UIA, in the United Arab Emirates, where oversight donation is not an option.

So it's often difficult to discuss women of advanced age with a reduced ovarian reserve, because looking at this number, I mean, of course, we don't have to talk about the 99 percent probability of having like three oblate blastocysts, but at least one, even then you need a number of, I mean, quite a high number which might not be reachable. So this sometimes leaves me a little bit in the limbo how to properly counsel those patients. So, yes, I mean, we can counsel them and say, we go ahead just for a peace of mind.

But I would really like to hear your opinion on this one. Anyone else? Alexandra? Expectation settings, right? Like, I think we have an ethical obligation to share with our patients our best guess about the chance of success with whatever route they choose. And while age is still the overriding factor, and I'm not sure there's much difference, fresh, frozen, the problem here is that typically the outcome is so delayed, whereas in a fresh cycle, it's immediate.

And if it fails, you can try again. I mean, as you mentioned in the talks we had previous to the journal club, I mean, it's about the very long process, like it's a very, very long endpoint. So you don't actually know actually what will happen.

And I think that patients are very optimistic about their chances. And I'm just fear that in the end, they will not be disappointed. Because I think as Amalia was mentioning, in New York nowadays, 50% of clinics see mostly egg freezing patients.

And therefore, it's a phenomenon that actually is happening. And I think that this paper was good enough that with the graphs that they presented, actually patient can be counseled. Yes.

What do you think, Alexandra? Well, first of all, congratulations, as Barbara said, for this paper, which renews the information we had from some studies before, including the opioidy of embryos, which is absolutely important for the outcomes of the patients. It's not just eggs, but having healthy embryos to transfer. I think that we have grown so much in fertility in our treatments that patients put so many hopes in what we do think we can do anything.

And it's good to have this information in order to give the proper resources for patients to understand what they are facing. It's not that we can do anything with our fertility treatments, it's that they need to understand what these treatments can give them, what they can do at a certain point, according to their age, to their expectations for future maternity. And we have to be able to explain this to our patients.

And I mean, this paper give us the tools to give that information and to really put hopes of patients at their real stages in order to not to create these false ideas of anything can be done with the fertility treatments. Nikos, anything to add? Yeah. What defines a good paper? So for me, my question is always what defines a good paper? And I always, as a clinician, I think number one is novelty.

Is it novel? Yes. Because I think you got it. I think what you got in this time is a completely different outcome from what we were used to see.

It's a smart primary endpoint that you go to euploid blastocyst because in this way, you remove confounders for the live birth counseling. You don't know the desired family, you don't know if they will come back. The major problem of the fertility preservation is the low return rates.

So there is only one study mentioning from the states 36%, but the vast majority is around 15 to 20%. So this is biasing all the assumptions about live birth rates. So going to euploid blastocyst, I think you got it.

And if you take into consideration that the previous paper was the Doyle paper that was a landmark, I was using it in my consultation, I think this is a beautiful, bigger study with 1,041 genuine contributions that makes you easy to make it clinically applicable. Because in the end, it's not only the novelty, it's the clinical applicability. As a clinician, I'm bored of seeing papers that they don't have any clinical meaningfulness, and I want a tool that would like to use.

So for me, well done, Amalia and Jim, that you were part of this, because I think you got it, a correct exposure at the age of eutrophication. So it's a fresh contribution, I'm sure that you will get a lot of citations. Congrats as a first point, well done.

And secondly, do you think it's clinically useful? I mean, the question is, do you think it's going to last? And first of all, what would be the impact this might have? Because I feel from what we do in France right now, I feel that not many patients are achieving that 20 kind of above 20 numbers of M2s that one would require to have high chances of pregnancy. So I'm quite in a difficult situation because I don't know how to change the counseling in a way that from now on, at least patient will understand the requirements. We are limited by the fact that it's free of charge for the patients, but also we cannot do more M2 cycles because we have guidelines from the insurance.

So what do you think, Nikos? Well, if you ask me, I understand your point and someone would say 25 oversights or 50 oversights I will never get. But still, what I would model also in this paper, I would possibly model the M2s needed for one euploid blastocyst, because it's not always feasible or practical to get three euploid blastocysts. Sometimes it's not needed.

You're thinking about the second baby. If you see the mortality rates in Europe or in Asia is 1.1, 1.6, most of them will go for one child. So I think it's interesting.

It's clinically useful because you see all these graphs and you can model it. There is some modeling and you can suggest about this, but it goes to three euploid blastocysts. And this might not be realistic endpoint in women with low ovarian reserve that they bank fewer sites and they would need to know their probability even with fewer sites, because even if a probability of 50% is there, I think it's realistic compared to zero for this patient is going to be 100%.

And secondly, for the patient of 40 years old, because you say the 50 oversights, but this is based on very, very small numbers. So I think for counseling there, I would be much more prudent on the way that they will guide my patients. Barbara.

Yeah, well, I was referring to the numbers, what we are seeing, because what I could imagine that we are now also breaking some ice. I mean, this fertility preservation is more and more in like public awareness. So whereas previously it might have been knowledge of some women with a better education, with some more money.

So now it might spread and maybe also we will have younger women who think about more family planning, who are more aware of the loss of oversights, numbers and quality. So maybe we'll have a shift that in general population becomes a bit younger. So maybe this discussion on numbers might not be that much prevalent anymore, because we see also younger women going for it.

Well, I think, I mean, when we with Jim, we discussed about this topic, the idea of going to tree euploid was because the patients that are doing egg freezing are not necessarily infertile patients. And of course, if you only reduce the target to poor or very spoiled, it's very difficult to handle this kind of message, because it's like you're giving them a very high reference that maybe we'll never achieve. But I mean, our idea, or it is mine, I know, Jim, please correct me afterwards if I'm wrong, is that these patients are all under 37, most of them, they are trying to ensure themselves of a future pregnancy in the future, not necessarily known future.

And it could be that the majority will be at least normal responders, or high responders. So I think that to get the message right, it should be only like include, let's say, good prognostic patients, how much they will need to ensure that they have that because it's always a matter of we are trying to, we have to give like a global message, not necessarily one targeted to a very difficult population, because it applies the same for endometriosis, like the endometriosis can have different severities to different patients. So it's very difficult to kind of, or you can actually compare it to a flight, not all flights are bumpy with, or with technical issues.

So of course, in some situation that can occur, but in most cases, you probably have good patients. So for them, in order for them not to be disappointed after five or 10 years, when you don't have the opportunity to cycle again, and so forth, I think it's very important that our message is as realistic as possible. Because as I mentioned before, I think there is always a discrepancy between what the doctor says and what the patient understands with respect to their chances of success.

Right. And if I can follow up on that point, that inherent optimism of patients can, you know, hit the reality of the outcome, but in a fresh cycle, it's pretty immediate, right? So we think they're going to get 10, they think they're going to get 20, we get eight, and we can, in a fresh cycle, within a month or two, we know whether it has worked. I find it useful in this context, to lay out what I think will be their egg yield, but also to circle back after the actual retrieval, and show the graphs again, and, you know, to kind of bring it down to the actual rather than the theoretical.

And sometimes that is sufficient to entice people to give another try if the egg yield wasn't what everyone expected. But at least they know what the real probability of success down the road will be. I think that most patients, after their first cycle, most of them are disappointed.

I think most of them believe they have an image of their fertility that is higher than actually. So, yeah, for sure. I haven't seen any patient being happy they had eight eggs when we were actually quite happy.

We felt like maybe they have nothing, you know? Yeah, yeah, yeah. But it is interesting because I think our counseling is probably, on the front end, pretty accurate. You know, I think you'll get 10 eggs, but they go home thinking they're going to be lucky and get 20.

So it helps, I think, as a practical matter, on their behalf, to take the extra step after the fact and have another discussion. This is where we actually land now on the basis of this larger data set. This is what we think the chances of there being one baby in this cluster of eggs or two babies, so that they don't, like, postpone the opportunity to try again.

I agree with you, and as a counseling benchmark, it's beautiful. But imagine that you have a low responder that will get four eggs and you accumulate, like, 10 eggs, 11 eggs in the end, and it gives you a probability, which is 90% of having one euploid blastocyst at the age of 30. I would love this.

I don't see it as a negative result, and the perception of the patient would be like, I don't have the three blastocysts, I need 50 eggs. So as a perception would be, oh my god, 50 eggs, I would never get them. And probably she would never get them.

But a 30 years old, poor responder, after a severe endometriosis and a surgery that cut half her ovary, and she has a probability of 90% to have one euploid embryo, it's a great success, and the message is very important. So for me, I would like to see the modeling for one blastocyst, especially for the young patients that have the best prognosis there. And I will say that's kind of the part of our, you know, the other graphs with the one, two, or three children.

And I completely agree with you. So we had a long discussion about what should our primary endpoint be. And so we thought at the end of it all, what does any patient want when they come through the door? They want you to guarantee a live birth as much as you can.

And so that's why we chose three euploids. But yeah, those secondary graphs with the one, two, or three children, they can look and say, okay, I have 10 m twos, and I'm 30, I have a great chance of having one child down the line. And so I think that's really important.

And kind of going back to Dr. Perez, other question of what should I tell a patient who can only do two cycles, I think this data tells me at least maybe we should consider moving the needle to a little bit earlier in life for these patients, if that's all that they have, if they can only do two cycles, because if you look again, age 38, that's where it really pushes things. And I think gives gives patients more realistic expectations about all of that. So that's what was interesting to me.

Would you be also able to give like patients, I mean, when you look further into your data, because you have data also on the AFC on the ovarian AMH markers and stimulation. So just to offer some right from the beginning, a kind of package that you tell them with your AMH with your age with you, you would need this number. So we would need to have like two treatments, three treatments, four treatments, so that you start right from the beginning that you don't, you know, you don't go step by step, you'll just don't go, we'll do one stimulation, we have five eggs, and now we'll have to do another one, surprise, and now we'll have to do another one.

So basically, you could go a step further that you put like a packet for them, you know, so see, are your ovarian reserve parameters, your basic characteristics, this is where we want to get. So most likely you will need X treatments. Yeah, we have seen also the related to these parameters that you look at when you start a treatment with a patient.

We have seen that nowadays, gynecologists are constantly in this fertility preservation for many patients, which is a good idea. And that has led to a lower age of freezing and normally better outcomes when we use that X. But what we see also is that since many women are performing these fertility tests, AMH, antral follicle count, just to know how they are, many of them are coming to freeze their eggs, when these results are not normal. And once they are normal, or if they have a normal AMH or antral follicle count, they say, OK, I have my time, I don't need to freeze.

So the idea of having this information would help us to counsel these patients also to say, OK, you have a good AMH, which would mean that maybe you just need one cycle to have an ideal number of eggs. But that doesn't mean that you can just wait without doing anything in the future. So these earlier tests that we can do can also help us assess patients and maybe to change the timings, as Amalia said, in terms of freezing before for some patients that might need that.

Yes. Jim, do you think the SART will ever report outcomes of egg freezing? Yes, but it's such a delayed report, right? And but the data are all linked within the large database. So it is a dataset that could be requested and analyzed.

Because maybe, because at the end, I will give you a very interesting question, because France now they offer this for free for everyone between 27 to 37. And of course, everyone is doing so back. This was actually backed by the guidelines, the saying that it's recommended to do maximum two.

Now, the problem is that I think, as we all mentioned, the use, I mean, now we are doing a lot of it, like many people are freezing their eggs for different reasons. And we're talking only about social reasons, not oncological reasons. So in this case, we are doing it, as mentioned, some most people probably do two cycles at the maximum.

I think on an average, probably we are even below two cycles. And at the end, they have some eggs. I think that having some kind of feedback of what's actually happening afterwards is necessary, because probably we are just going to freeze too many cells for no reason whatsoever.

And I think it's required that we actually know how many people are actually coming back and why the other ones are not coming back anymore. Because maybe in the future, we should filter because I'm not certain we can actually offer egg freezing for everyone who wants to do egg freezing as soon as possible. Because this population is enormous.

I mean, the demand for egg freezing, it's increasing like it's crazy. It's like the way it's increasing, it's over our possibilities of actually performing those cycles. And also, I fear that not all labs have validated correctly their cryopreservation technique for eggs, not for embryos, which is, it could be that sometimes it's a very complicated issue.

So we are talking about freezing eggs, like it's very easy, but it could be that it's challenging. I don't know, what's your opinion? I think France is the only country in the world that's starting doing this fertility preservation for free for all patients who want to, I mean, in this age, age limits, it will be a good example on how it would work if that was for free everywhere. Because I mean, when you have something for free, patients don't even think about it.

As Jim said, it's just two weeks medication, which is not a lot. And if it costs nothing, you just do it because you deserve it, because you have the right to and just in case. So maybe the use of these oocytes later on will be much lower because many patients will get pregnant spontaneously, they won't delay maternity, so maybe they won't be needed.

And maybe that will help to track and maybe that will be a filter also in the future to say, okay, this profile of patients are the ones that are getting the most benefits of fertility preservations, whereas these other profiles really won't use them. And there's no need to undergo all this medical treatment, which is a medical treatment in any case, and storage of cells for nothing. But you need equity in this to be equally correct to the people.

I don't think we are at this stage and we cannot decide as clinicians to whom we will offer. I think this is not correct at all. So all the people and I think what we see, what is interesting to see, if you see there is a French study that shows who are the people who freeze.

I think it was the study in RBM online in 2025, something like this. But they show that the highest, the people that they freeze, the women that they freeze in France, they were once in the 92% was in urban areas, not in rural areas. They were master or doctorate and they were women, maybe with health related professions.

So I think there is an inequality. So if you start offering it to specific or decide who's going to use them, you don't know their family plans, their lifestyle plans. So I don't think it's correct.

What I need to comment on this is that I think, and maybe Paul can help me on this. When this happened and France started reimbursing the fertility preservation, elective fertility preservation for social reasons, there was a boom of patients coming in the clinics. And this probably delayed people that they needed treatment at this moment.

And this is not correct. We cannot prioritize fertility preservation instead of giving IVF to patients who need it. And this is probably irrelevant from the US market, but for Europe, it's important.

So I think we need to rationalize this. But in the end, a benefit can be for everyone. Even if I have a 10% chance to have a baby or 2% or 5% chance, more than zero, it's something more.

So you cannot exclude people or women from the opportunity of becoming mothers if they want it later. And it's their reason, it's their independence to decide if they want to use these eggs or not. For me, I see it like this.

It's a revolution, the elective fertility preservation. Yeah. No, but Nikos, don't misunderstand me.

It's not that I'm just refusing some patients from doing it. It's just that I'm directing resources in a way. I mean, in Spain, you know, also, we have some limits of age, where social security takes all treatments, but beyond that age, it's not taken and that's a resource system.

So that would be the same. I mean, it's not not doing it, of course. I mean, the moment you have 1% more than you had before, that's a success and a probability for every patient.

The only issue is to determine how you share that resources in a country, in a society, or how you decide how to manage that. Completely aligned with you. Jim and Malia? We haven't yet run into the resource bottleneck that you described, although it could be coming.

More and more large employers in this country provide for egg freezing and many states now provide it for gonadotoxic therapies, you know, in advance of those. So the percent of our practice that is now involved with egg freezing is probably a third. And, you know, it used to be maybe two or 3%.

So it is a growing need. And I think from, as has been said, from the perspective of an individual patient, it's a win-win. I mean, if they don't need them, so what? It wasn't that risky.

And if they do, they have something to fall back on. I do think, as Paul alluded to, this pretreatment optimism can give women false hope. And so I think it's incumbent upon us to do our best to give post hoc predictions, right? This is enough for one baby 50% of the time.

And if they're cool with that, then that's fine. But I think they need to know that it isn't anything close to a guarantee. Any more than, you know, if we have a patient with outright infertility today, we can't offer them a guarantee either.

It's just that reality is immediate in a traditional fertility treatment paradigm, and it isn't here. Yeah. And I also, the other thing to think about that I counsel patients on is, you know, yeah, you go through an egg-free cycle, but that's not the end of it, though.

So kind of to add on to Dr. Toner, now you have eggs in storage, okay, you have to think about them, you have to pay that cost for storage. Eventually, if you want to use them, do you have a partner? Do you have donor sperm? You know, what are your options? I mean, there's there's more than some patients think, oh, you just go through this, and then I'm done. But actually, I think also, they need to think there is a weight here.

Now I have material, genetic material of my own stored. It's a kind of an, it's a longer process than you think to transfer eggs to different facilities. What if you're doing it across countries? So that's kind of the other part that I wanted to bring up, but all for egg freezing, but I do, the thing that I spent a little bit more time now with patients, like looking at this data, and like we're talking about a little bit earlier with Barbara, is that the average time from patients from freeze to coming back and warming in this study was around two to three years.

And so these patients were coming back pretty quickly. But what about the patients who are just freezing for a long time, they need to think about that. I mean, that needs to be a part of the counseling process as well.

So what we see in the UIA is that, I mean, also UIA, not only France, UIA, and I think Israel also, they are covering those treatments. So they are for free. So our women who want to freeze eggs, depending on the ovarian reserve, either they have to apply or it's covered for a low ovarian reserve, and they are also happy to take it up.

Because I think especially in a society where it's very important, hopefully, to have at some point children. I mean, it might be even a relief. Yes, we'll have to counsel properly that you, with 41, you don't benefit from just having two eggs frozen.

But I think it might also take a lot of social pressure or pressure from the women themselves. Well, I think the variability of your answers make this global journal so nice, because it's very mixed and heterogeneous, and it's very nice. Just to give you, as Nikos was asking, it doesn't work in France.

The delays are one to two years. We are facing big struggles with counseling these patients, because we were only used to infertile patients that were accepting many things like structure, appointments, and so forth, where we are facing now with a population that has their own agenda, and they are just adding to their agenda the treatment, which doesn't necessarily end in a very good way, given the constraints we have from the system. Because this treatment was proposed on the same platform, technical platform, that was previously offering IVF care for infertile patients.

So right now, as it stands, the delays, if you're lucky, it's one year. If you're not lucky, it's like two year and a half. And many patients actually choose to go abroad to some known countries to do so.

I'm not going to name them, but they are actually traveling abroad, unfortunately, to get those care. Now, Yannick has a question. Yeah, I was just thinking about the fact that the endpoint, as we said, is quite late when we speak about fertility preservation.

So we don't know. So the big problem is that we counsel our patient on numbers and probabilities. I don't know, what do you think will be the future? How we could measure all side competence? We heard a lot about artificial intelligence, metabolomics, cumulus cell biomarkers, and so on.

Do you think there is room in the future for counseling patient also on the quality, I would say, or the competencies of the oversights? And so trying to tailor a little bit the counseling? There's a big industry, for sure. So I think the industry is jumping on this and they try to find the crystal globe that you will see inside the oversight. But this still is based on, there are different tools by different companies and they go to other congresses and they can evaluate the competence and evaluate what is happening, which we don't know.

The patients want it. The patient ask it because there is a need to know how are the eggs. And then they have different tools and evaluate this.

But this is based on retrospective data. I don't know if they are externally validated. So we have to be cautious on this.

Also, a thing that I wanted to comment on the study is that you use the binomial model, which is actually the oversight. I was reading the methods and each oversight was treated as an independent Bernoulli trial, which I tried to read about this. I like statistics.

My mentor is in Stanford has done, is Johnny Anidis has done statistics there. So I have a little knowledge. So this is probably might be an issue because you ignore the clustering with a patient level because all sites with poor competence, they will create correlated failures.

So for me, I think that we might have a problem. It's a simplifying assumption that to consider that each oversight, it has the same independent chance to become a euploid blastocyst at an age group. But it's simplifying and biology is not like this.

So it's much more messier. So if I have a patient with a poor oversight competence, then they will cluster there. So I think this is a limitation also of the study, which is not mentioned.

And this goes with the competence of the oversight, which we don't know if it works and how we can assess it. I don't know if any one of you knows, maybe in 10 years or in five years, we will find maybe metabolomics is the issue. AI is investing on this.

I think we're too early, although there are tools that they promise a lot. Do you think there will be a need for a paper assessing the egg donors, how many eggs they had provided to get the first pregnancy, even if it's shared, because probably you are sharing donors like in between several couples, right? Because those patients would be not necessarily infertile, no? Maybe. But using frozen eggs.

Yeah. And nowadays it's more or less frozen and you are freezing them, defreezing them. And then you, I mean, for those, I cannot report it.

So I'm sharing with you the challenge. Do you think that's something that you could be interested in doing? I think it can be interesting because it is interesting for me. I would like to say that.

I think it's very interesting because all the results we have at the moment are relying on people. They are coming back. Yeah.

People are coming back. Yeah. And people, they are okay to do a PGTA and so on.

So for sure we have a big selection bias here. So for sure it could, it could be extremely interesting. I think now, as Alexander saying, just looking at the patient or donors with Creo preserved, all sides frozen, and then look if we have the same, the same curves or not for sure.

There are age limits, but it could be extremely interesting. Yeah. But I think this is one of the main problems that you have just most likely younger donors, right? Because usually you don't take a donor who is above 38.

At least I'm not aware of all the donor programs, but to my knowledge, it's usually women less than 35 just to reduce the risk for any aneuploidy. But so I think there's a vulnerable patient population is really like women above 35 who wake up and feel like they still want to have a family. They don't have Mr. Hyde around and they decide to freeze eggs.

So I think for those, for this population, donor data will not be very helpful. I think the information that can get is what is the, I would say the information coming from the competence of the egg, or if it's only about aeuploidy. I mean, if you can, you can divide this, this part in a sense.

So information would be for me, just, just this. And for sure, the range of age is not potentially representative of all the patients that want to freeze for preservation. I would agree with Yannick also, and the donors can be potentially social freezers.

They can be, they have the same age. So they are potentially fertile women, all of them. The ones they want to donate.

So in a different setting, the other ones, they want to preserve their fertility, but they don't want to be mothers at this time. A bit younger, maybe, Nikos. Maybe they are a bit younger because they are all less than 35.

I think the paper, there was a paper about one aeuploid blastocyst in 2021. And they look at donors, this paper, they included donors and then patients for more than 34. It's a theoretical model.

It's not a real data. And Jim was mentioning that one. The reason why I asked you is also because there is an audience, someone who actually asked, because in their, that's actually Brazil, they are actually connected.

And they're asking, their egg freezing is mostly under 30. Their question is, so their, their, their patients are between 27 to 29 years old. And the question is, what would be a number that will give them a hope for a good outcome in the future? Given that we, in our study, we looked at everyone below 35, because this is the SART age groups.

But this person asked what should happen below 30. We have that in our supplemental because that actually came up. So we had, I gave this as a, I think an oral ASRM one year, and then a bunch of people came up and said, please look at the patients that are younger than 30.

And they're very similar outcomes to the younger than 35. So I would give them the same numbers. I would give them, you know, a 10 to 15 M2 goal for three euploids.

And so it's a great question. And another question, yes, please. We have published some data that very young donors 19, 20, 21 will give you worse results.

So we have published this in similar, in several papers in RBM online, which is quite interesting. And I think that is consistent literature that these women 19, 20, 21, in the OSHA donation group, they perform worse compared to women at 25, 26, 27, 30. And I think this is a common secret within the clinics in Spain, isn't it? When we have very young ones, we're really worried.

When you have more than 20, you're feeling more comfortable. I don't know what Alexander would say. Yeah, I've seen more or less the same results.

I don't know if because they're more compliant with medication or they're too young to follow treatment sometimes. But it's like in the FANASIAC paper, when you are looking at euploidy rates, I mean, also it's like this U-shape. Whatever it is, I mean, also younger women obviously do less good.

I would argue it's probably related to euploidy. And also there is another interesting question. What do you think IBM will actually bring to the table? Do you agree? Do you discard? Do you disconsider? Well, I do think it's interesting.

There's a discrepancy between sort of natural fecundity in the 20s, which might approximate 20 percent a month. So one in five eggs is a baby. To what we see in the IVF lab, we never get to one in five.

We get maybe to one in 10. So maybe the stimulations aren't entirely useful. Maybe some of the eggs we get, we're never going to be helpful, but they're in the mix and we can't tell one from another.

And IBM, that doesn't happen, right? We're not stimulating in the normal way. So do you think in the future egg freezing will be done to new ways of performing in vitro maturation? Could be. Could be easier to perform.

It's a very long shot. It's a very, very long shot. I think the evidence that we have up to now with all the settings, even if the best settings, that I think the best setting reporting results is the CAP-IVM done by the Vietnamese group, by Tuong and Lan, that they have very good plasticity formation rates still, it's underperforming compared to IVF.

So if I had my daughter to freeze the eggs today, or within the next five, six years, probably I would never consider doing an IBM today. In 10 years, I would be old also. And one more question from the audience.

What is your rate of efficacy in defreezing eggs? Where I am. Everyone's going to be close to a hundred percent. No, that's not true.

Stop lying. No, no, but this is, this is, this is, so it depends on the different settings. You, you come up to surprises.

We know very well. So the rates, the global rate would be around 90, 95%. I think, you know, in the good clinics, but still you have patients that they surprise you negatively that you throw and it doesn't survive and you say, why? So I think these outliers that you don't expect them is that creates more agony to you and you don't know how to and there is relevant the question of Yannick, how about the competence and what can tell us about the competence.

And the blastocyst rate after defreezing eggs, where would you point it out to be? I think it should be beyond 50, around 50 once you throw your eggs with a survival rate, as Nico said. Yeah. It depends on the age.

I mean, I had the Swiss because you're talking about, I had the Swiss patient coming to me that she had only three oocytes frozen. And I said, what a disaster. She had one beautiful blastocyst and she's pregnant.

She done two cycles afterwards and she never got pregnant. So, but she was 32. So this is very independent on the patient.

You, we have all the success stories and we have all the unsuccessful stories. So in our human brain goes to the extremes always, isn't it? I mean, I don't know. I'm not there.

I mean, you're the experts. And I have a question for everyone coming from, you know, different countries, depending on your policies and what you can do. When do you tell a patient, okay, this is enough.

Like what is the maximum if you have a patient coming in and how do you kind of counsel them? And obviously it sounds like some countries are limited. So I'm curious to hear people's thoughts. That's a great question.

It was good for you to say about when you're young, 25 is a good number, because that's a very good question for me. There would be no limit. I mean, I would always want to have some more in order to be confident on what we've done.

But of course, once you have your patient and you know about the ovarian reserve and you have some expectations about the number of eggs you have in one cycle, you, as Barbara said, we normally make a plan and you just say, okay, we can do a couple of cycles, three cycles. And normally, according to the number you had planned and the number of cycles and also how she felt during the cycles and how she needs to complete her hope, we decide. Sometimes patients, what they do, they do a couple of cycles and they come back in a year to do another one just because they think, okay, I'm not still using them.

So I may have some more in order to just, maybe for a second baby. So they think about it and they come back again to do one more shot afterwards. But yeah, it's something we tend to talk about with patients and it's not a fixed number.

I completely agree. Often I also discuss, I mean, maybe say they have a prospect of getting married like in two years. So I tell them, let's, I mean, let's just be on the safe side and we are happy when we have 20, but some others who take like, I mean, really pick one egg after the others, they are just fed up after a couple of cycles.

So I think it's really very individual and this has to go into the counseling. So, but of course, ideally until now I was with those 20 eggs, 15 to 20 eggs. But also in order not to frustrate some women too much, I think we also have to be careful throwing numbers like 50 into the room because then everyone will just close up and go.

Maybe we are a good wake-up call, I don't know. No, for me, if you ask me, it depends. You have to discuss it.

The counseling is very important. You have to discuss with the patient what the probabilities, explain what you expect and also see the financial resources. So the women that they cannot afford doing three or four cycles, this you cannot overlook it.

So it's very important. Secondly, you have to see how they're feeling after the first cycle. There are women that they are feeling nothing and they can do up to three, four cycles.

Women, they are not willing to do into this. And then what is their family plans? If she wants to have one child and that's it, definitely my goal will not be 25 overcides. I think you don't need this and you will go for lower.

And I'm a person that loves stimulation and loves high doses. But still you have to discuss it with the patient sometimes. I think what we do, we're in the room and we forget that there is a patient with specific needs and vision of your future.

And there is what we have to invest more time, listen to them. And then we then decide together. If you have them on board, no patient would be complaining.

They will all be happy because they are on board with this. This is your decision. I feel like the discussion is really taking off.

So it's very nice. And I'm sorry to cut it, but we have to close this journal club, which has been amazing. I want to thank each of you for your time to participate and for your input in this matter.

I just hope that some messages from this paper will be passed to our patients and hopefully it will improve their clinical experience. And I'm looking forward if any new ideas on how to calculate the numbers of eggs we need to obtain a pregnancy in the future will be reported by some groups that are doing this. And I hope I will cross you soon in real life.

Thank you so much for your participation and thank you, Yannick, for co-hosting, although I hope you're still here. Thank you very much. Thank you.

Thank you. Thank you. Bye, guys.

Thank you.