Hi everyone, welcome to another Fertility and Sterility Journal Club Global, and today's is truly global. We're coming to you live with the European Group of Panelists and Discussants. My name is Piotr Boronleto, I'm the Interactive Associate in Chief for Fertility and Sterility and Media Editor for Defense Reports, and today I have the privilege of not hosting and actually turning it over to two people who some of you know very well, Dr. Paul Poitier and Dr. Donda Ziegler.
Paul serves as an Interactive Associate for Fertility and Sterility and Dom has served in multiple roles through Fertility and Sterility, but currently an Editorial Editor for FNS. Today we're going to be discussing a really cool topic, something that I think gained a lot of traction once it was published, something that I think clinically, academically, we've all been talking about and wondering, and certainly our patients are asking us. The question is, does diminished ovarian reserve impact embryo aneuploidy or live birth rates? It just so happens that we have a wonderful paper from FNS published by Dr. Yuval Folks, who's one of our panelists today, to discuss this exact topic.
I want to turn it over to Paul and Dom, your hosts for the evening, and I hope all of you enjoy tonight's Journal Club Global. Thanks, thanks Piotr, this is fantastic. This is another Journal Club in Europe.
It's dark here, it's the evening, and I'm going to hand over the mic to Paul, who is like me at Opital Fosch in Paris, and I just want to convey that we have good news from Dr. Micah Hill, who is doing better and is going to soon be with us again. So Paul is going to actually present the authors who themselves will present the paper. Great topic, quantity and quality, this is what it comes down to.
And then we're going to discuss that paper and we're going to discuss the results. Paul, the mic is yours. Hello everyone, so actually we are quite lucky to have the authors here with us today, so they will be presenting their results and conclusions.
As mentioned by Piotr and Dominic before, this is a very cited and discussed, debated paper. So we are going to start first with Denis Vovin, who is actually a productive endocrinologist at Boston IVF and Baptist Health Deaconess Medical Center. He's also actually an instructor at Harvard Medical School and the Director of Clinical Research at Boston IVF, who will conclude the results that will be presented first by Yuval, which is actually an OB-GYN from Tel Aviv Medical Center and currently working as a Research Fellow at Boston IVF, and he's studying quantitative methods in the MPH program at the Harvard Chan School.
So please Yuval, present the results of your paper and we are looking forward to debate on them. Great, thank you very much. Hello and thank you all for the opportunity to share this work with you.
So in this work, as you mentioned, we were trying to assess a long-standing debate about ploidity rates in patients with diminished ovarian reserve and also with patients diagnosed with poor ovarian response. Specifically, we're trying to account for the inherent design difficulties that arise when you explore this topic. So we can start, I guess.
The presentation is on air. Great. So embryonic and ploidity, we can do the next slide.
Embryonic and ploidity results from several types of chromosomal segregation errors and those segregation errors affect an exceptionally high number of human conception. They cause infertility and miscarriages and congenital disorders and those segregation errors basically have distinct age dependencies which impacts our reproductive lifespan. And in this sense, diminished ovarian reserve is a source of stress for patients but it's also a management challenge for the practitioners.
It is still unclear whether patients with DOR show their poor reproductive outcomes due to their lower ovarian response or whether there is an additional qualitative morbidity which could maybe translate to more genetically unbalanced embryos. So patients and indeed many physicians incorrectly conflate oocyte quality and quantity and the consequences of that could be missed opportunity for childbirth with the autologous oocytes. Next slide.
We performed a comparison of an ovarian ploidity rates based on propensity score matching. We used a large retrospective data set of patients younger than the age of 40 which were diagnosed with diminished ovarian reserve and poor ovarian response to stimulation as a secondary analysis. Additionally, we compared live birth rates per transferred embryos and focus on the events of cycles that ends up with no ooploids to transfer.
We can go next slide. In terms of study design, our study period was between 2014 and 2020. We have used only next generation sequencing platforms and basically the study started with 2200 patients roughly under the age of 40 in their first IVF cycle.
Of these patients, 383 patients were diagnosed with diminished ovarian reserve and 143 patients were diagnosed with poor ovarian response. The criteria for DOR were clinician diagnosis in charts, codes and an additional AMH cutoff of less than 1.1. For the first primary comparison that was the DOR versus non-DOR, patients were matched in a ratio of 1 to 2 and for the POR group, the poor ovarian response, the matching was 1 to 4. Next slide. Next slide.
So, we used propensity score matching as a statistical technique to construct an artificial quote-unquote group by matching each treated unit with the non-treated units of similar characteristics. Using those matches, we could then estimate the impact of the exposure, which was in this case, the diminished ovarian reserve diagnosis. So, we chose age, BMI and cycle year as covariates in order to avoid an unbalanced model.
Let's talk about the results. So, the propensity score matching is basically the new output sheet here and we can see the characteristics of the DOR versus non-DOR patients and the matched populations, which were matched successfully on the top of the table. And as seen in the post propensity score, the unmatched characteristics such as the ovarian markers and the cycle performance, AMH, AFC, FSH, and the stimulation still differ between the group as obviously expected.
And the unemployment rate in the given stimulation, it's still the previous one, the simulation cycle between the DOR and the non-DOR group did not differ significantly after applying the propensity score matching and the rate was 42.2 versus 42.1. So, for this specific comparison, even though that it's part of the table, we performed a Poisson regression analysis of aggregated data in order to model the total number of embryos biopsied in so-called offset. That means that we wanted to see the clustered embryos between each subject that obviously differs between those two groups. The meantime, couples attempt to conceive did not differ between the groups.
It was 40.1 months versus 13.3. Having this new matched population set, we wanted to check for several potential classifiers, as some have been previously mentioned to be potential surrogates to ploidity. So, first, we went to check AMH for correlation with ploidity. The AMH was divided into three subgroups by percentiles, less than 25 percentile between 25 and 75 and more than 75.
And after age adjustment, there were no differences in the ploidity rates. And that was also reported two years ago in another study. Next slide.
As to fertility outcome, our results show the same per-transfer rate. As you can see, we had similar per-rate miscarriages and pregnancy rate. And when it comes to cycles that ends up with no aeoploids to transfer, those were actually higher.
The crude number was actually higher in the DOR group. However, next slide, when we plot the expected frequencies of those scenarios of cycles that ends up with no aeoploid to transfer, we can see that each group, in each group, the two polar conditions, all aeoploids and all anaeploids, were both fairly frequent and much more frequent in the DOR group. And the reason for us was simply that the mean number of biox embryo per subject were lower in the DOR than the control.
Therefore, the observations of cycle that end up with no aeoploids to transfer is basically the numerator and not the denominator. It's basically what the patient feels. So after adjustment for age BMI, there were no differences in ploidity rates here.
So, to conclude, our result indicates that patients diagnosed with diminished ovarian reserve, who achieved intublast stage, have the same chance of achieving aeoploid embryos to their peers in the general infertile population. And once an embryo is transferred, blasts and biops, there is a similar live birth rate. Thus, the true rate limiting factor of achieving live birth in those specific patients would be the extent of their response to stimulation during a given cycle.
Moreover, patients should be informed and reassured that cycles that concludes with no aeoploid to transfer are the main results of their lower ovarian response and are not associated with any qualitative morbidity or reduction. Thank you very much for your interest in this work. Thank you for your listening.
Dennis, can you conclude on these results? Because they are very important for our field and for the clinical work that we do every day with our patients. Yeah, terrific. So I think the big take home message is that in patients under the age of 40 who can obtain a euploid embryo, they can be reassured that their embryo is as likely to be euploid when biopsied if they're able to achieve that blastocyst, which, as Yuval said, is a challenge in itself.
But once we've obtained a blastocyst, as likely to be euploid and subsequently as likely to end up in a live birth as somebody without diminished ovarian reserve. And so, you know, obviously, we're going to get into the nuts and bolts of the study. But just a couple of things to point out up front.
You know, I think that we have some limitations in that obviously it's a retrospective study. We needed, the patient needed to have one blastocyst to biopsy in order to include them in the study. And as we know, that can be a challenge for patients with diminished ovarian reserve to make a blastocyst.
However, we did look at blastulation rates between the two groups, and they were similar when we use two pronuclei embryo as our denominator. And also, we didn't report mosaicism in, and that's a Boston IVF protocol. We don't report mosaicism, but we know from, you know, work by Carlos Simon and others that low and medium grade mosaic embryos behave as well as euploid embryos.
And so, each of the labs that we used have their own various cutoffs. Most of the embryos in the study were analyzed by three main labs. But we know that there are some differences in ploidy rates according to the lab analyzed.
So, there are some limitations there. But overall, I am, you know, excited and happy that this journal or this article was chosen for this journal because I do think it adds to the existing body of literature to reassure these patients. And as Dr. Falk said, there are patients who won't get a euploid embryo, and they're more likely in these diminished ovarian reserve group.
But we know, again, from a great article by Richard Scott earlier this year in FNS that those patients can cycle again and they're no less likely to get a euploid and another cycle without a euploid embryo. So, patients should be reassured overall that if they don't get a euploid embryo, they should be encouraged to try again, if possible, if they feel up to it. And if they do get a euploid embryo, that their outcomes are the same as somebody without diminished ovarian reserve.
Thank you, Dennis. So, actually, yeah, we chose this paper because we think that it's relevant and it is clinically useful and that it should reach out to as many specialists as possible because it could be the patient needs to be reassured. But we're going to start the debate.
So, I will first introduce you Sherry Mackens, who is actually the medical director and clinical professor at IVF Center of Oblique Medicine at Brussels Free University Hospital. And she actually has a specific interest in translational research, focusing on the role of the nematode in ART. Not the case right now.
This is about the embryo. So, Sherry, what are your takes on the results and this paper? Before Sherry starts, I just wanted to make one comment for the audience. You can actually have access to the article, which is published in FNS, and you can download the article.
So, check by yourself the facts. And now, Sherry has her comments to make. Yeah, thank you, Paul and Dominic, for the introduction.
I'm very happy to be with you tonight. And congratulations to the authors. I first would like to compliment you with your work.
As we said before, it's very important data, especially to counsel patients, of course, who are scared when they get this label of a diminished ovarian reserve. So, it is extremely interesting that we have this reassuring data from your study after the matching that you performed, taking into account the pitfalls of the retrospective vision of your study. Very interesting data.
However, my main question and my first question when I saw your tables and your article is what we also see in daily clinical practice, which is how difficult it is to label patients that never went to IVF to have diminished ovarian reserve. You included them before their first cycle. And then what you see, actually, is that they had quite a nice number of oocytes.
They have nine oocytes at the moment of pickup. Probably because, indeed, you select the ones that did have embryos to test for PGTA. So, how do you think that we can improve this also for the future? This labeling of a diminished ovarian reserve and re-estimating how patients will perform after stimulation, it's really a challenge for clinical practice.
And do you think that this patient population that really has a diminished ovarian reserve, do you think that you really capture them within the data that you have now? So, first, thank you very much. That's a great question. So, I think that in terms of your first question about how did we determine the press cycle and the diagnosis of DOR, I think that that was the main importance here, that we have picked them up by the AMH, AFC, and FSH level.
And then by this, let's say, by this medical determination, re-evaluate them almost blindly. But our second, please remember that our secondary analysis was actually the POR, the poor viral response. And in those cases, basically, as we can see in the study flow chart, we have almost validated our results, and they were practically identical in cases of DOR and POR.
And there was also a population overlap between those two. And the fact that we got the same statistical and clinical inferences for those group is actually pretty reassuring, first, for the clinical designation of the very definition of DOR, and second, for the validity of our result. Yes, exactly.
I think that you did a very good job with looking at diminished ovarian reserve, but also your second analysis that you did, where you really looked at the outcome. I fully agree with you that this really strengthens your message. Another question that I ask myself when I see patients at consultation is whether I should take into account their reason of having a diminished ovarian reserve.
I imagine that a patient that has a diminished ovarian reserve, iatrogenically, after an operation for endometriosis, for example, can be a completely different patient than somebody who has no surgical history and where we cannot really pinpoint the reason of having a diminished ovarian reserve. Do you have any ideas on how we could have other approaches towards these different kinds of patients? I would like to, before you answer, I would like, I mean, this is an excellent question, excellent question. I would like to expand.
Did you check for smoking? Okay, now in Europe, I know in the U.S., people don't smoke anymore, but in Europe, people still smoke, and this may have an effect on oocyte quality, and this may actually be different than women who've had, as Sherry said, surgery for endometriosis. That's a good point. I think just to back up to the original question, you know, the pre-cycle diagnosis of diminished ovarian reserve is notoriously challenging, and, you know, clinically, we at, you know, Boston IVF will, in order to assign somebody a diagnosis of diminished ovarian reserve, we really try to look at the patient holistically and not just one isolated data point, and so typically, you know, for this study, we use AMH of a 1.1, but also the enthalphalic count is taken into account, also the FSH is taken into account, but to both of your points, the underlying rationale or reason behind the diminished ovarian reserve also has to be taken into account, and like Tom said, fortunately in the U.S., the smoking rates are extremely, extremely low, at least tobacco smoking, now marijuana smoking is starting to increase, but in our population of Boston IVF, it's only about 1% of the population that smoke, or at least that report smoking, and so that in itself is unlikely to play a huge role, but other reasons such as previous exposure to kinetotoxic therapy, for example, that's a reason patient may have diminished ovarian reserve and may also affect egg quality, but overall, I still think that, you know, age is going to be the single biggest predictor of outcome here, irrespective of ovarian reserve.
Sorry to interfere, but the question is why did you put a cutoff at 40? Why didn't you go to 42, or even more? So, yeah, that's a great question. So we have, in my head right now, there are three major studies around this topic, one picked up the age of 40, the other 38, and there is a, you're right, there's additional one who picked up 42, which comes again to the broad and heterogeneous definition of DOR, there is no specific agreement about the specific cutoff. We have chosen 40, as most of the studies previously have chosen 40, and it's important to mention that we haven't done any variable screening or pre-analysis or on our own material to pick up the threshold, we just pick it by literature knowledge.
Yeah, it's somewhat arbitrary, you know, granted our blastulation rates are going to be dramatically lower in the patients over the age of 40, and our aneuploidy rates are going to be much higher, but it is somewhat arbitrary cutting, choosing 40 as a cutoff. So, I have some more questions, but Sherry, yeah, go ahead, please. Yeah, it's probably a very, very difficult question, but you had this number of patients, and I guess that you started the retrieval of your patients with the embryos that were there for biopsy.
Do you have any estimation when you take the same parameters for your diminished ovarian reserve population, how many more patients you would have? It's probably very difficult to have an idea on this and to retrieve them, but do you have any estimates on that? We didn't look for this particular study, we didn't look at it, but it is a really good question, and I'll pose this, I guess, to the group in general. If we were to design a retrospective study to try to delve a little bit deeper from almost like an intention to treat analysis, how do you think that best would be achieved? Because obviously, we recognize the limitations in choosing those patients who only make a blastocyst. How would you guys go about analyzing a large data set to try to get down to the core question here, which is the OSI competence in these patients with diminished ovarian reserve? We're going to... This author who is presenting his paper is now asking questions.
This is a reverse order. The participants have to answer, I guess. I always like to be contrarian.
Yeah. We're going to leave Cindy Argento to actually debate also on your paper. Cindy is actually a fertility specialist in Clinica Vale Giulia, GeneraLife IVF Rome.
She's there since 2018. Then before that, she was actually for 10 years in Modena. Everyone knows what Modena is known for.
Cindy, please, we'll try to debate the paper and maybe answer then on the question he has. I have to thank you for inviting me here. I'm very excited to be here.
I'm very happy to discuss about this topic because it is so accurate, so important. One thing I would like to say, yes, I think one of the main features is actually the definition of these patients, you know, the diminished ovarian reserve. We have a very particular setting.
You know that Italy is probably one of the places, one of the countries where couples decide to have children later. So that in the first place is a problem. It's an issue.
Patients that, the mean age of patients that we see in our clinic is 39.6 years old. So our population is generally diminished ovarian reserve because of age simply, even if we don't want to look at other features for their infertility. So we have, I'm very happy about this paper because this expresses exactly what we see every single day.
And the data that are, that come out of this beautiful work is actually what we see. And it confirms what we find in our general clinical practice. I think the main issue is actually that these data are so important to counsel patients because even if they are actually coming in for their first treatment ever, although I must say it is not, it's often not like this in our setting because being a private clinic, many couples have already undergone other treatments elsewhere.
But apart from this, we have, I think the, we have to counsel patients. And the first thing we have to tell them is actually that, yes, you don't expect to come in and just say, I do the treatment. It's either yes or no.
No, we have to make them understand that it's probably a journey they are starting. And these data actually helps us, help us to correctly counsel couples before starting. We have enough evidence now to assume that although their ovarian reserve may be diminished, although their age may be not so young, they still have the possibility to achieve a healthy embryo and their history of diminished ovarian reserve has no impact on their live birth rate.
But this can help us to actually find strategies to avoid patients like dropping out after the first cycles because either they haven't obtained a blastocyst at all or they have obtained a non-healthy blastocyst. You very well know that we work a lot with the double stimulation protocol and that helps us a lot because it actually gives us a chance to accumulate more oocytes and more blastocysts to test and eventually to have more euploid blastocysts to transfer in these patients. So it's a thank you because this actually helps us to show patients that there are consistent data showing that they have to go on and continue with maybe more than one treatment, but they have a very good possibility to achieve euploid blastocysts regardless of their diminished ovarian reserve in the first place.
I would like to make a comment, just not a comment but a request to Cindy. You talked about dual stimulation. Do you want to say a couple of words about that? Because I know your group has been working a lot on this and I think it's important when you go ahead and just tell people what it consists in.
It's actually the possibility to do two subsequent stimulations in the same menstrual cycle starting on day two with a conventional stimulation and doing a normal egg retrieval when it's supposed to be done and then five or six days later after the egg retrieval we start a second stimulation on the luteal phase because we have seen and data have shown now it's not they're not they're not I mean they're now very consistent that the eggs retrieved are pretty much the same or even more in terms of number and the blastocysts produced from the two cycles then are pretty much the same as far as quality as far as euploidy rate. So that means that patients that have a diminished ovarian reserve or a high age can have lots of advantage in trying to do actually two cycles in one month and apart from the fact that they actually can retrieve more oocytes and have more embryos it actually reduces dropout because once they start they're actually you know on the run and it helps that helps them being consistent on the treatment till the end of the two stimulations and it's giving us lots and lots of satisfaction I must say. Great and I think just to comment on what Cindy just said I think part of our job as reproductive endocrinologist is not just to choose you know the optimal protocol for the patient in order to maximize outcome but really to support these patients through the journey you know without giving them false hope but be able to predict and realistically predict their outcomes and just make them aware up front that this is not likely going to be a one-and-done situation they're likely going to have to go through multiple cycles so that they are comfortable and accepting of that fact up front and they're not shocked when the first cycle doesn't work out as we might hope.
Yeah so Deniz I'm going to try to address the issue of how to assess the data so I fully agree with you on the topic that data on a DOR it's very complicated. First of all the criterias for DOR were arbitrary so we just like put a cut off there and we assume that that's the real case but data even today after the blown Poseidon and everything data on DOR is very let's say non-conclusive and it seems that from what I've seen and read that most of those patients behave much better on a second cycle than the first one so if you were to say like you talked about your limitation by the fact that some had the first attempt done and probably behaved better than you estimated based on AMH FSH for equal count is that in the end you can never get to the bottom of it because maybe in the next cycle they will even do better than the first one so I think it's something that you cannot control for and I think that between DOR and POR so diminished ovarian response there is also a big difference because your diminished ovarian response is based for example on AMH quite variable some patients don't really act of course AMH is important but not that precise like one oocyte or more and also in some patients maybe you have let's say you had more oocytes but doesn't mean anything they don't fertilize and this is why for me the fact that you calculated for vacillation rate and fertilization rate was quite convincing so I do not have a clue on how to ideally calculate the data actually I'm very happy with what you did and I probably would have done the same if I would have thought of it my only question is around the mosaics because so we are talking about limited embryo patients so we don't have that many and you have excluded mosaics but and you know that nowadays that those data that show that some mosaics in plant are true but they also say that some mosaics are actually euploid so it seems like 20 to 30 percent of those embryos who have been labeled mosaics with the new techniques and new logistics they seem to be euploid and that's actually the I mean it's 2018 in your in your data but there are laboratories that actually right now they acknowledge the fact that due to the pressure of having to deliver a precise result or label for the embryo in some cases where they were like non-conclusive or anyway signs of not euploidy they they label it right away an euploid or mosaic in this case and therefore they would not have been included in your data great I think you know ultimately that comes down to a limitation of the the testing technique itself right we know that PGTA by trophectoderm biopsy is not perfect and we're trying to make a generalization from four to six trophectoderm cells of the general representation of the entire embryo at a particular snapshot in time of development of that embryo and we know that there can be changes in the relative proportions of aneuploid or different cell lines as the embryo grows and develops and so I think ultimately you know that's one of the strengths and limitations again of this of this study is that you know maybe looking at aneuploidy rates by trophectoderm biopsy isn't the end all and be all ultimately obviously is take home baby and looking at a study like this in in embryos that are just transferred rather than going through PGTA in itself would be would be interesting but that wasn't the question here because PGTA is so commonly used in the United States at our clinic actually is a little bit less than than the average for the United States we do PGTA in about half of our IVF cycles but it's it's not a perfect test but do you think that would have changed the conclusion I don't think so because it should be evenly distributed among the groups I really don't think that would have changed our outcome dramatically even if you include sorry even if you include mosaic in your study of course it's a trade-off because because you can end those and have a different denominator however when you when you do have mosaics and you discuss with the patients about the mosaic and you have different lab with different thresholds it's kind of a different story when you compare it of being blind to all of that it's quite less noise in your data your data without everything is just it's not pure it heavily of course it's limitation but on the other hand there is also a counterargument for for including various types of mosaics virus type types of call rates the discussion itself with the patients do you agree to transfer this kind of mosaic yes or no I think it will it will add more confounders to the issue it will be an advantage also yeah I agree it's a trade-off and not every patient would be comfortable transferring a medium mosaic or a high mosaic and that in itself would change our live birth rates at least I would like to sorry I would like to for a second to get back to the issue of quantity and quality because we talked I mean the essence of the paper is to really convey the message that when quantity is diminished quality is preserved 48 okay so that's very well taken that's the essence of the message that you are conveying my question is uh there were uh data there was particularly one very spectacular seminal paper by the group in Belgium which concluded that irrespective of how many eggs you get the retrieval you approximately need 20 oocytes for a baby do you have any idea in the numbers that you got I know it's not discussed in the paper itself but did you have any idea as to whether this uh quantity issue remains a parameter for uh ART efficacy um so we previously looked at you know trying to come up with an optimal number of oocytes during an IVF cycle and and we've previously demonstrated that even if the relative efficiency decreases as the number of oocytes increases the absolute number of embryos is still higher and therefore you have more embryos available to transfer so if we look at cumulative live birth rates from one retrieval ultimately the more eggs that we can can retrieve the likelihood is that that will correspond to a higher number of live births per per retrieval so I'm sorry to bug in but um so given your experience now that you've looked into this data given these patients with DOR POR what would be for you the incidence of recurrent aneuploidy complete aneuploidy because this is like a more clinical question because the question is you could do an IVF you have nothing to transfer you do the second one you have nothing to transfer when do you start to worry or what's your take-on or the likelihood for you to believe that this patient will achieve someday to have euploids to be transferred given that it's a DOR patient? That's a good question um you know I think looking at Richard Scott's paper at least 50 percent of the patients who didn't get a euploid embryo in the first cycle subsequently had a euploid embryo so I do really think that for the majority of patients that it's a numbers game and that if you do enough cycles and they're getting to embryo biopsy and that it's only a time before they get a euploid embryo now it's a very different situation for patients obviously who cannot make blasts but I do think that at least when I'm counseling my patients clinically I do encourage them not to read too much into a single cycle or a single data point and that it's really the pattern that's emerging from the behavior of her oocytes across several cycles that would lead me to conclude her overall prognosis. Cannot agree more? I fully agree with what Dennis says so in Brussels we're not working in the in the PGTAA setting it's not common to test our embryos but you feel it clinically that when your patient has the potential to develop a blastocyst then they keep on getting these consistent chances to conceive with a morphologically normal blastocyst you just have to take into account the 40-45 percent aneuploidy of course corrected for age that Yuval and Dennis also show in their paper so you need more embryos because you do not see aneuploidy but when you have blastocysts and when you continue we also see in our clinical data that their implantation rates and their live birth rates that they stay consistent over multiple cycles and this really relates to your paper as well Paul where you check your consecutive euploid embryo transfers where we see quite consistent chances and it's a play of statistics and I think that this play of statistics is really the answer for many many of the questions that we are answering in today's clinical research questions yeah so Dominic and I were talking today Dominic do you want to have a word on the paper that we discussed today well yeah we looked at the paper that came from Italy from Antonio Lamarca who at first glance seemed to indicate opposite results but when you look carefully this is an article that came out in Human Reproduction but it actually looked at the chances of having a one-euploid embryo and in that paper they conclude that with diminished reserve you have less chances goes back again to the issue of quantity and quality of course if you have less 2pns less embryos to begin with your chances having one euploid is going to decrease but as you said the euploidy rate or aneuploidy rate is not modified so I want to convey this and Paul is right because this is an article that came out at about the same time and gives the false impression that it is providing results that are in conflict with those of the BOSNA IVF group I don't think so I think it's a different perspective and I think nothing is the right perspective either so actually this is those are my thoughts about this article it's important to say that because some of our people in the audience may have been aware of that article and I don't think that it stands in opposition it's just a different look at and it's a look that confounds the issue of quantity into their results you probably read this article so you want to comment on it yeah I agree that it's the papers that paper is slightly different to ours and I don't think that it is exactly contradictory and I think that there are many other papers that have been published in Fertility and Sterility that show slightly different results to ours too but it you know every paper is not without its limitations we've acknowledged ours but I think it is interesting and it is important for us to have different results among different groups because it gets the conversation going stimulates discussion and moves us hopefully closer to the ideal study or to get the ultimate answer because as we as we recognize nothing is perfect and not all results are generalizable across different populations I would like to expand a little bit your conclusions into a practical issue which is that of fertility preservation we have more and more women sometimes the cost is covered by employer like amazon or whatever to actually undergo fertility preservation so that they they're not disrupted from working and they can postpone childbirth now at one point there was a concept that if AMH is low they shouldn't do that because it ain't gonna work do you want to comment on that because that doesn't seem to be true no well honestly I think the efficacy of the oocyte preservation is age dependent I mean if I have a 30 year old or 32 year old and she has four or five antral follicle count and a low AMH I will do it maybe I will do two retrievals but I will definitely try and you know push her to do it even even more because if she hasn't reduced to very reserved when she is very young and she postpones childbirth when she gets to you know the time when she would like to would want to do to have a baby situation will definitely not be better so absolutely yes and I think it is age dependent more than AMH dependent because if I can you know I have an older patient who wants to freeze her eggs when she's like 39 or 40 even if her AMH is average and it's okay for her age what can I do with those eggs in the future so I think the challenging part there is you know we there is a nice paper by Jamie Griffo and the folks at NYU looking at utilization rates but we really don't have a lot of outcome data on elective planned oocyte cryopreservation and it's we're mathematical modeling that people are using to give patients estimations of what it's likely to look like at the other end when we go to thaw those oocytes but I have a bad feeling that there's going to be a lot of patients disappointed because right now only 15 percent of patients who freeze their eggs at Boston IVF have come back to use them so we have a lot of stored eggs and you know it's going to be disappointing especially for those older patients but they are not infertile patients in the first place so that's why probably they will not use their eggs because they will conceive naturally who knows that could be a reason I would like to make a comment on the utilization rate okay because this has been said by many that women for the most part don't come back this does not mean that fertilization preservation has not helped them sometimes to actually relieve the stress allows them I'm gonna make it this a little French way and maybe not politically correct but this is gonna probably allow them to go from looking for Mr. Right to actually actually falling in love with Mr. Not Too Bad and so it may help even if they don't use it we do quite some vitrification of oocytes here in the center and what Dominique says is exactly the return that we have out of our patients so we counsel them very correctly and each and every of these ladies is aware of the fact that we can give no guarantees but they really have a peace of mind knowing that they did what they could and it really helps from a psychological point of view and the return rate is not that high because many of them conceive naturally but when we ask them afterwards whether they regret of having done this this is not the case at all it's a very very important remark I think yes I absolutely agree I think that you know it's just important for especially for our older patients who are freezing their eggs who are you know in their late 30s early 40s and feel really positive that they've frozen 15 eggs and it sounds like a lot and then you know when they come back unfortunately the as we see the thawing fertilization blastulation rate is lower and I've had you know the opposite of patients who said I was falsely reassured that I had eggs frozen and I was holding out for Mr. Wright because I had the luxury of having these eggs frozen or so I thought so putting all your eggs in one basket so they say.
In terms of talking about oocyte quantity and quality and AMH I want also to convey a comment from a paper we had several years ago when I was still in Switzerland indicating that AMH does not predict women's fecundity we had looked at AMH in women who attempted to become pregnant and had done something very smart they had stopped taking the pill okay and we looked at the time it took them to conceive anywhere from 1 to 15 months there was no AMH measured before there was no correlation whatsoever in all these women who conceived and delivered there was no correlation between their AMH level and the time it took them to conceive so women who come and now they're being panicked and they measure their AMH at the age of 30 it can be high or low but does not predict fecundity just pretty much like body height not a prediction of intelligence I mean this reassures me because I'm not very tall but this is again I think that's it that's an important point and one of my all-time favorite reproductive medicine articles was published by Ann Steiner in JAMA in 2017 and looked exactly at that look at patients who are planning to conceive over the subsequent 12 months and demonstrated what you just said Don that AMH was not predicted and ovarian reserve markers in general were not predictive of fecundity so that's important for our patients especially those who are planning on getting pregnant in the near future it's a very different situation for those on the ovarian reserve who are not planning on conceiving for many years so given that actually we are going still eight minutes left so I'll make I'll leave you just a few moments to try to make some conclusions for the end of the discussion for each of you I will just make two announcements so the first one is that the best of ASHRAE and SRM conference will take place in March so this is an event that takes place every two years it's one time in Europe one time in the US this time is going to be in Orlando United States it's going to be held between 2 and 4 of March and the second announcement is that the next general club will actually happen during that meeting so the second to the fourth of March in Orlando so we count on you and your presence there and I think it's going to be very interesting so look it up so now please we're going to start with the authors or no let's go for the ladies first Shari what's your conclusion on the discussion of today so again congratulations to the authors you you did a very good job I think it's extremely important information we have now in our consultation boxes to reassure patients that have a blastocyst two tests that they perform equally well no matter how many all sites were present in the beginning of the cycle but we need to be aware of the fact that it does not cover the entire spectrum of what we see in Clinica and that the study only started upon these blastocyst two tests but very reassuring and important counseling information congratulations Cindy yes I actually yes exactly what Shari said it's as I said before it was really it's really good to have these consistent data which are real data it's not only your opinion as a clinician to show patients and it is thank you so much we hope to have more and more publications like these because they give you actually you know precise information that can be really useful and not you know just abstract data that are quite useless for you know the man in the street so thank you so much you will and then is do you have some key points you underline first of all thank you very much for your words I think again that our most significant limitation here is that our study is prone to to these survivals bias those embryos that did not reach into blast stage are simply overlooked and that's not only our in our study that's in every other retrospective study however this this notion does not mean does not limit our generalizability it's just limited to the specific scenario again that when a patient which is DOR diagnosed as a DOR or poor viral response patients reach to a blast stage her chances are similar to her peer with an other non-DOR diagnosis and that's the essence I think of our of our data go ahead go ahead on this no I just was saying that I would you know use this data along with the the um EVRMA data to really encourage our patients um to help counsel that not only um not to be too upset or disappointed if the first cycle doesn't work out that if they are you know persistent and and uh show tenacity that eventually a large proportion of them will have success and so I think that's reassuring for patients who either have diminished ovarian reserve or who don't get a euploid blastocyst on the first cycle this this was a great a great journal club a journal club in Europe I want again to that we all convey our best wishes to Micah Hill who actually uh was in charge of the journal clubs and was the first one who actually contacted me to have them uh also in Europe on the European time this was a great experience and we're going to continue that uh Fertility and Stability is a journal as an international journal we're all under the uh guidance and uh of Kurt Barnhart and this is a fantastic uh journal the journal club is an extension of our journal and we may have journal clubs being held now also in other places in the world not just Europe and the U.S. but possibly Asia and elsewhere so again thank you all for participating thank you Paul for directing this discussion thank you for the authors thank you for the ladies you did a superb work uh last but not least superb work in discussing uh these articles uh quality and quantity two different things what counts is quality not quantity thank you all thank you for the organizers at Fertility and Stability who are behind uh screen and actually uh make this possible T.R. Wright uh thank you all and uh have a good evening and have a great day if you're in the U.S. bye bye thank you have a good night thank you
