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Fertility and Sterility On Air: Live from the ESHRE 41st Annual Meeting (Part 2)

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Fertility & Sterility on Air is at the European Society of Human Reproduction and Embryology 41st Annual Meeting in Paris, France (Part 2)! In this episode, our hosts Kate Devine, Eve Feinberg, and Micah Hill cover:

  • Discussing the state of assisted reproductive technology in Brazil with Giuliano Bedoschi (01:01)
  • Whole transcriptome and genome sequencing of standard embryo biopsies can potentially reduce failed euploid transfers with Kaylene Ready and Jeremy Grushcow (09:03)
  • The use of AI in ovarian stimulation with Eduardo Hariton (19:45)
  • Modeling embryonic adhesion at cellular resolution within a microfluidic endometrium-on-a-chip platform with Sofia Zaragozano (32:33)
  • Assessing the ploidy status of atypically fertilised embryos – recovery of embryos for potential clinical use with Sharyn Stock-Myer (40:41)
  • Role of micronutrients and probiotics supplementation on reproductive outcomes in an oocyte donation program with Sara Maggi and Silvia Bonta (42:47)
  • Male infertility, life expectancy, and long-term health risks: exploring what can sperm reveal about health with Omar Ammar (58:00)
  • Mitochondrial DNA ‘reversal’ is common in children born following meiotic spindle transfer, potentially reducing the efficacy of mitochondrial replacement therapies with Munuse Savash (01:05:57)

Welcome to Fertility and Sterility On Air, the podcast where you can stay current on the latest global research in the field of reproductive medicine. This podcast brings you an overview of this month's journal, in-depth discussions with authors and other special features. F&S On Air is brought to you by the Fertility and Sterility family of journals, in conjunction with the American Society for Reproductive Medicine, and is hosted by Dr. Kurt Barnhart, Editor-in-Chief, Dr. Eve Feinberg, Editorial Editor, Dr. Micah Hill, Media Editor, Dr. Pietro Bortoletto, Interactive Associate-in-Chief, and Associate Editor, Dr. Kate Devine.

We are back live at ESHRE in Paris 2025. I'm Micah Hill, the Media Editor, and I am joined by a good friend of the F&S On Air podcast, Giuliano Bedoschi. You say your name right.

You say it. How do you say it? Giuliano Bedoschi. Oh, that sounds so much better when you say it.

I don't have the accent right. So, Giuliano is from Sao Paulo, Brazil, correct? Right. And you are an REI? Amanda is with us also.

You guys practice? Yes, she's an REI as well, and we practice in Sao Paulo, Brazil. Nowadays, I'm serving as the Vice President of the Brazilian Society for Human Reproduction, and I was very glad to receive, to welcome Micah and Pietro in Brazil in our last conference, past conference in May. Yeah.

I'm a great enthusiast of long-form fertility research, and also it's good to be here at ESHRE and meet some friends. So, amazing to be here, Micah. Thank you for the invitation.

Well, we appreciate the invitation to come out to Sao Paulo. Pietro and I had a wonderful time. We were so impressed with how many REIs are in Brazil, how scientific the meeting was that you put on, how big the meeting was that you put on.

It was very scientific and very professional. So, just give us a scope of sort of IVF in Brazil. Wonderful.

So, Micah, nowadays we have more than 200 million people living in Brazil. Yeah. So, huge country.

And our IVF, Micah, comparing to different countries, it's not so large, it's not so big. We're doing probably something around 50,000 cycles per year. Okay.

So, we're doing okay, but not as much as we should. So, probably we have a big, huge access problem in Brazil. In Brazil, the reproductive medicine fields, the patients get access by public health or private health.

So, we don't have this supplementary health, the health insurance companies, they don't go over for IVF treatments in Brazil. And the problem is that we think for public health, we only have 10 different centers around Brazil. And from these 10 different centers, we only have two that do the fully IVF for free for patients.

Okay. The other eight, they do like, okay, the treatment, the IVF, the lab treatment, but the patients need to pay for the medications. Okay.

And so, I think that nowadays what they're facing in Brazil is trying to deal with the access for patients, because we know that we have the capacity to treat more patients, but they don't have access. Okay. So, I think that this is now what we're facing in Brazil, the difficulties.

But we have a large community that is very dedicated, they're dedicated doctors, embryologists, and nurses, psychologists, and we're trying to do big conferences. And we're very glad to have Micah and Pietro with us doing a live journal club in our edition, in our press conference. So, we're trying to do the best that we can to improve.

Yes. And that journal club will be dropping soon. So, for all of our listeners, be sure to log into fertilityandsterility.org and listen to that amazing journal club that we did in Brazil.

It's in English and it was a very good discussion. So, that's fascinating about you have the capacity, but the access is an issue. In the US, access is an issue, but so is capacity.

We're also, we need more professionals, embryologists, good nurses, REIs, urologists. Yeah. Micah, we're facing the same problem, because we don't have too many centers to form, in a proper manner, specialists.

Right. So, this is also a difficulty that we face in Brazil. Okay.

Very good. So, how have you liked ESHRE so far in Paris, apart from the 103 degrees today? How have you liked Paris so far, in ESHRE specifically? Micah, you being a Brazilian, it's very hot for us as well. But despite of that, it's amazing to be here in ESHRE.

We really enjoy to be here. I think that the Brazilian community here in Brazil is very large. If you see for the different countries, Brazil, I believe it's in the top 10.

That's in an ASRM conference. In Brazil, I like to go there. And it's amazing, Micah, I think to see, to be on the top of the science for the best papers that are presented.

So, I had the opportunity to see some conference about the randomized controlled trials that were presented. So, we had the section on that. As I was talking to you earlier, I liked the conference on artificial intelligence, that I think that will be the future, not only in the lab, but also to improve our assistance with patients in the clinical part.

And also now, I was just listening to some great lectures on genetics and infertility. Now, especially, I was listening to a part in an andrology session in male infertility, and how many genes were discovered these past few years. So, it's very good to be on top of the research, to know everything that we can offer, these tools that we had to then try to use these to counsel our patients.

So, it's good to be here internationally. Yeah, that's wonderful. That section with the randomized controlled trials, had some really interesting findings.

A lot of null findings, but that's also helpful to discover that that's something that's not an intervention we should be doing. And for our listeners, we've invited most of those researchers to come talk on the podcast. So, you'll be hearing them throughout these two episodes of F&S on Air, live from ESHRE.

So, I just want to give a shout out to the meeting in Brazil. The next one will be in two years, is that right? In two years, in Belo Horizonte. That's a nice part of Brazil? It's a nice part of Brazil.

Is it near the beach? It's a countryside city. It's a countryside state, yes. But it's a nice place.

It's a beautiful countryside. Beautiful countryside. And also, they are wonderful with the pool scene there.

Oh, okay. So, amazing, amazing. Well, I had the best steak of my life when I was in Sao Paulo, so I highly recommend going there.

So, if you've never been to Brazil, I encourage you to check out that meeting in two years. As you, I'm sure, will put on another spectacular meeting, and I would encourage you to consider attending. So, thank you.

And, Micah, can I give only one? Can I finish our interview? Yes, close us out. Yes, okay. So, I don't know if you guys know, but in Brazil, we have a big community that enjoys a lot the podcast, and I think that the job that you're doing, Micah, it's wonderful because you increase the access to research internationally, and also, I think that with the young generation.

So, I really, I appreciate, I have an admiration for the job that you are doing. Thank you. And I would like you, I would like to incite you to keep going because in Brazil, a huge community, and really, the Brazilians like to listen to podcasts while they are doing gym.

And Pietro did the shout-out. Oh, so, we were in Brazil, shout-out to Brazilian people, the Brazilian community. Yeah.

And then, when they wake up, a sick WhatsApp message, your phone is blowing up. Yeah, they decided the Brazilian conference, and that was amazing. So, really, keep the great job that you are doing.

It's amazing. And for us that were abroad, the U.S., it's good to, it's a feeling that we are close to you. So, thank you so much for that.

It is our pleasure. It's wonderful to hear that you enjoy the podcast all around the world. Thank you so much for coming by and saying hi today.

It's great. Thank you, Micah. Hi, and welcome.

I am here with Kaylene Ready. And Jeremy Grushcow from Juniper Genomics. Wonderful.

Thank you so much for joining us, and welcome to the Fertility and Sterility On Air podcast. We saw your presentation, and we were really just blown away by some of the clinical implications. The study question you guys asked was, can whole transcriptome sequencing of embryos and whole genome sequencing of parents and embryos identify variants associated with embryo viability? So, tell me a little bit about what that means and why you chose to study this.

So, what we realized is that PGT-A, which has been revolutionary in many ways, has stagnated and is really just not good enough. And so, we wanted to see, are there additional genetic causes that may affect implantation or pregnancy rates? And we decided to look at the whole genome in order to find those. So, I mean, I think classically, PGT is 23 chromosome analysis, and we know that in the best of circumstances, we have 65% of those embryos will implant.

And so, I think that the question that everyone's sort of searching towards is, what about the other 35%? What happens with those? And so, tell me a little bit more about whole genome sequencing. What are some of the things that you are looking for? Some of the things that you wanted to see to identify whether or not that could explain why embryos don't implant? Sure. So, there's two reasons why we're looking at the whole genome in order to help answer these questions for clinicians and patients who have failed euploid transfers.

And the first is that we know from product of conception studies, from pregnancy loss genetics, that if you look for explanations of those pregnancy losses, at least 85% of the time in total, you can find a genetic explanation for that loss in the embryo. It was never viable to begin with by doing whole genome trio sequencing on product of conception. And you're saying even in euploid embryos that fail? So, 50% of that is aneuploidy.

But in addition to that, of the failed euploids, 50% of those cases can be genetically solved by looking at the genetics of the embryo. So, half of euploid losses from 12 weeks to birth can have a specific genetic ideology that meets clinical criteria or that meets near clinical criteria for being caused by genetics. And when you say that, what type of genetic abnormalities are you seeing? Yeah.

So, these are like individual changes in a single base in the embryo that disrupts a gene that is necessary for development. And how many different genes are there that have been characterized that we know are necessary for development that have these single gene alterations? So, we're looking at a collective. We are doing whole genome sequencing, but across disease genes that are known that can cause implantation or miscarriage.

And then additional development genes. It's about 10,000 genes. So, it's a really large effect.

Wow. Yeah. That's a huge number.

And so, it's a single base pair alteration. And how do you know whether or not that's a variant of unknown significance versus a pathological variant? Yeah. So, in some cases, they are single base pair alterations.

In other cases, it could be a large deletion or something, a frame shift that is a little more obvious. In the case of the single base pair, the base ends mutations, we are using computational models to help us predict the impact on the gene. And in those cases, so when you did the products of conception analysis, are you also looking at parental DNA to make sure that those are not just heritable single base pair differences? Yeah, of course.

So, there's two data sets that are really important here. One is the living population of everyone who's ever been sequenced, right? Because no variant in anyone who's ever been sequenced across the millions of people we've now done whole genome sequencing on around the world, none of those are dominant lethal mutations because all those people are here and alive. Right.

By definition. Yeah. And then the second one is the biological parents of these particular embryos where the same analysis applies except for those parents.

Now, we have all of the super rare variants that are in those populations that would be novel in those parents for the first time, but we also know that those are not dominant lethal. So, basically, living people are an outline of all of the things that could be lethal. And then within that set of things that are not in living people, we look for things that are going to disrupt the function of these essential genes.

And are those mostly sporadic mutations? And so, if somebody has a clinical loss, and I'm just trying to think about how would I counsel a patient or how would this change how I might counsel a patient, are most of those just one-off sporadic mutations that are not likely to happen again? It's actually a mix. So, we expected to see a lot more de novo one-offs. And what we actually saw is a handful of de novo and one-offs, and then a good number of recessive or X-linked recessive variants.

And so, clinically, tell me a little bit about what you presented here, and then we can talk about how do we use that information clinically. So, what we found across 30 donated embryos is that 12 of those embryos had these viability variants, is what we're calling them. Some of those were... Just to go back, these were embryos that you used in the study that are donated embryos that were not transferred, correct? Okay.

Yes. None of these were transferred. The parents who agreed to donate had completed their families, and so let us use the remaining embryos.

And so, in a handful of those, what we saw is they had compound heterozygous variants. Some of them had X-linked recessive variants, and we only report those in male embryos. And then there were two embryos with de novo variants.

And then from the group of donated embryos, did you have any patients who had been totally unsuccessful with their cohort of real embryos, or were these all people that had had children, and these were just donated embryos? In that set of 30, it's the latter. We've also worked with some research families where they've had loss after loss after loss, and we thought, when we first started looking at that family, they had, I think, eight or more losses all before six weeks, and they kept getting pregnant spontaneously. And they started using IVF because of all the losses, and they started using a surrogate because of all the losses, and we thought for sure there was going to be some consistent genetic factor that would just be a single thing that was causing the same loss all the time.

So they just had so many variants between the two of them, it just, I think it stacked the odds against them, is the bottom line. How do you counsel a patient who has that? Do we say, keep on trying and you'll eventually get there, or are there some patients where no matter what they do, it's just not going to work? So this is exactly why we've launched Juniper as a clinical test, because the ability to identify these variants to begin with is the ability to look across a set of embryos before they have to experience these losses. To look at the embryos, to look at the parents, to say, this is the distribution of things that we see.

It might take an extra cycle to find an embryo that doesn't have these things affected, but you don't have to experience that decade of trying and losses. We can identify these variants in your embryos the first time you make a set of embryos, and then we can counsel you appropriately based on whether we've identified a viable one. And in the families that we looked at, every one of those families had at least one embryo that was clearer, that didn't have any reduced viability variants, that didn't have any genetic disease variants.

There was a clear choice for a first transfer. So that's what the data supports so far, is that most families are going to have an embryo that you can prioritize for transfer that is more likely to succeed than a current euclid embryo by far. So not to play devil's advocate, but you know that's what I love to do.

You could argue that if you were to just simply transfer all of those embryos, that the cumulative likelihood of cumulative probability of live birth is going to be the same, whether or not you do testing. And it very well might be, but that is time and money and emotional kind of trauma for those patients. Absolutely.

And I'm just, again, playing devil's advocate to say, or, you know, again, from an access perspective or for those patients who can't do PGT or can't, you know, spend the additional money to do advanced testing, I think it is nice to know that that's available, but also somewhat reassuring to look at the data and say, if you do nothing, you'll eventually get there. Yeah. And I think that is the case for some families.

And I think some families, like we're seeing, do have so many variants that it might make sense to invest up front. The other thing is, like, the transfer is not free. So if you have to keep transferring, at some point, actually, it does economically make sense to do more testing.

Totally agree. And I would absolutely practice in that particular way. But I think just to think about it holistically, similar to PGT, where it's not going to improve, your cohort is your cohort, it's not going to improve the overall probability.

But I think if you look at emotional trauma, time, cost, etc., that's where this becomes really meaningful. And I think, you know, clinically, we all have those patients who just have loss after loss after loss, euploid loss after loss after loss. And so I think that it's uncovering a lot of discovery in terms of what else could there be besides just the 23 pairs of chromosomes that we're constantly measuring and baffled when they don't work.

So I think this is really fascinating. And I'm thrilled that you came on the podcast to share these data with us. Thank you.

Thanks for having us. We are back. I'm here with Kate Devine and Eduardo Hariton.

Thank you so much for having me. Thanks so much for being here. You gave a great talk this morning on the use of AI in ovarian stimulation.

And obviously, not everyone who's listening was there. So I'd for you to just talk a little bit about some of the work specifically that you're doing with regard to managing an IVF cycle using AI. Thank you.

Thanks for inviting me. It was a well-attended talk, which was exciting. And I think AI is the buzzword of the year or decade.

Everybody's excited about it. Yeah. Every talk this meeting that I've been to has some form of AI from oocyte selection to managing stimulation.

Yeah, I don't think it's going away anytime soon. I don't think so either. What we focused on in my talk was trying to help the audience understand what are the different ways in which ovarian stimulation can be helped by AI.

So we went everywhere from prediction of outcomes. So we started by saying, can we use AI to give a patient an objective evidence-based estimate of what the likelihood of success is, whether they're doing inseminations or IVF or an egg freezing cycle, and help the patient understand it might take more than one cycle. It might be a low success rate because your chances are not that good and make the right decision with the counseling of their providers.

Yeah. And I really liked you showed some data where when you see a new patient, you kind of buddy them up with other patients who have similar profiles. Can you talk a little bit more about that and how you use that model to help counsel patients on realistic likelihood of success? Absolutely.

So the way that this tool works, we call it the AI pathway to parenthood. It's a tool that allows us to find patients like that patient. So for example, you have a 32 year old with unexplained infertility and an AMH of 2.5. It will look for patients that have those same characteristics and it will find what were their or what were their actual success rates with one or two or three IUI cycles and one or two or three IVF cycles and help that patient see what that looks like so they can make an educated decision and it finds patients that are similar to them to drive that.

Does it matter? So I realize that those data use the entire network of U.S. fertility, but are the success rates similar enough across all of the practices in the network where if you see a patient in California, is that patient going to see the same success when she sees Kate Devine in DC? Is the success rate translatable enough to make those realistic predictions for each? Well, Kate does such an amazing job of bringing our outcomes up in every clinic that it gets closer and closer, but the reality is that we don't have enough data or no one does at a single center to be predictive at that site. So we have to really focus on getting the network wide data to give a better prediction. And then what I do as a provider is that I explain to our patients in my clinical experience and with our lab outcomes, I would expect this number to look a little bit higher or a little bit lower or based on the fact that you have not only endometriosis, but like I don't know or something else, I'm a little worried that your numbers might be less.

So this is not to replace clinician judgment. I think that's a really important fact. AI is not going to replace us, but it's going to help us counsel our patients better.

We still need to use our clinical judgment and experience and apply that filter of what might it look like in our own heads in our lab. So, you know, obviously being a convert insofar as I'm in the same network and use Pathway to Parenthood tool myself all the time, I'm here playing devil's advocate, but I was asked yesterday by somebody who is aware of our using this tool and the nearest neighbor methodology and the machine learning algorithm that's fueled by, you know, data across the network. Aren't you afraid when you tell patients that they're going to get X number of eggs that if you then underperform that you've disappointed them and they think that you've done a bad job? I know my answer to this, but I'm interested to hear your answer, Eduardo.

I mean, I think certainly I think it's more disappointing for a patient not to have the right expectations of success because everybody's optimistic. We are as physicians, of course, we remember the wins. We don't remember the losses as much because otherwise it would be a depressing job.

So yes, there are some patients that are going to say, I thought I was going to get 10 to 12 eggs and I only got six. What happened? And you're going to say, there might be something about you that is inherent to your egg quality, that is inherent to your recovery that just didn't perform well. Or this is what we learned during your cycle about your specific parameters that make you have a little bit of a worse outcome.

We need to rethink what we do for that second cycle. We need to go back to the drawing board and see if there's anything we can change to improve it. But I think that counseling is important and setting what we thought you were going to get and what you got is also helpful in trying to counsel those patients that may not have the best chances of success that perhaps this is where they're showing that.

I think that's all 100% right on target. The other thing that's nice about the way that the data are framed, and I would encourage others to consider similar tools, is that the patient isn't just shown a number as to their prediction. They're shown quartiles in terms of all of the nearest neighbors like them.

What were 50% of the patients that are like, you will get this, 25% will get this, 25% will really excel. This way, when they are in the minority that has unfortunately underperformed, they know that that is not a rare outcome and it's not the case that they feel you failed them. Rather, they feel that they were informed of the possibility of that outcome early on and then they are not somebody who's going to drop out and feel betrayed and go to your competing clinic.

And that's absolutely true with our attrition tool because it shows you, this many eggs you'll get on average, this many eggs will be mature, this many blastocysts will be created, and if you do PGT, this many will be eucloid. And often for the older patients, that range includes zero. So it's a really great opportunity to drive home the fact that we might not have a eucloid embryo at the end of the cycle.

We might need to do this again. Yeah. How else are you using AI for stimulation specifically? So the next stage of this was dosing selection.

We don't use it in our network for dosing selection, but there's good data that in those responsive patients, you can optimize the dose, improve the outcome, and have the same dose or slightly lower. And in those non-responsive patients, you can lower the starting dose and the total dose of gonadotropin to the tune of saving $500 to $1,000 to that patient or whoever's paying for that cycle without impacting the outcome. So that, I think, has the potential to save the patient some money and let them use it for something else in the cycle.

Where I'm super excited about it is, my thesis was on Trigger. There's a lot of papers that have come out. I think we can trigger better using these Trigger tools.

But when we look at our lab and the downstream consequences, I'll tell you a little story. And this is when my partners got excited. We were going through a busy month right before the end of the year when everybody wants to cycle.

And we had four days where we had 15 retrievals, 15 retrievals, one retrieval, 14 retrievals. And the lab wanted to kill us and the OR wanted to kill us. And we realized it's easy to know when to push if it's looking busy, but it's not easy to find out if it's going to be busy in three days to pull some forward.

We all know for some patients, it doesn't seem to make a huge difference. So the tools that allow you to level load the lab and think about the capacity and how many eggs are you putting through and how many embryos will that mean that they'll have to biopsy in five to six days. And really thinking about the whole system, because it is not good for your lab to have embryologists there at four in the morning and there till seven.

It is not good for the lab to open those incubators constantly when it's really busy. It's really helpful to make sure we do the right thing for every single patient and do it in the day that makes sense. But when it doesn't make a difference, let's work with what we know is going to help our lab.

Yeah, I thought it was really interesting looking at the data that some patients have to have one specific trigger day and some patients can have a trigger day that's a day in either direction. And some patients have more wiggle room for their trigger and being able to personalize to say this patient can be triggered on days one, two, or three. This patient can be triggered only on a certain day.

Really using AI in that way to optimize the flow, I think is also going to make our lab team just that much happier. And it will also help you prepare. I think a lot about the ROI or the return on investment of these tools.

Some companies build these tools being like, if you build it, they will come and we can charge whatever. But that's not the reality. Patients don't have unlimited pockets and neither do the clinics or the networks.

So we need to think about how do we create tools that can pay for themselves, but either increasing efficiency. And this is one of those where you can very measurably understand what you're saving in overtime costs, in nursing, in DOR, in dish prep. If you know how many eggs you're going to get, on average, you can prep big case, small case much more precisely.

You can balance that workload and try to be as efficient as you can, which will not only help the outcomes, but also help the economics of the clinic and give us some wiggle room to incorporate these tools. So I'm going to play devil's advocate again here, though. Seeing a pattern.

Sorry. So we all do this a lot, right? So as experienced REIs and showing my age a little bit here, you get to a point where you can manage a stimulation fairly well, fairly quickly. And some of these tools, when brought to market, are going to be pretty pricey for the clinic.

So when we get back to ROI, if you can manage a stim in 15 seconds a day, what does this need to be priced at, do you think, for this to be something that's really valuable to the market per IVF cycle? I think we need to, you know, I don't know that I have a dollar amount, but I can tell you it's lower than what the Venture Capital investors think they should be priced at. I think we need to think about what is the value that we are deriving and how do we measure it. So my advice to founders, to people who are incorporating this tool is to define success ahead of your pilot.

Like, what are you solving? Are you solving for, you know, a smaller standard deviation in your workload in the lab? Are you solving for more M2s? Are you solving for standardization? And then build a model around that. And then go to these partners and say, I want to incorporate this tool. At scale, this is software, right? The tools are built.

The variable cost of running these tools is quite low. It's really the expense of building them, of getting the data, of paying those developers. So those costs are sunk in.

We need to figure out how do we lower the cost of a cycle so that when we can maintain it and incorporate these tools. And I think the trigger one is hard because we don't, the clinics don't make more or less money if they get two more eggs. But if the patient can save $500 or $1,000 in gonadotropins and get the same outcome, you're generating some savings.

If the clinic can save a lot in the operational cost of running through the clinic, then you can generate some savings. And then these tools start to make sense. We can't just keep making this more expensive.

If we're thinking about access to care, we have to figure out how do these tools help us deliver more access more efficiently, but at the same or lower cost. And it's really finding that delta in what we save and sharing that with the company that worked hard to develop these tools and then with the patients and the system. Great.

Well, thank you so much for sharing all of your insights with us. I think it's just fantastic. And I can't remember what the quote was from the person that spoke before you, but it was.

Doctors are not going to be replaced by AI, but doctors who use AI are going to replace doctors who don't use AI. Right. I love that quote.

And I just think that it's so timely and really speaks to the need for implementation and the implementation thoughtfully and mindfully of new technology. Thank you so much for having me. We are back here at Paris ESHRE at the Fertility and Sterility On Air ASRM booth.

And I am so fortunate to be joined here today with Sofia Zaragozano, a Ph.D. candidate working with the Carlos Simon Foundation, who presented at this meeting her fantastic work entitled Modeling Embryonic Adhesion at Cellular Resolution with a Microfluidic Endometrium on a Chip Platform. Sofia, welcome. And thank you so much for taking the time to speak with us today.

Hello. I'm really glad to be here talking with you. Fantastic.

Well, let's just dive right in. Tell us a little bit about your work and what you found, what you presented to us yesterday. Yeah.

At the Carlos Simon Foundation, the project I am working on, it is just basically to develop an endometrium on a chip, a model, just because we want to study the adhesion phase of the human embryos. You have to know what is happening between the embryo and the endometrium in the different spaces because people have developed different models, but the adhesion is not yet studied. Got it.

And so tell us specifically what you did in your study with your endometrium on a chip model. Yeah. All this time I was developing the model, just working with endometrial biopsies to obtain the cells, just also to establish the model, characterizing it using confocal microscopy, doing different types of immunochemistry, and also analyzing the response of the cells to hormones to establish a secretory phase.

And then finally, we want to work with mouse embryos just to establish and to be sure that our model works in the adhesion. And finally, we work with human embryos to study the adhesion phase at this stage in human embryos. Wow.

So you've made quite a bit of progress already moving from mouse to human. Tell us what you found. Yeah.

We are able just to be sure that the adhesion in our model by human is initiated by the trophotolerances. That is how it's occurring in the natural implantation. And we also characterize that when the adhesion occurs, there are some embryo remodeling.

That is something that has been studied that occurs when it happens. So we are able to establish the different states, and we are establishing the first lines to continue studying what happened and to know what are the physiological events that take place there. Okay.

And dive in a little bit more on the details in terms of what specific markers of adhesion you're looking at that are most pronounced. Yes. To characterize what is happening, we are using marker of embryo.

Yes. GABA3 to characterize the trophotolerance, or O3-4 to characterize the inner cell mass, and also NR2F2 to characterize the polar trophotolerance. Yes.

All of that to characterize embryo. And if we want to talk about the cells, we use pancytokeratin to characterize epithelial cells, preventin to characterize the stromal cells. So specific markers of its cellular type.

Amazing. And so what are your next steps? How do you foresee this as a potentially clinically useful tool? Yeah. We want to study what is happening in a genomic area.

So we want to do transcriptomics or epigenomic analysis to know what is happening and what is happening in the communication between the endometrium and the embryo in the adhesion phase. And also we want to prove some potential therapeutics or new contraceptive therapeutics. Just to know.

And do you think this is something that ultimately will yield knowledge or be helpful to patients who are experiencing recurrent implantation failure or other such pathology in our field? I don't know because we have to continue working, but it would be fantastic maybe to work with implantation failure to see what is happening there or other diseases to see if, for example, endometriosis or adenomyosis have something to do with embryo implantation failure or something like that. Got it. So tell me if I'm understanding correctly.

So the chip that you've developed is meant to model normal endometrium and normal endometrial response, correct? Yeah. Nowadays it's just we have a healthy endometrium because we want to study an endometrium that resembles the physiological characteristics and this is the first step we did. Yeah, of course, always best to understand normal physiology first since it's an area that we unfortunately don't understand as well as we'd like.

Do you have any specific targets in mind that you potentially would want to model to better understand aberrant endometrial receptivity or you think we're just not quite there yet in terms of our understanding even to plan a model like that? No, not yet. Yes, we are looking for what is happening in the embryo region and we are resembling the endometrium and what is happening between all of that. I think it is a lot of information just to research and continue doing because there is a lot of things to do.

Yeah, and anything surprising about your findings? Obviously it's amazing what you've been able to do and that you've created this model. Anything when you were exposing the chips to the opportunity for implantation that you found that you were not expecting to see? No, just we are able to reproduce the physiological characteristics that take place in the adhesion. Just the mouse in natural adhesion, they are there by the molar trophectoderm and that's what happened in our model and then the human embryos are there by the polar trophectoderm and that's exactly what happened in our model.

So I think we have established a really great model to study embryo adhesion, not just maybe in human but maybe also in other species that is not our interest but could be to another one. Sofia, one more question for you. I'm really interested to understand what your next steps are in terms of studies using this tool that you have now created, the model that you've created and validated really.

What experiments do you have planned? What future applications do you see for your model? You know that our model is composed by two channels that are separated by a porous membrane. This gives the opportunity to the model to recover all the things that are treated to the beginning of the stroma in a separate way but also establish a communication that is really important between the cells. So maybe we can, for example, test drugs to see how they affect in different diseases like asthma disease or thin endometrium and see how the different cells with different therapies act and maybe we can use this model to study potential therapeutics or see how is the response of our cells in a different way to different treatments or something like that.

Yeah, I could see that would be hugely valuable. I know many studies looking at the endometrium as a functional unit in the past are limited and confounded by the inability to isolate the two major cell types. So that is a huge strength of your model and I look forward to what you'll find next.

Okay, we're back here at Paris ESHRE meeting with Dr. Sharyn Stock-Myer from Melbourne, Australia. She is a PhD and presented her work on 1 and 3PN embryos and their reproductive potential. Welcome Dr. Stock-Myer.

Thank you so much for being here with us. Thank you. So let's just dive in.

Tell us about what you found in your study. Okay, what we found in our study was that the size of the third pronucleus is really, really highly correlated to the ploidy of the embryo. So this is when you have 3PNs.

So when you have three pronuclei and all of the pronuclei are really evenly sized, they're almost always triploid, those embryos. So particularly if the second polar body has not been extruded or has been extruded and then reabsorbed. So if there's no second polar body, and there are three even sized pronuclei, almost always those are triploid and in our study all of them were unusable.

However, if there is a much smaller third pronucleus and it is about 60% the size of the largest pronucleus, none of those embryos in our study were triploid and many of them were usable. Wow, that's, first of all, makes a lot of sense to me anyway. But tell me how you explain that biologically? How does it make sense to you? What is the biologic plausibility that led you to look at the size of that third pronucleus relative to its probability for being euploid and diploid? There was already a small number of studies that had been published that suggested that these embryos that were also called micropens or 2.1pens may actually represent a batch of embryos that are normal.

And so we wanted to delve a little bit further into this and actually define what you call a 2.1 or a micropen in relation to the size. And regarding the biology of why this would be, so why is it that when it's small it doesn't end up being triploid, that's a very interesting question and it may be related to the amount of DNA that's within that pronucleus. So it seems logical that when you've got in a complete extra set of chromosomes that the pronucleus is larger than when perhaps you've got a few chromosomes in that pronucleus.

That would have been my supposition as well and it would be that the size correlates to the amount of DNA with more DNA of course being associated with triploidy. So you, I think very appropriately, did PGT-A on these embryos. About how many embryos did you have the opportunity to look at? So far we've looked at close to 140 3-pen embryos with a differing size of that third pronucleus.

There were about 60 in that micropen size, which is a reasonable data set. It's still small numbers really, but it's a reasonable data set compared to what's published. And so those 60 you said were 100% diploid.

What was the euploidy rate? Yeah, so that was what was really interesting in this study is that the euploidy rate is a lot higher than you would expect it to be based on the age of the patients. So it seems as though maybe that third pen in a large proportion of zygotes, so a large proportion of embryos resulting from those zygotes may actually represent aneuploidy. So there may be, it may be that that third pen is forming because there's aneuploidy within that zygote.

So that it's some sort of self-repair mechanism or something of that nature to evacuate that abnormal chromosome? Yeah, I'm really not sure, but it's very interesting. So we saw about a six, about 67% aneuploidy in that group, whereas an age-matched group of two of patients who had two pens was about 39% aneuploidy. So it was 39 versus 67% aneuploidy.

So quite a big difference there, very statistically significant. Yeah, fascinating. Of course, it could always be by chance, but such a large difference, I would say it's unlikely to be.

So going back to the PGT-A, there have been other studies that, this is sort of a hot topic recently, is abnormal fertilization, quote-unquote abnormal fertilization, and whether these may represent a pool of potentially usable blasts to improve our patients' cumulative probability of live birth. Do you personally feel that a specific PGT methodology needs to be done, additional checking for diploidy or any other specific analysis when we are considering transfer of embryos that were initially assessed as other than 2PN? Yeah, absolutely. You can't just use a copy number based PGT-A test to test for diploidy.

So you need SNPs really. So our testing incorporated a SNP array. So we had quite a number of SNPs that we were able to assess diploidy as essential to that type of testing.

Certainly, I understand the reason for that. In a study that we did recently, we did the same. That said, you could almost make the argument given that the ones with the smaller 3PN were 100% diploid, that at a certain point, you'll have enough data to say that you could forego that step.

Well, that's true. That's only based on that kind of data though that we're generating in studies like this with SNPs. Yeah.

Well, great study. Certainly not a lot of data out there on 3PNs particularly. So I look forward to reading the manuscript and I love any study that reduces embryo wastage in our field in this era of PGT.

So thanks for doing this great work and for taking your time to join us on the podcast. Thank you very much today. I'm Dr. Sara Maggi and I'm a gynecologist working in Spain in Next Fertility Valencia and I'm very proud to be here to present the results of our study.

Yeah, welcome. Hello everyone. My name is Silvia Bonta.

I'm a gynecologist and I work with Dr. Maggi in Next Fertility Valencia, Spain where I manage the egg donor program for our gamete bank named Gametea and it's a pleasure to stay here today with you. Fantastic. Thank you so much for coming.

So I was really curious. The title of your study or your study question is, does the administration of micronutrients and probiotics supplement during an oocyte donation program improve fertilization, blastocyst development, and pregnancy outcome? Which I thought was actually really interesting. I think it's a pertinent question that all of our patients ask us really more for themselves.

What supplements and micronutrients should they be taking? So tell me just a little bit more about why you did the study and what the study really sought to look at. Yeah, the idea of this study started when we we do a reflection. Follicular development, oocyte maturation are very very complex processes in which micronutrients and also the microbiome could have an influence because there is an important interaction between these two parts of our body.

In terms of regulation of inflammation, regulation and protection against reactive oxygen species and also we know that microbiome could have an impact and an influence also in hormonal effects in the absorption and production of estrogens and also when we give micronutrients, microbiome could affect the way in which these were used and the absorption of these. So we decided to realize this study in which we analyze the effect of a combination of both micronutrients and probiotics. And so you gave a combination and it looks like in your abstract it looks like it was a combination of myoinacetal, folic acid, melatonin, coenzyme q10, vitamin d3, b6, b12, e, iron, zinc and then lactobacillus, two strains of lactobacillus.

So when did you administer these to the oocyte donors? How far in advance of their stimulation cycle? Yes, we know nowadays that all these components are very important for the quality of oocyte, for the fertilization rate and at the end the quality of embryos. So we decided to administer these supplements, these micronutrient supplements at least one month before starting ovarian stimulation. And so the donors took the supplements through ovarian stimulation and then the recipients did not take supplements, is that correct? Yes, in our study the recipient didn't take this supplement but we know that it's very important also for them to take vitamins, minerals, antioxidant agents.

But the study is focused on the effect of these supplements on egg donors. Okay and so tell me what you saw, tell me what the findings were. When we analyzed the results of ovarian stimulation in donors we obtained very interesting results because in terms of follicular development in the group in which we used the supplement we obtained a better follicular development, a mean increase of six follicles in the supplement group with a significant difference.

And when we analyzed the oocyte yield in terms of total oocyte collected and mature ones we obtained significantly higher oocyte yield in the supplement group. How many eggs were there in the control group compared to the supplement group? How many mature oocytes were retrieved? More or less four or five oocytes more in the supplement group. That is a very important result overall because we are talking about an oocyte donation program in which this could be an important difference in the frequency and efficiency of the program.

And so my understanding though is when you looked at when you looked at fertilization, blastocyst development rates and pregnancy rates in the fresh part of the cycle there were no differences. But then in the frozen embryo transfers you did see higher pregnancy rates. Is that correct? We detected an impressive result because there were no differences in the general population in terms of fertilization and blastulation rate.

It's trending higher pregnancy rate in the general population when we use the supplementation. But the significant results we obtained in the when we use V35 oocytes in which despite fertilization and blastulation rate that were similar we detected an higher pregnancy rate when we use oocyte V35. This could be an interesting result that could mean that the supplementation enhanced the oocyte competence during the replication and could lead to better results.

Did you see any differences in the warming rates or was it just on the back end you saw higher pregnancy rates? Like I'm trying to tease it out as to what specific factor we think may have been improved by the supplements? For example, the oocytes could be affected by oxidant. Oxidant stress is a very important negative factor in influence the oocyte quality. So maybe give a correct quantity of oxidant during a simulation could improve this aspect.

But the most important things of the study was to try to find the correct combination of this with probiotics to enhance the positive effects. So we we think that this could be the reason why we obtain this kind of result. Yeah I think it's really interesting.

What's the next step in this in this study? Sure, a large number of patients and in order to evaluate the effect on pregnancy rate, life birth rate, we start as always with a small number of patients. So we want to increase the number of patients and the number of cases. Yeah, very interesting.

Any final thoughts? I think that this study opened a door to something that we never analyzed before. That is this combination, this specific combination of micronutrients and probiotics. Because right now in literature we only have studies that analyze single antioxidant, single micronutrients or combination of that.

And no one study nowadays to our knowledge analyze this combination. So this is the way in which we want to improve our investigation and also with a more personalized approach in terms of detect specific microbial status of the patient, specific deficiency of micronutrients. So we want to use specific combination for each patient.

So this is the future direction, personalize the supplementation. Right now we have opened the door. We obtained interesting results and we want to continue in this sense but in this more personalized way.

Yeah, no thank you. Thank you for coming on the podcast. I think this was really interesting and I think novel research.

I certainly haven't seen any sort of supplementation studies in oocyte donors. I think we more often think about it on the implantation side, especially probiotics with things like endometrial receptivity and the endometrial microbiome. Though we're hearing a lot of controversy in that area too.

So I want to thank you both for coming on and speaking with us today. Thank you very much for your invitation. And we hope this is useful and we want to continue to improve.

Thank you very much. Welcome back to fertility and sterility on air. We're still here live in Paris, 2025 at ESHRE.

I'm Micah Hill, the media editor, and I'm joined by one of my friends from ESHRE and from Human Reproduction. So we are with Omar Ammar. Did I say that right? Yes.

Okay, perfect. And Omar is a senior embryologist. He does a lot of research and he also does the ESHRE Journal Club Global.

So Omar, just tell our audience a little bit about yourself. Hi Micah, thank you so much for the invite. I'm Omar Ammar, a senior embryologist and I worked across Middle East, UK, and now in Europe.

Currently developing an end-to-end IVF management system utilizing AI. And I'm also one of the Journal Club editors with ESHRE and Human Reproduction. And we do a lot of science communication and research in the field of Human Reproduction.

If you don't follow him on social media, I highly recommend that you do because he's always giving very good educational posts. And I think you have a very scientific mind and criticism of the literature and how you think about things. Thank you so much.

Thank you so much, Micah. So tell us what was... I caught the Journal Club that you did here at ESHRE. Tell us what the topic was and what the main discussion was that you had.

So there was a very recent paper published in Human Reproduction about actually how semen analysis and semen parameters are actually not only related to fertility and related to fatherhood, but they go actually beyond that into overall health. And the paper briefly found that when men have less sperm counts or less optimal sperm parameters, they actually have higher mortality rates or they live shorter in comparison to men with good semen parameters, especially sperm counts. So the whole discussion yesterday, we tried to discuss actually, can we use a simple, non-invasive, affordable semen fluid analysis in the context of overall health and longevity and life expectancy, not only fertility.

And we tried to tackle this specific question from a basic science perspective, from methodology that the paper actually used to inform the research question, but also clinical relevance and public health relevance. And the discussion was great. We brought really an expert panel from all around the world with different specialities to discuss these issues.

And what was very interesting, the expert panel and the audience, they both agreed that we should use semen fluid analysis, not only in the context of fertility, but also to assess general health of men. For example, literature shows us men with not really perfect, let's say there is no perfect semen fluid analysis parameters, but with really less optimal parameters, they have more chance to get autoimmune diseases. They have more chance to get cardiovascular diseases.

So if we can use it as a biomarker, and if we find something actually wrong with semen analysis, we should not only counsel patients regarding their fatherhood possibility or fertility, no, we should actually also counsel them about other health risks. And that should be not only on the level of gynecologists, urologists, GPs should take into consideration that semen fluid analysis is a biomarker of future overall health. But also part of the discussion was, could we predict future health using semen fluid analysis? I think we still don't know that.

And such kind of studies are really difficult to conduct because to have a registry, a medical registry that has semen fluid analysis and fertility data connected to mortality and like follow up registries, it's really difficult. And I think the Nordic countries, they do it really well. And that's why we got this amazing study.

Yeah, the study was great. I remember when it came out and reading it, and there's a lot of discussion online. And I think the last point you made is a good one.

Oftentimes we'll see associations between a marker and an outcome. But then when you actually apply it as a predictive test, it doesn't always hold up. In other words, you can have an association, but it can be weak.

And then for the positive predictive value or negative predictive values of those tests might not always apply at a clinical level that's applicable. And so I think you're right. Longer term studies will be important, but they'll be hard to do.

Was there any discussion? Because one of the criticisms I've seen online from people who are say internists or in other areas of medicine is that we already have better biomarkers that are better predictive of things like autoimmune diseases or inflammatory diseases or cardiovascular diseases. Was there any discussion about how much this adds compared to some of those other markers that we already have? I think this is my own perspective. And also I think when we are thinking about biomarkers for future health, like the bottle in the neck is oxidative stress.

And one of the most parts that are affected by oxidative stress are the germ lines and the germ lines will yield in sperm. And then to access these tests for testing like a general or like future health and longevity, I think they are first expensive and they are mostly need blood samples or like invasive or they need specific lab settings. And if we can get very something that is very, I would say, like very simple to get to predict future health, I think semen fluid analysis makes sense.

Why not? Okay. That's a very good answer. I like that.

My last question for you is what's been the most exciting or interesting thing that you've seen at ESHRE 2025? What science or what new innovations sort of sparked your interest? Yeah, I think I really liked so, so many talks. But as an embryologist, I was in the embryology pre-congress and I liked how there are two generations like facing a research question, which is the AI for embryology. You have like a big team supporting AI.

Then you have people like, no, AI is not that really helpful. And I liked to see this conversation happening between two generations like pro AI and yeah, not against AI, like questioning AI. I really liked this aspect.

Yeah. You can make good arguments on both sides. I think most of us see the potential, but most of us also see maybe things being oversold at early stages of development or overhyped.

So I can see the criticism side of it. Yeah. Different thing.

As I said on my LinkedIn, I think like many people are overwhelmed with so many things happening, but we always need to remember whether this technology or intervention, does it increase LBR or pregnancy? Does it reduce miscarriages? Is it making patient journeys and staff journeys easier or not? If it doesn't take any of these, then I think it's just an add-on. Yeah. I agree with you.

You're following David Sable's things that he says have to be improved to really move the field forward. Well, thank you so much, Ammar. We really appreciate everything you do both for the field and for the human reproduction in the journal clubs and helping us all be educated.

Keep up the great work. We're still here live at ESHRE 2025 in steaming hot Paris. This is Micah Hill, your media editor, and I have the honor of being interviewing Munuse Savash.

Did I say that correct? Munuse. Munuse. I'm so sorry.

I even just went over that. So Munuse is a scientist at Oxford in the UK and had a article on sort of mitochondrial reversal after mitochondrial transfer. So tell us sort of the background behind the story.

What was the question that you're asking? Why were you looking at this? Of course. So the affordance of the mitospinal transfer, or originally mitospinal transfer, is used to prevent the association of mitochondrial disease or mutated mitochondria with other mitochondrial diseases. However, MST doesn't only substitute the cytoplasma, it must be the entire cytoplasm.

And as we know, the cytoplasm is super, super important for embryo development as it carries the embryo through its first few days of division. So we then thought, well, if MST can be used to completely substitute or take the entire cytoplasm, could this potentially be used to treat or improve oocyte quality? So those patients that might have laxative formation or mild implantation rates, that could avoid that a lot of time that learns that they're now in support of that quality. So we thought we could potentially use MST as a treatment for those people that have been filled out of the oocyte course.

So in 2023, we published the first kind of study that showed that out of 25 bubbles, out of 19 embryo transfers, 7 of those didn't oocyte. So this was super, super exciting, which is the reason none of these patients previously had diastasis reduced. And 21 out of 25 actually had one with the quality of that.

So as well as looking at embryo development and birth rates, we also took upon ourselves almost an opportunity to see, OK, how effective means are just to move that stuff, in making sure that the very, very, very low levels of the maternal rates of embryo are just translated into the maternal rates of embryo. And we did a single piece of research that showed the levels of maternal rates of embryo increased confidently. So that is basically a proportion of the total population of the embryo that now originates from the mother.

So in this case, none of the children was planning any kind of pregnancy. So the child in question could end up in the womb for any amount of time. But we were considering the intent of transmission.

At that time, it was one out of seven. So we thought maybe this could all be something rare. And with the continued study, we did with our second-year students.

So now that this may be something a lot more common, of course, we would only know a certain amount of the embryo, but continuing the experiment is pretty small. If we didn't need more reversals, it wouldn't be that far off. Even in two that we saw, it almost shows that maybe it's not an event.

We'll just have to spend the transfer. Right. And yeah, it's not ideal.

What percent of maternal mitochondria are you talking about in these two patients? Was it 50 percent, 100 percent reversal back in the first level? What were the levels? So the originator side that we did, kind of like day five versus 12 days, they just made a curve of less than one percent. Okay. So very, very, very low.

So just those results in it as a whole, same for pregnancy is pretty good. But when we did see these, they did range in one case, which is 35 percent, and in the second, 30 to 46 percent. Wow.

In theory, that would probably be enough if they did have a mitochondrial disease to have expression phenotype of that disease. Really, really important data. A few follow-up questions.

Do you have any ideas of why this could happen? Is there any hypothesis of how they take that out, you do the transfer, and yet it reverts back? Well, that makes sense. Four areas for future research. Hopefully, we figure this out.

As I listen to you describe this, it's almost like a story that's both discouraging and encouraging. The discouraging is from the standpoint of our ability to treat mitochondrial disease, and it sounds like even one in seven, something that we'll have to figure out and solve to make it more, the safety and the efficacy better of that procedure. But it sounds to me like, could you take this information to be encouraging from the infertility side of it? You had these patients that weren't making blastocysts.

You did this. They got blastocysts. Many of them had pregnancies.

And while there's maybe some reversal in those children, because there's not mitochondrial disease, the children are fine. So it enabled patients to get pregnant that wouldn't have otherwise. Do you think there's at least a positive story out of this? I mean, the study was definitely encouraging.

Of course, we can't straight-up say that MST is amazing to do. But results are definitely there to show that maybe this is a possibility. More research should be done to see if this is definitely the case.

Of course, you know, doing a randomized trial, and then we've got more individuals. Joining the study must be great and allow us to act on that. But yeah, definitely encouraging.

One input I've heard is that although these children are, they are more healthy and achieve more sense. There has been some studies in mice where different hormones could cause a lack of high temperature, even if they're normal. So that's why we are encouraging these children.

Just to make sure what we did see in the mice is what they're going to think about these children. To add to that, we did get a lot of input from mice. These habitats are very, very diverse.

Oh, they are? Okay. However, the metabolism in humans are very, very impressive. So we're hoping that they're a little bit comforted by the fact that the mice are so diverse.

So we're hoping that the same goal is to get mice in humans. But I think some of the children are like three to four years old, and they're old. They're not healthy.

Yeah. So you probably know in the U.S. mitochondrial transfer is not allowed because the FDA has concerns over making chimeric embryos, essentially how they describe it, as three-parent embryo, even though I think most of us don't think that's what's happening with the activity of mitochondrial DNA. How common is this in the U.K.? Are you at a specialized center that's the only one doing this? Is this very common, kind of rare? So in the U.K., the first baby born from MST was an infant to 18-month-old in a focus group.

Yeah. So that, of course, would, again, lead to a three-parent baby, which we try not to mention. That's a little bit weird.

Then parents of the child is a biological infant, and the mitochondria is only donated because they know their relation to U.K. DNA. Right. They don't say it's a three-parent baby.

I try. Yeah. I think that's a wrong way for the FDA to look at it.

But that is how they look at it, unfortunately. Yeah, I think it's common. So it's always important just to mention that, you know.

Well, it has been mentioned that it's three-parent, but there are only two parents, and it's a third of the product. Very well said. Yeah.

Well, this is fantastic. Thank you for coming on to Fertility and Sterility on Air and sharing this. It's very cutting-edge science.

It's very niche, but it's really fascinating. It seems like you've discovered a problem that hopefully we can figure out why it's happening and maybe come up with a solution for that. But amazing research.

Thank you for sharing. This podcast was developed by Fertility and Sterility in conjunction with the American Society for Reproductive Medicine. This podcast is produced by Dr. Molly Kornfield, Dr. Adriana Wong, Dr. Elena HogenEsch, Dr. Selena Park, Dr. Carissa Pekny, and Dr. Nicholas Raja.

This podcast was developed by Fertility and Sterility and the American Society for Reproductive Medicine as an educational resource in service to its members and other practicing clinicians. While the podcast reflects the views of the authors and the host, it is not intended to be the only approved standard of practice or to direct an exclusive course of treatment. The opinions expressed are those of the discussants and do not reflect Fertility and Sterility or the American Society for Reproductive Medicine.

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ASRM Today: Genetics - Episode Nine

Explore ethics, identity, and humanity in a dystopian love story as ASRM Today discusses Never Let Me Go through the lens of genetics and reproduction. Listen to the Episode
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ASRM Today: Genetics - Episode Eight

Explore ethical considerations in embryo transfer, PGTM, and genetic testing with Dr. Sigal Klipstein on ASRM Today’s genetics-focused podcast episode. Listen to the Episode
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ASRM Today: Genetics - Episode Seven

Dr. Elizabeth Ginsburg discusses PGTA, its benefits, limitations, and proper use in IVF based on age, ovarian reserve, and embryo quality on ASRM Today. Listen to the Episode
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ASRM Today: Genetics - Episode Six

Explore how genetics may unlock the secrets to longevity, reverse aging, and extend life through telomeres, gene therapy, and cellular reprogramming. Listen to the Episode
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Fertility and Sterility On Air - TOC: May 2025

Explore new fertility research on IVF triggers, thyroid autoimmunity, prednisone use, and genetic impacts in this expert-led review of May 2025’s F&S journal. Listen to the Episode
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ASRM Today: Genetics - Episode Five

Explore how personalized medicine is transforming reproductive healthcare, from IVF optimization to ethical issues in genetic testing and AI-driven care. Listen to the Episode
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Fertility and Sterility On Air - Best of ASRM and ESHRE 2025

Experts explore recurrent pregnancy loss, embryo testing, IVF mental health, and stem cell banking at ASRM–ESHRE 2025. Insights from leading fertility voices. Listen to the Episode
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ASRM Today: Genetics - Episode Four

Explore how genetics shapes agriculture and reproductive medicine, from GMOs to CRISPR and lab-grown meat, in this ASRM Today podcast episode. Listen to the Episode
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Transfer of embryos affected by monogenic conditions: an Ethics Committee Opinion (2025)

Patient requests to transfer embryos with serious monogenic disorders detected in preimplantation testing are rare; this opinion discusses physician responses. View the Committee Opinion
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ASRM Today: Genetics - Episode Three

Explore how genetic mutations cause disease, and discover breakthroughs in gene therapy like CRISPR offering hope for treating conditions like cystic fibrosis. Listen to the Episode
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ASRM Today: Genetics - Episode Two

Explore the nature vs. nurture debate, epigenetics, and how genetics and environment shape behavior, personality, and modern precision medicine. Listen to the Episode
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Journal Club Global: Embriões mosaicos ao Teste Genético Pré-Implantacional para Aneuploidia (PGT-A): o que fazer?

Discutiremos embriões mosaicos ao teste genético pré-implantacional para aneuploidia (PGT-A) View the Video
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Journal Global Club From TSRM 2024: Preimplantation genetic testing for aneuploidy in unexplained recurrent pregnancy loss: A systematic review and meta-analysis

Explore the effectiveness of PGT-A in managing unexplained recurrent pregnancy loss, featuring systematic review findings, insights on miscarriage risks, and live birth rates. View the Video
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Genetics: Counseling Fertility Couples About Their Evaluation

Caitlin Hebert discusses fertility counseling, the importance of carrier screening, and overcoming barriers for patients while highlighting the role of genetic counseling. View the ASRMed Talk Video
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Use of preimplantation genetic testing for monogenic adult-onset conditions: an Ethics Committee opinion (2024)

Preimplantation genetic testing for adult-onset monogenic diseases is ethically allowed when fully penetrant or conferring disease predisposition. View the Committee Opinion
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Codes for Embryo Biopsy

When doing a preimplantation genetic test (PGT) biopsy, can you bill for each day a biopsy is performed or can you only bill once for the cycle? View the Answer
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The use of preimplantation genetic testing for aneuploidy: a committee opinion (2024)

PGT-A use in the U.S. is rising, but its value as a routine IVF screening test is unclear, with mixed results from various studies. View the Committee Opinion
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Journal Club Global: Recent clinical trials in Fertility and Sterility from the Asia Pacific region

Join ASPIRE 2024 for a Journal Club Global on PGT-A and IVF. Learn from top experts discussing recent clinical trial data and pregnancy outcomes View the Video
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Coding for an endometrial biopsy/Mock cycle

We had patients request us to bill their insurance for the two monitoring visits and the Endo BX and change the diagnosis code to something that is payable.  View the Answer
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Journal Club Global: Cost effectiveness analyses of PGT-A

Infertility treatments can be financially burdensome, often without insurance coverage, making understanding the cost effectiveness of PGT-A crucial. View the Video
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Coding PGT requisitions to the PGT lab

Do you have any recommended codes to use for PGT requisitions to the PGT lab?   View the Answer
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Genetics: Is Expanded Carrier Screening the Standard of Care?

Hannah Green, a genetic counselor at NYU, discusses the benefits and limitations of expanded carrier screening, highlighting its impact on clinical practice and patient care. View the ASRMed Talk Video
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Genetics - Extra Testing, Passthrough or Money Maker?

Danielle Soltesz of RMA New York discusses the complex economics and ethical considerations of genetic testing in reproductive medicine, exploring costs, patient care, and sustainability. View the ASRMed Talk Video
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Journal Club Global - Revisiting the STAR trial: The Fellows debate PGT-A

We are excited to host a debate covering the pros and cons of PGT-A and how new technologies should be validated before clinical implementation. View the Video
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Indications and management of preimplantation genetic testing for monogenic conditions: a committee opinion (2023)

ASRM has updated its opinion on PGT for monogenic conditions, providing guidance on clinical and technical complexities. View the Committee Opinion
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Results Review

What CPT code is most appropriate to submit for Physician Time to review CCS/PGS/PGD results? View the Answer
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Sperm DNA Fragmentation

Is there a CPT code for HALO DNA Fragmentation for sperm? View the Answer
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ICSI and Embryo Biopsy

How to bill for ICSI or embryo biopsies that occur in different days?  View the Answer
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Embryo Biopsy

Have any new codes been introduced for the lab portion of PGT? View the Answer
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Embryo Biopsy Embryologist Travel Costs

Can we bill insurance for the biopsy procedure? Can we bill for travel expenses? View the Answer
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Embryo Biopsy PGS Testing

What codes are appropriate for PGS testing? View the Answer
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Genetic Counseling

Does ASRM have any guidance for how to bill for genetic counseling services provided by a genetic counselor?
View the Answer
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Assisted Zona Hatching

Can assisted hatching and embryo biopsy for PGT-A; PGT-M or PGT-SR be billed during the same cycle? View the Answer
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Journal Club Global - PGT-A - Can non-invasive approaches based on spent medium analysis

PGT-A by trophectoderm biopsy aims to select available euploid embryos for transfer. View the Video
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ASRM müllerian anomalies classification 2021

The Task Force set goals for a new classification and chose to base it on the iconic AFS classification from 1988 because of its simplicity and recognizability. View the Committee Opinion
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Journal Club Global - Accuracy of Preimplantation Genetic Testing for Aneuploidies

One of the highest aspirations in reproductive medicine is to develop a technology allowing for ID of embryos that have true reproductive potential.
View the Video
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Reproductive and hormonal considerations in women at increased risk for hereditary gynecologic cancers: Society of Gynecologic Oncology and American Society for Reproductive Medicine Evidence-Based Review (2019)

Providers who care for women at risk for hereditary gynecologic cancers must consider the impact of these conditions. View the Joint Statement
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Disclosure of sex when incidentally revealed as part of preimplantation genetic testing (PGT): an Ethics Committee opinion (2018)

Clinics may develop a policy to disallow selecting which embryos to transfer based on sex and choose to use only embryo quality as selection criteria. View the Committee Opinion
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Best practices of ASRM and ESHRE: a journey through reproductive medicine (2012)

ASRM and ESHRE are the two largest societies in the world whose members comprise the major experts and professionals working in reproductive medicine. View the Committee Joint Guideline
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Preimplantation Genetic Testing Special Interest Group (PGTSIG)

The ASRM PGTSIG coordinates research, education, and training in preimplantation genetic diagnosis (PGT). Learn more about the PGTSIG

Topic Resources

View more on the topic of ovarian stimulation
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Fertility and Sterility On Air: Live from the ESHRE 41st Annual Meeting (Part 2)

Live from ESHRE Paris 2025: Fertility & Sterility On Air features latest IVF, AI, embryo genetics & implantation research with top global experts. Listen to the Episode
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Use of Code 99211 for a Monitoring Appointment

Is it appropriate to use code 99211 if a patient is scheduled for a monitoring visit View the Answer
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Intro to REI Ultrasound

Leslie King explains the basics of ultrasound in reproductive medicine, covering key techniques, anatomy, and abnormalities for new nurses and clinical staff. View the ASRMed Talk Video
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Ultrasound for Ovarian Cyst

When a patient has a cyst from a previous Clomid or gonadotropin cycle, is it appropriate to bill the insurance company for the ultrasound with a N83.x? View the Answer
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Coding of transabdominal vs. transvaginal ultrasound

I recently was informed that CPT 76857 can be used for a transvaginal ultrasound when done for a follicle check by a fertility practice. View the Answer
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IVF Consent Counseling

When a patient is scheduled to undergo IVF and the provider schedules the patient for a 30-minute consultation is this visit billable? View the Answer
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IVF Lab vs Physician Practice Billing

We are planning to open an IVF lab that is not contracted with insurance companies. View the Answer
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Oocyte Aspiration

Should one bill oocyte aspiration as a bilateral procedure? View the Answer
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Journal Club Global: Management of poor ovarian response

A poor ovarian response to what should otherwise be a successful stimulation cycle presents a clinical conundrum for clinicians. View the Video
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The role of immunotherapy in in vitro fertilization: a guideline (2018)

Adjuvant immunotherapy treatments in in vitro fertilization (IVF) aim to improve the outcome of assisted reproductive technology (ART) in both the general ART population as well as subgroups such as patients with recurrent miscarriage or implantation failure. View the Committee Opinion
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Comparison of pregnancy rates for poor responders using IVF with mild ovarian stimulation versus conventional IVF: a guideline (2018)

Mild-stimulation protocols with in vitro fertilization (IVF) generally aim to use less medication than conventional IVF. View the Guideline
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Best practices of ASRM and ESHRE: a journey through reproductive medicine (2012)

ASRM and ESHRE are the two largest societies in the world whose members comprise the major experts and professionals working in reproductive medicine. View the Committee Joint Guideline
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Executive summary of the Stages of Reproductive Aging WorkshopD10: addressing the unfinished agenda of staging reproductive aging (2012)

The aim of this article is to summarize the recommended updates to the 2001 Stages of Reproductive Aging Workshop (STRAW) criteria. View the Committee Guideline
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Abdominal Paracentesis

We do a lot of abdominal paracenteses on patients at our facility.  View the answer