Fertility and Sterility On Air - Live from the ESHRE 42nd Annual Meeting (Part 1)

(Please excuse any sound quality issues, as some interviews were recorded in a large hall where background noise and echoes were hard to avoid.)

Fertility & Sterility on Air is at the European Society of Human Reproduction and Embryology 42nd Annual Meeting in London (Part 1)! In this episode, our hosts Micah Hill and Yannick Hurni cover: 

• (01:49) ASRM President Robert Brannigan on the effect of lifestyle factors on male fertility and a look ahead at the 2026 ASRM Annual Meeting
• (07:25) The 2-shot protocol: a randomised controlled trial of a novel two-injection ovarian stimulation strategy with Valeria Donno
• (14:49) Paired trophectoderm and ICM analysis redefines segmental aneuploidy and embryo usability in poor-prognosis IVF patients with Balsam Al Hashimi

View Fertility and Sterility at https://www.fertstert.org/

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.

Welcome to Fertility and Sterility On Air. We are here live in the Excel Center in London for ESHRE 2026. We're here with the F&S team, some of the editors from our podcast who you are familiar with.

It is myself, Micah Hill, the Media Editor for F&S, and I also have my co-hosts at F&S On Air, Kate Devine and Eve Feinberg, and two of our F&S colleagues from Europe, Paul Pertia and Yannick Hurni. We'll be bringing you some of the best of ESHRE, including interviews from authors presenting interesting research, message from our presidents and vice presidents, and some other interesting research topics that are already published that we wanted to talk to the authors about. So listen to the next one to two episodes, and we hope you enjoy catching up on ESHRE if you didn't have a chance to make it here this year.

We're back here in the Exhibit Hall in London at ESHRE 2026. I'm Micah Hill, the Media Editor, and we are very excited to have a special guest. We have our president of ASRM, Dr. Bob Branigan.

Bob, it's really good to see you. Micah, thank you so much for the chance to visit with you today. I'm excited to catch up about this meeting and other stuff that's coming down the road.

So I heard that this morning ASRM had its session here at ESHRE, and all the presidents of ASRM were talking about things like lifestyle and its influence on fertility. Tell me about that. Yeah, so Dr. Toner talked about the female side, and Dr. Sparks talked about the laboratory side, and I, of course, took the male side.

And I think we see this all the time. Our patients want to be empowered. They ask us, like, what can I do to help optimize my fertility? And there actually is a lot that they can do.

If we take a careful look at the literature, we find that, you know, obesity and then the components of metabolic syndrome that go along with that on the male side can have a substantial negative effect. It can impact the HPG axis, causing lower testosterone. Just the obesity itself can also cause an impact on the testicles, overheating the testicles, and interfering with spermatogenesis.

Then also, you know, taking a look at just the inflammatory state that patients with obesity have, that also can cause an impact with sperm DNA damage. So many, many ways in which obesity is just one example can adversely affect male fertility. So we talked about interventions that can counter that, and I think one of the takeaways is that diet and exercise seem to work.

Bariatric surgery, the literature just does not show a benefit, generally. And so there might be some factor that is going on either with deprivation of nutrients with that approach, or some factor that just passes through the gut. But we do see, again, diet and exercise, a strong signal for those being supportive.

I'll just add in, you know, everyone's wondering about the GLP-1 agonist. And so one RCT so far published, and I talked about that this morning. And the bottom line is, as long as weight is maintained either through exercise and diet or GLP-1 agonist, it seems that, at least based on one study, that there are gains in sperm production, sperm concentration and fertility.

What do they think is the pathway behind that? Is this an inflammatory changes, or do they know what mechanistically, sort of what they think the benefits are? I don't think we fully understand, but we know the pathophysiology with obesity being associated with hypogonadism. Again, just the visceral obesity causing an increase in the temperature and scrotal area, and then the inflammatory state causing DNA damage. So probably all those areas of gain, but really that's the only RCT that's out there so far, but we're going to see other ones coming, maybe even in time for our meeting in October.

Yeah, well, that would be great. So actually, speaking of the meeting in October, this is going to be your presidential year for your meeting. What's the theme? What did you come up with for the theme of our Congress? So I'm really excited about it, because I think we're at such an inflection point in society globally with a lot of advancement.

So the theme is discovery, innovation, and advancement. And I think there's no better time than now for that theme for the meeting. We all are being empowered with tools to help us not only in our day-to-day lives, but also in our practice of clinical medicine and research.

And so I think it's me to take a moment to reflect on some of these different technologies. And so we've got speakers from across the globe that are going to be presenting cutting-edge research, looking, of course, at AI and other basic science and clinical advances. So a very exciting time.

I mean, think about when you and I first started in practice, Mike, and how much things have changed. I only wonder 20 years from now, 25 years from now, what's it going to look like? Yeah. It seems that AI and sort of the political climate around our field has sort of spurned a lot of interesting innovation that's happening, both within AI and outside of it.

And so I heard that, speaking of that, this is the second year that the Innovate Conference will be following up the day after ASRM. Is that right? So the Innovate Conference is a full-day conference where folks with an entrepreneurial spirit, people that want to get engaged with startups, can come and present their work. So it's very different than our regular Congress.

I had good fortune to attend the Innovate Summit last year, and it's just a different vibe. People with really, truly cutting-edge ideas, people who are looking to operationalize these ideas. I think for someone who has a growth mindset and wants to see where the field might be in 15 or 20 years, maybe 10 years, come to the Innovate Summit.

A lot of really fun sessions and really nourishing for our soul to be able to see what is out there. So it's a great meeting that ASRM has put on, and for the second year, I'm excited to be part of it. So if you're like a clinical urologist, a clinical embryologist, an REI, and you're maybe not doing a lot of research, but you're interested in maybe connecting with some groups that are and sharing your expertise, is that something that happens? What you realize is that anyone can have an idea.

I think what's sad is you realize that some people, they're curious, they have an idea, and maybe they shut it down themselves. If you have an idea that you think is out there, come to this meeting, and you'll see that a lot of people up on the stage that are moving their ideas forward are ones who also had ideas that they themselves maybe doubted at the inception of that thought. So great place.

I encourage anyone to come. If you have an original idea or you want to learn how to be creative and have that thoughtful process in your own life, your own career, come. I mean, it's a little bit different than one of the basic science and clinical science that we do at the Congress.

It's a very inspiring meeting. Yeah. Well, I will definitely be there.

I'm excited about it. We invite all our listeners, if you've got to, to come to the Congress and come to that extra day of innovation. Well, Mr. President, it's a pleasure to have you on.

Thank you for your leadership for our society, for ASRM, and we look forward to seeing you in Baltimore. Micah, thank you so much. Really enjoyed it, and congratulations on the podcast.

Thank you. Thank you. Welcome to Fertility and Sterility On Air, recorded live from ESHRE 2026 in London.

I'm Yannick Hurni, Interactive Associate for Fertility and Sterility, and today, I'm joined by Dr. Valeria Danon, Reproductive Medicine Specialist and Scientific Director of the Reproductive Medicine Department at Excelsior University Hospital in Barcelona. Valeria, thank you for being here. Thank you, Yannick.

So today, we'll be discussing your presentation, the Two-Shot Protocol, a randomized controlled trial of a novel two-injection ovarian stimulation strategy. Before we get into the details of the study, could you tell us what was the question you were trying to answer, and why you felt it was clinically important to explore it? Yeah, sure, sure. So the idea is that we know that in ovarian stimulation, we had in the last 50 years a big evolution.

We started with a natural cycle, then we introduced gonadotropins to try to increase the efficiency of the ovarian stimulation. To have more control, we introduced the agonists first, then the antagonists. But then, in the last 50 years, we have, like, a change in the direction, the evolution of ovarian stimulation, trying to make it more easy for patients to reduce the burden of the treatment.

So in this, the idea of the Two-Shot Protocol is to try to achieve ovarian stimulation with just two injections, to try to reduce the number of injections for our patients. This was the idea behind the study. So I think this is very interesting.

It's an approach very, I would say, patient-friendly. This is the main idea of your study. And how did you evaluate this new protocol? Could you briefly describe the trial design and the main outcome you were looking at? Yeah, sure.

So what we did was, at first, looking at the efficiency level when we use colifilutropin alpha, that we know can replace one week of injections. So what we normally do when, in a conventional protocol, when we use colifilutropin alpha is starting from day eight with daily filutropin. So the question was, what happens if we add another injection of colifilutropin on day five? Can we achieve ovarian stimulation with just two injections? Can we achieve, can we maintain the FSH above the threshold? So this was the idea.

So what we did was, we designed a non-inferiority randomized control trial. We selected a population of good diagnosis patients that were elective fatigue preservation in age from 18 to 40, and with a 19-11 hormone bill of three. And the point we wanted to understand was the number of mature oocytes.

And what we did was a randomization in two groups. One was the study groups, it was the two-shot protocol, in which we had two injections of colifilutropin alpha, one in day one and one in day five. During the protocol, we used the Surgestrel 75 micrograms to suppress the LH, whereas in the other group, we did in the day one, colifilutropin alpha, 150 micrograms, and then starting from day eight, they were FSH.

The trigger was in those groups with the ovulus, and 36 hours after that, we did the Rosetta trigger. So the primary outcome, as I told you, was the number of mature oocytes. That's great.

And what did you find? Well, what we found was that when we analyzed the primary outcome, in general, we analyze also the length of the stimulation and something else, but if we focus on the primary outcome, we found that the number of oocytes was, the mean difference was 1.04, which was not statistically significant. In favor of? In favor of the conventional group, so the control group, yeah. But when we, if we focus on the confident interval, we found that the lower limit of the confident interval close the limit of inferiority that we set at 1.5 mature oocytes.

So this means that the study was not able to demonstrate the non-inferiority of the two shock protocols compared to the other, even if the difference was not statistically significant to just one mature oocyte. So it was- For sure. So something is statistics, something is methodology, and something is clinical implication.

What do you think this results as an implication for your clinics and for your future research? Yeah. First of all, I think that the results of this research demonstrated that we can achieve an ovarian stimulation with just two injections because we also perform normal profile in which we see that FSH was higher in the study group as compared to the control group in day eight and until the trigger day. So it means that from an MNR point of view, we have enough FSH with this protocol, so it's good.

From clinical implication, as we didn't demonstrate, it's true that we didn't demonstrate the non-inferiority, but I think that from a clinical point of view, there is a selected population in which we can consider the two-shock protocol when we can accept a small reduction number of mature oocytes in favor of a big reduction in number of injections. So it's something that for selected population, we can consider. And for sure, for more extended application, we need more studies, maybe to address it and to investigate also the embryo profile, the pregnancy outcome, because as we select the population with elective fertility preservation, we have no data regarding the embryo development, lab and pregnancy outcome, which will be very interesting.

I think it's really interesting this changing in the paradigm and the idea and the mindset on how we construct protocols. And so thank you for sharing these results and for trying to push the limits, I would say. What are your next steps? Are you planning to do other studies on this or not? Well, we already did a little step forward in this direction as we perform a pilot study that we are publishing in which we explore the one-shock protocol.

So it means just using one injection of colifluidoprene alpha plus clomiphene citrate during the valence stimulation. So this will be the step forward. So I mean, the direction that I think we need to consider, and it's something that really it's important, is that the patients that we see now in our reproductive units are not only infertile patients, are patients who come for egg freezing, for egg donation.

So in these settings, make an easy planning, make treatments, reducing the burden, reducing the number of injections is something which is very important that we need to consider. It's something that we need to change. I completely agree with you.

Thank you very much for sharing your results with us. Thank you. Good luck for your presentation tomorrow.

Welcome again from ESHRE 2026. I'm Yannick Hurni, Interact Associate for Fertility and Sterility, and I'm joined by Balsam Al-Hashimi, Embryology Laboratory Manager and Head of Genetics at the London Women's Clinic and a PhD researcher at University College London. Balsam, thank you for being here.

Thank you for having me. Today, we will be discussing your study. Pair Trifectoderm and ICM analysis redefine segmental aneuploidy and embryo usability in prognosis IVF patients.

Balsam, could you start by explaining the problem you were trying to address and why segmental aneuploidies remain such a challenging finding? First of all, thank you for having me and for highlighting this topic. I find segmental aneuploidies is very fascinating in genetics field and in embryology. The main thing, because the main research focus on full gain and full loss of chromosomes.

In the last few years, we start seeing actually the platform is the genetic platform that will see the genetic results or the PGTA platform showing more segmental events. When we say segmental aneuploid, it is a partial gain or loss of chromosomes. We don't know their origin.

We don't know their biological mechanism. We don't know how important they are, but the main thing we know they are associated with reproductive and developmental adverse outcome. Therefore, the aim of our study was to investigate the original segmental aneuploidy, their origin, and to see whether there are concordance across their embryonic lineages and also how we can clinically manage those embryos that they have segmental aneuploidy.

If I try to rephrase a little bit your answer question, would it be fair to say that you wanted to understand whether a single trapezoidal myopsy provides enough information to guide clinical decision for embryos diagnosed with a non-mosaic segmental aneuploidy? Definitely, we wanted to first of all investigate their origin, their mechanism, and then slowly, slowly, when we start getting the results, the main thing we wanted to see was the ICM, and many studies in this field explored the segmental aneuploid clinical significance, but there are rare studies showed what's inside the ICM, the endothelial mass of the future baby. So, the importance of this study, we bypassed the ICM, and then with two trapezoidal myopsies, we start analyzing those results, and then slowly, slowly, I asked myself the question, would it be possible if we have a second biopsy, we can regrow those embryos? And then to answer that question, I went back to the results, and interestingly, I found that those ICM actually either nucleoid or either mesoid, which means by taking a second trapezoidal myopsy, it gives us more biological information with regards to biological or chromosomal status of those embryos, and therefore, in my study, we found around 47 percent of the embryos used in this study can be reclassified and used for clinical treatment, and obviously, you will need genetic counseling. The patient had to be aware of the consequences of transferring an embryo if this mesoid, or if that segmental endoploid was a real embryo, and then they make a decision.

If I'm understanding things well, so probably there's a difference between the biopsy of the perfectoderm giving you a result of a whole chromosome, a nucleoid, and when the result is a segmental endoploid. So what do we expect? So I would say that the positive predictive value of those results is different. Is it correct? It is different because we try to see the concordance for segmental endoploidies across embryonic lineages and the whole chromosome endoploidies as well.

So when you come to the segmental endoploidies, the embryos show real heterogeneity when it comes to a segmental endoploid. So we have observed around concordance one-fourth, which was around 19 percent concordance, versus the chromosomes that were... So concordance, it means that every biopsy, the biopsy number one perfectoderm, biopsy number two perfectoderm, and biopsy of ICM were concordant. Concordant together.

Okay, so it means that 80 percent were not concordant. Not concordant. We have seen around 50 percent, there were two out of three concordant, and then the remaining were non-concordant.

So this mainly highlights the biological heterogeneity of the segmental endoploidy. And then I asked myself another question, if I want to see concordance of whole chromosome endoploidies for involving the chromosomes who have segmental endoploids. So for instance, if I have partial deletion or duplication in chromosome one, and then I can see the whole copy change in chromosome one, what's the concordance of the whole chromosome across all embryos? What I found is the concordance were around 73 percent for the whole chromosome endoploidy, but then I have around 27 percent, they're showing two out of three concordance.

The two out of three concordance, they show intrachromosomal effects. And then when I wanted to see what's the origin of intrachromosomal effect, I found actually there were paternal origin abnormalities. So this led me to conclude that paternal chromosomes are more prone to chromosomal remodeling when it comes to a segmental endoploid.

But then, on the other hand, when I removed the chromosomes that they are involved with the segmental endoploid, I have the concordance nearly 98 percent across embryonic lineages, which again suggests that chromosomes without segmental endoploidies are more persistent across embryonic lineages. What I found particularly interesting is that this study challenges the assumption that a single trifectoderm biopsy always tells us the full chromosomal story of the embryo. For segmental endoploidies, the biology appears much more dynamic and heterogeneous than we may have expected, with potentially important implications for embryo selection.

What do you think are the most important clinical and research implications of these findings? This finding, the main core of this study, we know what's inside the ICM. That's what makes this study really fascinating and the results more reliable. Because in other research, they take multiple trifectoderm biopsy.

Microdissecting the ICM, it's an extremely difficult technique, and we've done it in this study. So by aligning them with two trifectoderm biopsy, actually having two trifectoderm biopsy could give us some indication and we could reclassify those embryos. So what's this study basically suggesting, and definitely we need larger sample size and we need further research, if we take two trifectoderm biopsies, we could reclassify those abnormal embryos or embryos that they deem to be abnormal in the first PGT-A results, and then they can use them for treatment, especially for prognosis patients.

So that's another question for you. When we have results of a trifectoderm biopsy showing a segmental endoploidy, should we re-biopsy the trifectoderm, or should we just transfer the embryo, or what we should do? What do you think? Given the heterogeneity and the mechanism that a segmental endoploidy is arising, they could be either meiotic or mitotic origin. At the moment where we are, it could be safer to have a re-biopsy, but then I think down the line we're going to be just transferring those embryos, and maybe many genetic counselors listening to our podcast, maybe they're not going to like it.

But I come from an aspect as an embryologist, we transfer many endoploid embryos per day. We don't know what's their genetic status. For me, as long as the patient is counseled and fully informed, I think we're going to reach up to a point in the future, once we have the segmental endoploid embryos, we can just transfer them.

And of course, if they are not associated with compatible life, abnormal pregnancy, for instance, maybe it should still be away from chromosome 13, 18, and 21, whereas the segmental endoploidies could be in the future just transferred. But it's going to be in the future. We'll see.

It's extremely interesting. Thank you very much for sharing your research. Thank you for being here.

Okay. Thanks. Thank you very much for having me.

This concludes our episode of Fertility and Sterility on Air, brought to you 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.