Fertility and Sterility On Air - Live from ASRM 2024: Part 1

Fertility and Sterility On Air brings you the best of ASRM 2024! In Part 1, our hosts bring you: in vitro maturation with Christian Kramme (1:40), uterine transplant data updates with Leigh Ann Humphries (9:21), novel characterization of ploidy abnormalities with Ludovica Picchetta (21:50), maternal age and euploid transfer success with Philip Romanski (24:45), ultrasound assessment of ovarian stiffness to evaluate reproductive aging with Elnur Babayev (32:45), cost effectiveness of PGT-A in good prognosis patients with Ariel Dunn and Josh Combs (42:33), long-term follow up of oocyte donors with Jerrine Morris (51:16), and combining platforms to improve identifiation of mosaic embryos with Christopher Weier (58:28).

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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 discussion with authors, and other special features. FNS On Air is brought to you by 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, and Dr. Pietro Bortoletto, Interactive Associate-in-Chief.

Hi everyone, and welcome to the FNS On Air. We're recording live from the ASRM 2024 meeting in Denver, Colorado. We have wonderful science from this meeting.

We've scoured the abstract booklet to find some of our favorite science, some of the most innovative stuff, and some of the stuff that we just don't know a heck of a lot about and wanted to learn a little bit more. I'm here, standing directly across from me, Blake Evans, co-host of FNS Unplugged. Hi Blake.

Hi Pietro. Fantastic to see you in person, and not on Zoom. And I like to tell Blake every time I see him, he is taller in person than you actually think, listener.

How tall are you? We've got to be pretty close. We did this last year. I'm 6'4", you're 6'3 1⁄2".

He would say otherwise. But that's neither here nor there. Back to the science, Blake.

We'll do this later. Listener, we have a really wonderful group of authors, scientists, clinicians that are going to be stopping by the FNS booth from the meeting this year to tell us a little bit about their science. And kicking off the podcast and the live recording session from the meeting, we have Dr. Christian Kramme, who's the chief scientific officer at a company called Gameto, which some of you may have heard about, but I imagine many of you will be hearing about in the coming days at the meeting.

Christian, welcome to the podcast. Thank you so much. Excited to be here.

As we were scouring the booklet, we noticed that Gameto kept showing up over and over and over again. What's the total count of abstracts at the meeting this year? Seven. We will have seven.

That's awesome. Very busy meeting for you all. It is.

It is. Many competing PowerPoints. Christian, with all the wonderful science that Gameto is doing, let's start from the beginning and just tell the listener a little bit about what Gameto is and what's the science that you guys are working on.

Absolutely. Excited to be here. Gameto, we're a biotech company that's based in New York City.

I know definitely at ASRM there's probably not too many biotech startups that are here, particularly ones that are entirely wet lab and cell culture focused. Our science actually comes from Harvard University. That was a spin out of there.

I've heard of it. A small, small little school. In Cambridge.

In Cambridge. Really our specialty, what we do is cell engineering. That's my background.

That's what I did my PhD in. Most of our team are various forms of embryologists and cell engineers. Specifically what Gameto does is that we're specialists in in vitro maturation.

For those who don't know what that is, it's really the attempt and the approach to IVF treatment in which the eggs are going to be matured outside of the body. Where does cell engineering come into all of this? Well, kind of what Gameto's whole intent and purpose is, is that we've got an approach to IVM called OSC-IVM. That stands for ovarian support cell IVM.

As that name kind of suggests, we actually engineer these cells that can support the egg outside of the body. What they are is basically mural granulosa cells. How we actually make them is we take induced pluripotent stem cells and we engineer them to become these granulosa cells to be used outside of the body to mature the eggs and recapitulate this kind of ovarian environment to really try to trick the egg to thinking it's back in a follicle and to get a better outcome.

We generally think granulosa cells are pretty good, pretty important, helpful. So we're hearing that you could use this technology for in vitro maturation. Are there other potential applications of the technology that extend beyond maturation? Absolutely.

So where this work actually all started was actually in ovarian modeling. So you can actually use these cells, culture them for about four to six months, and what you actually get is folliculogenesis in a dish. What we're able to do is actually build two to three millimeter follicles that you can physically look at in a dish.

And the cells self-assemble, they organize and form these antrum that are fluid filled, and that fluid really resembles follicular fluid. So we use these cells, we know they do these ovarian functions, and that's why we try to put them in what is probably the most difficult of all applications, which would be to try to get an egg to mature as well outside of a body as it does inside. We're, as a company as well, looking at uses for menopause and cell therapies for drug development and screening.

We think it's a cell type and a platform that's extremely underutilized, it's understudied, and is difficult to obtain in a way that you can actually culture and work with. So we're excited about what we can do for this pretty broadly. Would you say the majority of the patients are fertility preservation cancer patients, or I know you mentioned menopause, but tell me about that.

Yeah, so really when it comes to IBM historically, it's pretty much been entirely limited to either PCOS patients or oncofertility patients. And the main reason for that is that really you're either using this in a case where the patient might not be the best candidate for a full controlled ovarian stimulation, and that kind of control emphasis might be a little difficult in these patients, or for patients like an oncofertility where they really don't have the time or the ability to wait to undergo treatment. That's also been kind of paired with the fact that historically IBM has underperformed IVF, just really from the way that you're maturing these eggs and how many embryos and specifically the number of blastocysts that you can get.

The whole purpose of Gameto and our approach is to try to solve that exact problem. We're trying to mature more eggs and make more blastocysts out of those eggs. And I think that's something we've been very successful in, and it's really allowed us to actually move this technology towards more conventional, normal ovarian reserve patients, egg donors, egg freezers.

We really think that anyone could benefit from lowering gonadotropins and making the process shorter and faster, more efficient, and hopefully more cost effective, as long as that efficacy is there. Great. And in terms of efficacy, are you able to delve into that? Clinical outcomes similar, have you found? Yeah, what are we expecting to see at the meeting in terms of what you'll be presenting? Absolutely.

So later today, I'll be presenting a kind of case series on egg donors, egg freezers. What we show is that with two to three injections of Gonal-F, so about 300 to 450 units total, you can retrieve about 14 oocytes. You can mature anywhere from nine to 10.

And from that, you're getting about two to three vitrified day five or six blastocysts for transfer. This is something that we see pretty consistently in clinics in Peru, in Mexico, as well as some of our kind of earlier research in the United States. We published last year in Human Reproduction that we're able to convert about one in every... Never heard of them.

Oh, a small regional reproductive medicine journal. I wasn't too interested, but no, I mean, we showed that we're able to... Is he allowed to say that on this podcast? We are. Yeah.

We were able to convert anywhere from basically four to six input oocytes to a transferable blast. At the end of the day, that's the kind of rate that you're going to really need to see IVM reach because you are usually going to start with less oocytes than you would with a conventional full-blown stimulation. And so every egg counts.

And so for us, we really benchmark success at converting kind of anywhere around 15 to 20% of those oocytes into something that can be transferred. And for us, what is transferable is the day five to six blastocysts, even a euploid blastocyst, which is one of our more recent studies. Very fascinating.

Euploidy rates, are they overall similar? Yeah. So for patients under 35, we see about 60 to 70% patients who are over 42. So we did a study of rescue IVM where one, you're dealing with oocytes that are being rescued.

So probably a little bit less of a good quality source. And two, the patients tend to be older and those, your euploidy rates can drop down to 50% or less. But yeah, basically for us, two in every three embryos for a patient who's under 35 is euploid.

And really we tried to kind of preference towards good day five blastocysts, day six. And I think that's been kind of our advantage over standard approaches where if you can make a blast, great. You often don't.

So you're doing cleavage. And if you are, it's tending to be a day seven or a poor Gardner score quality. So we care a lot about quality.

Sure. Absolutely. I think listeners, I speak on behalf of all of us, it's great to see innovation happening in the field of women's health.

We don't see a heck of a lot of it. And this is, I think, something that's hopefully going to move the field in a new and interesting direction and just give us some more options. Christian, thanks for coming by the podcast.

We're excited to pop into your sessions over the course of the week. Absolutely. And one last plug, there is an IBM special interest group at ASRM.

I think it's one of the pretty cool parts of ASRM to actually bring a lot of people in the field together. It's a small group, but it's exciting. Gameto's not the only one in this space.

We're not the only team that's working at it. So definitely stop by and get involved where you can. Awesome.

Thanks, Christian. Congratulations on all of your work. Thanks so much.

Hi, this is Eve Feinberg, live from ASRM with my co-host for this afternoon. Molly Cornfield here, helping out Eve today. Yeah, welcome.

And we have Leigh Ann Humphries. Hi, Leigh Ann. Hi, happy to be here.

Leigh Ann, you're at Penn. Is that correct? I just graduated from Penn. I was a fellow in REI at Penn.

I graduated in 2024, and I'm doing a second fellowship at Newton Wellesley, Mass General Brigham, in minimally invasive gynecology. Gotcha. I did not realize that.

Congratulations. And I know that this abstract was submitted when you were at Penn. Yes, yes.

The affiliation was listed. But yeah, I mean, I would love to hear more from you about this work. So the title of the abstract that we're reviewing is Eight Years of Uterine Transplants in the United States, Update on Surgical Reproductive Neonatal and Child Development Outcomes.

So tremendous work. Congratulations on this. But I'd love for you to walk us through, like, what this abstract, what it says and what you've learned.

Sure. This is the joint effort of four programs and many, many collaborators. So there are currently four uterus transplant programs in the United States, of which the University of Pennsylvania is one.

Also, the Cleveland Clinic, Baylor University in Dallas, and now a new program at the University of Alabama at Birmingham, so UAB. And so this is the combined work of all of those programs since 2016, reporting outcomes across donors, recipients, and the children born from uterus transplants up until October of 2024. Yeah, that's amazing.

And so all of these data are U.S. data, not worldwide data, correct? Correct. The U.S. data represents about half of the experience of uterus transplant worldwide. So it's a large proportion of all of the transplants that have been published, but this is just domestic data.

Great. I had the privilege last summer of being in Australia and meeting the first Australian uterine transplant recipient who just had a live birth this past year. I've been following her and in touch with her on social media.

And I have to say, it's remarkable. I think when I first started hearing about uterine transplant, admittedly I was a little bit, I don't want to say opposed to it, but I think my knee-jerk reaction was, why would we think about transplants when we have surrogacy? And I think after hearing the stories and really diving in and looking at the data, I'm much more convinced that there's a huge role for it. So I'm curious to hear, tell me a little bit about what the landscape is and what we found.

So the field of uterus transplant in the United States has come a long way since the first transplant in 2016. So that first transplant and actually the next three transplants were all unsuccessful. So they all resulted in graft loss.

The fifth transplant was successful and resulted in a live birth. And then since then, including that transplant, we have had 34 total live births. The field has just continued to improve in terms of surgical technique and also outcomes for all parties involved, for donors, for recipients, and for children.

So with those 34 live births, we've had 22 recipients who have had one live birth and six who have had two live births, and there are seven ongoing pregnancies. So these numbers will change as time goes on, as more of these recipients deliver. And we can't neglect the fact that there are some important complications associated with uterus transplant.

So that's one of the things that we report are the different grades of complications experienced by donors and recipients. The important point, though, is that the vast majority of these complications occurred very early in the experience of uterus transplant, so in the first two to three years. And so we've shown that there's a learning curve, and that's been reflected in the outcomes as well.

Yeah, so I remember being at the first ASRM in Hawaii, and Mats Brannstrom, I think, dazzled us all with these incredible videos of uterine transplant. And I remember the surgeries were taking, like, eight and nine hours. Tell us a little bit about how that's changed, and is that part of why you're doing a fellowship to learn how to do transplant surgeries? Yeah, so the first transplants were investigational.

Like, we were still trying to figure out what the best techniques were and what the best systems around the surgery needed to be, as far as preoperative planning and postoperative follow-up. And as all of that has become streamlined, the surgeries itself have become shorter. The differences in terms of what vessels have been used, you know, previously they were often spending a lot of time looking for the uterine, the inferior uterine veins, and now we've found that the superior uterine veins are sufficient and work very well.

So there are changes that you can make intraoperatively that have shortened the time of the surgery, but then also just the approach. So starting out, the donor surgeries were done by midline laparotomy. Now the vast majority are done by robotic-assisted laparoscopy.

As far as my interests, I would love to be able to do a uterus transplant at some point in the future. The reality is that it is very large collaborative teams that work together. It's transplant surgery.

It's gynecologic surgery. It's often urology. So never is it a single surgeon making those types of operations happen.

So I noticed the complication rates for both donor and recipients, but I really noticed it for the donors was much higher than I'd expect from like a simple hysterectomy. But I haven't seen these cases before. I never saw them in training.

I don't know much about them. Can you explain that a little bit more, why that complication rate is so high? Sure. First, for recipients, one of the major complications is graft loss itself.

So if you've undergone this transplant and then your transplant fails, that requires a graft hysterectomy. So now two surgeries with no ultimate goal of a baby. As far as donors, there have been some complications that aren't as common in just hysterectomies for a benign indication.

For example, vaginal cuff dehiscence. But then also several patients have had ureteral complications. So either ureteral obstruction or one patient had a ureterovaginal fistula.

These were early in the experience of uterus transplant in the United States, and fortunately these complications have become very rare in recent years. And the complications seem somewhat standard for a radical hysterectomy or for other non-benign indications. Higher than simple.

Yes. So a donor hysterectomy is much more involved than just a benign hysterectomy because you are preserving the vasculature, the organ itself, and the vagina. What about neonatal outcomes? How have the pregnancies gone and how have the neonates fared once delivered? The pregnancies have been overall very successful.

The plan for delivery is typically at about 36 to 38 weeks. We have had patients go to term. There have been a few preterm deliveries, and some of those are planned preterm deliveries, some unplanned.

But in general, the pregnancies have been very well tolerated and have made it to either late preterm or early term. The neonates, those that are born early or born preterm, have had typical NICU stays according to their gestational age. They have had weights that are appropriate for gestational age.

And as far as longer-term neonatal outcomes, we have monitored them for childhood disorders or neurodevelopmental outcomes, and they've done very well. The one notable finding is that two of the 29 children that we followed have been diagnosed with autism. It's unclear whether this is something that is a correlation or has any implication in terms of the transplant itself or if this is just a finding in the data, but it's something we want to continue to follow.

It's really phenomenal that you guys have these long-term child development outcomes. It's exactly the things we're thinking about when we hear about these procedures and, hey, what actually happens on the back end? So that's great. And whether some of those are complications related to this late prematurity as well.

I would love for you guys to make a little descriptive study spinoff of this of just the characteristics of who is donating their uterus and we know who the recipients are, but are there relationships between the donors and the recipients? Is it more like an anonymized donation? I think that would be a cool study just out of my curiosity. So only one of the donors is what we call a directed donor, meaning someone known to the recipient, and that was the patient's friend. So whereas you may see that in other countries and with the early transplants, you might see a mother donating to a daughter, in the United States all of the transplants except for one have been from altruistic donors that have volunteered and have no relation or familial ties to the recipient.

Yeah, that's interesting. The Australian donor was the aunt of the donor, which then brings up ages in terms of have there been age limits that have been established for the donors? The screening eligibility criteria for donors and recipients are still being worked out. So because those early donors and recipients were primarily within trials, it was based on the trial protocols, which of course are very strict and require very healthy young patients.

But now in Baylor, in Dallas, and at the University of Alabama, these transplants are being performed outside of research protocols. So the sites have to define what their eligibility criteria are. Right now there are so many more donors and recipients that want to participate in uterus transplants than have had transplants.

So it's still ongoing trying to determine who is eligible, who should be eligible, how do we make those decisions. And what about deceased versus living donors? Can you speak to that a little bit? The majority of transplants in the United States have been performed with living donors, so around 60 percent. That's mostly site-specific.

So Cleveland Clinic and the University of Alabama have performed only deceased donors, and that's just because that's how their protocols were set up. The University of Pennsylvania and Baylor have performed both deceased donor and living donor transplants. The differences are obviously where the uterus comes from.

Is it from someone who has been identified through a local procurement bank and is donating other organs for life-saving procedures? Or is it someone who has volunteered and is giving their uterus? The benefits of using someone who has volunteered is that you can plan. You know exactly when the procedure is going to happen, and there are so many benefits if you have to coordinate all these teams to being able to plan the surgery. Well, fascinating.

Thank you so much for coming on the podcast. Good luck with your presentation. I understand you're going there right after here, and we really appreciate it.

The work is fantastic. Thanks so much. Good luck with your second fellowship too.

Thank you. Hi, it's Molly Kornfield again, and we have a very exciting guest. I'm going to let her introduce herself and the name of her abstract.

Hello, everyone. It's Ludovica Picchetta from Juno Genetics. I'm a clinical and research scientist there, and today I will talk you through the paper entitled Novel Characterization Tools for Human Ploidy Abnormalities Reveals a Link to Meiotic Recombination and the Identification of a Previously Undescribed Phenomenon.

Wonderful. We're so excited to talk about this great topic today. So how did you come up with this research idea? What clinical question was your team trying to answer? So our team was trying to investigate more into pre-implantation human embryos because in the past few years we have always been focused on aneuploidy, which we all know it's really important towards, for example, reproductive competence of the embryo.

But we also know that the embryos may be affected by something else, like, for example, ploidy abnormality, which is what we investigated in our work. Oh, wonderful. And how many embryos and how many participants were in your study? Oh, we had a uniquely large sample size.

We had over 96,000 trophictoderm biopsies that were taken from blastocyst stage embryos. I'm guessing this was Juno worldwide, not just in Italy. No, this was actually just from the U.S. Oh, wow, just the U.S. data.

Oh, wonderful. And what did you find? So we found something novel that we were describing, like the incidence of these ploidy abnormalities. And we found that even after a normal fertilization, still, ploidy abnormalities can occur, which is something that was maybe not to be expected.

And following that, we also dive a little bit deeper into these ploidy abnormalities. And, for example, we investigated the origin, like, for example, whether it came from the mom or whether it came from the dad. But then we also went on with, for example, biomarkers that can potentially be related to their occurrence to just try and understand why these ploidy abnormalities were occurring in pre-implantation embryo and whether there's something that is clinically related that may explain their occurrence.

Did you have any pregnancy or birth data on this, or were these embryos that were not going to be used for transfer? No, unfortunately, most of these abnormalities are not compatible with later stages of development. For example, haploid is something that does not even implant in utero, so all of these embryos were affected, and therefore they were not transferred. Ah, okay, okay, yes.

It's interesting because we all use different forms of PGT platforms, and many of us aren't even going to catch this information on the platforms that we're using. And I think it may be a really significant cause of recurrent euploid loss, these haploidies and trisomies and all of that. So, thank you so much.

What's next for this project? What's next on your plate? Well, since we discovered something so unique, like, for example, the advanced maternal age correlation with the event of triploidy, but also a lack of recombination, we just want to dive a little bit deeper into that to try and understand how we can clinically use these biomarkers and how we can translate this basic research knowledge into clinical practice to better counsel our patients in the end. Oh, wonderful. Well, thank you so much for being here today.

Thank you for the invite. We appreciate it. Yeah, very exciting topic.

So, it's Molly and Eve, and we have another very exciting guest today. It's 3 o'clock. I think you need to make some coffee, Molly.

I need a second coffee. So, we're interviewing Phillip Romanski on his wonderful abstract Association Between Maternal Age and Euploid Transfer Success in Autologous and Donor Egg-Derived Euploid Embryo Transfer Cycles Among Patients with Advanced Age. So, thank you for being here.

Yes, thank you for having me. Thanks for being here, Phil, and I promise this is not the oral boards. Okay, no sweat then.

So, tell us a little bit about what you studied and why you chose that. Yeah, absolutely. So, there's been some recent studies that have been published looking at euploid embryo transfer outcomes with increasing age of the recipient, and what has been shown and was published in a recent meta-analysis in fertility and sterility was that even when transferring euploid embryos, there's a small but subtle decrease in live birth outcomes as maternal age increases.

The question remains, what is the cause of that decline? Is it still something that's related intrinsically to the health of the egg as it's coming from an older patient, or is it perhaps related to uterine aging? Yeah, and what did you think? I guess going into it, I think I would lean more towards egg as a hypothesis, but where were you guys and your mindset about that? This was our hypothesis as well. Part of this is because even in younger patients, we see these euploid embryos are not always successful, and a likely explanation in many of these cases is that there's still something in the embryo itself, whether it's the epigenetics, metabolomics, et cetera, that we just don't have the ability to test for. And so our suspicion was that if that's ongoing in the background at any age, those abnormalities are more likely to become more common as age increases.

And so we thought we would likely see a greater association in patients related to the oocyte age itself. Okay, so walk me through. How did you do your analysis? Okay, so we thought the best way to look at this would be to have two cohorts, one using autologous euploid embryos and another using donor egg euploid embryos.

The donor egg group, of course, would be using eggs that are a younger overall age. And were those fresh donors, frozen donors, combination of both? So it was a combination of both based on where the eggs were coming from, the egg bank, et cetera. So it was a combination.

Of course, all of the embryo transfers were frozen embryo transfers because these were all PGT euploid embryos. Okay, and so how many patients did you have in each group? So in total, we had over 16,000 patients. There were over 15,000 patients in the autologous group and over 1,000 patients in the donor egg group.

What did you find? So when we looked at the entire cohort together, we observed a similar trend, as had been previously reported, that live birth rates did significantly decline as age increased. We looked at patients with maternal age between 35 and 50 years, and we observed a small but significant decline with each increasing age category. We then separated them based on autologous versus donor egg, and we observed among patients using the autologous euploid embryos, again, similarly, we saw a decline in live birth as age increased.

How much of a decline are we talking about? I'm just going to try to pull up the abstract, but roughly, what are we looking at? So in our cohort, it was around a total decline of 10%. Patients who were in the 35 to 37 group had a live birth rate around 55%, and then each age category was about a 2% to 3% decline. For patients above 45 years, the live birth was 45%.

So, I mean, still pretty remarkable live birth rates for a 45-year-old. Yeah, absolutely. But, you know, I think that, I always hear people saying PGT is the great equalizer, and it's not entirely true, would you say? Yeah, I think this data would support that, that there probably still are other components related to the health of the egg, the health of the embryo, that we still just don't have the ability to assess for.

Yeah, I mean, I think chromosomes are a huge part of everything, but they're certainly not everything. Yeah, definitely. Yeah, I thought it was interesting that in the live birth in the 35 to 37-year-old, you actually had, I don't know if it's statistically significant, because you probably didn't compare, but you actually had better birth rates for autologous euploid embryos than donor egg euploid embryos.

Do you think that was a component of the freeze-thaw? Yeah, this is an interesting finding. So, first, just to discuss the overall live birth in the patients using donor egg, what we observed was that their live birth remained comparable as age increased. So, we didn't see that same trend, that same difference we saw in the autologous group.

And this really did point to, likely, some, likely the age of the oocyte is contributing to this slight decline that we see here. But as you pointed out, we saw a surprisingly lower live birth rate when looking at the donor egg group for patients that were 35 to 37 years. I think that live birth rate was just below 40%, and that was a little bit surprising.

My hypothesis for why that was is that it might be a different prognosis patient who's 35 years old who's using donor oocyte. That patient may be more likely to have some systemic illness, some other health comorbidities that are contributing to the decline and the success rates that we saw there. My hope is that maybe you can take these data and you can separate out the PGT live birth rates of those that were from a frozen oocyte versus those that are from a fresh oocyte.

On the podcast that I think is actually coming out next month in November, we reviewed data that looked specifically at this question from national databases, and they saw that they compared frozen to fresh oocyte in fresh transfer and frozen transfer, and the oocytes that came from fresh donor oocytes that were fresh transfers had much higher live birth rates than those that came from frozen oocytes that were frozen embryo transfers. There was greater than a 10% absolute difference in live birth rate. Really, I think that the frozen donor eggs that then do PGT and are frozen again have a much lower likelihood of success.

I wonder if this is another opportunity to look at that and get a little bit more information in that arena. Yeah, I definitely think it would be an interesting angle. It's such an important question.

Fortunately, with the fresh and frozen eggs, we see overall good live birth rates. Of course, going one route versus the other has pros and cons, but still trying to understand is that slight decline from freezing the egg or from a gamete that's being frozen twice for egg and then embryo, what exactly can we do to try to optimize outcomes for these patients? Yeah, I think your data's a really unique way to look at it too. Hopefully, we'll dive in more there, but thank you.

I think this is really great, and thanks for coming on the podcast. Yeah, thanks again for having me. Yeah, great question.

Something we can use in the clinic with our patients tomorrow. Thanks for being here. Absolutely.

Eve and Molly are back, and we are interviewing Dr. Elnur Babayev from Northwestern. Title of this abstract is Assessment of Human Ovarian Stiffness Using Shear Wave Elastography as a Noninvasive Biomarker of Reproductive Aging. Hi, Elnur.

Hello. Nice to see you guys. So nice to have you on here.

So what is shear wave elastography? Yeah, so shear wave elastography, it's an ultrasound-based methodology, and it's being used in the liver. It's the most well-known mode of its use where you measure the stiffness of the liver as it progresses through the stages. Fatty liver.

It's stages of cirrhosis, so it measures the elasticity of the tissue or stiffness of the tissue. So in short, not to bore you with too much detail, it's an ultrasound-based technology where ultrasound sort of administers a push pulse of the ultrasound, and that causes the displacement in the tissue perpendicular to the ultrasound waves. And the algorithm, it measures that displacement of the speckles and tells you based on how fast those waves are moving in the tissue, how stiff the tissue of interest is.

So again, the most accepted mode is in the liver. In this study, we applied it to the ovary. Yeah, and I feel like when I was at ESHRE last summer, so not this past year, but the summer before, people were using ultrasound, maybe not elastography, but they were using ultrasound to look at myometrial contractions, myometrial stiffness and adenomyosis.

Is this kind of a similar technology? Yeah, it's certainly been used in research settings. We recently put out a review, sort of going through the clinical applications, which is essentially just liver, as well as a lot of research applications, even beyond the reproduction. There's thyroid, breast cancer in the uterus.

People have been looking at the cervix. Can it be predictive, the stiffness of the cervix? Can it tell you the risk of the preterm labor? So the novelty in this project, and we're certainly not the first group to apply it into the ovary. There's studies that looked at it in the PCOS setting, but we're the first group, we believe, that applies it in the setting of reproductive aging.

And it's based on the basic science studies that our group has done that makes us think that the stiffness of the ovary will be measurably different with this technology. That's the hypothesis. And so this was really more of a descriptive study talking about the protocol that we use for this, correct? It is the establishment of the standard operating procedure, as well as a small pilot of about 38 patients we have here, but it's an ongoing study.

The goal is to recruit 200 patients for the pilot. So we are funded to do it with 200 patients. And so tell us a little bit more about who's included in this study and what are some of those protocols that we're trying to establish as standard operating procedure? Right, yeah.

So we've done a lot of sort of the work early on trying to understand who you can measurably, who you can reliably measure the ovarian stiffness. And what we've realized that, you know, we are using an ultrasound machine that is not routinely used in the clinical setting for this purpose. So it is being used to do pelvic ultrasounds, but we had a collaboration with the GE or we worked with the company to help us to be able to do that.

So we are essentially, we have a very broad inclusion criteria because we don't really know if this measurement is valuable to begin with. So we're sort of casting a wide net with Zik and recruiting women across their reproductive lifespan. But what we are trying to do is to sort of control the way they are in this cycle.

So all of our fertility patients who come for their baseline ultrasound, typically in the early follicular phase between days two to four. So those are the patients across ages that we are recruiting. We have very few exclusion criteria for this pilot study.

We are excluding if there's any obvious ovarian pathologists, if there's a massive cyst in the ovary, or if the ovary is more than three centimeters away from the probe, then you cannot with a high confidence measure the stiffness of the ovary. So it's essentially measuring it, again, the stiffness across ages. We're also collecting fertility data, IVF outcome data, as well as their demographic data.

So obviously the primary hypothesis is association of age with the stiffness, but we also want to see could this measurement be a biomarker of an IVF response. So that's why we're collecting all those endpoints as well. And so you've done some translational work looking at stiffness in the ovary, and so this isn't really, for you, I think for our listeners, probably more of a novel concept, but talk a little bit about what some of the, just the basic to how did you even get to think of this clinical question.

Absolutely, that's a wonderful question. So it all started with my collaborators, so Dr. Francesca Duncan and I are co-senior authors on this abstract. So the story started in 2016, where they made a fundamental observation in the lab that when you remove the eggs from the ovaries of mice, the older mice have much stiffer ovaries.

I feel your listeners and REIs can appreciate that when we do the egg retrievals, not every ovary is the same, so the difference is in the stiffness there. And the scientists, they made that independent observation in their mouse model that this ovary is stiffer, like we're having a hard time to get the eggs out from the ovary of older mice. So then they started coming, using all this basic science tools we have, you know, staining for collagen, and we can also, obviously, remove the ovary from a mouse, and there's a technique called nano indentation, where you indent the ovary, and that tells you how stiff exactly that ovary is.

So it was well-established in primarily mouse model and additional animal for clinical models as well, that the stiffness of the ovary increases with age, and then they got it, the team got access to the human ovarian samples, and we stained those ovaries as well, and they had more collagen as well. So this is where the story sort of began in the animal science world, always the very clinical models, but the exciting thing is that now emerging studies show that if you treat animals with anti-fibrotics, you do delay reproductive aging or reverse reproductive aging. So that's certainly valuable to us as REI if we can sort of treat some of the negative adverse effects of the reproductive aging on the ovarian parenchyma, then this could be valuable.

So to be able to do that, you have to be able to measure ovarian stiffness, and obviously, you can't take the ovary out and measure in our REI patients, so that's where this technology, we're piloting this to see, could this be a tool to help us measure the stiffness? Is this a biomarker, or can this be a biomarker for us? If it is, then the next step is we have thoughts on designing studies and trials and testing some anti-fibrotics. Some are commonly used, others are still in clinical trials, and see if that could improve the outcomes for us. Yeah, I mean, that's fascinating, and I'm so curious to see what you will see in terms of what the variation is among the different age groups.

So the 26-year-old who has an AMH of 0.1, is she going to have a more fibrotic ovary than the 40-year-old who has an AMH of 6? Absolutely, yeah. So that's exactly why we're doing this study, and in the pilot, we are reporting some statistical significant association. We are finding that older women have more variable measurements of the stiffness, so it's not like we're measuring one spot in the ovary.

So with the ultrasound technology, you have a five-millimeter region of interest, so you sample different parts of the ovary. One statistically significant result, again, is a grain of salt of a good caveat of 38 patients so far, is that we're seeing more heterogeneous ovary in the older women, or relatively older women who's increasing age in a univariate analysis, and that is consistent with what we're seeing in the lab. We are seeing that the collagen accumulation of fibrosis, it's not uniform.

It's not like ovary, everywhere it becomes fibrotic. It's the spots of the ovary, where we're seeing, both in the mouse model and the human model, becomes fibrotic, and it seems like the ultrasound is replicating that, but we'll see what more... Yeah, I also wonder, I mean, we all see these patients where they have unilateral responses to ovarian stimulation, and time and time again, the left ovary will respond, the right ovary won't respond, and I think that if you think about it in the framework of fibrosis, well, maybe that ovary is just more fibrotic, and maybe that's something that we may be able to predict a priori before they go through IVF to maybe better counsel somebody that, hey, your AMH looks normal, it's 1.2 in a 38-year-old, but because your ovary's so fibrotic, I actually think that you're probably going to be someone where we are able to retrieve a lower number of oocytes than we would anticipate. Absolutely, yeah.

I think you hit the nail on the head, is that's one of the applications. The thing I'm most excited about is being able to manipulate this parameter. If we can manipulate the fibrosis in the ovary, and there are a lot of new antibodies coming out that blocks the TGF beta release from the ovary and things like that, and obviously science will keep moving forward, so we can have a reliable metric to measure the stiffness and establish that it is something that correlates with the outcomes.

I'm excited about this as being potentially translational. And I think another exciting thing is from 2016 to 2024, eight years later, we're translating a fundamental observation in the lab in the mosque to a clinic already recruiting patients. That just sort of speaks to the collaboration we need to have in our field between fundamental scientists and physician scientists.

Yeah, thank goodness for translational researchers like yourself. Yeah, I'm imagining this future where I'm looking at the AMH, AFC, and the stiffness index in order to design an IVF protocol, and the therapeutics are great because we often find something in the mouse, and then we just can't replicate it in the human, so the fact that you already are seeing it in both populations is really promising. So, very exciting work.

Yeah, thank you. Congratulations. Thank you.

And thanks for sharing it with us on the podcast. Thanks for having me. Hi, all.

It's Molly and Eve again, and we are here with two very exciting guests who are talking about their wonderful abstract today, and I'll let them introduce themselves. My name is Ariel Dunn, and I'm one of the third-year fellows at the NIH. And my name is Josh Combs.

I'm a staff REI in the Air Force, but on loan to Navy Medical Center Portsmouth in Virginia Beach. Welcome. So, the title of your abstract is Cost-Effectiveness Analysis of PGT for Amyopoiety in Good Prognosis Patients, which I think is actually, like, a very hot topic and one that we talk about a lot on the podcast.

So, tell us a little bit of why you decided to do this, and then we can dive into some of your data. Yeah, so this was really born out of a clinical question. I was sitting there counseling as a fellow all these IVF consults.

I had a lot of young patients that were interested in PGT, and they're like, well, do I need it? And I was like, probabilistically, you do not. But from a cost standpoint, I don't know. And I work with a lot of military patients who have limited resources, and even though we're allowed to provide it to them, they still have a hard time paying for these services.

So, what I was really looking for was, for my young patients, which we see a lot of, so, like, 28 to, like, mid-30 range, would it be cost-effective for these patients to save them potentially a transfer of a fresh, untested embryo and looking at doing PGT? That was essentially where the idea came from. And then looking at the literature that's already published. I'm sure you guys already know this, but most of the 35 and under are lumped as a group.

And so, I really couldn't tease that out from the data that we had. So, my goal was to look at it from a real-world standpoint, so, using real clinical data from a large center in our area to try to answer this question. Yeah, and so, how did you parcel it out? Like, what were the specific age groups that you looked at? And then, what were some of those decision points? So, our interest group was 26 to 34, and part of that was because of Dr. Franasiak's paper back in 2014 that informs on euploidy rates.

So, we thought that was a good starting point to look at and to try to update those numbers from the NGS platform. And so, that was our main goal, was to look at that age group, but we actually extended it out to age 40 to make sure we would find that turning point at which PDTA would become cost-effective, because a lot of studies have differing age groups that say that it becomes cost-effective depending on how many embryos you have, etc. And so, you assumed, and then what data did you use to model your assumption on what the euploidy rate in that population was? Was it real-world data? Was it based on Franasiak's data? So, it was all real-world data.

So, we pulled from Shady Grove, several Shady Grove sites in the DMV area, as well as in Tampa and Pennsylvania. And so, it was over 105,000 embryos that were biopsied over a six-year time period, so December 2016 to December, sorry, January 2016 to December 2022. So, we updated all of those euploidy rates using NGS when that became standard of practice.

Okay, great. And what did you see? Yeah, so we found pretty much what is similarly seen in the literature for the good prognosis group. So, up to age 34, PDTA is not cost-effective, and then 35 and older it is.

So, our incremental cost-effectiveness ratio, or ICER, becomes negative at age 35. So, when you see a negative ICER, it means that a health intervention is overly dominant, meaning it's cost-effective and clinically effective. So, it saves the patient money, and it's also more clinically effective for them to use that intervention.

And I saw you guys have this great 7% number. Can you tell me about the 7%? Yeah, so we also did update, like, live birth rates. So, we looked at euploid transfers and untested transfers in each individual age group as well.

So, when you look at the 35-year-old age group, the 7 percentage points difference between an untested versus a tested transfer, that is what makes it more cost-effective. We also didn't really discuss it too much, but quality-adjusted life years is part of this cost-effectiveness analysis. It's a mathematical model.

It's somewhat complicated. It's hard to explain, but all of these percentages are baked into that model, and then the quality-adjusted life years are given a numerical value, so $50,000 U.S. All of this is put into that mathematical model to tell you the cost, essentially, for a live birth. Something I wanted to ask about, did you guys factor in the quality-adjusted life years for, like, the emotional burden of miscarriage or a failed transfer, or were you looking at the medical costs of those things, either of which would be reasonable? Yeah, so just purely the medical costs.

I think it's really difficult to assign a medical or a numerical value to that. And I know that's an argument for using PGT-A for patients to help with, like, potentially patient dropout rates. The argument, I think, is also true that PGT-A may not help with dropout rates because if you have no embryos to biopsy, a patient may be just as likely to drop out from IVF and not continue.

I think, you know, a lot of this is the devil in the details. So one of the things that I saw was for age groups 26 to 34, PGT-A added an average cost of $4,700 per live birth. Where did you get those numbers? And do you think that those reflect real-world experience? So this is all part of the mathematical modeling that we do.

And what we're looking at is it's not quite as simple as the cocktail napkin in terms of being able to sit down and figure out, well, this is what I have to pay in addition to this cycle to be able to implement or get a gain from PGT-A. And so we're looking at the probability of live birth per transfer. And so the model rolls all that in, that even if we do PGT-A and we know this is what our live birth rate would be per transfer with a euploid embryo, we still have patients that we transfer a good embryo in, and then they either don't have implantation, they miscarry, et cetera.

And so the model factors that in, that they may have to go through an additional transfer or two. And so in looking at the group as a whole, knowing that not everybody will follow this exact same pathway each time it generates or we're able to derive those numbers to get a ballpark figure of what the cost would be. It's never going to be per patient, sit down, write it out.

This is what your bill is going to be different, but that's because of all the probabilities that are baked into the model itself. But did you look at average costs over multiple centers? Did you take just costs that are at one center? How did you actually estimate the cost that you were putting into the model? Because I think that that's where you can see a lot of differences in cost-effectiveness analyses. So these costs came from published data, and we did pull from, we have six or seven different publications where we use that data.

Everything has been updated by the Consumer Price Index to match what our current dollar value would be in terms of per unit. But then you're exactly right. So when you look at a cost-effectiveness analysis, there's always a concern of how truly applicable is this, and that's where the sensitivity analysis really comes in.

And so for our paper, what we have published as far as our abstract and what was presented here, which Ariel did a fantastic job with, we're now planning to expand this out in terms of a much larger model. And so we'll have multiple transfers rolled into that. There'll be Markov simulations where we'll go through 10,000 iterations within each arm to really try and flesh out and make this much more robust in terms of what does this look like in the real world, and can we consider all of these different variations in univariate and multivariate analysis.

Yeah, I mean, I think it sounds like a lofty goal, but a very good project, and I think one that's very clinically relevant and applicable, so congratulations on it. Not just for counseling those individual patients you have, but whether or not they should pay for PGT-A, but for our insurance companies that cover IVF. I guess you guys may be in a mandated state.

I'm not, but for the few that do, to decide when will we cover PGT-A for these patients as well. That 7% number kind of comes into hand. So congratulations, wonderful job.

Yeah, and I still think it's amazing how many young patients choose to do PGT, even though it's not cost effective and doesn't necessarily increase the likelihood of success in that population. Well, hopefully the goal being that we can get knowledge with which to counsel, but then also knowledge with which to teach and to give that to the patients, and so that's out there for them to be able to look at, to digest, because a lot of patients already come to the office with their plan in mind, and they know what they want, and so if we can get this into their hands, then that may help with that conversation on the front end and the back end as well. Great work.

We're back on Fertility and Sterility on Air, live from ASRM 2024, Denver, Colorado. I'm Micah Hill, the Media Editor from FNS, and I am joined by Dr. Jerrine Morris. She's currently at Shady Grove, Baltimore, but this is a labor of love study going all the way back to her fellowship at UCSD on long-term follow-up of oocyte donors, thoughts and feelings about donation and future contact with children from the donation.

Fascinating title, Jerrine. Tell us, what were you asking, and why did you think this was an important question? Thank you so much, Dr. Hill, for having me present on our study. This study actually comprised work from clinic practice at UCSF, as well as at one of the private fertility clinics in the Bay Area as well.

I said UCSD. I apologize. UCSF.

Let's get that straight. Thank you. Absolutely.

Our colleagues were interested in understanding some of the long-term implications, whether psychosocial or medical, as it related to oocyte donation. This was a study in which we really wanted to reach out to donors who had previously donated. It had to be at least two years since their prior donation to determine different factors.

How do they feel like being an oocyte donor impacted their overall health? Did they have any concerns outside of health related to being an oocyte donor? That's how the study came to be. Gotcha. Like any type of study, there's various levels of quality and rigor.

This one seemed pretty rigorous reading through it. Just walk us as the listeners through the steps that you took in your study design before we get to the results. Absolutely.

For this, we used a mixed methods approach. We first started off with a qualitative component to the study. We had former donors that we actually interviewed.

It was a very standardized interview process from an individual who was not directly a part of the research team to provide a very unique and very uninformed approach. I guess I should say informed approach, but unbiased approach. This interviewer interviewed donors about their overall experience.

We actually used those interviews to set the backdrop for the questionnaire component for the quantitative aspect of the study. For the quantitative aspect, and a lot of the findings we presented throughout ASRM this year were based off of the findings from those questions that the former donors were asked to complete. In terms of the quantitative component, it took well over a year to make sure that the survey was rigorous, make sure that it answered the questions that we were hoping to answer.

We also wanted to make sure the verbiage was appropriate, so we had former donors complete the survey just to make sure it really fell in line with ultimately what our goals were. From there, we had a pretty rigorous approach to reaching out to former donors at both clinics. We wanted things to be as standardized as possible, so we had a clinical research coordinator who individually, outside of the study investigators, reached out in a very stratified way with 10 donors at a time, making sure we had multiple modalities to reach out to the donors to basically encourage their participation in survey completion, yielding the really exceptional, I think, response rate of 63%.

I think a combination of having a high response rate, having a survey that was really informed by interviews from donors and not just what we as investigators thought were actual important themes to include made this study not just impactful, but a pleasure to be a part of. Fantastic. A great research question, very rigorous methods, what we all want to know.

What did you find? Yes. The findings for the presentation that is a focus right now really pertain to the psychosocial considerations. We found that most donors were happy that they were former Oocyte donors, which is something that's just good to confirm.

There were, however, close to 25% of donors that did express some concerns on being a donor and how that may have impacted their health. We did find that donors were open to, for the most part, being contacted from the children born of their donation. That was the most surprising part to me.

That really blew me away when I read that. Correct, correct. Actually, some of the donors did remark that they thought about the children born of their donation, which is something I think that's fascinating that we don't counsel patients about.

We don't counsel donors about that when we are recruiting them to serve in this capacity. I think that those findings are really important. I think that we do want to build upon, particularly those individuals who expressed concerns, to see what characteristics of their donation or of them individually would lead to why they're concerned about the overall effects of being a donor on their current health.

Right. Obviously, an incredible study. You spent a lot of time thinking about this.

What do you think are the next steps? What do you think are important future questions or steps in this study to address? A number of things. First off, our primary goal is to actually get the findings out to make sure the readership can also look at the psychosocial impacts as well as the medical impacts and review the literature or the data, I should say, for themselves. I hope that by reviewing the data, it'll encourage other investigators to think about other questions, to study in a more prospective fashion.

We were, of course, limited by those individuals who responded. Not everyone had long-term follow-up. There were some individuals who had a shorter time since the time of their last donation.

I think that in the future, obviously I want individuals to read the paper and get additional ideas, but I think for us, it's important to just underscore the importance of education. A lot of the findings that we saw are centered around the fact that I think some donors have some just questions about this process and some of their concerns that were listed were valid, and I think a lot of them were rooted in education and just how we perceive donation as clinicians, but then also how we should be counseling them as patients who this is a health thing that would have happened to them that they're going to take with them for the rest of their life. Right.

Well, a fantastic study. Often when I read survey studies and you look at the response rate, I'm often worried that the response bias is going to bias the study towards negative findings or negative responses, and like you said, some of these were 25% concerned, but a lot of these had the majority of the responses were very positive about the experience and about the process, and so I just found these results fascinating. So congratulations on your study, and thank you for sharing it with our listeners on FNS OnAir.

Absolutely. Thank you to my study team. A special thank you to Drs. Lauri Pasch, Dr. Sarah Hawley, Dr. Elodie Joshua, and Dr. Ryan from one of our fertility clinics in the area. Everyone has been fantastic, and without them, we could not have gotten the study done after several years of working on it. Congratulations.

Hi, everybody. This is Kate Devine. I'm here with Molly Kornfield, and we're very fortunate to have Christopher Weier, PhD, here with us to tell us about the work that he and the team from CooperSurgical presented yesterday at the prize paper session.

His abstract was entitled An Integrated Preimplantation Genetic Test Combining Primary Template Directed Amplification, Copy Number Variation, and Allele Frequency Data to Generate the Most Complete View of Embryos. Welcome, Chris. How are you today? I'm wonderful.

Thanks, Kate. Thanks, Molly, for having me today. It's a real pleasure to be here.

So, you know, tell us a little bit about your work. Obviously, we're all searching for the best way to do PGT for our patients, and what's the best platform. So how did you go about trying to assess that? That's a good question.

So it's obviously a very broad field. There are a number of both individuals and companies who are exploring, you know, how we get the most out of the embryonic genome. How can we extract both actionable and accurate data from it? And, you know, at Cooper, we've chosen a couple of different directions to take that in.

The paper that you highlighted yesterday was one where we really tried to perhaps combine two of the sort of principal methods. Obviously, you've got a debate that's been formed around NGS versus, say, microarray and the collection of SNP data versus copy number data. And while both of those approaches are valuable, there's certainly, you know, some negatives from each side.

And with that approach, we actually tried to take the strengths from both of those methods, combine them, and try to resolve that. And in that paper, we particularly focused on mosaics, but certainly has implications across the board, both in PGT-A and obviously in PGT-M as well. That's fascinating.

So what benefits did you find by combining these two modalities? So, you know, from an NGS standpoint, traditionally you're looking at a copy number variation, and it can certainly be very sensitive in that approach. But it can also be somewhat volatile, especially at low-pass sequencing. So while we use the sort of copy number variation to highlight regions of interest, we then look beneath that to look at the SNPs and the allelic balance that was generated from that same data.

And what we found was that, for the most part, particularly in the middle-range mosaicism, if we want to call it that, that was confirmed. But once you get to sort of the low-level and high-level, SNP-based data was actually able to resolve that, to either confirm that this was a true mosaic or to show that actually the allelic balance supported a true aneuploid, a full copy loss ordain, or conversely was able to sort of, you know, reject that misclassification and pull it back towards a euploid. So for, you know, an embryo that may only have a single region of mosaicism, being able to really confidently say that, yes, that is in fact a mosaic versus actually the SNP data tells us that it's truly aneuploid or euploid really does help us in our transfer decision-making process.

In order to do both of these methods, did you need more cells or more DNA than in a standard PGT-A biopsy? No, we approached this, you know, in trying to have minimal impact on any of that sort of upfront pre-analytical work. Certainly from an embryology standpoint, we don't want to put any more burden on the labs that way. So no, we actually, you know, used sort of the standard trifecta in biopsy, five to six cells worth of DNA.

I will say we did leverage an amplification technology that is exclusive to Cooper right now, a primary template-directed amplification, which, you know, we've seen in our hands at least and from other studies outside of our group that, you know, it does provide more accurate, you know, I'll put, better coverage. And particularly for mosaicism, you know, it conserves allelic balance. And, you know, if you're looking at how proportionally SNPs contribute to the call of mosaicism, preserving the true allelic balance from what is actually in the embryonic genome is critical.

So naively, when I think about two slightly different methodologies yielding two different results, I wonder about validation. Was there some kind of validation step that occurred? How were you able to confirm that the summation of these two technologies was yielding the ground truth? That's a great question. So we obviously had what's coming out of, say, the pipeline that is standard, what's in place currently.

You know, I think it is difficult in this situation to validate that most of these mosaic embryos would not be transferred. So getting that outcome data from what potentially is a nontransferable embryo in a lot of clinics is a little bit difficult to collect. We are looking a little bit deeper at that.

We do have embryos that have been, you know, provided to us that are for research use only where we could take multiple biopsies, where we could look directly at the ICM to try to confirm that. And that is what we're doing right now. Well, we'll look for those data.

Are you also using this kind of methodology clinically at all, such that we'll be able to confirm with clinical outcomes, hopefully even live birth outcomes at some point? So currently the pipeline that we're putting in place does use that tiered approach where we're using copy number data to propose regions of variation that can then be confirmed by a whalic balance. And so eventually, I think, you know, that is the idea, that we can get to a more confirmed data set. So naively, what is the difference between the platform that you're publishing on here that's novel and the currently commercially available SNP NGS platforms? That's a great question.

So just to be clear, the entire platform that we propose is sequencing based. We're collecting both copy number data and SNP data in the same run, the same pipeline. Again, we're incorporating that prior amplification step that gives us a little bit more of a digital discrete approach to identifying SNPs because it does present an allelic balance.

But in the same run, we're collecting both of those data sets and comparing them collectively in the analysis part of the pipeline. In a SNP based approach that's exclusively SNP based and collecting through sequencing, you're actually not going to get that same kind of copy number data or that sort of digital approach to assigning allelic balance. Awesome, that really cleared it up for me.

Thanks so much, Chris. If you could imagine this being used in clinical practice, I'm a clinician, right? I'm already jumping ahead five steps to what am I ordering for my patient? Do you see this as potential for the upfront biopsy analysis or is this something you might use on the back end if you get a mosaic result to then confirm or even re-biopsy the embryo for this analysis? Yeah, again, I think we really do want to minimize any kind of impact from a clinical standpoint. And so I think what we intend is that this is used.

And let me make it clear that it is currently in place in the pipeline that's being used when PGT-A is ordered right now. And so the mosaic analysis isn't separate from the standard analysis. Whole chromosome aneuploidies, gain and loss, are also analyzed in a similar way, looking at both the copy number change and then the SNF that's supported underneath.

So it's similar to the mosaics as well. This is all happening in line with the pipeline that's already in place. Okay, great.

Well, we're all looking for ways to salvage more usable embryos. So I think this is a step towards that. Thanks so much for your work and for being with us today.

This concludes our episode of Fertility and Sterility On Air, brought to you by the Fertility and Sterility family of journals in conjunction with the American Society for Reproductive Medicine. 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 hosts, it is not intended to be the only approved standard of practice or to direct an exclusive course of treatment.

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