Fertility and Sterility On Air - TOC: Jan 2025

Take a sneak peek at this month's Fertility and Sterility! Articles discussed this month are:  

02:59 Preimplantation genetic testing for aneuploidy is associated with reduced live birth rates in fresh but not frozen donor oocyte in vitro fertilization cycles: an analysis of 18,562 donor cycles reported to Society for Assisted Reproductive Technology Clinic Outcome Reporting System

19:37 Sperm concentration remains stable among fertile American men: a systematic review and meta-analysis

26:02 Preovulation body mass index and pregnancy after first frozen embryo transfer in patients with polycystic ovary syndrome and insulin resistance

36:54 A retrospective comparison of the impact of industry payments on assisted reproductive technology practice and outcomes

44:55 Preimplantation genetic testing for aneuploidy in unexplained recurrent pregnancy loss: a systematic review and meta-analysis

61:03 Initiation and outcomes of women pursuing planned fertility preservation

65:49 First successful ovarian cortex allotransplant to a Turner syndrome patient requiring immunosuppression: broad implications

View Fertility and Sterility October 2025, Volume 123, Issue 1: 
https://www.fertstert.org/issue/S0015-0282(24)X0014-X

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 discussion with authors and other special features. F&S 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.

Hello everyone to this New Year's issue of Fertility and Sterility. I'm here today with Eve Feinberg, Kurt Barnhart, and Pietro Bortoletto, my amazing co-host. How are you all doing today? Great.

Good morning, everyone. It's always nice to see you. Okay, we'll dive right in here with our front matter for this issue.

There's an inkling by Dr. Anuja Dokras, really delving in, in a way that I love, to the topic of GLP-1 receptor agonists in the PCOS population. She astutely notes that there are more challenging unanswered questions in the use of these medications in this population than there are answers, and these include things like the appropriateness of their use in adolescence, their safety in pregnancy, what's a safe and appropriate duration of use, all things that really fall to us to answer because of the immense potential benefit for this population, but also risk that we haven't yet characterized. So please do dig in there.

I'm hopeful that we'll see lots more research in FNS in the months and years to come to try to answer some of those questions. There's also a Views and Reviews by editorial editor, Dominique de Ziegler, that looks back over the history of ovarian stimulation for ART and starts out with his intro entitled Ovarian Stimulation 2.0. So I certainly would recommend that all of our listeners read through these Views and Reviews. I would say especially, and unfortunately I can no longer count myself in this group, our younger REIs because fascinating historical perspective on where a lot of our ovarian stimulation protocols come from.

They talk through how ovarian stimulation protocols impact endometrial quality, oocyte quality, and furthermore, different ways of starting ovarian stimulation protocols, and also how can we do treatment that's more effective for our patients. So with the, I consider misnomer progestin-primed protocols, but you know, in our freeze-all world should we now be using these more cost-effective methods? So do take a read, highly practical information for the practicing REI. Okay, so I'm excited to talk about the seminal contribution from the January issue.

This article is entitled PGTA is associated with reduced live birth rates in fresh but not frozen donor oocyte IVF cycles, an analysis of 18,562 donor cycles reported to SART cores. The first author is Dr. Julian Gingold with senior author, Dr. Sangita Jindal. So this was analysis of live birth based on whether PGTA was used in donor egg IVF using a SART cores database derived from donor egg retrieval cycles that were reported to SART in 2014 and 2015, and the linked transfer cycles to recipients reported in 2014 to 2016.

In total, 11,400 donor egg retrieval cycles were from fresh eggs and about 7,200 cycles of presumably lots of frozen eggs were analyzed. And these were analyzed completely separately, which was totally appropriate in my opinion. The primary outcome, again, was live birth from the first embryo transfer, and then cumulative live birth was also analyzed from all transfers over the study period only for those that had used fresh donor eggs, and the authors give the rationale that the variability in lot size among those using frozen eggs would have rendered that analysis less helpful.

Multiple logistic aggression analysis accounted for recipient age, recipient BMI, recipient gravidity, and infertility diagnosis. So both the fresh and frozen egg cohorts were skewed towards non-PGTA cycles, thankfully in my opinion, with 15% using PGTA in the fresh cohort and 7.2% using PGTA in the frozen cohort. PGTA utilization was associated with a lower BMI, null of gravidity, null of parity, less frequency of an explicit diagnosis of DOR, obviously with the caveat that this is dependent upon complete data entry, and PGTA utilization was also associated with less prior treatment and specifically fewer prior fresh and frozen transfers.

So in the fresh group where successive transfers were followed, PGTA was also associated with having more available 2PNs, with undergoing more total transfers from that linked cycle, and having more embryos transferred overall. In the fresh egg cohort, PGTA was associated with a lower live birth for the first transfer. So again, PGTA not only did not help, but was associated with fewer live births per transfer, specifically 47% in the PGTA group versus 53% live birth in the no-PGTA group.

It was further associated in this fresh egg cohort with a lower cumulative live birth, so only the first live birth per linked retrieval cycle was counted, and 58% of those patients who did not, rather, who did use PGTA had achieved a live birth by the end of the study period versus 67% of those patients who did not use PGTA. And so this was statistically significant both for live birth from first transfer and cumulative live birth, and this difference persisted as statistically significant upon adjustment for covariates. Moving to the group using frozen donor eggs, PGTA was actually associated with a higher live birth from the first transfer at 48% versus 41% in the unadjusted analysis.

However, this difference was no longer statistically significant after adjusting for covariates. Lastly, the authors looked at multiple gestation, preterm birth, and low birth weight and found them all to be reduced with PGTA overall, but this was not the case when the analysis was limited to single embryo transfer. So basically, to summarize that, patients that used PGT were more likely to have a single embryo transfer and therefore experienced better obstetric outcomes.

However, the better obstetric outcomes did not vary by PGT when we limited the analysis to single embryo transfers. So I think this is an important study with the kind of like knock you over the head take home message that I hope everybody listening to this podcast already held as a close belief, we shouldn't be using PGTA in donor egg cycles. The authors make the argument that we shouldn't be using it, especially in the setting of fresh eggs.

I'm not so sure that this analysis can differentiate in that way. I think there are some potential confounders that couldn't be included. That said, fact remains and is consistent with prior data that PGTA is really not warranted in this setting.

So a couple of things that the authors called out as limitations to the study, they weren't able to control for, or even to report or analyze the age of the donor at the time of retrieval. And we can imagine, and authors acknowledge this as well, that patients who are using fresh donor eggs are more likely to be using a known egg donor. These might be older.

And in that population, PGTA may be totally appropriate, in fact. One thing that I was very surprised the authors really didn't address is fresh versus frozen transfer. So for the analysis of the first transfer, they just compared them apples to apples, whereas some of those would have been transfer of a fresh embryo and others would have been transferred of a frozen embryo.

And this was not controlled for in their analysis or really analyzed. And you can also imagine that part of the hit that PGTA causes in terms of implantation rate and potentially trickling all the way down to live birth may derive from vitrification and warming, right? And they actually excluded cycles that did use PGTA of fresh embryos. So all of the embryos that had PGTA in their first transfer were frozen, whereas a large percentage of those that did not use PGTA would have been fresh embryo transfers.

And then you could also imagine that this may have differed between the fresh egg versus frozen egg group. I think it's common practice to sometimes create a whole freeze-only cohort when you're using frozen eggs, because this is sort of an ultra pragmatic approach. You use the frozen eggs, you create the frozen embryos, they can be moved even around the country.

I think a lot of us are practicing in this way, but that may sort of wash out the effect size of any detriment that PGTA causes for these folks. And I think that that's something that we really have to take into account. They saw no difference, PGTA versus no PGTA, in the frozen egg group.

But if that was attributable to a greater proportion of first transfers being from frozen embryos, we wouldn't have seen that necessarily in this analysis. The other things to take into account here is that this was almost certainly not using contemporary PGT methodology. Again, this is 2014-2015, prior to most folks using either NGS or SNP, which are the two main methodologies used now.

Another take-home that I had from this was way too many embryos being transferred from donor egg-derived oocytes. So in both the fresh and the frozen group, they had 1.4 embryos being transferred with PGT and 1.5 without. Way too many.

So we hope that this is going down. This is a huge goal of ASRM and SART in terms of helping patients have healthy pregnancies and healthy babies and keeping moms healthy for that perspective. And so, yeah, that's pretty much what I took from this.

I think it's a very important paper. Totally appropriately a seminal contribution, confirmatory, I think, of some of our, again, closely held beliefs, but important to show, you know, that we should be fashioning our treatments in a way that is efficient for our patients. And I would fully consider PGTA to be an unnecessary add-on in the setting of donor eggs.

Pietro and Eve, what did you guys think? It's important to point out to the listener that there were a lot of cringes on our faces when Kate said that 1.4 number of embryos transferred number, we all cringed appropriately. So you're right to point out that this is a big mission of SARTs to reduce this number and something that we spent a lot of time on in our committee. And Kate, obviously as the chair of the SART QA committee, spends a lot of intellectual time thinking about.

I really enjoyed the discussion section of this paper. I think that this was a long discussion section because there was so much to talk about. One point that we didn't really mention was the differential use of fresh versus frozen egg donors, depending on certain specific ethnicities or races that patients were trying to prioritize.

We know at baseline that patients have a hard time finding non-white European donors in the frozen and fresh egg banks. I'd be curious to see what you guys think about the bias towards or away from fresh versus frozen for those ethnic minorities that are trying to use eggs and how that may or may not be affecting their outcomes. Are they willing to take slightly older egg donors to prioritize a ethnic match that kind of accomplishes them, allows them to accomplish their family building goals within a certain ethnicity? Or even more likely to use a known donor because they're unable to find a younger donor of the ethnicity that they're looking for.

Yeah, I think that's an excellent point and something that we certainly see in our practice all the time. The other point that I think is really worth discussing is that the cumulative live birth rate from fresh cycles without PGT was the highest. And I think that's because PGT leads to discard, potentially discard of embryos that maybe have classified as abnormal.

And again, the technology was different. Maybe those would be classified as mosaic today and not aneuploid as they were in 2014. This study and then the study that we discussed back in November that elegantly looked at this in four categories, frozen, frozen, frozen, fresh, fresh, fresh and fresh, frozen with fresh egg donors having fresh transfers, having the highest likelihood of success.

And so I think that we are seeing this again and again. And so I think that PGT on donor eggs does not work. I'm not sure how many more studies we need to drive that point home.

I also want to highlight, and the authors did talk about this in the discussion section, but they talk about term deliveries, better birth weights with PGT, lower complication rates. And that really is not due to PGT. It's due to the lower likelihood of multiple gestation because in the PGT group, they saw higher rates of single embryo transfer.

And so a lot of the morbidity that they're seeing that they're attributing is really due to multiple gestation. So I want to jump in on this too. I think the discussion we should have is why are they performing PGTA on donor eggs? What's the goal? What are we trying to gain? So we kind of just said it.

There's no way that PGTA is going to improve your cumulative live birth even if PGTA was perfect. And it's not perfect. You're going to potentially discard embryos and you're potentially going to damage the embryos with all the technology and going off.

So that I want to say. So it must be a cost thing that you're willing to pay more money to have your first embryo transfer work at the expense of embryos and efficiency. Is that what it boils down to? Is this all driven by I want to get pregnant on my first transfer at only and therefore I'm willing to sacrifice embryos and time and cost? I think we're suggesting this.

I think that's some of it. But you can't discount the reason for why people are arriving at donor eggs, right? There's a lot of people who are arriving at donor eggs from age-related, aneuploidy-driven, recurrent miscarriage and just want to reduce their risk of miscarriage as much as humanly possible and control the knowable and the unknowable factors. And there's a percentage of those patients who say, I don't want three kids.

I want the next kid. And I want to reduce the risk of miscarriage as much as humanly possible. And it's really hard to counsel them out of that.

But that's not really the answer because the data doesn't show we're reducing miscarriage. And the paper specifically looked at that, which I didn't go into it for the purposes of brevity, but it specifically shows there's better implantation without PGTA and there's no difference in terms of the rates of miscarriage. So, you know, I hope that this paper can help put this to rest.

In terms of your question, Kurt, I think it's well phrased as to what are patients after in terms of doing PGTA. So the authors do state that they excluded elective sex selection. That said, it's very hard to know how they could have done that effectively with a SART cores database, perhaps if it was marked off as the indication for doing the IVF.

But if patients happen to be doing donor egg IVF and wanted to select for sex, that's not going to be notated. So I would think that some proportion of these patients are doing this for sex selection. And then I was surprised by the association of PGTA utilization with less prior treatment because, you know, to Pietro's point about like kind of PTSD from prior poor outcomes, particularly among older patients who are using their own eggs.

I certainly have patients that say, yeah, I get it. You don't recommend PGT for donor eggs. But after all I've been through, I just can't not do PGT, anything that could reduce my even if you tell me if it doesn't reduce my risk of miscarriage.

But then, in fact, it was the association was the inverse of what you would expect there. So I don't understand if we've sold that message to the patients or the patients are selling it to us. But the message in my mind just doesn't make sense.

And in most aspects of medicine, we say, you know, you don't need that test. That's just adding more. That's adding more complication.

That's adding more cost. Yet in this case, I just still wonder which is the chicken and which is the egg, you know, because everyone always says on the boards, well, the patient asked for it. Well, that's not the reason to do it.

So I won't pontificate on that, but it really brings. And that's why I made this disseminal contribution, because I hope that this does generate discussion on this. I mean, this isn't the world's best papers.

Our course papers always have limitations. And just because it's published doesn't mean we condone it as a society. So I hope it does generate discussion.

I think the elephant in the room is PGT is a revenue source for clinics. And I think you can't discount how money affects people's behaviors and recommendations on a clinic level and on a network level. And I wish it weren't true, but I think it's a way to capture more revenue per cycle for patients that are already spending a significant amount of money on egg donation.

But that is a great point. They're getting more because because they're getting a higher price. So, you know, things that cost better, more must be better.

Yeah, that's a that is a soapbox that I stand on when I wear my other hat every every day. That's not a reason to be doing this. And I think we as physicians who are advocating for our patients need to keep on shouting that from the rooftops.

Anyway, great discussion, everyone. We should move on, I think, to the next paper that we'll be discussing today, which is going to be you, Kurt, discussing an andrology paper. So I have a meta-analysis.

Fertility and Sterility doesn't always publish the number of meta-analysis we get submitted. But every once in a while, there are some that really can add a little bit to our conversation and our knowledge. And this one is entitled.

I'm sorry. This one is titled Sperm Concentration Remains Stable Among Fertile American Men, a Systemic Review and Meta-Analysis by Kieran Lewis and Scott Lundy out of the Cleveland Clinic and Houston Methodist Hospital. So for those of us that don't follow this at home, there's been quite a controversy about whether male sperm counts have been declining over time, time meaning like the last few 40, 50 decades.

And the idea is that it could be lifestyle, it could be toxins, it could be all sorts of reasons for the fall of humanity. And most of these cases, or at least reports, are international. So this study decided, with its novelty, to say, well, what about the best data we can get from the United States? And do we see a decline in semen analysis in data only in the United States? So this meta-analysis has done well.

It uses the PROSPERO categories. It looks at data from 1970 to 2018. And it appropriately does a CASA WideNet, starts with 874 articles, goes down to reducing the duplicates.

They were able to look at the full manuscript of about 160, found about 58 are eligible, and that's what they're summarizing. And the 58 eligible articles summarize 75 different populations, if you will, groups of men where they can compare semen analyses. And we're talking about covering around 12,000 men.

So all that buildup was to basically say that they don't find a difference, and that semen analysis or sperm counts are not changing, at least in the samples from the United States. They do a few sensitivity analyses, as they should. And they find, for example, in some analyses, they do find a slight trend of about 0.3 million over the years.

But in another sensitive analysis, they find an increase of about 1.1 million per year. So they conclude that there is no difference. So then I guess that's the take-home message.

But for those of you that really want to dig into it a little bit, so why is it different in the United States than in worldwide data? And it's possible that the variability in the studies is the difficult problem. It's possible that the United States is different from the world, and maybe we don't have environmental exposures or changing lifestyles or things like that. Hard to make that argument, but that was brought up in the discussion.

But probably the devil is in the detail of just the noise of all the data. For example, the slight differences that I just described matter if you take only fertile populations versus unknown fertility populations. It matters a little bit if you're, for example, studying men before their vasectomy or men that walk into a fertility clinic.

But the bottom line is it doesn't seem to be the fire that has been raging in the male literature about the demise of all men because their sperm counts, if you follow trajectory, are going to be zero in 30 or 40 years. So it's a little bit reassuring. Maybe it's not completely generalizable, but I like that well-done and thoughtful reviews do occasionally get infertility and sterility to stoke this debate.

I think this is probably one of those questions that has huge importance and ramifications, but we just don't have the methodology in the studies to have the granular difference to say that these subtle differences are there or not. So generally, good study, fun to read, should impact your knowledge, but it's probably not going to change your belief at this time. It does pose some interesting questions when we go to meetings overseas on whether it really is the developing world where male fertility is a problem.

That still might be the case for other reasons, but at least in the United States, we can say that men seem to be handling themselves well despite the obesity epidemic and poor eating and all of those other things. So we'll see. Maybe it'll go up when we start addressing those things with many of the lifestyle modifications we have now.

So what do you guys think? It sure gets a lot of airplay on social media. Here on social media, people cannot stop talking about male fertility is declining globally and we're headed towards a window of time and evolution where we will not be able to reproduce. And I'm glad that there are smart people like Scott Lundy and his colleagues from the Cleveland Clinic that have looked at this and decided to hold on, wait a minute, let's actually use some data in North America to assuage some concerns.

I did like your last point, Kurt, about what's going to be the effect of these GLP-1 meds and will we actually see any improvement as we better treat obesity? I'm hoping that some smart urologists are thinking about how to design that study because we're going to have a lot of pre and post data, I think, coming up in the next couple of years in that patient population captured within health systems that are being prescribed these GLP-1 meds. It'd be cool to see. Yeah, I think the inherent bias, though, is who's doing a semen analysis and how are these studies being conducted? I mean, it's not a routine test that you're doing with your internal medicine doc or PCP every year.

And so it's hard to say, like, are we seeing an increase in infertility due to female aging and then as a result, we're seeing worsening parameters on semen analyses of those male partners? I think that the data just are so large and difficult to really get to that granular nature that I'm going to quote you, Kurt. You've got to just let it flow over you. Yeah, I agree.

I mean, it actually was fun if you get into the nitty-gritty of the paper. The studies that look at that semen analysis are quite diverse. I mean, you've got men seeking fertility.

You've got tests like before and after sperm banking. You've got donors themselves. You've got studies about environmental exposure.

I mean, when you lump it all together and take the time to filter this all out, luckily, it doesn't give you a signal. Yeah, I'd say that that is reassuring. And though we must let it flow over us, it's good to be able to tell our patients that there's no cause for hysteria, at least at this juncture.

So, kind of similarly on the theme of what Pietro just raised about obesity and how we might be moving a little bit in the right direction with new interventions, I'm going to turn it over to Pietro to discuss a study on BMI and patients with PCOS and insulin resistance. Thanks, Kate. I have a nice little study from Lian et al., coming out from China, entitled Pre-ovulation, BMI, and Pregnancy.

After first frozen embryo transfer in patients with PCOS and insulin resistance. PCOS gets a lot of screen time in our literature. Why? Because it affects probably 10-15% of the world's population, and insulin resistance often coexists with PCOS.

As many as 50% of PCOS patients have a diagnosis of coexistent insulin resistance. Several studies have identified relationships between insulin resistance and BMI, and it's a real vicious circle. Insulin resistance is more common in people with obesity, but obesity is often driven by the underlying insulin resistance.

But if we've paid attention to this podcast at all over the last few years, we know that BMI can have several negative impacts on ART outcomes, specifically in the PCO population, lower maturity rates, worse embryo quality, worse implantation outcomes, and an increased miscarriage rate have all been reported through literature in fertility and sterility. This study sought to reinvestigate this correlation between BMI and success of the initial frozen embryo transfer in patients with PCO who have comorbid insulin resistance. This was a small single center study from China, and I say small, small for Chinese standards.

It was only about 250 patients. Between 2020 to 2023, like I said, in patients undergoing their first frozen embryo transfer after an autologous IVF cryo wall cycle. Patients were diagnosed utilizing the Rotterdam criteria and insulin resistance was diagnosed calculating the HOMA IR index, which stands for homeostasis model assessment insulin resistance index, just simple formula, fasting blood glucose multiplied by fasting insulin divided by 22.5. Values of 2.6 or higher were classified as meeting the diagnosis for insulin resistance.

Now, you're probably wondering frozen embryo transfer cycle. There's more than one of those, and you're right. The minute you kind of get into non-U.S. literature, it's a kind of a Pandora's box of legal support and what we define as hormone replacement.

This one was actually pretty straightforward. Their natural cycles were supported with vaginal or oral progesterone. Their modified natural cycles utilized letrozole and a trigger shot, and their hormone replacement cycles uniformly used estrogen initially two times BID, but eventually three times BID.

Gluteal support here is where things kind of differ. You had IMPROG at 60 milligrams plus oral progesterone, or you had vaginal progesterone with oral progesterone. And notably, the authors mentioned that all of these hormone replacement cycles where estrogen was utilized also utilized 50 to 100 milligrams daily of baby aspirin.

And the reason they give was that these cycles where exogenous estrogen was given were at an increased risk for clot. So this was given to reduce the risk of thermoembolism. Notably, some patients were downregulated with Lupron in the hormone replacement cycles for one month, but the explanation for why and in whom I think left me a little lacking.

They said only in patients with elevated LH levels to improve the pelvic microenvironment and increase endometrial tolerance. Big head scratch for me there. They evaluated all of the pertinent pregnancy outcomes and performed multivariable regression for their analysis.

And in total, 282 patients were included, 35 percent which were overweight, 10 percent which were frankly obese. The vast majority of cycles were hormone replacement cycles, 66 percent. And the percentage between the obese, overweight, and non-obese categories was similar.

So what do they show? I think no surprise here. They show that BMI was negatively correlated with the rates of embryo implantation, biochemical pregnancy, clinical pregnancy, ongoing pregnancy, and all of these rates decreased as BMI increased. That was in their univariate analysis.

The study rightfully so considered confounding factors that may affect these pregnancy outcomes using a five model multivariable analysis, gradually adding each confounding factor to the analysis to help sort out what the true effect was. This of course did not change the top line outcome of a negative correlation with BMI and reproductive outcomes. I know Mike is not here, but he would appreciate a little statistical pearl here.

There are a bunch of different ways to build a multivariable regression model. There is the what makes sense to include in the model version. That's kind of just does it make practical sense clinically.

Two, there's the strong correlation version. So look at your dependent variables in your univariate analysis. Look at the ones that are most strongly correlated and pluck those out to include in a multivariable model.

But then probably my favorite and probably the trickiest and most time consuming one to do is DAGs, directed acyclic graphs. So DAGs are actually just physical diagrams that you draw down on paper. They represent causal relationships with lines and arrows, and they basically have directionality and flow to them.

They're very helpful for researchers who are trying to identify variables that can be controlled for in a multivariable regression to eliminate bias, reduce confounding. They're not super intuitive. There's wonderful papers describing how to do this.

There are wonderful YouTube videos describing how to do this. But it seems to be the most kind of thoughtful and rigorous way to build a multivariable regression model short of like, does it make good clinical sense? And what have other authors used before? Because those approaches, as you can imagine, can absolutely introduce bias and confounding despite attempting to reduce both by being thoughtful about what to include in a model. So top line finding here is obesity is bad in patients with PCOS and insulin resistance who are undergoing their first fresh or first frozen embryo transfer, regardless of the cycle type.

Kurt, Eve, Kate, anything you're going to do differently with this data, any kind of clinical pearls that you pluck out from this data, to me, it really just reinforces that the elephant in the room when we're talking to our patients who are having negative reproductive outcomes despite good age, euploid embryos, why aren't these embryos sticking, darn it? Or why aren't they staying stuck? I think you have to address BMI, and to Kate's point, what's the most effective way to address BMI in the era of GLP-1 meds, I think is what remains to be seen. And can we actually bend this curve back towards a better reproductive outcome? Yeah, I would certainly refer folks again to the inkling in this issue by Dr. Dokras that digs in pretty deeply on that. So I will tell you one thing that I would not infer from this to kind of go in another direction is while we know, and this paper nicely reinforces it, that higher BMIs are associated with worse reproductive outcomes, and this nicely isolates it to the population of patients with PCOS and insulin resistance, I do not think that we can infer from this that policies such as BMI cutoffs and basically insisting that patients achieve short-term weight loss to be able to undergo treatment, which unfortunately has not been shown to be helpful, should be part of our policy.

And I want to give a shout out to those who at ASRM were part of the panel in Journal Club Live that discussed this issue. Those of you who haven't listened to that should definitely take a listen. And so while we want to help these women optimize their health overall so as to also optimize their reproductive health, we also want to make sure we're not taking a punitive approach or insisting upon interventions that may ultimately be adverse to their long-term health and also adverse to their patient autonomy.

Yeah. And I think that while we're seeing worse outcomes, I think that the success rates of these patients overall are still quite good. And so I want to echo that, that we shouldn't be denying treatment to patients who haven't elevated BMI.

And I think that it's always in the spirit of shared decision-making. If treatment is not working, I think intuitively we might think that losing weight, especially short-term weight loss with a GLP agonist may be beneficial, but we actually don't have data to show that. And so I think that that's the real question that needs to be answered is whether or not short-term GLP agonist use rapid weight loss actually is going to improve success.

And I don't know the answer, but I am really curious to see what comes from it. A couple other points, I'll jump in. One, please remember that we as REI and IVF doctors have a short window of our attention span.

It's not just the pregnancy that matters. If you use these short-term weight lines and then they stop and then you rebound while in the first trimester of pregnancy, you might actually be having all sorts of problems with some literature suggests miscarriage and other cases, greater weight gain in pregnancy and greater perinatal issues. Now that's all theoretical, but I just wanted to bring it up to say that it's not just simply optimize your weight so I can do an embryo transfer.

There are greater implications than that. And Pietro, you triggered me. I have to say something about DAGs.

Let people close their eyes about DAGs and say, why do I need to do it? I fight with a lot of authors about fertility and it's really about what the heck is a DAG. But the whole idea is that it looks at your logic when you're performing a study, as you said, it has a flow and it can really say, like, I should have controlled for something. But what people don't understand is that it also tells you what you should not control for.

For example, the best knowledge I can give you is if you're looking, if your drug changes IVF outcomes, but if you control for embryo quality, that might be the pathway where the drug is working. So if you control for it, you might get something called collider bias. That's the new keyword for the day.

And collider bias can give you absolutely the wrong answer. So epidemiology is evolving, and I hope that the rigor of our studies in FNS evolve, which is why I wanted to say something short about DAGs. It really is something you should learn and pay attention to if you really want to get the highest quality studies.

Great discussion. My only disappointment is that Micah wasn't here to smile when we talked about DAGs. He'll be smiling when he listens to it later.

But yeah, that was a nice aside and a lesson for all of us. So thanks for that, Pietro and Kurt. We're going to move on now.

And the next study that we'll be discussing is, again, we've got themes in our podcast today, the impact of industry. So this one is looking at the impact of industry payments on our patients' outcomes. Thanks.

Yeah, this was a novel and unique study. And the objective of this study was to determine whether industry payments to physicians are associated with a difference in ART practices and outcomes. And this was a study that was done by Meaghan Jain and Harry Lieman from Albert Einstein in New York.

So the authors hypothesized that IVF centers with a higher percentage of physicians receiving industry payments would translate into lower live birth rates, reflecting profit-driven practices adversely impacting patient outcomes. The program was enacted under the Physician Payment Sunshine Act of 2010, which aims at improving transparency of financial relationships between industry and physicians that may affect patient care. The specific outcomes that they looked at in this study were live birth rate, frozen embryo transfer rate, ICSI rate, PGT rate, and the percentage of patients over 40 were obtained from the CDC 2020 database.

So there were 1,724 REI physicians that were identified while mapping physicians via IVF center websites, which sounds about accurate. And just over half of these physicians received at least one payment that year. The sources of payment were largely from pharmaceutical, medical device, and surgical device companies.

So as I would have expected, and I'm curious to hear your thoughts, but there were not meaningful differences in outcomes between physicians who had industry payments and those that did not. So to break it down a little bit more specifically, the live birth rate did not significantly differ on the basis of the percentage of physicians in that practice receiving industry payments. When they looked specifically at FET, PGT, ICSI, and cycle cancellation rates, those also did not significantly differ between IVF centers by the percentage of physicians who received industry payments.

When they compared large centers versus small centers, and they had that break point at five physicians, so greater than five MDs was a large center. When they had large centers who had physicians receiving payments, there was more PGT performed, but they showed no differences in clinical outcomes. And so overall, I think the study provides some meaningful data that industry relationships in our field may not influence patient outcomes.

I'm glad they did this study, and I'm glad it was published in FNS. Personally, I think it's crazy that payments over $10 are tracked for physicians, but there's zero mandated reporting or regulation for our Supreme Court justices. With that being said, industry payments also mean a lot of different things and are not necessarily about physicians pushing a certain drug or a certain technology.

I do think that industry payments and relationships can be a meaningful way to accomplish things that might not otherwise be funded. So as an example, and this is my conflict of interest, I worked with Ferring and Engaged MD to create educational modules to onboard new nurses into a fertility clinic. As for their finding that larger centers perform more PGT, I strongly suspect that that's a correlation.

Large centers in general perform more PGT and not causation. Here's what you all think. Kate, Pietro, Kurt.

I have $132.81 to disclose in food and beverage from last year before I march into the podcast. But I think there's so many steps removed from participating in an industry-sponsored event where they buy you dinner to actually changing your practice pattern that can have a positive or negative impact on the patient outcome. I think this is interesting.

It's cool to see the math kind of shape out in our field. But I would tell you that take a look at neurosurgeons, orthopedic surgeons, some of the heavy-duty surgical subspecialties. They are much more lopsided in terms of industry involvement and industry payments than our field.

So I think it's just worth pointing out that REIs are involved in industry, but I think to a significantly smaller degree than the average subspecialist. But I think it's also a leap to say that someone who has an industry payment, and again, lumps it all into, you know, is a pharmaceutical payment going to drive somebody to do more PGT cycles? Like, I can understand in the situation of Ortho, you're sponsored by one company. You then might favor using that joint for replacement.

But I think that there are a lot of different avenues where industry payments happen. And I'm just not sure personally, and again, maybe that's my own bias as someone who's done some industry work, that I don't think it has anything to do with my clinical practice. I think those two are very completely separate.

And the things that I've worked on from an industry perspective have largely been in the education space, in nursing education and patient education, and not in the arena of drugs and clinical practice. So I have strong opinions on this, as you might imagine. First of all, I'm pleased this article got in, and I'm pleased it does show the industry is not motivating.

But a couple thoughts. First of all, industry would not be paying physicians if it didn't bias them, if it didn't work. I mean, they're too smart to throw their money away if they didn't get impact of their money.

Now, having said that, industry, the way they define it, is historical here. We are not really working with big industry anymore. We the REI field.

So I understand the link between getting paid by Merck and IVF might not be a strong link. But we can't discount the link between other biases, owned clinics, AI companies, genetic labs, all those kinds of things which are really not pull up in there. So we really have to be careful of this bias.

And we do see it in some of the articles in FNS. I don't think every industry article that says it's sponsored by industry is necessarily a bad thing and can't be good science. But if we don't believe that involvement of industry biases us, then that's kind of just naive.

No, and that's not what I'm saying. But what's being tracked by the Sunshine Act is not necessarily the real conflict of interest that people have, right? So the Sunshine Act is not tracking whether or not you're private equity backed and whether or not you've received a large buyout payment in your practice and whether that might influence how you practice, and to our point earlier, the number of PGT cycles. No, my point exactly.

Yeah. So this study is not actually studying the real industry payments. And the Sunshine Act is not really capturing those real industry payments.

The Sunshine Act is capturing a very small fraction of what it is, and I think a very insignificant fraction, and people's real conflicts are not being reported. I agree. Yeah, the magnitude of contribution that any particular physician is compensated really probably, in my opinion, has a pretty big impact on how they practice.

And I don't know whether it would trickle all the way down to outcomes because, again, at the end of the day, as we've discussed, PGTA can improve the cumulative live birth and so on and so forth. But I am glad, even though the Sunshine Act is imperfect, I'm glad we have something. I agree with Kurt that we need to be tracking these and we need to be cognizant of it.

So good paper and good reminder here. So we'll move on now to a paper on early pregnancy that Kurt will be discussing, and that is entitled, Preimplantation Genetic Testing for Aneuploidy in Unexplained Recurrent Pregnancy Loss, a Systematic Review and Meta-Analysis. Thanks.

This is a good paper that everybody should read. This is, again, a meta-analysis that is timely and of high quality done by Momo Soglu and Boris Ada. The title is, Preimplantation Genetic Testing for Aneuploidy in Unexplained Recurrent Pregnancy Loss.

And again, it's a systematic review and meta-analysis. And it really breaks down a number of questions that logically flow for us to kind of understand. The caveat of this whole thing is we'll go through the questions, but, you know, the data supporting them isn't always the best.

So be careful of what the answer we get. So the goal of the meta-analysis was to try to go with live birth rate as the primary outcome and then secondary outcomes could be other things like aneuploidy rate or clinical pregnancy rates and pregnancy loss. And it's trying to look at things, multiple questions at the same time.

So let's go through kind of the overview. It looks at about 118 studies to start with, and it ends up with about 18 in the meta-analysis. And again, my buyer beware is those 18 studies are not all terrific.

Some of them are observational, many of them are observational, and very few are randomized. But let's follow the logic. So the first one is they ask, what's the risk of miscarriage with people that have recurrent pregnancy loss? And they try to summarize that point for you.

It's kind of more of a teaching moment. And they summarize the literature in saying that if you have one loss, your next loss is 17%. If you have two to three losses, you're up to 28%.

Four losses, 39, and five losses, 50. So those are numbers you'll get quizzed on your boards about. But it also points, gives you the points that it does increase.

But even after five losses, it's still 50-50 on whether the next pregnancy will be normal. So that was the first summary. The next summary was, do women with recurrent pregnancy loss have a higher euploid rate in their embryos? And the way they go with that is basically saying, compare people that had PGTA testing with recurrent pregnancy loss versus those that had IVF for other reasons, and they do not really find a difference in the euploidy rate or the aneuploidy rate of these two populations, suggesting that women with recurrent pregnancy loss aren't making a greater percentage of aneuploid embryos.

So that was good data to say that. Now, there is some subtlety to this. If you've read the paper, they said perhaps there's, in some age groups, it might be higher than others.

But when they actually control for that and control for aging, meaning a lot of people get to recurrent pregnancy loss later in life, so therefore that might be a higher rate. But if you control for age, it's the same. So I wanted to break from a usual pattern.

And what do you think about that? Was that a surprise to you that I hear many people say off the cuff, the reason that you're recurrent pregnancy loss is because you have a higher chance of making abnormal embryos? I mean, I hear that all the time. What I am more curious about and what I see a lot in my clinical practice is some of these patients have a lower blastocyst conversion rate. And so that's what is beyond what can be captured by these data.

And so I think you can be reassured that if you do PGT for RPL, that once you get that blastocyst and you test that blastocyst, that you're going to have an equal chance of having a euploid blast. But what these data fail to capture is that potentially lower blastocyst conversion rate that I see in my clinical practice with patients with RPL. And it may reflect that there's a higher degree of aneuploidy and those 2PNs just simply aren't progressing to blast.

And so I don't think that we can look at this and say, aha, like you have normal eggs. I think you have normal blastocysts, but you have to look at a few steps before that. And then you get into that spiral where you have one euploid blast and a patient who has RPL.

And what are all of the things that we can do to optimize the transfer of this blast, be it ERA, Receptiva, immunotherapy, you name it. And that's how you get into this like death spiral and add-ons for some of these patients because of the limited number of actual blasts at the end of it, for sure. So I just want to go back to what you said.

So what you said is an IVF finding. Theoretically, if you were not doing IVF, those patients wouldn't have gotten pregnant with those embryos if they stopped growing before blast. Well, we don't know that, though.

I mean, they may grow better in the human body and that may account for... I mean, we don't actually know that the pregnancies that you lose are cited genetically different than the findings that we see. And so I think that theoretically, you're right. But you could also argue that within the human body that it may allow for implantation or may allow for blastocyst growth for things that would not grow to a blast in the lab.

And it's theoretical. Well, back to the paper. That was the first question.

One of the questions they came out with was just trying to answer the question, is there a higher rate of aneuploid embryos in women with recurrent pregnancy loss? And their conclusion, according to the data, is no. So that was an interesting thought. Yeah, but I don't think that you can really... I think that you can't really say that.

So you can say that once these oocytes made it to blastocyst that they had an equal chance of being euploid, but you're just looking at a small fraction of what made it to blastocyst. You're not looking at... Leave us in the camp that we don't know the answer yet. Yes, I'm in the camp that I don't... I'm not ready to definitively say that the egg quality is the same and that the euploidy rates are the same without looking at blastocyst conversion rates.

OK, I'm going to give Baris Ata your email and you guys can battle it out. But the third question was, if you have a euploid embryo, is the pregnancy loss different in women with recurrent pregnancy loss versus not? And the answer, again, is if you get a euploid embryo, the miscarriage rate and the implantation rate is the same. Therefore, the argument is they don't think it's the endometrium either.

So again, this is what the literature is saying. They're basically saying we know miscarriages increase with age. We know that some of the apparent bias we see is that women with recurrent pregnancy loss might be older.

But if you account for that, they're making the same number of euploid embryos. And when you transfer a euploid embryo, the pregnancy rate's the same. So that's what this meta-analysis is saying.

I understand it's controversial. But what do you guys think of those findings? I'm not sure I believe them. I mean, I think it sounds reassuring.

It doesn't feel like what you see day to day in clinic. Correct, correct. Like, I don't have as much confidence in PGT strictly for RPL.

I think it's one tool that can help. But I don't think that all of RPL that we see all the time is from aneuploidy. While I don't personally prescribe IVIG or other immune protocols per se, I'm also not willing to say that immune function isn't at least a part of implantation and a part of recurrent pregnancy loss.

So I wouldn't say that PGT is a cure-all, that you get a euploid blast and you're going to do just as well as somebody who doesn't have RPL. I think it can be a very helpful tool in this particular circumstance. But I think that it's part of the puzzle and not the whole puzzle.

I think it does two things really well, though, in that population, Eve. I think one thing that it does is it eliminates causative variables, like why did the miscarriage potentially happen, which can be helpful psychologically for the patient, but I also think also helpful clinically for us when we're trying to understand what is the true etiology of what's going on here. And then probably the most important, the part where I kind of interface the most with is it reduces iatrogenic harm.

So we are transferring embryos that may miscarry at slightly higher rates if they're untested, and then we get into that vicious circle of DNC, Asherman's, thin linings, treating thin linings, and that's a whole other loop of care that this patient now has to deal with by nature of starting off with that RPL diagnosis. So I don't want to discount the utility of PGT here in this patient population entirely, but it can be helpful in specific scenarios. I think that that effect size is pretty small.

Even in this study, we see that actually the reduction in miscarriage is pretty small. That said, you know, the time lost by these patients is felt so heavily. So when there is a miscarriage, the ability to go back and get more embryos, whether there's a true clinical benefit that warrants its use, I think the jury is still very much out on that.

Psychologically, as you mentioned, Pietro, and is that a good enough reason? You know, again, jury's out. I think it's a big deal for these patients. And then not to belabor this article, it's a great discussion though.

You know, we had a very similar discussion a couple months ago, or I think it was last month when we were talking about the PGTA-PGTM paper, you know, where Kurt, you and Micah were on the side of, no, I don't think that patients who have these worse outcomes are necessarily attributable to aneuploidy and it's going to manifest in terms of worse PGTA. And I was more sort of on the side of Eve that, you know, I do think that patients that have worse reproductive outcomes, whether it manifests earlier as infertility or later as RPL, I do expect these patients to have higher rates of aneuploidy. And whether that presents pre-blastocyst, as Eve, you're suggesting, or in the PGTA outcomes, you know, I steadfastly believed, I guess I should say at that point that it was there.

But I think there is accumulating evidence that that may not be the case. We did a study at our center the year that we switched over to blastocyst transfer. So we looked over our entire patient population who, you know, had fewer than four 2PNs available where those patients previously would have had cleavage stage transfer.

And then the next year we moved to blast transfer only. And what we found is that while those patients actually had a lower overall pregnancy rate, mostly due to, you know, cycles with no transfer, they ultimately, so I mean the patients that had blast transfer, as opposed to cleavage stage transfer, they were less likely to have a transfer and therefore had less pregnancies, but they had no fewer live births, right? So that also kind of points more towards what this article is saying in a way from what Eve is saying is that it's very unusual. I would say that these embryos are not going to make a blastocyst in the lab, but are going to make a baby in somebody's uterus.

So not to be on too much of a tangent, but, you know, an interesting conversation. So let me finish up the last piece on the paper, but that was a really good discussion. And I expect more after I give you this summary point.

So the last thing they did in the meta-analysis was, what about ART with PGTA versus ART without PGTA? In a sense, they're lumping the recurrent pregnancy loss together saying, if you're going to do ART, you should do PGTA. Well, what happens if you do PGTA? And you get, they're basically saying, no surprise, if you do PGTA, you have a higher cumulative live birth on the first, I'm sorry, higher live birth on the first transfer. So there's, and there's a lower loss rate on the first transfer.

So, but that's asking if you did IVF, the next part of the discussion is, what if you just left the patient alone and didn't do anything and just did expected management? And they acknowledge that expected management in these people is a live birth of 60 to 70%. So it's hard to argue that the IVF is actually increasing the live birth. Perhaps it's reducing the miscarriage rate, but it's hard to compare apples to oranges here and it's back to time.

So let's go through the take-home messages one more time. Recurrent pregnancy loss patients have a very good success with IVF and without IVF. That's approach is 60 to 70%.

But perhaps because of the age and the time, that would be an argument to have a medical assistance. The second point was that patients with recurrent pregnancy loss don't seem to have aneuploid, a higher aneuploidy rate. That's the message of this paper.

And then when you actually look at good quality studies only, they got rid of some of the observation studies, the live birth rates with euploid embryos seems to be the same in reproductive pregnancy loss versus regular IVF patients. And they came up with, they wanted to refute a hypothesis they never heard of. They called it the checkpoint hypothesis, where that for some reason women with reproductive pregnancy loss might have an endometrium that's more receptive to a bad embryo.

And that's why people were getting losses. And according to this data, they're saying that doesn't hold up either. So they do mention again, the take-home point that these patients might be farther along in their process because they've had miscarriages and are therefore older.

And therefore that goes back into the choice of ART. So then we get into the debate, which I think they frame pretty well. Like all patients, PGTA may facilitate single embryo transfer, which has benefits.

It may reduce pregnancy loss in that transfer, which has benefits. It may decrease time to pregnancy. And it may importantly decrease the dropout of patients in this long reproductive cycle.

Now I want to talk about that, the whole Blair podcast that we completely moved the goalpost of why we do PGTA. It's no longer benefit. It's, we don't want to lose our patients, but I'll stop that for a second.

But PGTA opens the door for misdiagnosis of your embryos, potential damage to the embryos because of the invasive aspect of it. So you're not going to improve your cumulative pregnancy rate. In fact, you might harm it.

And it clearly impressed costs. And it, again, theoretically, even in the best hands cannot improve your cumulative pregnancy rate. So let's go back to the main question of this.

Now that we've looked at some of the subtleties, their final conclusion is really can't say whether to recommend PGTA in someone with recurrent pregnancy loss compared to expectant management. We can't really make that comparison. And perhaps it makes sense to use it in people that have good ovarian reserve, because you've got a lot of embryos to choose from.

And therefore you actually can decrease the time, but not all patients. And then finally, it does end with the recommendations from ESHRE and ASRM, which says, again, our societies don't recommend this as primary treatment for reproductive pregnancy loss. So even though we got into some subtleties, I want to get back to the beginning there.

So good discussion and a good paper. I'm glad it got into FNS. I agree.

Great paper and great discussion. It's somewhat unsatisfying because we're all looking for things that we can intervene with that are really going to help. But good to know the truth.

And we're going to let this rest in the spirit of time. But I want to say the one other thing that's missing about this is the emotional impact of recurrent loss. And so I think we can talk about age.

We can talk about time. But I think that what's missing is the devastating emotional impact that recurrent loss can have on our patients. And so if there is something that can reduce that likelihood of loss in the next transfer, I think that that is a really good argument for PGT.

So I think that the jury is still deliberating. For sure. OK, Eve, we're back to you discussing fertility preservation.

Thanks. So this article is titled Initiation and Outcome of Women Pursuing Planned Fertility Preservation. And this is David Boedeker from Walter Reed with a host of other authors, including Alan DeCherney and our very own Kate Devine and Micah Hill.

I really like this study. And I'm not just saying it because two of the authors are our co-hosts, but I think it provides some really excellent counseling nuggets and some very good insight into patient outcomes. So the objective was to study cycle outcomes of women who chose to pursue planned oocyte cryopreservation.

And the group recommends that patients under the age of 38 freeze 15 to 20 M2s. And for women who are age 38 to 40, that they freeze 25 to 30 M2s. And this was based on a previous study published by Joby Doyle in 2016.

So this study has 10 years of data from Shady Grove. During that time, there were close to 6,000 patients who were seen for an initial planned oocyte consult. And of these, 59% proceeded to complete at least one cycle.

So 80% of patients presenting were single. 52% were white or Caucasian. 19% were Black or African American.

12% were Asian. And only 4% were Hispanic or Latina. And Black and Hispanic patients were found to be less likely to move forward with a cycle compared to white and Asian patients.

They also found that patients who achieved higher education were more likely to move forward with a cycle. But the part of the paper that I really liked and I think that I will find most useful in counseling are the cycle outcomes. And these are mostly in figure one.

So not surprisingly, as expected, younger women had more eggs retrieved in their initial cycle. But the numbers still overall, I think, are a little bit on the low side. And the reason I think it's important to note this is when we talk about cycle splitting or egg sharing, I think it's really important to understand what realistically women will get from one cycle of egg freezing.

So those who are less than 35 had an average of 13 eggs retrieved. Those who were over 40 had 7 eggs retrieved. And the numbers decreased with age.

So only 57 patients. So less than 5% of patients achieved their recommended number of eggs in a single cycle. And to me, this is probably the single most important takeaway point and that we really need to be counseling patients upfront that this is not a one and done process.

Going back to the idea of egg sharing, that if you are splitting your eggs with a donor, so you are giving up half your eggs for a donor cycle, that would translate to needing to do four cycles rather than two cycles in order to achieve your maximum number or your recommended number of eggs. So what they found was that 57% of patients pursued more than one cycle. And then in aggregate, only 38% of patients achieved the recommended total number of M2s banked, even with more than one cycle.

And so my guess is this is largely limited by cost, but can't ignore the fact that women may have been potentially frustrated and disappointed or dropped out of treatment. We also can't ignore the possibility that women may have gone to another center for subsequent cycles. And I think that it's an area that's really ripe for research, especially qualitative work, examining barriers to seeking care, and especially more qualitative work in the Black and Latina populations looking specifically at reasons for not moving forward.

So I think so much to talk about here, but I think that we really need to be very upfront and counsel women that most will require multiple cycles and that one cycle or even two cycles may not be sufficient. Only 38% of patients got to their recommended number, even with more than one cycle. Yeah, I mean, can't be overstated.

Say to the patients five different times, five different ways. Denial is not just a river in Egypt. Everybody thinks they're going to be the one that gets all of their eggs in one round.

And unfortunately, that's pretty uncommon. So I'm interested to see what these numbers look like 10 years from now. I don't know if you all agree.

I see my patient population currently just seemingly overnight, the majority of my egg freezing patients seem to have coverage, whereas previously they were self-pay. So I hope that that changes the landscape in terms of patients achieving their goal numbers. So in the interest of time, we've got a fascinating paper on Turner syndrome that I can't wait to hear Pietro tell us about.

Kate, before we move on from the last article, there's nothing worse than the patient who freezes too few eggs. It's that double whammy of, I think you have a lot more in the bank than you actually have. And the actual reproductive potential of those eggs is blunted.

It's the worst when they come back. No question. Yeah, I agree.

It used to be just counseling about freezing eggs. Now there's so many patients about why I didn't get pregnant after I used my frozen eggs, and it's getting disheartening. I want to plug this article.

I don't want to tell you the whole story, but I think everyone who is a reproductive medicine person who's listening should read this article. This article is entitled First Successful Ovarian Cortex Allotransplant to a Turner syndrome patient requiring immunosuppression. By Sherman Silber and colleagues from St. Louis and Johns Hopkins.

At a high level, this is a 20-year-old woman who's a non-mosaic 45 exo-Turner syndrome patient with an AMH of 0.01, an FSH of 67, who for religious reasons could not accept donor eggs. She did happen to have a 22-year-old sister with a 46XX karyotype who had previously had two children at an AMH of 4.9 because they were related. They were luckily an HLA identical match, but they were ABO incompatible.

This is really where the plot thickens. You're thinking ABO incompatible. I thought that that was a big no-no for transplantation.

Well, if you're interested in learning more about this topic, you should read this article. They'll tell you a little bit more about ABO incompatibility, the difference between revascularizing versus diffusing into a solid organ transplant. But I'll jump to the end.

This actually worked. They took a strip of ovary from the sister, transplanted it into the streak gonad to the recipient. And after a couple of months, the FSH plummeted.

The patient resumed cycling. The uterus that was now appropriately estrogenized increased in volume. And lo and behold, an unassisted pregnancy resulted from this transplanted tissue.

So lots of stuff to unpack in this article. I encourage everyone who's interested in this topic or even just looking for what's the medical first that happened in FNS this year in 2024, check out this article, read a little bit more about it. It's super interesting.

Truly amazing. What a great story as we head here into the holidays. You guys can't see us, but Pietro is wearing an amazing Christmas sweater today.

There's elves and they're crossing the street. It's actually, you know, Abbey Road, I think. So we've got the Beatles elves supported by Pietro.

So happy holidays to all of our listenership. Read this amazing January issue of Fertility and Sterility, and we'll look forward to talking to you next month. Happy holidays, everybody.

And as part of that, I want to say thank you to all of the reviewers who have helped Fertility and Sterility. In this month's edition, we thank the reviewers. So you can see your name in print.

We have practically a thousand, if not more than a thousand individual reviewers, and I can't thank them enough for all their diligent efforts that gets literature through and published for you to read and for us to debate on this podcast. So thank you very much. I just want to say happy holidays.

And I think by the time our listeners are hearing this, it's January. So happy new year, everyone. And I hope 2025 brings lots of health and happiness for all.

Hear, hear. My special thanks to the Interactive Associates and all of the folks who work to bring this journal to you on audio, on social media, and Meredith and Natalie who live behind the scenes and make sure that this journal is as successful as it is for both authors, reviewers, and all of us. 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 and Dr. Adriana Wong. This podcast was developed by Fertility and Sterility and the American Society for Reproductive Medicine as an educational resource and 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.

The opinions expressed are those of the discussants and do not reflect fertility and sterility or the American Society for Reproductive Medicine.