Welcome to Fertility and Sterility On Air, the podcast where you can stay current on the latest global research in the field of reproductive medicine. This podcast brings you an overview of this month's journal, in-depth discussions with authors and other special features. FNS On Air is brought to you by the Fertility and Sterility family of journals, in conjunction with the American Society for Reproductive Medicine, and is hosted by Dr. Kurt Barnhart, Editor-in-Chief, Dr. Eve Feinberg, Editorial Editor, Dr. Micah Hill, Media Editor, Dr. Pietro Bortoletto, Interactive Associate-in-Chief, and Associate Editor, Dr. Kate Devine.
Hello, everyone, and welcome back to another episode of FNS On Air, where we are discussing the April 2026 Table of Contents. I am your co-host, Pietro Bortoletto. I'm joined with a small but mighty group this morning, Dr. Eve Feinberg, Dr. Kate Devine.
Good morning, you two. Good morning. We are a special shout out to the two other pillars of the podcast, Micah and Kurt, who could not be with us this morning, but will hopefully be on your next month's episode.
We have some great content today. We have a letter from the Editor-in-Chief, which you don't always see in Fertility and Sterility, but when you do, it's probably worth paying attention. If you've been reading the journal over the last several years, you've probably noticed that there's been an increase in AI showing up in our journal.
As a result, we thought that it was important to come up with responsible use of AI in manuscript preparation. This letter is a guidance document that tells fellows, junior faculty, senior faculty who are accustomed to publishing in FNS, but now have these wonderful tools at their disposal, how to use them appropriately, how to cite their help appropriately, so that everyone's aware what is human and what is AI-generated or assisted. So that's one that I'll point all of our contributors to, to take a listen.
We do have a wonderful views and review section this month. We're talking about the microbiome. There's so much that gets talked about the microbiome.
In my clinic, when I'm talking with patients who have questions about probiotics and whether or not they need their microbiome assessed, and is the reason their euploid embryos not implanting, is it because of their microbiome? This takes a really nice deep dive, both from the male and female side, particularly with the focus on reproduction. So point everyone towards that wonderful group of articles in this month's FNS. And then our very own Eve Feinberg is participating in a fertile battle.
Eve, why don't you tell us a little bit about concurrent gestational surrogacy? Thanks, Pietro. Shout out to Michelle Bajewski, who actually had the idea for this and reached out to us to see whether or not this would be a topic of interest. And I think it is, and I think it's becoming more and more prevalent.
And the question that we sought to ask and answer is whether concurrent surrogacy is ethical. And concurrent surrogacy is when you have two gestational carriers that are pregnant at the same time. And that can either be almost exactly at the same time with embryo transfers within a close time frame or more distant time frame, maybe spaced out by about four to six months.
And so the pro and the con sides are really intriguing. And I think that both sides make excellent arguments for this discussion. And I will say, I try to remain neutral as the curator of these pieces, but I think it really got me to think.
And I would highly encourage everyone to read this and weigh in and form your own opinions here. And I shout out as well to all of our fellows at PCRS who are going to be doing a debate as well on whether or not it is appropriate to use surrogacy outside of the setting of a medical indication. So topic of the moment, as usual, FNS is dealing with everything that we're wondering about how to take care of our patients ethically and while providing them the full scope of care.
Great. And I'm especially pleased to hear that. That was a fertile battle that I put together probably about six months ago.
So I will be tuning into that debate. Yeah. I have a feeling the fellows are very grateful that they had that fertile battle to refer to as well for their debate.
Good pros, good cons. Kate, we're going to start with you this month. We seldomly start with an andrology article, but we have a really cool one as part of our original article section this month.
Tell us a little bit about embryologic outcomes using surgically retrieved sperm. Yeah, this was, I think, a clinically useful paper for counseling and falls under the category of reassurance, which we're all always hoping that we have good evidence to give our patients. And so this is a paper with the first author, Haley Genovese, and they are at IVY RMA and then collaborating as well with Jim Hodling from Utah.
So a great group of authors here trying to answer the question as to, can we really tell our patients who have indication to use surgical sperm, firstly, non-obstructive vasospermia, looking at microtessi-retrieved sperm, and obstructive vasospermia using tessa-retrieved sperm. Do these patients have the same outcomes as patients who are using ejaculated sperm? And they're really kind of specifically focusing in on those who do get sperm. So they did a retrospective cohort study of all patients undergoing their first IVF cycles.
They had 211 patients that went through a microtessi, 156 patients with a tessa for obstructive vasospermia, a much larger cohort as expected when we're, I think, looking at consecutive patients, 9,074 who had ejaculated sperm and were doing IVF for a wide variety of infertility indications. And then they had a group of 536 patients, just another side of that control group, that were using frozen donor sperm. And so I think this is a really helpful paper insofar as what they looked at were both laboratory and clinical outcomes.
A really important caveat here when you read here is that the denominators are different, and necessarily in some cases, I think you could quibble as to whether that was appropriate in other places in terms of each of their comparisons. So they look at fertilization rate. And again, not surprisingly, they did find that the fertilization rate was at lowest in the M-tessi group, then the tessa group, and then it was equivalent between the ejaculated and donor sperm groups.
But we have to keep in mind that when we look at per initiated cycle, more than half of the patients in the M-tessi group did not have sperm retrieved. So when we're talking to patients and counseling them to reassure them that the fertilization rates are similar, although slightly statistically significantly different, and then they go on to also find that the live birth rates were the same among those patients who had single euploid embryos to transfer, that we're not exactly comparing apples to apples if we're thinking about this in terms of initiated cycles. So just to kind of run through the results in a little bit more detail here and the groups that were involved, the other thing that we need to keep in mind is that they did exclude patients that had karyotypic abnormalities in the surgically retrieved sperm group, but not in the two control groups.
They may have chosen to do this because, of course, fewer of our patients will have had a karyotype in the other groups that may or may not have indications for that, but also has the potential to change or introduce bias. So we need to be considering those things as well as we interpret these data. Looking at their primary outcome of fertilization rate, as I already mentioned, controlling for both male and female age, what they found, again, was that small but statistically significantly lower fertilization rates in the TESI and the TESA groups in that order, but equivalent rates in the ejaculated and the donor sperm groups.
In interpreting those data, also important to notice here that there is a mixture of fresh and frozen sperm that is used in the TESI and TESA groups, as well as in the ejaculated sperm group, whereas, of course, all frozen sperm in the donor sperm group. The percent that were fresh in the TESI group was 34 percent, 25 percent fresh in the TESA group, and 92 percent fresh in the ejaculate group, and this is not something that was adjusted for in their analysis, so, again, something to think about as we interpret these data. When they move on to their secondary outcomes, they did find that the blastulation rate was lower in the TESI and TESA groups, but then they note that the overall mean number of blasts obtained was the same throughout.
Denominator here, again, changes, though, because we're looking at blastocysts per 2pn, so if we're looking at blastocysts per mature egg, it's even more significantly lower, and probably the mean numbers would also be lower there if we're looking as a starting point at all those that had mature eggs to fertilize in the first place with ICSI. Again, I think the real conclusion here that the authors state, and I would agree, is that of those patients who obtain single-euploid blastocyst, whether they used surgical sperm, regardless of the underlying diagnosis for azoospermia or the way the sperm were retrieved, those patients can expect to have similar live birth rates to those patients that had ejaculated sperm to use or that were using donor sperm, so that is really kind of the main take-home point, is that, as I think we would all expect, once you get to a euploid blastocyst, we expect good outcomes for these patients, but it's still nice to have these data to point to when patients ask us. It's also really important, as you read through this paper, to bear in mind the denominators and the fact that more than half of the patients in the non-obstructive azoospermia group did not have sperm to work with in the first place, and that, you know, for better or worse, these patients oftentimes do have a pretty steep hill to climb, and the onus is on the reproductive endocrinologist and the reproductive urologist to counsel these patients and to contingency plan as to what are we going to do if we just unfortunately do not find these sperm.
Pietro, Eve, what did you think as you read this paper in terms of how it might impact your practice? I will say I think the findings that we see in our center are similar. I do think that there's still a role, and I think it was really hard to tease out the data, as you had mentioned, in terms of which tessies were fresh versus frozen. I will say we see huge differences in non-obstructive azoospermia, specifically in fresh micro tessie, so I think that in many cases you can normalize those rates.
The other thing that I think is perhaps not the most fair comparison is in many patients where it's pure male factor infertility, azoospermia, you do tend to have a healthy female along with that, not without diminished ovarian reserve, without endometriosis, adenomyosis, and all of those different diagnoses, and so you would almost expect that those patients might do better. That's what I thought. The fact that they did the same probably speaks to that male component to it, that it's decreasing the overall likelihood of success, and while euploid embryo transfer is the same, arguably in these young patients that are under 35, like why are we doing PGT on them? And so I think they were able to achieve similar pregnancy rates when they looked at it by euploid, but if you were to look at it by intention to treat, you're going to see a huge delta there, in part because they're not getting sperm from every patient, and if you look at the numbers, there was much more of a drop-off from mature oocyte to 2PN in the microtessi groups.
100%, and you hit the nail on the head. I was wondering whether you saw the same things, that in fact, the clinical pregnancy rates among the euploid transfers from the severe male factor groups were statistically significantly higher. It didn't trickle all the way down to live birth, and that may have been a sample size issue, given that that was not what they were primarily looking for.
Fertilization was really their primary outcome, but yeah, just read with a careful eye to the denominators in this paper. Again, another thing you'll note is that the group were younger undergoing transfer than they are undergoing retrieval, indicating all of those patients who fall out that never get a euploid blast in the first place. So, some pearls in there, but just be careful what you conclude from an initial read of the abstract.
Thanks, Kate. It's always cool to have a nice andrology paper that supports counseling and helps us guide patients who are making these tough decisions about going to surgically retrieve sperm or pivoting to donor sperm to optimize an outcome. Eve, we're going to talk about a topic that I think is near and dear to all of our hearts, egg freezing.
I like that in the title, the authors use, quote-unquote, egg freezing clinic. Probably a poke to, this isn't a pejorative term, but let's produce some data from this clinic that was a first in many ways when it opened several years ago in New York City, but it's nice to see some of their long-term outcome data. Tell us a little bit more about this paper, Eve.
Yeah, spoiler alert, I'm also going to focus on the denominator here, which is a huge problem with this paper. So, the title of this paper is Freezing First, Insights from Eight Years of Planned OC Cycles at a, quote, egg freezing clinic, and this is by Josh Klein and others from Xtend Fertility. I think as everyone who practices in this field knows, planned OC cycles have grown dramatically over the past decade.
U.S. cycles increased 880 percent between 2010 and 2016. Despite widespread adoption, outcome data on actual oocyte warming remains sparse, as fewer than five centers have published peer-reviewed oocyte warming outcome data. The estimated return or utilization rates in the U.S. is approximately 10.8 percent, and we're going to talk a little bit more about this.
So, the study reports eight years of both oocyte warming and oocyte cryopreservation experience at Xtend Fertility. As you said, a clinic originally established specifically as an egg freezing center, although they have subsequently expanded to full-scope treatment. This was a retrospective cohort study of all planned OC cycles from Xtend Fertility from January 2016 through December 2023, and all warming cycles through August of 2024.
It was approximately 400 OC cycles per year that were frozen, not warmed. Patients 18 to 46 were included. Those freezing for medical indications or due to absence from on the day of retrieval were excluded.
The primary outcome was cumulative ongoing pregnancy rates and live birth rate per oocyte warming cycle stratified by age at OC and number of mature oocytes warmed. Secondary outcomes included survival, fertilization, blastulation rates, and euploid embryo yield from PGTA. So, in total, 4,659 OC cycles were completed for 3,138 patients over eight years.
The mean age at OC decreased significantly from 36.9 years in 2016 to 35 years in 2023. So, of patients with at least four years of follow-up, 10.4 percent returned for oocyte warming. Of that 10 percent, donor sperm was utilized in 25 percent of all cycles.
PGT utilization was high, and across 271 warming cycles, the mean number of M2 oocytes warmed was 15, with the overall survival of 90.7 percent and fertilization rates of 77 percent. So, this is where I have an issue with the numbers. So, cumulative ongoing pregnancy and live birth rate for patients under 40, they say is 70.3 percent, ranging from 58.3 percent with 1 to 9 M2 oocytes warmed to 81.8 percent for those with more than 20 M2 oocytes warmed.
So, I really got in the weeds here with the tables and my calculator, and the biggest issue I have with this paper, and I think you have to really dive in and look at the numbers for yourself, they present their data by embryo transfer, and they use 138 embryo transfers as the denominator. They had 272 warming cycles, and they should have used that larger denominator of 272 to come up with those live birth rates, and when you recalculate it, the live birth rate is considerably lower. And so, what accounts for this difference? Not every egg survives the warming, not every embryo progresses to a blast, and when you're PGT, not every blast is euploid.
So, when you do this paper, you need to look at it in terms of the number of eggs warmed as the denominator. They say live birth rate was 70.3 for all ages, but in reality, it's actually 35.6 percent when you use the correct denominator. So, I'm a little bit surprised that the reviewers did not pick up this, and a note to all of our listeners, this is exactly why we've been doing review sessions as fertility and sterility editors coming around to all the fellowship programs.
So, shameless plug for that, if you want some editorial assistance and teaching you how to do good reviews, ping us. So, euploid embryo yield per M2 oocyte was approximately 20 to 30 percent for women under age 38 at the time of cryopreservation that dropped to 8 to 9 percent for those ages 38 to 42 and was zero for those ages 43 or older, which is not surprising. So, overall, the conclusions are that oocyte cryopreservation success is higher with a younger age at freezing and more eggs warmed, and I think that that's common knowledge.
I think the most surprising statistic that I took away from this paper, and I think, quite frankly, it's a little worrisome, is that the overall utilization rates were incredibly low, 10 percent. If we think about how many cycles are being done and how many patients are freezing eggs, the really low number of return, I think, skews that risk-benefit relationship in terms of counseling on informed consent. So, I also think there needs to be an upper age limit where we don't freeze eggs.
In our center, we stop at 42, which seems very reasonable based on these data. And this really makes me wonder, overall, if we're doing too many egg freezing cycles as a society. And finally, I think that 25 percent donor sperm rate may contribute to better outcomes compared to older male partners.
So, you know, my words of caution, I think, to everybody, when you read a paper, you can't just read the abstract. You can't take the results at face value. You really need to dive into the data and see whether or not the data presented align with the stated conclusions.
And I think it's really important to be honest about this idea of what your denominator is and what you're really looking at. So, I think that egg freezing, and I'm a huge fan of it, and I think that there's a big role for it, but I think that it's definitely not an insurance policy. We have to counsel patients on the limitations of it.
And I always say that the best, your best likelihood of trying to have a baby is trying to have a baby. With that being said, I never want anyone to get pregnant when they're not emotionally, financially, socially ready for it. So, there is a role for egg freezing, but I think perhaps maybe somewhere in the middle.
Maybe we're doing a little too much freezing. Kate, Pietro, what are your takeaways from this? Well, it's a theme on the denominator, for sure. It's interesting that the similarities between these papers in that way.
I had the exact same thought. And on the eve of PCRS, Eve, I guess, no pun intended, it's a throwback to a debate that you and I did, like, during PCRS, during COVID, about should everyone freeze their eggs before they're 30? Which is to say, you know, on the one hand, I think there's a lot of consistency in the data, which is reassuring, and keep on hearing this number over and over again, that, you know, you really need about 20 mature eggs to get above an 80% live birth rate, even in good prognosis patients. And it's been remarkable to me over many, many papers, you know, starting with my friend Joby Doyle's paper a long time ago, a lot of the work that you've done as well, Eve, that that number just is extremely reproducible across many centers.
And then the other thing that I think, again, reminds me of that debate that we had all those years ago is this low utilization rate. And you had the side, and I know they were assigned the side that everyone under 30 should freeze their eggs. And I had the, what I think is probably the easier to defend side, which is that, no, because a lot of these patients are not going to use their eggs.
And the younger you freeze, when you don't know what the future holds, the less likely you are to need them. And so, you know, just a point of counseling, as you say, that it's not an insurance policy, but there is kind of a sweet spot. I agree with your Northwestern policy not to freeze too old, because those eggs are not helpful, but also not to freeze too young, unless there is some intervening, you know, medical or risk factor for really needing to use those eggs, because for those patients can be less than 10%.
That's a lot of time, money, effort, even some medical risk to take on for those patients. Yeah, we did a SART cost-effectiveness analysis, and shout out to Jen Bakkinson, who's the first author on that. But we did sensitivity analyses, balancing cost versus success across multiple age groups.
And we looked at it from age 25 to 40, and found that that sweet spot was actually age 33. So, you know, it was interesting. I saw a 25-year-old the other day with an AMH of 8 who wanted to freeze her eggs, and I told her to, like, come back in a couple of years.
And I got a very not nice call from the referring OBGYN asking me why I sent the patient away. And I said, I didn't deny her. I just said, you know, come back when you're 30.
You've got plenty of time. You're 25. Your AMH is super high.
And see where life takes you, and let's re-discuss it. I just think that there's a very high likelihood, 90%, in fact, that she's not going to use the eggs. Can I talk a little bit about the other end of the age spectrum in this paper? So, the patients who are freezing eggs at 41, 42.
They went up to 46 in this paper. Correct. So, let's talk about that as a field for a second, because I feel like those are, yes, we all have the young patients who want to freeze eggs, and those are relatively straightforward counseling visits.
What about the patient who shows up to your door at 42, 43 with an AMH that's better than age appropriate? What are the pearls of wisdom that you're sharing with them about utilization, success about their future eggs, expectations for their embryos that they will create from these eggs? Those, I feel like, sometimes just have a totally unrealistic expectation of their reproductive horizon and potential. I struggle more with those than I do with the really, really young ones who want to freeze eggs. It's certainly a grimmer view that we have to share.
So, less fun counseling session, but it all comes down to reviewing the data in an honest way and taking the time. I mean, we have the data. Those patients do not do well with frozen eggs.
They may be in a slightly better position if they can get more, and if well-counseled and they want to do this, we actually don't deny them. We will fully deny them at 44 and above, but it should be a conversation about, okay, maybe this needs to be a really deep look at your life and reproductive plan as hard as that is, and should we be freezing embryos here or doing IVF or doing IUI? Because as Eve says, some of these patients still do have fertility, but their eggs are likely more fragile, and it's really probably not in their interest for them to go through elective oocyte cryopreservation. Yeah.
So, I will offer those patients who have a great AMH at 42, 43 who come in wanting to freeze eggs the opportunity to make embryos and freeze euploid embryos, and I've had success with that approach, but the reason we cut off at age 42 is we didn't have any live births beyond that from frozen eggs, and it didn't matter if you had 20 frozen eggs or you had two frozen eggs. More poor-quality eggs is more poor-quality eggs. It didn't translate in the same way that you see that dose-response relationship in a younger patient, where more definitely equals better success.
Well said. We'll leave it at that. Thanks, Eve.
All right, I'm going to bring it back to me for this next article. I love a good surgery article in FNS. This one is entitled, The Effect of Collagen Scaffold versus Intrauterine Device on Preventing Recurrence of Intrauterine Adhesions.
Colon, a multi-center randomized controlled trial, which you see increasingly rarely in our field, but particularly with the surgical stuff, so when we have it, it's important to highlight. I think anyone who's taking care of a reproductive age patient knows of the dreaded recurrence of intrauterine adhesions. You do that beautiful first adhesiolysis.
You're like, we've crushed it. This cavity is perfect. Lo and behold, six weeks later, it doesn't look great.
We've all used all kinds of different first-line prevention methods. Estrogens, our Foley balloons, our Cook balloons when they were on the market, and all of them work okay, but recurrence rates still hover right around 30 to 40 percent and even higher with more severe first cases. This RCT asks, can a biodegradable collagen scaffold do better than our currently available devices? This study is being done in China by first author Huiyan Wang and senior author Yali Hu.
In China, the use of an IUD is actually quite common. I would say that is not common practice in North America. I'm not too familiar with Western Europe, but in China, the use of an IUD is very, very routine.
This study looked at a collagen scaffold, which is an acellular dermal matrix that's derived from bovine skin, so you can imagine a world in which some patients might have a yuck factor about bovine skin products in their uterus. This basically has a 3D architecture that's porous with pores as little as 20 to 200 micrometers. There had been preclinical studies that had shown that this promotes endometrial proliferation, migration of basalis cells, and neovascularization, which are all things that you want after a big, bad lysis of adhesions.
This study was multicenter. It was open-label and was designed as a superiority RCT. It took about a year and a half in over six tertiary centers in China.
This study enrolled over 400 patients and randomized them to receiving the collagen scaffold or an O-shaped IUD, which is a funny shape for us in North America. We're used to our T-shaped. They purposely tried to include patients with advanced in treat or adhesion, so AFS scores of five to eight.
These are mostly young patients between the ages of 20 to 40 with low BMIs who are actively trying to conceive. All patients underwent adhesiolysis with scissors. There was no electrosurgery that was used.
Interestingly, in a technique that I really like and use in my practice, they used real-time trans-abdominal ultrasound guidance to make sure that they were in the right plane, heading in the right direction, and did not cross go and collect $100 by perforating the uterus. Their primary endpoint was rate of no intrauterine adhesion recurrence at a second look hysteroscopy. Importantly, the second look was done at two months, which is a little bit longer than I think most fertility patients would wait for a second look and what other studies have done in the US, but a perfectly reasonable time for if there are adhesions to be seen, they'll be there by the two-month mark.
So their primary outcome, there was the rate of no intrauterine adhesion recurrence in the group that received the collagen. That rate was 78%. In the group that received the IUD, that rate was 58%.
That was a statistically significant difference. What they noticed was that the AFC score and the AFC decrease at that second look hysteroscopy was not significantly different between two groups. So it didn't really modulate the severity of the recurrence, but it did reduce the rate of recurrence, which was really important.
There are some important subgroups, and as you imagined, the more advanced the adhesions, the more dramatic the benefit of the collagen scaffolding, but the collagen scaffold appeared to be safe. There were no significant adverse events. The scaffold degraded in all subjects confirmed.
There was no visit where patients had to have at the time of second look hysteroscopy pieces of the collagen plucked out or any retention of the collagen. I'm personally really excited about this. I think anything where you move the needle for patients with a new method to prevent intrauterine adhesions is really exciting.
Right now in the U.S., there is one FDA-approved product, Womed, that is just starting to get distributed. You can't get your hands on it just yet, but I believe over the summer you will. There's another product, which full disclosure, I participated as a clinical investigator called Juvena, which is a hydrogel that is actively going through FDA approval.
This one is not available in the United States, but it would not be inconceivable for there to be a potentially third differentiated product for adhesion prevention in these patients coming to the U.S. This trial was funded by the company that manufactures this collagen scaffold. Two of the co-authors are company employees, but that does not mean this is a poorly designed study with bias. This seems to be a really well-elegant design trial that answers a specific question.
I think all of us who treat adhesions are really excited about potentially another option for these patients. Eve, Kate, when you guys tackle adhesiolysis or have patients refer to your local surgeons for adhesiolysis, what are people using in your neck of the woods for adhesion prevention? What's the strategy? I think it depends on the severity of the adhesions that I see. Certainly, we're using a lot of balloons still.
One of our faculty members is enthusiastic about amniotic graft placement, which is not bovine. I think hydrogel has some interesting future potential, although I feel like I was a participant in a hydrogel trial, or I saw those years and years ago at the time of laparoscopy for adhesion prevention. It didn't work so well back in the day, but I think that there's a lot of promise.
I do still worry, I will say, I do still worry that once you have significant adhesions that nothing that we do is going to regenerate the basalis layer of the endometrium. I think that these are all marginally moving the needle a little bit, but what we really need is a way to replenish stem cells in the basalis layer. I think that's where we're going to really see the best improvements.
The Carlos Simon Foundation has a treatment that is on the market in Europe and is being brought to the U.S. for clinical trial where they are infused, they are harvesting through plasmapheresis circulating bone marrow derived stem cells. They are amplifying them and then they're using an interventional radiologist to reintroduce them back to the uterine artery after adhesiolysis to try to repopulate that basalis layer. Their data seems really, really promising for regenerating damaged lining.
Obviously, lots of steps and expense to be able to do that compared to a gel or a collagen stent that goes into the uterus, but I think gets to your point, Eve. You can keep the cavity patent and restore volume, but are you actually doing anything under the surface that's meaningful for these patients? Yeah, I also think we need to pay careful attention to obstetric outcome in these patients who have had multiple adhesiolysis. I recently had a very catastrophic case and so I'm a little bit scarred from it, no pun intended.
Oh, intended, that was a good one. But she had just a really catastrophic outcome and is now using a gestational carrier, but it's just because you can open the cavity and you can get an embryo to stick. Those are not the outcomes that we need to be looking at.
We need to look at healthy, intact live birth rates. And then fortunately, the data to be able to counsel them about what the risk is quantifiably are so lacking as well. So lots of good things coming down the pike, as you say, in terms of reducing the adhesions.
And I can't wait as well for Carla Simone's data to be published from Europe and to potentially be a tool for our patients. All right, pivoting back from the uterus towards the male, let's talk a little bit about another great andrology paper in this month's research letter section, which as a reminder for our listeners, if you have a science that is worthy of publishing, but has a narrow singular focus that you think could be summarized in a much shorter manuscript type, the research letter is your article of choice. Kate, tell us about the submission on completion rates for male in sperm cryo.
Yeah, so this is a great paper. I think all of our readership should take a look. Again, very accessible in this research letter format.
First author here is Miriam Safrai, and there is a transnational, international group of authors that contributed. We're always all looking for ways to make it easier for our patients to access treatment, to get a complete workup given all of the logistical challenges that they face. Here, these authors are looking at the feasibility and specifically the completion rates of sending in sperm to be cryopreserved among men who have a variety of indications to do so.
It could be anything from facing chemotherapy for obviously malignant causes or for patients who just maybe they're getting a vasectomy, but they want to keep their options that door just that tick of the way open and not have to later do a controlled jailbreak or a vasectomy revision or reversal in order to be able to have kids if they change their mind. The authors report an incredibly successful rate of men going on to actually submit more than 85% across all age groups submitted a frozen sample. Now, it's really important to note here that in contrast to what's been previously reported, which is around 30%, these are men that specifically self-directedly ordered the kit.
They planned to submit the sample otherwise they wouldn't have self-initiated this process. That part of it, I think, is not at all surprising, but still good to see that there's follow-through there. The authors did go on to look at factors that might have influenced whether they did proceed after ordering the kit with submitting the samples.
What they found to be associated with completion was age. The sweet spot in the middle of the age groups were most likely, whereas men, obviously, who were more likely to have completed their desired family size were less likely to actually complete. They also found that those that lived in suburban areas were the most likely to submit the samples and urban potentially a little bit more likely than rural.
Those things are interesting, but again, they all had a very high rate. That's the take-home message here. I think more importantly, and this is something that we have been talking about a lot at our center, and there's a nice reflections on this as well by Ken and Omertag and his group, is that, okay, but what about the counseling? Then even beyond that, what about the utilization potential for this sperm collected in this way from a regulatory perspective? Who is telling these patients that if they were ever, for example, to want to use a gestational carrier, FDA testing should have been done, and it's unclear given that it wasn't done at any particular brick and mortar whether it can be used post hoc.
Without associated infectious disease blood work and status for these men, is there really a means to use the sperm? At our center, there probably would not be at this point. We would hate to have these men believe that they have preserved their fertility only to then come back and not be able to use the sperm. In a way, as much as it's great that they're freezing it, it may be even worse than not having done it at all for some of them.
Again, Ken and colleagues touch on a lot of these issues as well that, okay, what about the mail-in period? What about the 52 hours? What about what happens to motility during that time period prior to freezing? How is that going to necessarily impact their outcomes as opposed to going and collecting on-site versus bringing it in right away? We don't have outcome data here, just completion rate. Then also, gosh, how devastating would it be to freeze your sperm pre-orchiectomy, come back with your partner excited to start your family and be told that you have to use donor sperm. Really important addition to options for our patients just absolutely has to be accompanied by counseling and also probably ought to be accompanied by infectious disease blood work.
I couldn't agree more. That was my huge issue with the study. My other question is, at what point do these men pay for the semen analysis? If they pay for it when they order the kit, then I'm not surprised about the high completion rate.
I think that that's just showing a minuscule fraction of what's out there. Again, it's limited by the circumstances and the company who is producing the data. They're only seeing those patients that order the kit and then calculating their follow-through rate.
But how many patients are recommended? What's the true numerator on how many patients are recommended to bank sperm that just never get online, never order the kit? Those who order it have high follow-through rates. That's great. But I think that it needs to be more comprehensive.
If I can put a suggestion in there is that perhaps these men can go to a lab like a lab core and have a tube of blood that's drawn that gets mailed in concurrently so that they can have infectious disease testing done at the same time. I think that you can make it a little bit more comprehensive without making it so much more burdensome. I think that the company that is offering this fellow, I think that that will be soon to come.
I think that what they're providing in terms of ease of getting a semen analysis is a completely different question and really a game changer. But this piece, I would just hesitate for folks to say, oh, you have cancer? Just mail away for a sperm kit. I think that it's a little bit higher stakes than that.
All right. Eve, let's go to your last article before I round us out with a ex vivo hysterectomy study, which you don't always hear about infertility and sterility. Tell us a little bit about anxiety and depression in women with endometriosis.
Yeah, this is a French study titled Anxiety and Depression in Women with Endometriosis, a comparative study across fertility contexts. So anxiety and depression are among the most commonly reported psychological conditions in patients who have endo. And the study aimed to compare psychological outcomes between women with and presumably without endometriosis undergoing IVF or ICSI compared to those undergoing planned oocyte cryopreservation cycles for fertility preservation.
Secondary goal was to identify factors associated with anxiety and or depression in the ART context. This was a single center observational cohort study over an 18 month period of time that started in November of 2023. Patients completed a 55 item questionnaire.
They only completed it once on the day of egg retrieval. And that questionnaire included the validated hospital anxiety and depression scale. Endometriosis was diagnosed via transvaginal ultrasound and or MRI, so it was not surgically diagnosed.
Multivariable logistic regression was used to identify independent predictors of psychological distress in addition to endo. 324 women were included. There were 196 IVF and ICSI patients, 73 with endometriosis, and 123 without.
And then there were 128 patients without infertility, presumably without infertility, undergoing planned oocyte cycles, 38 with endometriosis, and 90 controls. In the IVF and ICSI group, depression was significantly more prevalent in women with endometriosis versus controls, and it was 5.5% versus 0.8%. So still, like, actually a much lower percentage than I would have envisioned. Anxiety rates were numerically higher in the endometriosis group, but this did not reach statistical significance.
And then in the planned OC group, there were no significant differences in anxiety or depression that was found by endometriosis status. So women with endo in the planned OC group more frequently reported prior psychological support or current psychotropic medication use, so 13% of them were on meds. On multivariate analysis, severe deep dyspareunia was the only independent predictor of anxiety and or depression.
So I think from this study, and again, I think it's not without limitations, but I do think that it really does nicely show that depression is significantly more prevalent among IVF-ICSI patients who have endometriosis compared to controls, and that's worse in patients who have severe deep dyspareunia. No significant psychological differences were found between endo and non-endo in the fertility preservation population. And again, back to that point on severe dyspareunia, that appears to be a key driver of psychological distress, perhaps more so than endometriosis diagnosis itself.
And I think that routine, the authors conclude that routine psychologic screening in ART programs is strongly recommended, especially for women with severe pain, and I don't disagree with that. I think the question is really just how and what resources do we have to adequately act on that. So overall, I think it was a nice study.
I think there are some limitations. I think the high proportion of deep infiltrating endometriosis is somewhat unique to this population at a tertiary center who gets a lot of referrals for endo. I think it's probably not reflective of the broader ART population.
I also think the control group may include and probably does include undetected cases of asymptomatic superficial endometriosis. They're just using MRI and ultrasound. And as we know, a lot of women have superficial endometriosis and you can't diagnose that on MRI or ultrasound.
And so that could dilute difference between groups. Their response rate was, I thought, pretty high, 41%. But it was only at a single point in time, and it was on the day of egg retrieval with peak estradiol levels being very high and discomfort, particularly in those patients with endo, discomfort probably at peak levels.
And so I think that longitudinal follow-up is needed. And then, you know, the association between endo and depression was established, but I don't think that this study shows causality. I think it's just an association, and we have to take it for what it is.
So Pietro, Kate, what do you think? I had a lot of questions about the timing of when they administered the study. I guess from a methodology perspective, it's where you have the outcome potentially most prevalent, most commonly found, and you're likely to capture some interesting data. But might it have been more similar than different at baseline, or after the initial consultation, or the period preceding med start? So that, to me, would have been interesting.
I don't think any of this is surprising. I think anyone who takes care of patients with endo, either as part of their practice or as a majority of their practice, knows that this is a patient group that, unfortunately, is taking 8 to 10 years to get to diagnosis, has been worked up by other subspecialists and told everything's fine, everything's fine, your colonoscopy's fine, you don't have H. pylori, there are no cysts on your ovaries, it's not endo. I can totally envision a world where these patients absolutely experience more depression and more anxiety.
The tougher question for me, who fortunately does take care of a lot of these patients, is, well, what do we do about it? And what's the right time to do things about it? And the more I've been in practice caring for these patients, the more I think that there's value for multi-modal care for these patients. I can do surgery until the cows come home, and I'm going to make them feel better for a short period of time. But if I'm not pairing it with pelvic floor physical therapy, if I'm not pairing it with acupuncture, if I'm not pairing it with CBT to help treat the years and years of being told it's all in your head, I'm not really moving the needle a heck of a lot.
Yeah, great wake-up call. This study, even though I agree in terms of big surprises or firm conclusions from an analytic perspective, I don't think that's really something that we take away from this. I think we live in a world of increasingly fragmented care.
There are so many fewer centers now that have an in-house or even closely associated, really expert psychological care provider. And so it's just, again, the onus on the reproductive endocrinologist to remember to offer that and recommend it early and often, and not just in our endo patients, but anyone who is going through the process of fertility treatment is greatly at risk, as we well know. And yes, I agree.
I probably wouldn't have asked them at the time of their egg retrieval, but we do need to keep this front of mind. And this article is a nice reminder of that. Yeah, I also think they're happier in France than they are in the U.S. Depression rates were markedly lower than what I think ours are.
I did enjoy table one when you looked at their professions, 6.8% were craftsmen or shopkeepers as their stated profession. Yeah, different, but I agree. I think we need to pay more attention to mental health.
And as someone who practices it with an embedded mental health program, we still feel like it's not enough. There are real limitations to what therapy alone will do. And so I think you need much more comprehensive care as Pietro talked about.
All right, let's bring it home with something that you probably weren't expecting to hear about. I have a really nice little research letter that I'm glad Kate assigned this month. And just for the listener who's wondering, how do we pick these articles to assign? We take turns.
Everyone on the podcast will take a month, will read through the table of contents and tries to pick the articles that they think speak to our individual strengths as presenters, but also clinical interest for us and clinical interest to the field. I somehow always get stuck with the really good surgical papers, which I really dig. So thank you, Kate, for assigning this one.
This was a paper entitled Comprehensive Evaluation of Residual Myometrial Thickness of the Caesarean Scar in Uterine Samples After Hysterectomy by first author Kobra Taramanish from the Rasul Akram Hospital in Tehran. You've probably wondered to yourself, well, this patient's had a C-section scar. I send them for an ultrasound.
They have a residual myometrial thickness of seven. She's probably fine. What if the true thickness was closer to three or four millimeters and you didn't really account for one of the quote unquote elephants in the scar, the adenomyotic cyst that is sitting right in the middle of the myometrium? Well, this study looked at when you took uteruses out of the body and actually measured the myometrial thickness with histopathology information about the presence or absence of these adenomyotic cysts.
What are we looking at transvaginally with an ultrasound and what is reality? So one of the important concepts for this paper is that the minute you violate a tissue plane to, for example, perform a C-section, when you were repairing that tissue plane, inevitably you will blur the lines and things that should have been in the subendometrial space will end up within the myometrium. And this is how you end up with adenomyosis after Caesarean sections within the Caesarean scar. And when it's sitting within the Caesarean scar, you can imagine how a big old cyst or even a smaller medium cyst might affect the measurement of that residual thickness.
So this was 83 women who were undergoing a hysterectomy, all for abnormal uterine bleeding, who had at least one prior low transverse C-section. They had had a preoperative transvaginal ultrasound with measurement. They had a hysterectomy and within 30 minutes, they had a macroscopic evaluation and a histopathologic examination to help understand what do we see on ultrasound, what do we see histopathologically, and what did we see microscopically.
So interestingly, they did find that we were missing a lot of these cysts within our gross measurements. So about 20.5% of specimens had a macroscopically observed adenomyotic cyst within them. And that number increased to 36.1% when you looked at histopathology.
That meant that we were consistently overestimating residual myometrial thickness by just using ultrasound alone. That's crazy. That's a lot.
But you're probably wondering, how much and did that difference actually matter? Well, on average, it looked like about two and a half millimeter difference between what we saw in ultrasound versus what we saw macroscopically. Now, for patients who had a seven millimeter myometrial thickness going down to five, probably not very clinically meaningful. But what if they were 3.4 and they went down to 1.5? Is that a patient who your antennas are now sticking up and thinking, maybe I should think about a cesarean scar revision or repair? Maybe that patient shouldn't have that third cesarean section attempt.
These are questions that the surgeons within the REI community grapple with a lot. There's such a paucity of data on cesarean scar niche revision surgery. But I think this number gives me a little bit of pause of how good is our ultrasound, how good is our MRI when we're not accounting for these cysts that are sitting within the field of measurement.
So I really like this article. I know probably not super applicable to everyone who's listening. But the next time you have a residual myometrial thickness question in front of you, eyeball the scan yourself.
See if you can see these little pockets of adenomyosis within that measurement that may either further worry you or further reassure you that this residual thickness is okay. I really like this paper as well. I mean, it's just rare that we get to see this kind of correlation data and think about it clinically all the way through from what is the endometrium sparing c-section closure outcome and how should OBs be addressing this? How should we as reproductive endocrinologists be interpreting the diagnostic studies we get? How and who should we treat? So knowing that some of these patients have less residual myometrial thickness than we think is, I think, fascinating and maybe surprising for some of us that said, what do we do about it when we have the patient in front of us who's thinking about their next frozen embryo transfer after c-section number two? And we're like, huh, that one looks a little thin.
Because again, most patients out there are not having these evaluations prior to trying to get pregnant again. And most of them do reasonably well. Obviously, uterine rupture is quite uncommon as are most of the other potential complications that could result.
And so do you let them try or not, I think, is a question that we all grapple with every day. But again, I love this paper too. And of course, that's why I signed it.
Where a lot of us, I think, interface with caesarean scar niches is in the diagnosis portion, or at least raising the concern of like, oh, this looks a little thin. And a plug for anyone who's scanning that patient and is wondering, 2D ultrasound is good, but not great. If you're really trying to fully understand this niche, perform a saline sonogram.
You'll get much more rich information about the size, location, depth, and breadth of the caesarean scar niche. You'll be able to use AIUM criteria to be able to formally make a diagnosis of what is a niche versus what is just a history of caesarean scar in the lower uterine segment. And then I think will be much more useful for the surgeon who ends up seeing them and is able to counsel them more effectively on, is surgery indicated? Is surgery useful? And what might surgery make better or worse? Right.
But I would imagine Pietro, that it's uncommon that you would be, you know, recommending surgery still a priori in these patients. Yeah. I would say for every 10 consults I get, I think one to two of them truly would benefit from surgery.
Everyone else is me talking them out of surgery, which is unusual when you're a hammer, everything is a nail. But if the surgeon is telling you, I don't, I wouldn't do this if I were you, we would run for the hills. We've covered a really wide range of articles from andrology to uterine hysterectomy specimens to even mental health.
I think this continues to show that FNS is a home for every kind of article type. We're seeing so much more AI in our field. We're seeing really wonderful embryology papers.
If you're thinking about submitting something somewhere, know that there's the FNS main journal, the FNS family of journals, reports, reviews, and science. And then finally, consider this section, which lives on the internet in front of the paywall and is a really rich space for people to have less structured conversations than what a peer-reviewed article will have, but still topics that are worthy of discussion in a public forum. That's all the time we have for today.
Eve, Kate, thanks for a nice morning. And hopefully see you next time. We will be podcasting from the PCRS annual meeting next week, live from the Rancho Mirage in Palm Springs.
And we will be excited to share that audio with all of our listeners after that fellows debate as a special podcast episode. Thanks Pietro, see you in Rancho Mirage. Bye everyone.
This concludes our episode of Fertility and Sterility on Air, brought to you by Fertility and Sterility in conjunction with the American Society for Reproductive Medicine. This podcast is produced by Dr. Molly Kornfield, Dr. Adriana Wong, Dr. Elena HogenEsch, Dr. Selina Park, Dr. Carissa Pekny, and Dr. Nicholas Raja.
