Fertility and Sterility On Air - Unplugged: April 2026

In this month's Fertility & Sterility: Unplugged, we take a look at articles from F&S's sister journals! Topics this month include: effect of pyschological stress and emotional regulation on outcomes in infertility (03:50), impact of embryo transfer catheter bacterial contamination on fresh and frozen embryo transfers (13:19), correlation between levels of PFAS in folliclular fluid with live birth rates in IVF (24:36), and transportation timelines and delays for preimplantation genetic testing biopsy specimens (37:38).

F&S Reviews: https://www.fertstertreviews.org/article/S2666-5719(26)00004-6/fulltext 
F&S Reports: https://www.fertstertreports.org/article/S2666-3341(26)00050-4/fulltext 
F&S Science: https://www.fertstertscience.org/article/S2666-335X(26)00018-2/fulltext
Consider this: https://www.fertstert.org/news-do/rethinking-transport-timelines-trophectoderm-biopsy-specimens-cross-border

View the sister journals at:

• https://www.fertstertreviews.org
• https://www.fertstertreports.org
• https://www.fertstertscience.org

Welcome to Fertility and Sterility Unplugged, 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. Fertility and Sterility Unplugged 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. Molly Kornfield, Dr. Blake Evans, Dr. Daylon James, and Dr. Pietro Bortoletto.

Hello, and welcome to another episode of FNS Unplugged. By this time, you're tired of hearing me say it, but I'll say it again. I'm Pietro Bortoletto, your co-host, joined by the ever young, ever wonderful Molly Kornfield, Daylon, who seems to be aging, but slowly, and Blake, who I think is getting taller.

I didn't know a man could do that at his age. What's the other word for puberty at your age, Blake? Is there a word for it? I think it's gigantism. Yeah, a pituitary problem.

No, I'm not like Andre the Giant. I was recently started on Crestor, though, because I have coronary artery disease, it turns out. Oh, boy.

Wow. Well, my philosophy is if you don't go to the PCP, you can't find out what's wrong with you, so I'm as clean as a whistle. I have no medical problems.

Yeah, hair keeps falling out, but that's show business, baby. You're getting ahead of it, though, Pietro. It's high testosterone, we all know.

Baldness is high testosterone, as I'm married to a bald man. Swimming in it. Lots of DHT.

Anyway, enough about my Andre the Giant alopecia. Hi, listeners. Thanks for joining us for yet another playful podcast.

You should know that before we logged on, we were kind of debating how PCRS went. This is being recorded on the heels of the March PCRS event. I personally loved it.

We recorded a live fellows-led debate on the utility of using gestational surrogacy. Without a medical indication. And let me tell you, there was a lot of regional variability along the coasts.

As you can imagine, they were very wishy-washy of like, yeah, sure, we do it. In the academic programs, a lot less of it. But it was really eye-opening for me to see how much variability there was.

We reviewed practice committee documents and ethics documents that go over this topic. And that audio will be available for anyone who's interested in this topic. You should know that the fellows just prepare better.

So these debates were just so much richer than anything us adults could come up with. So I highly encourage everyone to listen to it. It was good seeing Molly in the flesh.

Daylon, I think, just doesn't go to meetings. And Blake, I think you're just too tall to travel now. Commercials.

Too tall to travel. TTTT, as they call it. Too tall to travel.

Get him on a PJ. What's that? Private jet? If you don't know, you can't afford it. Never mind.

We use Buffalo exclusively in Oklahoma. We don't use PJs. Primary mode of transportation? Yep.

Buffalo. You said it, not me, but I'm glad you said it. Listener, you should also know that before we logged on, we kind of drew straws on who's going to go first, who's going to go last.

Blake has a 52-pager to present today. He said that he could present it in 52 seconds. So let's just see what he can do.

Blake, tell us about your article from FNS Reviews. And again, no pressure. Thank you for that kind intro.

Don't time me. It may not be 52 seconds, but I personally feel that I summarized this in a very succinct manner. And you guys, I know, are very excited to go and just dive into this entire document on your own accord.

But I'm going to kick us off here and talk about an entitled paper, Maladaptive Emotion Regulation in Psychological Outcomes in Infertility, a Systematic Review and Meta-Analysis by first author Ticino Camilla from Rome, Italy. So big picture. And this, there is no question, this is extremely common amongst all of our patients.

But infertility is not just a medical condition. As it is no surprise to us, it is also a major emotional stressor. And so this paper looks at how people cope emotionally and, more importantly, which coping strategies may actually make mental health worse in all of our patients.

So, spoiler alert, and the core takeaway is that certain emotion regulation styles don't just reflect distress, but they may, in fact, amplify anxiety, depression, and psychological distress in our patients. So what this study did, it looked at multiple studies. It was a systematic review and meta-analysis.

And they primarily focused on what's called Maladaptive Emotion Regulation strategies. And so they discussed how these are linked to anxiety, depression, psychological distress. So think of it as which coping habits are maybe even hurting patients instead of helping them.

So the core maladaptive strategies they look at, so one is called rumination. So this is the patient, for example, constantly replaying thoughts like, why is this happening to me? What's wrong with me? And these are strongly linked to depression and anxiety. Another is called catastrophizing.

And this is essentially expecting the worst possible outcome. Things like, this will never work for me. I'll never have a child.

Another is called suppression, in which the patient will push emotions down instead of processing them. And this often leads to what the authors have found, increased internal distress over time. And then lastly, they looked at avoidance.

So avoiding triggers such as pregnancy announcements, conversations with a family member of, I got pregnant without even trying. And he just looks at me and I get pregnant, those type of trigger words. And this has been led to provide short-term relief, but worsens long-term coping.

Did you say that in a anchorman voice? It's important to avoid triggers, provide short... No, I'm sorry. I'm not going to do that. Apartment smells of rich mahogany.

We are all millennials here. Many leather-bound books. About five years of our life was just anchorman quotes, all conversations among we're loving.

Oh yeah, that's it. The trigger works 100% of the time, 50% of the time. That doesn't even make sense.

I know. I quoted that the other day to one of my nurses, had no idea what it was. So is she working? Tired immediately.

Yeah, I was going to say, she's no longer working with us. Yeah, how does she like working at the Piggly Wiggly? She doesn't, I'll tell you that. So back to the study.

So the main findings, they, across all the studies that they looked at, they found that these maladaptive coping strategies, as you probably could assume, led to significantly worse mental health outcomes, such as depression, anxiety, psychological distress. And so the authors discussed that with these correlations, this has been consistent across studies and suggests that these patterns are clinically meaningful, but also actionable. And why this matters clinically.

So the patients are, obviously they're distressed with undergoing all these emotions, but how they can regulate these emotions. And so instead of generic support for these patients, we can identify coping patterns early, which is what the authors are encouraging, teaching adaptive strategies. And so hopefully help the patients to adapt to these thoughts more easily.

And so the paper emphasizes, lastly, the need to promote cognitive reappraisal or reframing your thoughts, emotional awareness, not suppression, or acceptance-based coping. And this aligns with therapies such as CBT, cognitive behavioral therapy, or another treatment that they mentioned called ACT, acceptance and commitment therapy. So I'll say in summary with this, the study reinforces something that we see very commonly.

Infertility, as we know, is very emotionally intense, very taxing on our patients. But the way the patients cope with those thoughts and intensity can either protect them or maybe even make things harder for themselves. And so the authors encourage that this is something that these are actionable things that we can do.

Maybe refer them to counselors, psychiatrists, reproductive counselors or something. Do you guys have those available at your clinic or work with any reproductive counselors? And what are your thoughts on utilizing their services? We have an in-house psychologist. We don't have a reproductive counselor, but that sounds fantastic too.

And she's, but it's great because she just sits here with all of us and she can connect with patients who are really struggling in kind of acute situations. And then she can also coach a lot of my staff for patients who are really struggling about how to deliver bad news, how to deal with a patient who's dissatisfied with care for whatever reason. And so having her has, she's kind of a resource for all of us as much as she is for our patients.

She's in-house, you said? Yeah, she's physically here with us, which is really amazing. Yeah, that's great. Yeah, and these things, as you're going through fellowship training and just, it seems so simplistic, but how to even deliver bad news, you call a patient with a negative pregnancy test and how to appropriately talk to them.

These are things that are extremely important. And I think that's really helpful that you have someone in-house. We don't have someone in our physical building, but we have several that we work with, many of which are even our third-party counselors who talk to patients about donor egg or gestational carrier, for example, and they also will do reproductive counseling for patients that are struggling.

So I think leaning on these services is extremely important for our patients. I'm curious. I mean, the idea that you got to know how to deliver the news is obvious, and I get it about the maladaptive coping strategies.

But I wonder if there's any responsibility on the care provider to, not a responsibility, like it behooves you, but I wonder if one of the ideas with this article is, how do you redirect someone's coping? Because I feel like it's, put another hat on, guys. Like now you got to actually be in the room delivering the news, and then in real time, try and navigate someone's maladaptive coping strategies to get them on the right track? Or are you supposed to be like, you know what? You don't seem to be taking this well. Let's have you talk to psych.

Is there any direction there? I wouldn't say this goes over direction, so to speak. But that is something that happens all the time. Patients process things a little bit differently.

And so beyond what we tell them in the moment, a lot of times they just need to process things. But I think also just kind of tacking that onto this information that, if you have any questions, you need anything, or like, here's some resources we'd be happy to help you with. Anything you'd like to talk about this even further.

We understand you've been through a lot of issues, and receiving this news is difficult to hear. So I think just having that tool in your back pocket is helpful. Do you guys utilize any counselors, Pietro, in your practice? Or any that you work with? We don't have anyone in-house like you guys, and I'm jealous.

I know Daylon Cornell has for a long time had in-house mental health professionals that are experts and national leaders. And Molly, you guys having it is killer. But we partner with local people who have expertise in this area that are either trained in specific fertility, specific domains, or just have lots of experience doing it.

I think it's so important. We all talk about the number one reason why people drop out of care is not financial in my state because of insurance mandates. It's not lack of success because the clinic quality is high.

It really is just the emotional toll that being a patient takes on people, the physicality of it all. I think it's an absolutely essential part of modern fertility care to pair it with mental health. Yeah.

All right, Blake, you did right around 52 seconds. That was great. Excellent.

Thank you. Bow. Listener, he is bowing.

He stood up. He's off the screen. We can see his knees on the screen.

He is bowed, and now he's back in frame because he sat down. When he stood up, his head busted through the ceiling of University of Oklahoma's REI division, and now they have to call someone in to repair it. Yeah.

And normal ceilings. It's incredible. It's a constant struggle.

It's fine. The ceiling's too tall for me, though. Put that on a shirt.

Technically speaking. All right, guys, let's move away from FNS Reviews, everyone's favorite sister journal, and let's talk about the redhead stepchild of the FNS Family Journals. I'm talking FNS Reports, my old journal.

Molly, tell us a little bit more what's coming out from Reports this month. What? Reports is the best one. Everyone knows it.

Okay, so from Reports, what did I find this month? The paper I chose is called Catheter Contamination During Embryo Transfer, Impact on Outcomes of In Vitro Fertilization. First author, Asma Bughanmi, and last author, Olga Bari, and they're all actually out of a university in Tunisia. And so I think we're all really aware of the importance of the embryo transfer.

We've reviewed prior studies on this podcast, focusing on both embryo transfer technique, various protocols, and I think our fellows should all be aware that ASRM actually has a guideline that they've published regarding the literature on performing embryo transfer and what is appropriate technique to optimize success. Several studies suggest that cervicovaginal microbial contamination of the transfer catheter, kind of as presumed to be when you're passing the catheter into the uterus, is associated with reduced transfer success. And we all know that we don't use PrEP like Betadine or Hibiclens on the cervix in an embryo transfer like we would for a surgery because it can be toxic to the embryos.

So the authors report that these studies of contamination of embryo transfer catheters are understudied and that prior research used culture techniques that may actually underestimate what pathogens are being identified. And so they proposed a study that would also test for pathogens like urogenital mycoplasmas or Gardnerella vaginalis, which they thought would be more relevant for these cases. So the authors designed a prospective longitudinal study.

They include patients who are under or equal to 42 undergoing embryo transfer of at least one good quality embryo. They did not mention PGTA, so I'm presuming that they don't perform PGTA in their center. And when I looked at their demographics table, it didn't look like that came up.

And they only include people with sonographically normal uteri. And they excluded patients with severe sperm abnormalities, potentially because of the impact on transfer success. And they also excluded embryo transfers that were described as difficult and required converting to a rigid transfer catheter.

And for their study, they took three samples for each patient. So they did vaginal swabs from the fortices in the lower vagina, a cervical mucus swab with the Aspaglare device, and then the embryo transfer catheter itself. They took the two most distal centimeters and they cut it off with a sterile scalpel and sent that for culture.

They considered a positive culture to be anything other than lactobacilli growing out. And their primary outcomes were the biochemical pregnancy rate and the live birth rate. And they actually studied their power for 20% difference in pregnancy rates between contamination and no contamination.

So pretty clinically significant 20% difference. They included 210 patients. Overall, their pregnancy rate biochemical was 29% and their live birth rate was 17.5%. I think we would all say, oh, those sound a little bit low.

And I think looking deeper into this paper, they did a lot of day three transfers in their center. So over 70% in each group were cleavage stage. And so that's probably the reason we're seeing these lower low birth rates and average age is about 34 in the population.

So the authors reported that there was a positive vaginal culture in 79% of patients, which seems low. I would have thought that would be 100%. A cervical mucus culture was positive in 54% of patients.

And the embryo transfer catheter was contaminated in 34% of patients. The most common bacteria for the embryo transfer catheter was Streptococcus agalactiae and then Actinomyces odontoliticus and Gardnerella vaginalis. And I think we're expecting to see Gardnerella vaginalis.

The other ones I was a little less expecting. And in all the contaminated cases, they did also see those pathogens in the vaginal and cervical mucus samples. And also of note, they had a three times higher risk of catheter contamination in the fresh transfers than the frozen embryo transfers.

And then the authors did perform molecular analysis and they identified that about a third of the people who had contaminated catheters also carried Gardnerella vaginalis. So kind of proposing that could be a risk factor. And then the urogenital mycoplasmas were in just under 14%.

And then they also used the Nugent scoring system for BV. I didn't remember that. Maybe that's from back in my brain in residency, but we always used AMSALS criteria for bacterial vaginosis.

But using the Nugent scoring system, they used that to diagnose BV for some patients. And they found that those who had BV on the vaginal swab by that criteria were six times more likely to have catheter contamination. So that was a real risk factor for finding bacteria on the transfer catheter.

And then the primary outcomes. So they found that as they hypothesized, the pregnancy and live birth rates were significantly reduced with contamination of the transfer catheter. 8% biochem with contamination versus almost 40% without.

And then 4% live birth with contamination versus almost 24.4% without. So pretty substantial. And then lactobacilli at the catheter tip was actually associated with a higher pregnancy and live birth rate.

They also were really interested in if people have urella, vaginalis, or urogenital mycoplasma, did they have worse outcomes? They did note lower pregnancy and birth rates, but it was not statistically significant. They didn't note if they were powered for that outcome or not, but that's also a really interesting clinical question. So I thought this was a nice little study that answered some interesting questions and proposed a lot of ideas for new ones.

I think we've seen and talked a lot about endometritis. Oh, Pietro is raising his hand. Nope, he's not raising his hand.

He's stretching maybe saying hi. I'm not sure. You're just too attentive.

Oh, okay. And I think there's a lot of studies, especially older ones, around using antibiotics before or after transfer. It's obvious to me you don't want a contaminated embryo transfer catheter.

If my catheter accidentally taps the vaginal sidewall or taps something that isn't sterile, I switch it out before proceeding with the transfer. And it seems obvious to me that there is some inherent transmission of some bacteria across the cervix into the uterus, despite your best efforts. But I think, you know, we know from prior studies that clearing cervical mucus off, the external off, before your transfer improves outcomes, I always assumed it was just because you don't want cervical mucus in the cavity.

But now I'm wondering if some of that is because the cervical mucus carries more contamination. Maybe that's obvious to you guys, but just putting that piece together. I think this study kind of reinforces prior studies in a new way, reinforces an idea that makes sense to all of us because we know in the lab, it also includes some data on what kind of bacteria are present.

And so you could potentially redo a study maybe on the antibiotics at time of transfer. Hey, what if we use a different antibiotic targeted to these bugs? Now, of course, this is the Tunisia bacteriogram. It won't apply necessarily to my patients in Portland, Oregon's bacteriogram.

But I think, you know, area for inspiration. I think another limitation of the study that the author has nicely addressed is that it may actually just represent patients who have chronic endometritis or had already had preexisting contamination of their uterine cavities for whatever reason, and that you're just inoculating the catheter. So when you pass the catheter, is it that you're actually bringing these vaginal and cervical bacteria up into the uterus, or are you just sampling the uterus with your otherwise sterile transfer catheter? And so I think that's kind of a limitation.

Is it these pregnancy rates are so much worse in people who you've contaminated or were they just already contaminated or already had some sort of endometritis? The other piece to think about is why was the contamination rate higher in fresh versus frozen transfers? Could this be from the egg retrieval? They have some local seeding of bacteria to the pelvis. I don't know if their clinic routinely gives antibiotic with egg retrieval or what their process is there. And another hypothesis their authors had was they use vaginal progesterone for their fresh transfer patients.

So that was contributing. I don't know if you guys have thoughts about that. That's something I had written down is why was there a difference? And as you've been talking, I can't think of an obvious reason as to why the fresh versus frozen.

Did the authors say anything about that? Why they speculate there's a difference? It's speculated, yeah. Same as me kind of local seeding from the retrieval or the vaginal progesterone. Or could it be in this really high estrogen state? Is the cervix more patent? The change in cervical mucus? I don't know.

There's just some other ideas. I think if you're administering vaginal progesterone in a fresh cycle, that would make sense. Definitely more opportunities for bacterial introduction vaginally.

But otherwise, I can't really figure out why that would happen. Yeah, yeah. The last kind of piece I could talk for a while, but the last piece that I thought was worth bringing to the group, the authors proposed that infertile patients should be screened and treated for BV prior to IVF.

They said there are some French guidelines that support that. I thought based on the results of this study, that it ends up with a lot of testing, a lot of treatment, a lot of costs there, probably overtreatment. But I think, of course, yeah, further research, rigorously designed studies could change my practice.

And then I think they highlight what I think are really practical, reasonable recommendations. So in their practice, they're recommending cleansing cervix with sterile saline, aspirating cervical mucus pre-transfer, and then, of course, avoiding touching the vaginal walls with the catheter. But what thoughts do you guys have? What's kind of popped up in your brains as I talked at you? I was really underwhelmed by the methods where they didn't really describe what was the transfer catheter.

Do they do afterload, direct transfer? There's like so much detail that I would have wanted to know. Like, is your transfer technique the same as mine? I think we all do probably do it more similar than different, but there's some people who I think do it with a syringe, having the inner sheath of a wall-less catheter totally retracted as it makes its way into the cervix and then advancing it once you're beyond the internal loss. Some people are diligent about if you're going to put a bend in the catheter, do you do it with a sterile gauze or do you do it with your two fingers? Are you using sterile gloves or not? There's so much more that I would want to know before I get all hot and bothered about the technique you can apply to an embryo transfer the better, but I don't know that I'm ready to start screening people and treating them with antibiotics based on the findings of this study.

I think we all, speaking for myself at least, struggle with kind of recurrent or persistent chronic endometritis. And so I think chasing the BV route is probably our next direction as a field, but we don't have really clear guidance on that yet, at least from my review of the literature. All right.

FNS Reports does it again, incrementally adding toward knowledge and discussion about how to best manage patients. FNS Science, you've got big shoes to fill, my friend. No pressure, Daylon, but why don't you hit us with what science is bringing to the table this month? And I remember my first time podcasting.

You're muted, buddy. Buddy, I knew that. Like I like to say, no shoes are too big.

Like Blake has no ceiling too tall. For me, it's no shoes. I'm not afraid to give it a shot.

Me and you, Blake, brothers in size. I got a bit of bad news here. And this is an environmental toxin story.

And the news is not good. It never is. The negative correlations are always clear.

We're talking here about, I don't know, it's trending. We're talking about, moved on from the BPA. We're all about the PFAS, the per and polyfluoroalkyl substances, which are, I mean, you all know this, but I'm going to give you a little chemistry lesson anyway.

It's chemicals that are characterized by this fluorinated carbon chains, right? You know that, Pietro. I see you nodding. You're down with the PFAS.

And they've been used for almost a century now. Oftentimes fire retardants, a major source. So watch your mattresses.

Water repellent, oil water repellent, protective coatings, all kinds of industrial consumer applications. And the real kicker here is that they're universally detected in human serum, more so in women than men, oftentimes because of a lot of personal care products and oftentimes a direct interface like in terms of pads or tampons with the reproductive system, right? Nevertheless, universally detected in males and females in the United States. And while the concentrations of some of these PFAS, like, here's a little bit of chemistry for you, perfluoro-octane-sulfonic acid or PFOS or perfluoro-octanic, oh man, I screwed that one up, octanoic acid.

I'm sleeping on the PFOS here. That's PFOA. And those have declined because of production phase-outs, but just like with BPA, like then there's BPS.

They replace the bad ones or the identified bad ones. They phase out with other PFOS. So like while those are trending down, I can't say the names again, the ones that are trending down I just mentioned, there's other ones, I'm going for it here, perfluoro-ano-anoic.

That wasn't even close. That was perfect. That was bad.

Yeah, you guys should have a look and give it a try for yourself. That was PFNA or perfluorohexane-sulfonic acid. That was pretty easy.

That's like modest, stable or other of these novel, newfangled PFOS that they are emerging as substitutes for the old. The oldest trick in the book. They get under the regulations and they put something else in there and it's just as bad.

It's like one ring different but still mucks everything up. Those are increasing, right? And like what would you say as a guess? I'm not going to ask you to guess, but you probably say something like oh, a thousand, two thousand, five thousand. There's 14,000 PFOS chemicals that the EPA has identified and there's a whole medley of others that they don't even know about yet.

Unknown unknowns. And here's the thing, in the United States, unlike in Europe, you have to prove something is bad before you can get it taken out of the ecosystem. You don't have to prove it's good and safe in order to integrate it.

You got to prove it's bad to get it out. So we're up against it and there's been a lot of study in the last decade that's well established and I think there's consensus there. So with experimental models looking at PFOS in particular, there have been links to disrupted oocyte development mechanistically perhaps linked to altered PPAR signaling or disrupted intracellular communication between oocytes and then nurse-made granulosa cells or oxidative stress which is just generally a bad one.

And they cross the blood follicle barrier, right, and they're detected in follicular fluid. And I mean this is a twist, but you know if you take your brain and melt it down, there's like enough microplastics, it's not PFOS, there's enough microplastics in there to make a credit card out of. So these things are in our body.

You guys might have seen the news how they looked at like a bunch of different testes and they were like every single testis had microplastics in it. And the associations between in particular here we're talking about PFOS and ART outcomes, specifically follicular fluid PFOS and ART outcomes is inconsistent. So just a little, not a ton of studies, but a few people have taken a whack at it to varying degrees of power.

Like illustrated here, we got one study out of China with 378 women versus another study in the United States with 36 women. Both of these studies show a negative correlation between follicular fluid PFOS and follicle counts, embryo quality, blastocyst conversion, pregnancy rates. But then you have another study of 124 women in China that show no real association between PFOS concentrations and follicular fluid and pregnancy or OSI quality outcomes.

So mixed reviews here. In this study, which came from Shruthi Mahalingaya who is at a Harvard T.H. Chan School of Public Health, her and her group, they set out to investigate 36 women. All right.

So a nice round number, but I think more granular in terms of the outcomes here. They looked at these 36 women who are undergoing IVF and they measured 24 PFOS that were retrieved from the follicular or measured in the follicular and they focused and evaluated further eight of those 24 PFOS that were found in more than 90 percent of the samples that were evaluated. And like I said, you know, not good news.

Of course, there was a negative correlation between the level of PFOS and live birth outcome adjusting for age and infertility type. So I think a real clear outcome measure there and correlated with a pretty comprehensive measurement of multiple PFOS. And I think when you go down deeper into the data and I invite the listeners to have a look at this because there is something there.

They looked with a different degree of specificity at like linking the pathways that were enriched with certain PFOS and then looking at the metabolome in the follicular fluid samples and they showed that there was specific metabolic pathways that were associated with either live birth or no live birth and there was some overlap there with some of the unique PFOS features that were enriched in those samples. So in terms of causality, it's difficult with these clinical kind of slash epidemiological studies, but I think they made a really good effort here to try and create that link and not just establish a correlation. I think it's very clear that there is a link between the environment and all these threats and our reproductive health or health in general.

But why I like this study is because they went granular. They identified specific PFOS amongst the thousands that are out there. So really just the tip of the iceberg.

But then they went deeper on this kind of wholesale metabolic level and identified perhaps a link to specific pathways related to lipid, carbohydrate, vitamin metabolism amongst other factors. So maybe some targets. I mean, no one's saying we're going to take some prophylaxis for PFOS, but I think with as little as we understand about the problem, a study like this is really key in getting our arms around the problem.

It seems really impossible, but necessary given the ubiquity of these compounds in our everyday life. What do you guys think? Daylon, you're a scientist, presumably. These samples, they were collected from 1999 to 2003.

Do you worry at all about the reliability of these samples 27 years later when being analyzed? Degradation of the sample? Is this the kind of target that has some degradation over time? That's a great question. Is it accurate? That's a great question. I mean, my first question when I see something like that is, wow, this data, they've been sitting on this for two decades.

Has it just been in review? I think that that's not the case. I think this was more like an evergreen repository of these follicular fluid samples that presumably were stored at minus 80 and now are being applied and will be applied towards unique questions as we move forward. But I'm not too worried about degradation.

Assuming that they were stored correctly, but more in this case, specific to this study, you know what they call PFOS, right? The forever chemical. So measuring levels of these things, I don't think you're worried too much about their degradation. Would that we could worry about their degradation because it would mean that they weren't piling up and bioaccumulating like that credit card worth of plastic in your bald skull there, Pietro.

I use glass containers at home and I drink out of a diluted water bottle, so... Well, then you're safe. I think I'm actually fine. Glass in your brain is what he's saying.

Yes. Yes. I'll take plastic.

More benign than glass, my friend. So where do we go with this information? Are we just all doomed or what are we doing? Yeah, this is why I started with the it's a bad news story. I like to report these because they're very current, but in terms of like, where do we go from here? I don't think there's much.

And again, I want to emphasize that this is the question that I think the reviewers would ask. Maybe that's why this data was sitting around for 20 years, but I doubt it. But for sure, I would guess that that back end of this story where they look at the links between the specific PFAS and the outcomes is, I think, trying to draw a line in terms of the mechanism.

And in that case, it's not just about like, I think there's many ways you can go about it. You can take the attack of Pietro here and be pure and beautiful, or you can live in the world and maybe have kind of early diagnostic measures. I mean, you guys see a lot of people that are infertile.

You must think everyone's walking around with problems, but a lot of people having babies on their own. I think there's a way that we can maybe have some early warning signs or diagnostic measures at early age even to look for the risk. And then, of course, there's the idea of prophylaxis at the back end.

But in terms of that, I'm not optimistic. I think that we don't really understand the way these things work. And my philosophy, I also adhere to the philosophy of avoiding your PCP at all costs and staying healthy forever.

But the other thing I adhere to is, let's not treat everything. Adding more drugs into the mix to save us from the environmental cues may be doing more harm than good. So the long, long answer there for you, Blake, not 52 seconds, I'm afraid, is that we do nothing about it.

We weep, my friend. Great. It's very reassuring.

Cool, cool, cool. Great, yeah. I think about the balance of this paper with Blake's paper.

You know, if you go to your patient and say, yep, you're covered in PFOS, it's already all in your follicular fluid, the impact on your mental health around around your fertility is really, really impactful, especially for a patient who kind of is prone to anxiety and wanting to control everything. Yes. A lot of patients are saying, hey, what about environmental impacts? And I just tell them all, I think you're swimming in everything.

So these are the ways we're going to reduce, but we're not going to delay your cycle for any sort of lifestyle overhaul. We're not going to, unless you're smoking, obviously, then we will. We're not going to drive ourselves crazy.

We're just going to do a few practical measures and move forward. I love that bookend because this is not something that you want to inject into your patient's mental health quandaries, for sure. Maybe keep this to yourself with the doom element of it.

And I was going to say, in terms of maladaptive strategies, I'm all about suppression and denial. So let's go. You're talking my language, buddy.

Speaking of suppressing and denying, I want to take us home with a couple of questions with what I think is actually a good piece of information for us in the field. But I want to start with a quick question. How many of you, listeners included, have watched the movie The Terminal with Tom Hanks? Yeah, we've got one hand raised, Daylon.

I remember when that came out. I don't think I saw it. Do yourself a favor.

Go watch it. Great movie. Lighthearted.

Steven Spielberg, I believe. Easy watching. Based on a true story.

But essentially, this guy gets stuck at an airport because while he is in flight, his country disintegrates into civil war and he has no visa and no passport that allows him to enter the United States. And he essentially lives in the terminal for years as an individual without a country or state or flag in this kind of really unique geopolitical quagmire. But based off a guy, a true story, I think, Algerian man at Charles de Gaulle Airport in Paris Google it.

It's a cool story. This is similar. This is not a person getting stuck.

These are biopsy cells. Imagine a clump of trophectoderm cells getting stuck at customs for way longer than you would imagine. This is a case report.

This is an article where a very young 22-year-old woman who had not been pregnant before but was going through IVF with PGT and PGTM because of a familial risk of Greek cephalopolysyndactyly syndrome, the autosomal dominant disorder, went through PGT and had her biopsies collected on November 19th and November 20th of 2025. Fixed in your standard BSA sodium citrate solution and shipped to a central genetic testing laboratory. This was going outside of the country.

But lo and behold, these cells get stuck at the border. Immigration, snafu, mix-up, the specimens didn't reach the testing lab until December 18th, 18 days after the biopsy, which is more than double the recommended window for transport time for these precious cells. The genetic testing lab proceeded anyway.

They did a SNP-based microarray PGT with linkage analysis around this gene for their PGTM and lo and behold, these results were unambiguous. All six embryos were successfully analyzed. All six were euploid.

Five of them were heterozygous carriers of this pathogenic mutation but there was one euploid unaffected embryo that was cleared for transfer. No assay failures, no DNA degradation signals, no interpretive uncertainty. The lab reported clean results across the board for all of these samples.

Man, who would've been real worried about these samples and would've been making phone calls to the patient saying, hey, I don't know, I don't know if we can trust these results, there's a high chance that we may not even get anything, I'm really sorry, kind of leaping into damage control. I can envision myself being in those shoes. I think the takeaway from this case report is our current transportation guidelines may be creating a false sense of fragility for these samples.

These trifecta biopsy specimens that are fixed, processed, using modern SNP-based platforms, whole genome amplification and using all the appropriate buffers, they actually may be a lot more resilient than we've assumed. Delays will happen, can happen, and in an era of cross-border reproduction where we're centralizing genetic services and having to ship a lot of our samples pretty far distances, I think this provides a lot of reassurance for the physicians, the clinics, and the patients that, hey, if it happens, it's okay. Obviously, this is one case report, there's not a plethora of data out on this, but it's a nice way to start to have the conversation of, these samples are actually maybe a little harder than we think.

I think this day long goes back to the same question I asked you, these samples frozen 27 years ago, can we trust them? These samples that took a lot longer to get processed, can we trust them? At least in this scenario, it seems like we can. Daylon, again, presuming you are a scientist, I just asked twice to confirm, does this make sense to you? Are you surprised that everything was fine knowing what you know about how these samples are processed, handled, and analyzed? Pietro, you're really staffing me out, my guy. I'm going to have to put you on an hourly rate.

I don't get paid for this. Again, this isn't forever, but they'd be taking DNA out of the Neanderthals' homes. So it's very, very stable.

RNA is what you'd worry about. I think there's a happy ending here, but depending on how they're stored, I don't know, if they were in a place where it was like overheating, you can't account for the, I don't know, you can't account for it, is the problem. If the result, my question would be, if the results were ambiguous, you know, unambiguous results, great, but if the results are ambiguous, then you've got to make some phone calls, right? So does it happen often enough that the results are ambiguous, that they just got lucky this time? I mean, when the chain of custody is preserved, you still can get an ambiguous result, right? So I think they kind of dodged a bullet here.

I don't know if I'd be telling stories. I dodged a bullet on six separate embryos, which is like, I don't know, pretty good. Can you just imagine this package sitting in a FedEx warehouse at the border, just like rotting away on a shelf? It raises another question to me, is then, why is it ambiguous ever? Because the sample input isn't great? You don't get a good biopsy, I guess.

Classic scientist thing, blaming the technician who collected it. Yeah, everyone else's fault. You guys are just wanting a happy ending, and they're telling, writing an article about how it's all okay, even though they blew it.

I don't know. I think that it bears a bit of scrutiny, my people. So you're advocating that we still pay for the expensive shipping and overnight, is what I'm hearing.

Yeah, I'm afraid you can't get the paperboy to handle this one, Pietro. All right, fine. Has that ever happened to you guys, Molly or Blake? Any samples that took longer to transport and analyze that gave you some pause at your clinics? Not that I'm aware of.

I have a few, there's like some sort of weird billing issue, and they're like, I'm like, the PGTA should be back. I'm trying to get her into a transfer, and they're like, oh, there's some paperwork, but I'm sure it's being stored appropriately. And DNA is hardy when stored appropriately, as long as it's not contaminated or hot, as Daylon said.

but yeah, that's tricky, because you don't want to pay for all the testing if you think it's really not going to work, and have them pay for all those, you know, then you might just re-biopsy, but I think the fact that they proceeded made sense. Is that an option, you re-biopsy that embryo if it does go bad? It's not killer for embryos. I use the example, it's like deciding you wanted to make chicken one night, so you took the frozen chicken out of the freezer in the morning to thaw, you get home, you're like, nah, it's a pizza night, you put it right back in, and then the next day, you're like, all right, it's cheese quesadilla night.

That chicken the second time around is always a little bit different, it's not the same. That's the one I use, I like a good food analogy, patients get it. You could see like the testing company saying this is a liability for us, because it didn't arrive in the nine days, we're not going to run it, so I'm glad that the testing company said, hey, let's just see if this is ambiguous or not, and if we can use it.

And the stakes are high here, this is PGTM, right? I think PGTA, the stakes are pretty high, the stakes are lower, this is an awful condition that someone at a very ripe age of 22 has decided, I want to go through all of this rigmarole to prevent the next generation. It's a good story, but it's bad business. The stakes are high, it's the frozen chicken, it's not steaks, right? You're talking about the wrong meat.

This is your own analogy, I'm just, I don't know. I appreciate the Oklahoma guy getting a solid on our meats. Listen, I don't mean to confuse you, I don't mean to compare my patient's future possible children to raw chicken, but, you know, it's kind of offensive, Pietro.

I'm too shy. I'll take that under advisement. Listener, that's all the time we have for today.

We could talk and babble and yap, I believe is the word that the teenagers are using these days. But we appreciate you tuning in, as always, listening to us, share with us our favorite articles from reports, reviews, science, and consider this. Again, another plug, fertile battle discussion live from PCRS should be an episode dropping soon.

And if you haven't already checked out our new sister podcast, FNS Roundtable, a great place to hear more about these fertile battles and views and reviews, articles that we're publishing in the journal, but just aren't getting a lot of airtime on our individual podcasts. And one final plug, if you are listening to this and thinking, I could do a better job producing than the current producers, we're hiring. We're looking for a producer for the FNS Roundtable podcast.

Ideally, this is someone who is in training, young, tech savvy, and interested in getting their feet wet and supporting our efforts to disseminate knowledge and potentially get into a cool position where you're on air like Molly. Molly started as a producer and here she is now. We've come a long way, baby.

Look at you go, Molly. Congrats. Until we meet next time, signing off, Molly, Pietro, Daylon, and Blake.

This concludes our episode of Fertility and Sterility Unplugged, brought to you by Fertility and Sterility in conjunction with the American Society for Reproductive Medicine. This podcast is produced by Dr. Molly Kornfield, Dr. Adriana Wong, Dr. Elena HogenEsch, Dr. Selena Park, Dr. Carissa Pekny, and Dr. Nicholas Raja. This podcast was developed by Fertility and Sterility and the American Society for Reproductive Medicine as an educational resource in service to its members and other practicing clinicians.

While the podcast reflects the views of the authors and the host, it is not intended to be the only approved standard of practice or to direct an exclusive course of treatment. The opinions expressed are those of the discussants and do not reflect fertility and sterility or the American Society for Reproductive Medicine.