Thinking About Ob/Gyn
A fresh and evidence-based perspective of all things related to obstetrics and gynecology. Follow us on Instagram @thinkingaboutobgyn or visit thinkingaboutobgyn.com for show notes and more.
Thinking About Ob/Gyn
Episode 12.1 IVF Add-Ons and More!
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We follow the footnotes on a common gyn rule, then use that same evidence-first lens to question popular fertility add-ons and persistent pregnancy myths. Along the way, we talk pretest probability, counseling tradeoffs, and why simple cutoffs often replace better clinical reasoning.
• tracing the “biopsy Bartholin cysts after 40” claim back to weak citations
• using pretest probability and exam features to decide on selective biopsy
• weighing hysteropexy versus hysterectomy for prolapse with long-term cancer risk in mind
• breaking down a Lancet review of IVF add-ons and what actually shows benefit
• spotting how marketing and online forums amplify unproven fertility interventions
• reviewing data on sedentary time in pregnancy and why activity restriction persists
• debunking “walking progresses labor” with randomized trial evidence
• clarifying early diabetes testing as screening for preexisting diabetes and when A1C makes more sense than early glucose tolerance tests
Be sure to check out thinkingaboutobgyn.com for more information and be sure to follow us on Instagram.
0:00 Welcome And What’s Ahead
0:23 Bartholin Cyst Biopsy Age Rule
14:17 Prolapse Repair With Uterus Preservation
21:45 IVF Add-Ons And The Lancet Review
37:35 Pregnancy Activity Myths And New Data
50:53 Early Diabetes Testing And A1C
Follow us on Instagram @thinkingaboutobgyn.
Welcome And What’s Ahead
SPEAKER_00Today's episode features Howard Harrell and Antonia Roberts discussing IVF add-ons and much more.
SPEAKER_01Howard?
SPEAKER_02Antonia?
SPEAKER_01What are we thinking about on today's episode?
SPEAKER_02Oh, we've got so many things
Bartholin Cyst Biopsy Age Rule
SPEAKER_02to get to. It's a new season. The world never stops. But first, what's a thing we do without evidence?
SPEAKER_01Okay, well, I actually like this one. This was sent to us from a friend of the show and a listener named Ella Damiano. So she proposed a thing that we do without evidence is recommending excision or biopsy of Bartholomew Glancysts in patients over 40 years old.
SPEAKER_02Okay, yes. I think we all have heard this rule at least. So Ella did some research. She did her own research, as they as the patients say. Although Ella's qualified to do research. And she says she can't find anything from ACOG specifically about this, but that many sources cite an old American family physician article from 2003, which in turn, and I love doing this. When she sent this email, I love doing this sort of follow the chain of references. So that 2003 American Family Physician article cited a textbook from 1995, and then another article from 1998, also from the American Family Physician Journal, which in turn cited a 1992 paper, which itself had no primary data. She then finally found a paper from 1996, which was in the Green Journal, and that did include some data, but it didn't support universal excision in menopausal patients.
SPEAKER_01So she really went down the rabbit hole on this one, didn't she?
SPEAKER_02Yes, I love it. We have the best listeners. We should do an episode sometime of checking the footnotes and seeing what the citation is and et cetera, because a lot of things, I mean, frankly, what people do is they cite something, they see the reference, they copy the reference over. And if you've ever written a paper in college, you know you might have copied somebody's footnote. But I'm the guy that reads that footnote and then goes down and reads that footnote and goes and finds that footnote and find out what's going on.
SPEAKER_01Where is the arid like ground zero?
SPEAKER_02Yeah. Yeah. And I guess Ella does the same thing. So exciting.
SPEAKER_01Well, I aspire to this level of nerd.
SPEAKER_02Nerd alert? Is this a nerd alert?
SPEAKER_01Yeah. Yeah.
SPEAKER_02Well, could because it takes one to know one then. So I love topics like this. So many of the things we talk about all the time, especially the things we do without evidence, are illustrated, the principles are illustrated by this sort of topic. Things that we just do because we've done them that way, and they're minor things. Sometimes we take the least important things for granted. Of course, you biopsy a Barthelens on a patient after 40. There's so many things like that that you learn as an intern, and you never check the reference, you never check the citation, and it just gets copy-forwarded. So what we do know about the incidence of benign Barthelens duct cysts and abscesses is that incidence peaks between the ages of 20 and 40. And then it really sharply declines after menopause, not after 40, but after menopause. And at the same time, primary Bartholens gland carcinomas, which is this rarest of the rare GYN malignancies, super rare. I don't know if it's the rarest, but in terms of organ tissues, it is. It tends to peak in older patients, specifically between the ages of 53 and 57 years. So the concept here that's being illustrated with this maxim, and the one that we need to think about is just pretest probability. A patient who is older, who has a new or persistent Bartholin's mass, cyst, solid cyst in particular, has a much higher pretest probability for Bartholin's glan carcinoma than a younger patient would with the same findings. So somewhere in all of this mix, people just looked at the declining incidence of benign cysts and the rising incidence of Bartholomew's gland carcinomas, not really thinking about how rare those were, but just looking at the graphs. And somewhere in the 1980s or 1990s, somebody just drew an arbitrary line in the sand and said, okay, well, if they're over 40 or so, then maybe you should biopsy it.
SPEAKER_01Well, 40 is a pretty conservative number if the actual peak incidence is from age 53 to 57. And it seems very arbitrary. So my first question here is what would be the number needed to treat? So in this case, biopsy to detect a single case of Bartholomew carcinoma when you're taking patients from age 40 and up that have this. So let's say a 40-year-old, 41-year-old who comes in with a fluid-filled vulvarcyst, it's gonna be a very high number needed to treat, where you would biopsy rather than just drain or marsupialize. But obviously, that number needed to treat would be very different if it's patients with a firm nodular mass, had some solid features fixed to the underlying tissue, or let's say that it's chronically persistent, they've already been treated and it comes back quickly despite standard treatments. So so that that's not really based on the age, that's based more on clinical features, I think.
SPEAKER_02Yeah. And so pretest probability in my clinical reasoning book, one of the things I say is that like the chief feature of being a physician is to determine the pretest probabilities of the diagnoses on our differential. And so one of the characteristics is the peak incidence of the disease and the time things like that. And then you just mentioned a whole bunch of other ones. And so you're you have refined your pretest probability into something more granular by saying, is this a simple cyst that responds to treatment, or is this a solid nodular fixed mass or something that doesn't respond to treatment? And so that's how you would normally approach a problem like this. We take a history and a physical, and then we assign a pretest probability. And for that simple patient with the simple cyst that you first described, even though she was 40 or 41, well, you might decide that the number needed to biopsy was so high to find one carcinoma that it's not worth doing. But then if she came back and she had a lack of improvement or didn't respond to your treatment, or if initially she had other atypical and uncharacteristic presentations, then the number needed to biopsy to find one carcinoma decreases greatly. And so in those patients, then you escalate treatment, which in this case would mean to biopsy or resect the gland. And if you don't want to do all that cognitive work and rely upon your history and physical, then you can reduce it down to a simple, is she some age or not? The danger of that is not only do you over-biopsy a lot of patients who are above 40, but you also might miss it in a 39-year-old. If that solid fixed mass was staring at you in a 39-year-old, would you not biopsy it?
SPEAKER_01Yeah. And there is a difference between simple drainage, even marsupilization, and taking a biopsy or excision. That's why this is such a good example here. So if we just universally take every 40-year-old and up with a vulvarsis to the OR to do cut open, cut pieces out, or try to cut the whole thing out, then that we're exposing them to a whole lot more risk. Like what's the problem with overbiopsying? Really all the surgical complications. There's some blood vessels in that area. They can bleed and it can get pretty tough to secure. And if you're doing that really for no reason, no evidence besides that they're 40, then you're definitely doing some net harm.
SPEAKER_02Aaron Powell Yeah. And so if you just decide to do that at age 40 rather than 39, you're just making an arbitrary decision. And so the paper that Ella found from 1996 was by Visco et al. Although I think there was only one other author. So the Latinist, please don't send in your dirty emails. But this was in the Green Journal, and they estimated that the incidence of Barthelen's gland carcinoma was.023 per 100,000 woman years in premenopausal women, and 0.114%, so about five times higher, not percent, per 100,000 women years in postmenopausal women. So they concluded in that paper that Bartholomew's gland cancer was so rare in all women, including postmenopausal women, that they couldn't justify excision as an initial treatment of Bartholomew's gland enlargement at any age. And they recommended drainage and selective biopsy as an adequate initial management. And of course, selective biopsy would be based upon some of the characteristics that we were just talking about.
SPEAKER_01Yeah, so this gets into the inertia in practice that you always talk about. Because I I remember hearing this age 40 rule as an intern and just accepting it as this is the absolute truth, because my attending is telling me this. And it's all over reference sources, like up to date and lots of classic textbooks. But again, we need to be more like Ella and track down the sources and go down some rabbit holes and realize that the people who write these references are just reporting what they were also taught as interns and just kept doing forever and still are doing now. So especially with very rare diseases like Barthel and Glenn cancers, there's it's not like there's a whole lot of new literature or new breakthrough discoveries or other impetus to readdress or revisit these recommendations. It's the same old ones from generations ago that are just getting carried forward. But good clinical practice would be to assess the clinical presentation and individualized care instead of going straight to the OR every time someone over 40 or maybe even a 53-year-old, if it's a simple cis, they even they might not be a slam dunk that you have to go to the OR even for that.
SPEAKER_02Well, if you're a resident, let's actually do this experiment for a second. Because if you were my resident, I would want you to read Williams Gynecology and Williams obstetric as an intern. I don't think that's too high a standard, by the way. For all the interns out there listening, it's July and make a reading plan, and they're actually both very readable books, and you can read them in a year, and you'll be so far ahead if you do that. But let's look at Williams Gynecology. Now, the editor of Williams Gynecology, the lead editor is a good friend of mine, and I love him and I love this book. I I have read I've actually read each edition. That's how crazy I am. So we're not going to be critical at all, but I but this is how we read it, and I'm going to read to you what it actually says because people cite Williams gynecology as a reason to do this. So let's read what it actually says. After menopause, Bartholin gland duct cysts and abscesses are uncommon and should raise concern for possible neoplasia. However, Barthylin Gland carcinoma is rare and its incidence approximates 0.1 per 100,000 women. Most are squamous carcinomas or adenocarcinomas. Given the rarity of these cancers, barthellin gland excision is typically not indicated. Alternatively, in women older than 40 years, drainage of the cyst and biopsy assist wall sites adequately excludes malignancy.
SPEAKER_01Okay, so it sounds like even they don't recommend excision, may maybe just seem to encourage drainage and biopsy in women over 40.
SPEAKER_02Well, it says that that would adequately exclude malignancy. So it it definitely does not recommend excision. So that's the first point is should all these patients go to the OR and get a Barthlinectomy versus sample the cyst wall, which can be done in the office. The interesting thing though is that the citation for that statement that in women of f older than 40, the cyst biopsy, a cyst wall adequately excludes malignancy, the citation given is the paper we've been talking about. And so the paper says drainage and selective biopsy may be sufficient as initial management. So Williams Gynacology doesn't quote the paper exactly correctly. And there's a twist there. They say that it is adequate to exclude malignancy. If you need to exclude malignancy, then that's how you would do it. So let's put on our reading glasses again. It says Barthellan gland excision is typically not indicated. Alternatively, but in women older than 40, you could exclude it by doing by doing a biopsy. It doesn't say you have to biopsy everybody over 40. It's saying that it that Barthland's gland excision is typically not indicated. But if you need to, then that's a way of excluding malignancy. And the citation is the paper we've been discussing. So they don't have any more foundation for the statement that the paper that we're able to read. And the paper itself, again, was not arguing for universal biopsy. It was just saying that excision was usually unnecessary due to the rarity, et cetera. And they were arguing for selective biopsy based upon risk factors and the ones you mentioned before. So always read the sources.
SPEAKER_01Yeah. So the lesson here is be like Ella.
SPEAKER_02I'm going to get a t-shirt that says that. And only a few of the listeners will know what it means. We can wear them at Disney and we'll see how that goes. Okay, well, let's move on. There
Prolapse Repair With Uterus Preservation
SPEAKER_02was a paper published in JAMA Surgery on June 24th, 2026. It was a 10-year follow-up of patients who had previously been randomized to sacrospinus hysterepexy with mesh versus vaginal hysterectomy with a natural tissue repair for treatment of uterovaginal prolapse. The study had 175 women in it, half of whom had hysterexy with mesh, and the other half had hysterectomy with native tissue repair. And essentially they found no difference in this 10-year period in reported patient-specific outcomes like patient-reported prolapse or urinary or bowel function or sexual function or pain with sex or things like that in the two groups. There were slightly fewer clinical failures in the hysterexy group compared to the hysterectomy group, but this didn't seem to translate into noticeable differences in complaints for the patients. So they concluded that both are acceptable procedures.
SPEAKER_01All right. So that this may not happen as commonly as many other things, but we may both encounter sometimes patients who have prolapse and want it treated, but they want to keep their uterus. And so some kind of uterine-sparing technique like a hysteropexy could be an acceptable long-term alternative. And there are other techniques too without mesh. But I think we know enough from other literature that the hysterectomy group would essentially have their risk of uterine cancer eliminated after the surgery. And it would, even with keeping their ovaries, it would still reduce their ovarian cancer risk by as much as maybe 40%, especially if you're step injecting. Yeah, exactly. And not to mention cervical cancer, as long as you're also removing the cervix, too. So that would mean that for every hundred women who choose hysterectomy for prolapse as opposed to uterine preservation, then you're going to be preventing cancer in at least three of them, at least three per hundred. So more like one in one in 30, roughly.
SPEAKER_02Right. And so this study simply wasn't powered to see the differences in those sorts of outcomes and not even conducted for a long enough period of time. They had basically half of 175 women in the hysterectomy group for 10 years. So you're unlikely to capture a cervical or uterine cancer or ovarian cancer in that time period. But of course, many of those women are going to live a long time. And some of the women in the study were in their 20s, so you've got a long horizon for the development of malignancy for those patients. If you're counseling patients fairly about the difference in these two procedures, then I think you have to make those points. It's the article, you can't just tell them that the results of this article is there's no difference in outcomes, because we just know there's going to be three point something cancers that occur per hundred women in the ones who keep their uterus. So in a world where we do opportunistic salpingectomy as often as we can, where we're trying to expand that to general surgery procedures, and really anytime we're in a woman's belly who's done with childbearing, then these are very important and cogent arguments. Of course, you could do a salpingectomy at the time of the hysterpexy and still get that risk-reducing risk-reducing surgery, but that still leaves the three or so women per hundred who were going to develop uterine cancer, and however many women were going to have cervical dysplasia, procedures for cervical dysplasia, abnormal bleeding, cervical cancer, and other things out of there. There's a whole bunch of things that many of these patients are going to have, particularly if they're younger and have that long time horizon. So I think that in gynecology, we had this big move 25 years ago or so towards everything that could be done as an alternative to hysterectomy, everything that we could do to preserve the uterus. So endometrial ablations and ultrasound for fibroids and all sorts of things, as if removing the uterus was this inherently bad thing. And one of the consequences of that, that we've talked about, particularly with endometrial ablation, really done on poorly selected candidates, is that the there's been a rise of advanced stage uterine cancers, and we're at a point now where if it hasn't already in the next few years, we expect uterine cancer mortality to surpass ovarian cancer mortality.
SPEAKER_01And plus this kind of procedure begs further questions. If you're trying to spare their fertility and they want to get pregnant again, how is this type of procedure gonna hold up to pregnancy and childbirth? Are they just gonna reprolapse again? I think there is a rate of failure related to that. And then if they still end up getting a hysterectomy later on, maybe they develop abnormal bleeding. How much harder is that gonna is that surgery gonna be compared to if you hadn't tacked up their uterus as high as you can? And then obviously if they already have problems like dysmenorrhea or chronic pelvic pain, then obviously the hysteropexia is not gonna help those problems. So it it seems like a very limited case where this would be truly the right thing to do, both for the short and long term.
SPEAKER_02So just Yeah, I think the momentum is maybe swung the other way a little bit on hysterectomy. Hysterectomy is not this evil thing. Most patients benefit from it and do well. And a lot of that, if you go back 25 years ago, what a hysterectomy meant for most women in the United States was a an incision on their belly and a two-day hospital stay. And what hysterectomy means for most women in the United States today is a same-day surgery with return to work in a week or so. So that part has changed. We also took everybody's ovaries out back then. And half the time when patients come in and they say, Oh, when my mother had a hysterectomy or this, that, the other, like most of the negative consequences of it was surgical menopause. And so we're certainly doing a better job about that now. And so I would hope that the attitudes about hysterectomy have changed a little bit. And again, I think there's a lesson to be learned in overutilization of endometrial ablation in patients who were often considered poor surgical candidates, which meant often morbidly obese patients with irregular bleeding, and they were the very patients most at risk for endometrial cancer. And then we took away their warning sign for cancer, and now we're seeing these patients present with more advanced stage cancers. So anyway, it's it is an option for people who want to preserve their uterus, but I don't think that it's fair for them to say that the outcomes are the same between the two. If the only outcome you care about is prolapse, then sure, but the dysmenorrhea rates aren't the same, the abnormal uterine bleeding rates aren't the same, and the cancer rates aren't the same.
SPEAKER_01All right. Well, let's move on.
IVF Add-Ons And The Lancet Review
SPEAKER_01There's another article from the Lancet, also that same June 23rd edition, that's been getting reposted on social media. This was a systematic review and meta-analysis of the The safety and effectiveness of ten common in vitro fertilization add-on treatments. So I'll list what they were. Acupuncture, corticosteroids, embryo glue, endometrial receptivity assay, endometrial scratching, intra-lipid infusion, something called PIXI or PICSI, intraovarian injection of platelet rich plasma, intrauterine injection of platelet rich plasma, and then finally PGTA, or which is pre-implantation genetic testing for aneoploidy. Well, you're gonna have to explain some of those to us because I'm not sure if I know what two or three of those are, but uh most of them I don't know about it, and I have gone through I have gone through the whole IVF and embryo transfer process now. It's been a few years since the last time I lurked around on any online groups or message boards relating to IVF. I remember seeing some of these. That's where I saw some of these, but most of these I have never heard before. So I'm guessing my infertility doctors and the ones that trained me in residency, I guess they always stuck to the textbook basics because these things, but most of these things never came up.
SPEAKER_02Yeah, I've seen a lot of them, not just in reading about them in some of the literature and the lay literature, but my patients obviously they come back to me and they say, hey, they're talking about this, that, and the other. And in some of the big national fertility groups, many of these they list as add-ons and with pricing. So they're definitely out there. I don't know how prevalent they are, like you said. Now, hopefully some of the folks that you've worked with will join me in criticizing some of these trendy IVF add-ons. We've talked about some of them before. There's a whole cottage industry out there that, in my opinion, just upsells vulnerable patients with some of these non-evidence-based or at least very weakly evidence-based treatments because patients spend a lot of money on in vitro, and the probability of having a live baby out of that all that money is maybe only 30 to 40% per cycle. So these add-ons are sold to them as things that might help increase the chance of a live birth. And they know that patients would give anything for a baby, and you've already spent all this money. What's a few extra thousand dollars for some extra hope when you're already tens of thousands in the hole potentially? And it always reminds me of buying a car where you see the sticker price, but by the time you sit down with a sales guy and that they're trying to sell you extended warranty and tire protection plans and battery protection plans and all this stuff. And I know when I go to the car guy, I should never buy any of those things, right? Just don't buy them. And I usually have that skepticism that if they're trying to sell it to me, then it only profits them, not me. But what did the systematic review of these 10 add-ons say?
SPEAKER_01Yeah, I did buy some of those things too. It's a scam. It's a total scam. I'm talking like a car auto butler service. It's not. So yeah, let's apply that to back to here. So in in this review of these IVF add-ons, essentially the only one that they determined might be associated with increased chance of live birth was the endometrial scratching. So they considered the evidence for that to be moderate, and the odds ratio was 1.2 with a confidence interval interval of 1.02 to 1.41. So that still is overall a pretty weak effect and moderate quality at that. So yeah, that was really the only one that they concluded had any positive evidence at all.
SPEAKER_02And what is endometrial scratching?
SPEAKER_01So it's my impression is it's a minor procedure that scratches and disturbs the lining of the uterus. So I guess like when you would do an endometrial biopsy, except you're just not removing any tissue. I'm not sure how extensively do they scratch all around or just kind of a quick in and out. But the thought is there's some resulting inflammation and a immune response that might improve maybe the endometrial receptiveness to the embryo. And this add on will usually run patients anywhere from 100 to 300 extra dollars.
SPEAKER_02So the one that might work is probably also the cheapest of the 10, I'm guessing. I'm not convinced that this is totally risk-free, and I'm sure what the rates are for complications, pain, buterine perforation, infection, things like that. Maybe there's some people for whom it lowers the rate of success. But my thought is if this is, if it works, if it's a net benefit and we accept this with a consensus of science, then it should just be a normal part of how we do IVF. It should just be built into the cost. So not as an optional add-on at extra cost. So that might be overly jaded, but I have a real ethical problem with holding vulnerable people hostage and to get another hundred or two hundred dollars out of them. If it helps them, we should just do it. I think also there's a real problem with how we market and sell surgery. We've gone through this with cosmetic gynacology and some of the procedures and things that are sold as almost like franchises to offices. And there's a lot of ethical things of can you can people, can only the people with the right amount of money access certain procedures? And or is this just not how we do it? So again, if this works, then it should just be what everybody does. But the literature may not be that mature or two. Okay, what about the others?
SPEAKER_01And this one was not even presented to me as something. So I obviously I didn't have this done. Well, as for the other items listed, they they concluded that embryo glue, the endometrial receptivity testing, corticosteroids, and also surprisingly, the pre-implantation genetic testing for anuploidy have no impact on live birth rates. And they concluded this with a degree of certainty based on a lot of quality studies showing no benefit. And so if anyone's wondering, what is even the idea here? Steroids, the idea is to reduce inflammation, which is interesting because the embryo scratching is done to cause inflammation. But maybe at different times, and maybe it's like, what if this what if it's steroids for someone with recurrent loss and there's suspicion for autoimmune or something? So maybe maybe it's targeted for different people at different times. Then the embryo glue, it's just a different type of transfer medium. It has hyaluronic acid, which I'm sure most people have heard of with cosmetics and skin creams. And the thought is that somehow that is important for embryo implantation. And of course, that's not proven. The endometrial testing is a biopsy of the endometrium that assesses gene expression patterns. And then based on the results, the embryo transfer then is recommended to be either earlier or later than standard timing. But that has no imp no proven impact either. And then, of course, the PGT the idea there is that if you test embryos and find out that some of them are aneuploid, that you wouldn't transfer those because you'd worry about lower live birth rates, like higher rate of miscarriage. So in theory, the theory of those can make sense, but in in practice, the results just have been unconvincing, unfortunately. Really, out of all of these, the PGTA is the only one I was really familiar with. I did have this done, my and it was presented as just optional, like a similar thing to NIPT, but getting it before embryo transfer. But we know from prior studies that the testing methods themselves are far from perfect and they are not always identifying the truly annuplate embryos. And I think we could go much further into this. There, I think there's some nuance, but there's a really good summary about it in the ASRM committee opinion on PGTA that that's from 2024, and we can link to that. For example, they list some studies where if they're looking at advanced maternal age patients with higher baseline rates of aneuploidy, they may have higher live birth rates if they do this. But overall, even they conclude with ASRM that it's definitely not at the point of being a universal recommendation. And then for those other IVF service add-ons, either the theories themselves are just not even true, or maybe the theories are onto something, but the methods need work or some combination.
SPEAKER_02Yeah, and all of these could add several thousand dollars per cycle. The steroids are probably the only thing that's really negligible from a cost perspective. The other things can run a whole lot of money. I will say that the PGTA stuff is something that everybody's really learning about. And there are a lot of folks in the industry that are very defensive about it, too. Like they really believe in it. And so again, this will settle out over time about maybe there's a subset where it's appropriate to use it and a subset where it isn't. But really what happens is you're biopsying the outer cells of this, which were going to become the placenta, and the the some of these cells have the ability to self-correct. So two things happen. You are not identifying all the aneuploid pregnancies because you're not by the mistake is with the inner cells, and many or they're self-correcting, so you're over-biopsy, you're over-diagnosing aneuploidy in them. And so it's surprisingly not as accurate as people thought it was. And and yes, in an older population where there's a higher pretest probability, maybe there is some benefit. And so people are arguing about this, but overall, in this meta-analysis of the studies that are available, they said it didn't contribute to a higher live birth rate. So what about the other stuff?
SPEAKER_01Well, the other things they looked at don't even seem to have quality studies at all, let alone convincing evidence of benefit. There there are a lot of lower quality studies, for example, with acupuncture, but no no positive, no positive evidence. The intralipid infusion that's given IV, which is also thought to reduce not inflammation, but reduce natural killer cell activity and other immune cells in the endometrium, also has no evidence. The PIXI, I also hadn't heard of, but it's a technique that is used to select sperm based on their ability to bind to hyaluronic acid. And that's thought to be a sign that those sperm are more mature and capable of fertilizing an egg. But that also has no objective evidence of efficacy. And then neither do those platelet-rich plasma injections, either the ovary or the uterus. But at this point, there probably is a ton of anecdotal stories in online forums for people that they were given this whole menu and they picked off some of them and got maybe a good sales pitch, and then they either had a good outcome or not.
SPEAKER_02Yeah. If you added this and that was the pregnancy that worked after you've had a failure or two, then you can see the anecdotal burden there that people are going to believe that was the difference. And so we have to be careful with how we counsel patients. They are very emotionally vulnerable. And this is just true in general, but infertility in particular is rife for abuse of this sort. That same edition of the Lancet has another study, a trial, that evaluated an educational resource about in vitro fertilization add-ons. So basically, they made an evidence-based IVF website to try to improve patients' understanding of the benefits and risks, and along with the quality of evidence around these various add-ons. And of course, they found that having an evidence-based educational resource was helpful. This is one of those sort of no-brainer studies, but most of the online information available about these add-ons, like tons of other health-related information, frankly, well, it comes from people who stand to make money off of it, or it comes from people who have, like you said, have had a good outcome and they swear by it because it worked for them. So hundreds of clinics around the world have websites, and many of them talk about and sell these products, and then your AI search results or your Google search results are often just repeating the claims made in the websites. If you went and searched for embryo glue, you're going to mostly find people who are selling embryo glue. And so patients are overwhelmed with misinformation when they try to do their own research, not doing it the way Ella did, where she follows the footnotes and reads the papers, but just Googling around. So as part of this second study, they found that 60% of the claims made on social media forums about these add-ons in particular were unsubstantiated or contradicted by robust evidence. They found that three-quarters of IVF clinic websites advertise these add-ons, and almost always they claim that there's a benefit that wasn't supported by any evidence. And they found that 70% of patients who are undergoing IVF in Australia, New Zealand, and the United Kingdom, which is the emphasis of this particular paper, that they purchased at least one of these add-ons despite no benefit from scientific studies. And so we don't know what the rates are in the United States. Their emphasis was on those Commonwealth countries, but I'm sure it's similar or higher.
SPEAKER_01It really is similar to buying a car, at least out of in the US. I don't know. Not so much in Japan, buying a car was a lot more straightforward. But getting all these extra sort of scammy promises for a little extra money for your purchase for a car is one thing. But with IVF, you're buy you're trying to buy a chance at a new life and expanding your family and you're terrified it'll end in disappointment or tragedy. And it's very emotionally complex and vulnerable. So so definitely for those people that are on the exploitative side of it, that that's like fresh meat. That's it's like they'll buy anything. And there's an editorial that accompanies these articles from the Lancet. And I just want to read the first few sentences of that editorial. So they say, hope is indispensable in reproductive medicine. It is also vulnerable to exploitation. Few areas of clinical practice expose patients more directly to the collision of hope and commerce than in in vitro fertilization.
SPEAKER_02Yeah. Well said. Okay.
Pregnancy Activity Myths And New Data
SPEAKER_02Well, another article that we've got to talk about is from May 27th in JAMA entitled Adverse Pregnancy Outcomes and Sedentary Behavior, Light Intensity Physical Activity in Daily Steps. So way back in season 11, that wasn't that long ago, episode eight, we talked about the AWARE study that was published in the April 2026 Green Journal, and that found that among patients with a short cervix in the second trimester, sedentary activity was actually associated with an increased risk of preterm birth before 34 weeks of gestation and an increased risk of delivery at earlier gestational ages. And we talked a lot about the persistence of activity restriction advice in myths and prenatal care. Well, now we have a similar study. And you can see where people are wearing activity monitors and watches and pedometers and things like that, these sorts of studies are going to be more common because they're just easy to do, easy to collect all this data and follow outcomes. But in this new paper, they found that patients who sit 10 hours or more per day compared to just seven hours per day had a higher risk of adverse pregnancy outcomes. And engaging in seven hours a day versus three hours a day of light intensity physical activity was associated with a lower risk. So in other words, more activity, lower risk of adverse pregnancy outcomes. So this new study doesn't look specifically at preterm labor by itself as the AWARE study did, but instead looked at a composite outcome, including hypertensive disorders of pregnancy, which they did separate out, gestational diabetes, preterm birth, and small for gestational age. Then they had patients wear an accelerometer on their thighs 24 hours a day, and this was able to assess posture and intensity of movement. They also wore a watch-based device and they completed sleep logs. And basically they found that the less you sat down or laid down, the more you stood and the more you walked, all those were associated with a clinically meaningful reduction in the risk of adverse pregnancy outcomes and separately hypertensive disorders of pregnancy. So women with the higher patterns of sedentary lifestyle had twice the risk of adverse pregnancy outcomes compared with women with the lowest pattern of sedentary activities. And this meant that the risk of adverse outcomes was one in five with women who are more physically active and two in five for the women who were less physically active.
SPEAKER_01Well, and that also could make sense, but I guess we have to be careful with what makes sense to us. To me, this makes sense because we know already that exercise and physical activity are probably the single most important characteristics that separate people with poor health from people with good health. Like what's their activity ability? And so why would pregnancy be any different there? And this is also consistent with decades of scientific evidence. And yet they also concluded that the majority of pregnant women don't achieve the recommended activity goals. And many of them intentionally so out of fear that activity will somehow be harmful. And this could be, at least in some cases, probably a lot of cases, it could be getting reinforced by their own providers, especially if if they show up to triage with some preterm contractions, they're not dilated or in labor, but they're told, yeah, I was walking around a lot, and they're told to take it easy. Or let's say their blood pressure was a little high, they also might get easily told to just take it easy now. In this study, they did separate out the hypertensive disorder outcome from the other adverse outcomes on purpose, just to make it more clear that both the hypertensive disorders and all the other outcomes benefited from activity. Because I think I could easily see someone trying to argue that maybe exercise and just general fitness is good for your blood pressure, but increases the risk of preterm labor. Or I could even see it the other way too, where you know if you run too fast or lift too much, you'll raise your blood pressure, whatever. I I have heard that argument actually. So this study is shows that the more active patients were better off in every regard. And then when you combine this with the aware study with the short cervical length patients, then hopefully we should just never hear an OBGYN or midwife recommending activity restriction ever again, at least not for threatened preterm labor or hypertension hypertensive disorders or anything like that.
SPEAKER_02Well, and yet in a world where much of the counseling that we give pregnant women comes from, we talked about this before, this misogynistic U.S. government publication from 1930 that viewed women as weak and incapable, the majority of Obajuians still do recommend formally or informally some kind of activity restriction. We we talked about this on that previous episode last season, but the, like you said, the little easy statements like take it easy or go home and rest or just the even the idea that if you're having Braxton Hicks contractions and that they're associated or made worse with physical activity, that you would benefit by having less physical activity and therefore less Braxton Hicks contractions, these ideas are just incredibly pervasive. And it may be the triage nurse that says that to the patient, not even the doctor. The patient comes in and she's 32 weeks and she stays for a couple of hours and she's got some contractions, and well, you were out working all day today in the yard. That's why you're here with these contractions, and that's a bad thing. But in fact, it isn't. It isn't at all. And so we've got a lot of work to do. These myths are persistent among our patients as well. When women are at the end of their pregnancies and they start emphasizing walking or increasing their physical activity as a way of putting themselves into labor. I mean, how many times do you hear that where a patient's like, I'm I walked three miles yesterday trying to get this baby out of here? They're essentially reinforcing this myth. That physical activity restriction prevents labor if physical activity emphasis causes labor. Even when they come into the hospital for a labor check, they often want to get up and walk around as if that's going to help their labor progress. Let me walk the halls for a couple of hours and then recheck. Well, it's another way this myth is reinforced culturally among our patients and our nursing staff. A lot of natural birth misinformation centers around movement as a key to labor progression. And this is a myth. Movement may help your comfort level. And if you're trying to have a baby without an epidural, position changes and movements are ways of finding comfortable positions and helping manage pain, but they have absolutely nothing to do with labor progression. I once had a patient who had ruptured membranes and she was declining oxytocin for like a couple of days. She wasn't in labor. And her doula at one point said to me that she wanted to try natural methods like walking first. And this is a commonly repeated fallacy, right? And I said to the doula, if walking were a method of labor induction, then we would have patients avoid walking while they're pregnant so we could stop preterm labor. But it's pervasive, it's deeply pervasive, and people really believe them. Or even just standing upright in this idea that gravity helps the baby get into the pelvis. It's like that the opposite of that is bed rest. If you believe that upright posture encourages labor progression, then you must believe on some level that preterm labor can be aborted or stopped or have its progression stop by laying down and not having gravity. And so people really deeply believe these things. And we don't we know that bed rest doesn't prevent preterm labor, nor does it treat preterm labor, nor does it change the outcome out of it. But if you believe those things, then you'll encourage upright standing positions and as a way of augmenting or encouraging labor.
SPEAKER_01Yeah, that wouldn't have been so good for our evolution or survival if everyone needed a wheelchair the second they got pregnant. But yeah, I think people don't always think that through. But if anything, these two studies, the aware, and I guess this other one doesn't really have a snappy acronym, but this one about physical activity shows that the people most likely to have preterm labor are the ones who don't walk and lay down the most. So it is really ironic.
SPEAKER_02Yeah. May maybe the walkers at the end are slowing the onset of their labor. You know, like I'm not saying it's true, but but that's if you were actually just trying to be evidence-based, right? It wasn't long ago that women were told to not have their heart rate above 140. Like that was standard teaching while they were pregnant. And so so many of these myths are rooted in the fragile woman, the weak woman misogynistic fallacies of bygone days. And they're again, they're rooted in this idea that women, that miscarriages and lost labors and lost babies and all this are it's because the women are this weak vessel, and pregnancy is this incredibly fragile, delicate situation that's just teetering and has to be managed by men with activity restriction and protecting the weak woman. But these things are simply not true. And despite them filling my Instagram feed, so okay, we're gonna get angry letters over some things I've said. I feel it. But if Ella's listening, she'll want me not to make claims that I've made without data. So I would point folks to the best clinical trial we've ever had on the subject of movement and and and labor progression. This is a study done by Stephen Bloom and Ken Levino and others that was first published in the New England Journal of Medicine in 1998. Those names may sound familiar to you as older authors of William Sobstetrics. They did a randomized controlled trial and they took uncomplicated pregnancies who've presented in active labor and they assigned them to either walking or to no walking. And they actually used pedometers, they had them back in the 90s, to quantify their walking, and they recorded how much time they spent walking. And what they found was no difference in the length of the first stage of labor, no difference in the need for labor augmentation with oxytocin, no difference in the rate of utilization of analgesia, the same rate of cesarean delivery, and the same rate of operative vaginal delivery. And this was true both in noliparis and in Paris women, and the infant outcomes were similar in the two groups. So this is the largest by number of patients and the best done paper on this subject. It is at this point the definitive scientific paper about the topic. And if someone wants to make a claim that walking helps labor progression, then they've got to do a better trial and find fault with this paper. And but this is it. This is it, this is our definitive evidence about it. And it's, I don't want to ever say settled science, but it's not the only paper. But walking during labor does not help labor progression.
SPEAKER_01Well, in general, we do like walking and movement. We like it when a patient's able to do that in labor if they want to. But we also want our patients to do that regularly and consistently throughout their pregnancies, not just be total activity restriction now and now when you reach full-term labor, now suddenly you're walking everywhere, or maybe trying to go for a drive on a bumpy road or have intercourse or eat spicy foods or all these other things to try to get labor moving. We we just need people to stop acting like physical activity causes labor, or that bed rest and activity restriction prevents labor or other adverse outcomes. And the consensus on the scientific literature is that bed rest and activity restriction throughout pregnancy cause adverse outcomes.
SPEAKER_02Yeah, I think at some point we jumped the shark on movement during labor. And what I mean by that is movement and walking during labor helps with pain and comfortability of the patient. There's no doubt about that. And that's why ACOG and everybody else supports freedom of movement and labor for women who don't have epidurals. But then it was weaponized into an anti-epidural argument. So that if so if you have an epidural, then you don't benefit from the what walking and position change give you in terms of improving your comfort. So they had to make the walking and the position change an essential part of labor progression. And that's not science-based. We talked about that a little bit last season, too. So if you don't have an epidural, please walk and move all you want.
SPEAKER_01Yes. Do
Early Diabetes Testing And A1C
SPEAKER_01we still have time to talk a little bit about diabetes screening in pregnancy?
SPEAKER_02Oh, I love diabetes.
SPEAKER_01Okay.
SPEAKER_02I am diabetic.
SPEAKER_01I know. Well, oh, okay, well, good. So so we've talked a lot about the lack of data that would show benefit for early screening of gestational diabetes. And that is the current ACOG Clinical Practice update on screening for diabetes in pregnancy, which came out July 2024. And we'll link to that. So they recommend against universal early screening for diabetes in pregnant women. At the same time, they do recommend early pre-gestational diabetes screening in patients that have risk factors. So I see a lot of variation in practice around this area. And I think the distinction between screening for gestational diabetes and pregestational diabetes is not always that clear. And maybe sometimes it's also confused in the literature. This guideline is also not clear because it says we should consider testing in adults who are overweight or obese or who have one or more risk factors, including first-degree diabetic relative, an ethnicity with higher diabetes incidents, or history of hypertension, or PMOS, or I guess PCOS. Yeah, you're not getting yelled at. Yeah. Well, it's been drilled into my head from listening to that episode. So there we go. Or here we go. Inactivity or history of prediabetes or prior gestational diabetes or age over 35. I think that's a pretty comprehensive list of all the different diabetes risk factors.
SPEAKER_02Yeah. I think that's a problem. You're looking at table one in that bulletin that you mentioned. But essentially you just described all of my patients. I mean, throw in physical inactivity, right? I mean, it's a very broad list, especially when you include that physical inactivity, since we know that basically no one's getting the right level of activity. It sounds like the only person I'm not supposed to screen when you read that is some young marathon runner who also hopefully doesn't have a family history of diabetes. So doesn't have PMOS. But I think they're not saying, again, that you need to screen for pre-existing diabetes in every single patient who has any one of those criteria. They're just giving you a list of criteria, and we're supposed to use again our clinical judgment and decide who might have diabetes when we are looking at them. If someone has diabetes at the onset of pregnancy, we want to know that. And also, just to drill home that point, we're not screening for gestacial diabetes, we're screening for pre-existing diabetes. But is that person sitting in front of you diabetic? But again, I don't think this means that I need to screen everybody with a BMI of 26 who doesn't work out three times a week. So it doesn't mean that. This is like the Barthland's Gland biopsy issue to draw really neat lines in the sand and say, just do everybody above age 40 and we'll find these cancers. And that's the easy way out. And in this case, what you're seeing is, well, just screen everybody who's not a young fit marathon runner, and we don't have any of those in our practice, so let's just screen everybody and we'll find the diabetics. So this ambiguity is driven by a lack of clear scientific evidence of benefit of screening. But I think though, if you're worried that someone has insulin resistance or diabetes when you meet them for their confirmation visit, you should test them for diabetes. And I think that the distinction here that's important is you're not testing them for gestational diabetes because the method that you would use to do that test is going to be different. As you said, we have this ACOG document and it discusses literature that shows that screening for gestational diabetes, and in again, like, and they're talking about screening with a one-hour and three-hour test or two hour, the different ways that we've looked at screening for gestational diabetes, but doing that before 24 weeks of pregnancy didn't lead to any better outcomes. What it does sometimes do, though, is discover a person who's already diabetic. And so we're left with this ambiguity because we want to find those diabetics. I think the question is, how do you screen for pre-existing diabetes in early pregnancy? We use glucose tolerance tests specifically for gestational diabetes after 24 weeks, but again, doing that early on is not necessary. So it probably makes the most sense just to order a hemoglobin A1C because we're essentially going to use the same screening criteria for screening for diabetes in the first trimester or early pregnant patient as we would in a non-pregnant patient. And that's what ACOG says too. So you can use a hemoglobin A1C of 6.5 or higher, or a fasting glucose of 126. And you can also do a glucose challenge, like a 75 gram two hour, because you can do that outside of pregnancy. But why would you? I suspect you're not doing that with your GYN patients who come in and need screening for diabetes. You're not having them do a 75-hour two-gram. And anyway, it just really makes it a different conversation when you're just saying check an A1C rather than schedule them to come in and do a glucose challenge.
SPEAKER_01Yeah, I definitely do not order the two-hour 75 gram glucose test on any of my non-pregnant patients, even if they have risk factors. I'm seeing them, let's say, for an annual, or even if they are there for like a PMOS, PCOS workup, just doing a hemoglobin A1C.
SPEAKER_02Right. And so I think that's, to me, that's the big confusion about all this. Ordering a hemoglobin A1C at the time you do prenatal labs on a patient who has risk factors, whatever we're going to decide significant risk factors are, and you can use all the ones in table one of that thing if you wanted to. I think it's overkill. But it's super easy to do, doesn't cost hardly anything, and there's just no evidence that doing glucose tolerance tests on these patients before 24 weeks has a benefit to them. And of course, it's a lot harder for both them and us to do that. So prenatal care is preventative health care. And if you see a patient who has significant risk factors for diabetes pregnant or not, you should screen them for it. And you should probably do that in almost all cases with a hemoglobin A1C.
SPEAKER_01You can almost make an argument for universal A1Cs as a standard prenatal lab. And I do see that. And some of that comes down to the nuts and bolts of having an just an operationally effective approach in your clinic. So if you have a patient population that is at high risk of diabetes and gets v very little infrequent regular medical care. So meaning they're not getting annual visits, they're not getting regular screens for health issues like diabetes, hypertension, whatever else, then it might make a lot of sense to just standardize an A1C as part of the routine prenatal lab for everyone. And in many ways, it's probably a lot more beneficial now to our current patient populations than testing for rubella immunity, for example. And that's part of everyone's standard prenatal lab order set. On the other hand, if you see a patient population with low diabetes incidence and they are getting regular medical care, let's say they just had an annual visit last year, everything was perfect, then it's probably overkill to still be doing this universal early A1C on everyone. So you do end up over-screening when whenever you make a test universal.
SPEAKER_02Yeah, that's definitely true. And I wouldn't be surprised if this doesn't change over time. We've talked about like thyroids as a universal, and there's you can overdiagnose thyroid disorders in patients. That's why we don't make it a universal. The lab itself can be falsely depressed in the first trimester. There's other physiologic changes. But hemoglobin A1Cs are pretty straightforward. They're not that expensive. And I think we you may just we just may lack robust evidence about it. And if you are still able to assess a person's individual risk factor and determine if, as you said, they've been getting routine health screenings and what are their personal risk factors, then you can tailor this to your population. But at the same time, if you have a population that's undertreated and high risk, then it might just make sense to not miss anybody and institutionalize a hemoglobin A1C as a routine screen. So that's my point about gestational versus pre-gestational diabetes screen. I see a ton of people still screening for diabetes in early pregnancy in patients with risk factors by doing a glucose tolerance test. And again, there's just not a reason to do that. There are some studies that have addressed the equivalency of A1Cs to these tests specifically, and this is evidence-based. One of the things that you will see if you look in these studies is a debate over the optimal hemoglobin A1C level. So I don't think that's necessarily a settled question. ACOG still uses the non-pregnancy level of 6.5% in the bulletin that you mentioned. But there are data from other studies indicating that sort of the inflection point for risk is closer to 5.9 or maybe 5.7. That's analogous to what we call prediabetes on these A1C screens. And I can put a link to a couple of studies that demonstrate that. For example, in 2014, Hughes et al. in the journal Diabetes Care found that 5.9 was optimal for detecting patients who were at increased risk of poor outcomes. And in a more recent study from 2024, uh there they reported 5.7 is a cutoff that would identify patients at risk for hyperglycemic complications. So these are the same sorts of debates that we've we have when we talk about the what cutoffs to use for our one-hour and our three-hour test, how sensitive do you want to be? How many people do you want to label as having diabetes? And are we trying to find everybody at risk for complications, or are we trying to find patients who benefit from intervention? Is a question too.
SPEAKER_01Right. So so really the only practical thing that matters is finding the patients who benefit from intervention. Because otherwise, what do you do with that information? You just risk overdiagnosis and then the labeling effect that we've talked about before, where you may actually harm them by having overlabeled them and then acting out on that and in obstetrics basically doing cesareans when you don't need to. So we talked about before one example is that people who are like the label diabetic during pregnancy will have higher cesarean rates without without a corresponding improvement in neonatal outcomes. So we're not doing these tests just to see who might have a higher risk. We're trying to see who can benefit from, for example, insulin. And I think that's why ACOG has left the cutoff at 6.5, which is also just the cutoff for diabetes diagnosis outside of pregnancy too. Because those are the patients that in interventional trials do clearly benefit from diabetes management in terms of reducing their risk for adverse outcomes.
SPEAKER_02Yeah. And I'll emphasize again that we're not screening for gestational diabetes. If you did a glucose tolerance test, a person might fail the glucose tolerance test, but still have a reasonable hemoglobin A1C. And that's the importance, not to be pedantic, but that's the importance about are we screening for gestational diabetes or are we screening for diabetes? And so again, first trimester screening for gestational diabetes has shown no benefit. You would get more patients labeled that. People will fail it, but they'll have a normal A1C. But the people who actually have diabetes benefit from treatment. So there's also a small study that was in the American Journal of Pernetology reports that looked at using an hemoglobin A1C in exactly the way we've been discussing, meaning instead of doing the glucose challenges to screen for early diabetes. This was published in 2023, and they found, of course, that using A1C was perfectly fine to doing the challenges. And they just screened their high-risk patients, meaning those that they identified as high risk, but by that long list of risk factors that you said. And I don't think we're at a point, again, where universal screening makes sense for everybody, but I still think you're allowed to use your clinical judgment to determine who you would screen, and you're allowed to implement universal screening in your clinic if most every patient in your clinic has risk factors. But just do a hemoglobin A1C if that's what if that's what you're going to do.
SPEAKER_01All right then. Well, hopefully we haven't gone over time, but may maybe it's time to wrap it up anyway.
SPEAKER_02I guess. We should start a two-hour podcast. No.
SPEAKER_01Maybe. Yeah, I don't know. For nobody's sake.
SPEAKER_02The answer is no. Okay. All right. Well, we'll see everybody in a couple of weeks.
SPEAKER_00Sounds good. Thanks for listening. Be sure to check out thinking about obgyn.com for more information and be sure to follow us on Instagram. We'll be back in two weeks.