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 back to another episode of F&S Unplugged. I am your evergreen host, Pietro Bortoletto, joined by always the pleasant, the delightful, you thought I was going to say Molly, but I mean Daylon. Hi Daylon.
What's up partner? Evergreen? I don't know. I don't know. We'll see.
I'm also joined by the tall, handsome, dashing, you thought I was going to say Blake. I meant Molly. Hey Molly.
Never tall. Never once been called tall in my life. What about handsome? Definitely handsome.
Okay. And then our friend Blake. Hey Blake.
Hey. I was hoping you'd say evergreen because big news in my life, I'm colorblind. That's not new.
In case you guys don't know, I am colorblind. Did we know that? Did you not know that? Yeah. What color? Red-green? Well, that's what brought this up is mainly red-green, but I just got me a pair of those colorblind glasses.
Let me tell you, and I have no financial disclosures that I'm mentioning. I'm not sponsored by Enchroma, but pretty cool to be able to see colors like you fancy cats do. I went to my son's baseball tournament and man, that grass was popping.
Those trees, ooh, they're green. How do the glasses look? Do they look weird? No, they look like sunglasses. You can buy indoor and outdoor ones.
I opted to just try the outdoor ones at first. So they just look like sunglasses, but it's weird when you put them on. There's at first like a, just a shade of pink, or at least to me, it looks pink.
When my wife puts them on, she says it looks no different to her, but everything is kind of pink and then it takes about 10 minutes to adjust. But everything, particularly the reds and greens, the trees, the grass, street signs, safety cones, it just pop out. It's pretty cool.
That's awesome. Yeah. So I'm seeing the world in a new lens, literally.
Do you think you could operate on them? Would like blood look different for you? Like during a myomectomy or something? I don't know. Maybe I'll try that. Yeah, report back.
Yeah, I will. This brings new light to the fact that you wrote the paper about multiples with the color coded heat map that I use all the time with my fellows. But can you see the heat map? I can.
I know which area you don't want to be in, but full disclosure, I had to lean on Michael Hill for the color selection of the heat map. He was very crucial and instrumental in making the color aspect of it. But yes, I know like streetlights, I know for sure what's green, yellow and red.
I'm not just blitzing through an intersection when it's a red light. But yes, certain shades, certain colors, I get real tripped up, but not anymore. I've got some colorblind glasses.
All right, guys, and that's our show for the day. Yeah. All right.
And until we come back next time, any other sensory deficits that any one of the co-hosts want to acknowledge? No, I'm deeply, I got something missing inside though. My heart. Yeah, I think the great poet once said you have an icebox where the heart used to be.
I think that was Omarion, if I'm not about right. All right. Well, yeah, that sounds back to the science.
We got a nice set of articles to talk about today. Molly, we've seldomly start with F&S reports, but because you were the one who was most on top of selecting an article and sharing it with the rest of us, I think it's only right that we start with you. I'd love to go first.
Great. So I actually have another case report today. I think I had never brought a case report on the podcast or had not in a long time.
And now we have two in a row. So the article I chose today from F&S reports is called a spontaneous ovarian hyper-stimulation syndrome with a previously undescribed gene mutation of the follicle stimulation hormone receptor gene. A case report by first author and Kristen Loheat and last author Anna Kulterer.
So I thought this was a great opportunity to review some of the past physiology of OHSS as well as some of the kind of biochemistry in our field. And so the authors start out by describing iatrogenic OHSS, ovarian hyper-stimulation syndrome, and spontaneous OHSS. And both are defined by ovaries with multiple cysts, intravascular volume depletion, and extravascular fluid shift with associated potential complications that include renal failure and even death.
Iatrogenic is what we talk about the most. We talk about it a bunch on this podcast, a result of fertility treatment causing OHSS through the mechanism of the HCG trigger, increasing the vasoactive substances like VEGF. Spontaneous OHSS, however, which I don't think about very often, is rare and occurs when a naturally conceived pregnancy, usually around nine weeks gestation with the peak of placental HCG synthesis, tagging that point for my fellows preparing for their written boards the next couple months, and can resolve a few weeks later as the HCG level comes back down.
There are two spontaneous OHSS subtypes. So there's either overstimulation of a normal FSH receptor with either HCG, like if you're in a molar pregnancy, a multiple pregnancy, really high HCG levels, or severe hypothyroidism where you have really high TSH levels, or it can be due to the FSH receptor gene mutation. So the receptor becomes overly sensitive to either HCG or TSH.
And just a reminder, FSH receptors are usually pretty specific to FSH and would only respond to a pretty high level of HCG or TSH. But this mutation in the FSH receptor could cause activation with just physiologic levels of these hormones. So there are many known FSH receptor mutations.
Most are in the transmembrane domain of the receptor, but could also occur in the extracellular domain, which is where the HCG is binding. The authors of this case report are describing a case where there's a heterozygous mutation in the transmembrane domain with a sequence change, if anyone cares, C1379T changed to an A, and that replaces leucine with glutamine, and that that was the cause of this patient's spontaneous OHSS. This was a previously unreported mutation, which is why they're sharing it in this case report.
And so for my third year REI fellows preparing for written boards, again, a little plug here, I already emailed this to our third year, I would check out figure one in this case report to get a little review of the FSH receptor. And for the case they described, this was an individual who was at 12 weeks gestation, so not the classic nine weeks at presentation. And she presented with hyperstimulated ovaries, slight ascites, and reported that she'd had similar symptoms in two prior pregnancies.
The authors pursued molecular genetic analysis of FSH receptor abnormalities and found the abnormality previously described. She was admitted with surveillance, they gave her some IV fluids, and then around 14 weeks, the ovaries began to shrink. I assume she was starting to feel a little bit better.
She actually developed fetal growth restriction in the pregnancy and delivered just a little early at 38 weeks. So the authors didn't think the growth restriction was related to the OHSS, but there have been some studies saying it could be, and so it's sort of inconsistent there. I thought this was an important case report, not just because figure two had a really cool picture of like a 12-week fetus surrounded by hyperstimulated ovaries.
So fun, just to check out for fun. I know, not nice, not nice. But it draws our attention to this really unique presentation, and it's the kind of case that an REI would be consulted on, but really isn't seeing often in training or in practice.
We're just seeing a few of these cases probably in our careers. And I think it presents a really new way to think about it. And so when you see these cases of what you think is a spontaneous OHSS, you have to evaluate for roulade malignancy, roulade molar pregnancy.
You have to assess their thyroid, their pituitary markers. And in this case, they looked at prolactin, FSH, LH. They looked at the HCG level, which was sort of high normal for a singleton pregnancy.
And then I guess we should consider molecular genetic analysis of the FSH receptor. I don't know realistically how often that's happening in practice. I don't know if it really even changed the management of this patient.
And I don't know what the cost is, and I don't know how it was covered for this individual. But I think it's great in that it furthers our own understanding of the FSH receptor and giving us a new potential kind of target for what can go wrong. I have some patients who I'd love to get some receptors sequenced.
Is that something you guys have ever done in your practices or clinics? Just said, hey, this is a weird case. Let's go get the receptor sequenced. Yeah, I must say more and more, and I'm glad to hear it in our group meetings when we have tough cases, that's and everyone's batted against the wall and rung it out.
We send the patient for sequencing. And I think this is the new standard. This idea that the cost is prohibitive, I think is no longer an impediment.
And the knowledge to be gained is a major factor, even though it's, you know, we're talking about fluke mutations. But I think more and more, it's kind of like, you know, referring patients for oncofert early days, it wasn't the first thing you think of. But I think now more and more is when you have a really tough case that doesn't fit any of the paradigms, it shouldn't be such a heavy lift.
And it isn't to go to the to the genomics. And I think that the larger, at least academic practices are jumping on it. Should we just send specimens attention, Dale on James, Cornell, New York City, is that how we should best send it all to Tara.
Tara, you guys got the VC money, you can handle that kind of way. No VC money here. Yeah, I don't.
Um, this is super cool. I have not personally seen this. My one of my partners has had not this exact receptor gene mutation, but has had a patient was non pregnant.
And her ovaries look like she was undergoing IVF, but hasn't received any meds. And she had an FSH producing tumor in her pituitary gland, and has had a few resections of this year, like it keeps coming back, or there's still some tissue that's been retained in there. But I don't know that she did any receptor testing or gene testing specifically, I'll have to ask her.
But I would imagine if she got pregnant, it would be a similar type of situation. But that's very interesting. So these things can occur, it's it's good to have these in the back of our minds for when they do and very interesting graphics as well.
I think it's just kudos to the authors for getting this out there and just promoting awareness of this very rare thing that can happen. Just to clarify, by the way, I mean, it doesn't have to be targeted sequencing either. It's old school.
Nowadays, you blast the whole thing and put up against a reference genome and the mutations jump out at you. So even some maybe less straightforward etiologies might might be be revealed with sequencing. So again, I think the value for the spend is certainly there.
And just the change in the way that we administer care, not we, but you guys administer care to consider that as an option, I think is really an important step forward. That's why I love this case report. Keep sending.
Great. Well, I think next step for this one, it'd be cool to have some functional studies on the mutation that they found. There was also a nice editorial by Dr. Randy Morris that I would check out that comes with this case report.
And yeah, thanks for the discussion. Sounds like really bad luck. Could you imagine that patient rolling up into L&D triage and like, should we cancel REI on this one? I guess when she gets pregnant or when she's trying to get pregnant, maybe just take cabergoline daily and take metformin daily.
I don't know. Throw in a Lupron trigger in there for good measure. I don't know.
Sure. Yeah. Eat a bunch of salt.
Gatorade. Want to just keep throwing things out? Yeah, we can keep going. Albumin.
Good one. Yes. Serial paracentesis.
The fellows are drooling hearing all this. Wow. Didn't think we'd be learning this much today on the podcast.
Daily letrozole and aromatase inhibitor. Wow. Maybe a serial antagonist injection.
Some of these are not in the practice bulletin. That's why there's no hair on this head. It's just constantly thinking.
Anywho, as one often does, let's move away from human science and barrel towards the mice. Blake, I'm not talking about you. Daylon, it's you, buddy.
Tell us about male mice and their testes. It's something I haven't thought about in months, really. You should think about it more, partner.
It's the root of all evil, the male mouse testes, at least in my pantry. That's the problem. A little TMI there.
I had a little bit of an issue, but I took care of it, guys. Is it because you snack? It's because you're a snacker, right? Well, blame the kids. A little bit of engineering control goes a long way.
I'll leave it there. So this is a story that is apropos talking about how we treat in the new age, genomic sequencing, all that. We're going back to the future with this one, guys, because this is a story about the more natural remedies, medicinal plants.
I would argue that this isn't even really old school. There's a lot of these medicinal treatments that are famously derived from plants, going way back, aspirin from willow bark. We all know morphine, especially you, Blake.
Yeah? Yeah, you, Blake. What's that supposed to mean? Not just the plants. Nowadays, everybody knows this, right? Especially you, Blake, with the GLP-1 inhibitors from the Gila monster saliva, right? Talk about it.
I like where this is going. Are the GLP-1s really from the Gila monster saliva? Yes, partner. Oh, my goodness.
You didn't know that? You just thought you got skinny for free? Wow. You took the Gila monster saliva, a bucket of it. Is that why they go months without eating? I don't know their practices.
I don't study Gila monster, all right? I study mice, male mice and their testes specifically, but I digress. We're talking about natural remedies here, and I just want to underscore that you might argue that all of our remedies are kind of natural, if that makes any sense. At least a lot of them, not even knowing how they work, not even understanding the mechanism, have been applied the world over to great effect.
I think us medical people, me as a scientist, you practicing medical snobs, are all about the synthesized drugs, recombinant this and that, and some deep pharma, but you don't have to know. I'm a big decapeptide guy. Oh, you love to talk about the chemical sequence and signatures.
Oh, boy. Cereal this and that. Well, the drugs work, yeah, sure, but they don't necessarily encompass the entirety of our medical practice, not even close.
We have all these other remedies that we found in nature, and this is a similar one. It's coming out of Iraq. Not the medicine itself, but this story is coming from the laboratory of Haider Abed, Dr. Haider Abed, who is at the Al-Muthana University in Iraq.
We don't get enough stories out of Iraq, so I'm just trying to highlight this for that reason as well, but it is reminiscent of this old school style. You guys remember Tu Yu, who famously won the Nobel Prize about 10 years ago for identifying our tennessin, the antimalarial treatment, and the way she did this is she went into the old scriptures and identified like 400 different therapies, screened them methodically in the lab, and found a really effective treatment for malaria, won the Nobel Prize. So, again- Was that Old Testament or New Testament? This is extra new, brand new Testament, Pietro.
It won the Nobel Prize in 2015, although the work is much older than that, but the approach is centuries old, and it's looking into all the chemicals that we're surrounded by. This is a long intro to give a kind of short scientific story coming out of- I was making this up. No, no, no, it's all half true.
This is from Almuthana University, as I said, and the approach was effectively focused on the selimerin, I guess you'd call it, which is derived from the thistle, milk thistle seeds, and it's a flavonolignin for you, Pietro, because I know you've got to know the chemical words, but the way this thing works, and it's been used, it's in practice, it's an orphan drug used for treatment of liver, acute liver toxicity, even cirrhosis, and it works by scavenging free radicals and boosting the body's antioxidant enzyme machinery to mitigate oxidative inflammatory damage, and again, as I said, been in practice, although to modest effect. Here, the group tried to apply it in the context of another intense insult, which is chemo, right, and this is a kind of fertile protective mechanism in the context of cyclophosphamide in male mice. Took a bunch of mice, 16 each in five groups, which was control, CP alone, they had two doses of the selimerin, and then just selimerin alone.
They went 28 days that they treated these mice with the selimerin. On the 22nd day, they gave them the CP, and then they looked at the body weight, testicular weight, serum testosterone, LHFSH, they looked at histology, looked at sperm criteria count, all mice, I know, you guys are rolling your eyes, but the selimerin had a dose-dependent effect, and the high dose really markedly restored the sperm quality and had no detrimental effects when it was delivered alone. Now, look, I don't know, yeah, go ahead, let's try it, I'd say, sure.
But that's not why I'm presenting this story. I'm presenting this story, again, to highlight this idea that I think we're bringing back of all the medicine that we're surrounded by. And also, yeah, to highlight this model as a, I think, effective and straightforward means of delving into these fertile protective mechanisms that are prophylactic.
This is a huge unmet need. The idea that we're freezing whole ovarian tissue or testicular tissue in these young patients who are increasingly surviving childhood cancers, it just doesn't seem sustainable. We need a better way.
So I think we've got to kick open the door with approaches like this, natural or not, for prophylactic fertile protection. Guys, give me your thoughts. You ever talk to anybody in your practice about these natural remedies? What's the one you hear about all the time besides McDonald's french fries? Pineapple core.
Not even the good part of the pineapple. Yeah, is that a thing? Just the spiky core. Yeah.
How does one find Sylmarin, Daylon? Is that an over-the-counter thing? Do you have to speak to an animal? Yeah, I don't know if it's over-the-counter, but it was declared an orphan drug FDA not that long ago. If you want it, you can get it. And I think there's always the milk thistle, too.
If you want to go right to the source, extract it yourself. Looks like 90 tabs of it on Amazon are about 10 bucks. Not bad.
Well, there you go. A lot cheaper than a lot of other fertile protective measures. Cheaper than that Ivermectin you take every day.
That is for certain. How else will I get rid of the worms that are in my horse? Of course, of course. Thanks, Daylon.
We'll keep an eye out on the Sylmarin literature and the mice testes to see if the story kind of evolves. Yes, keep your eye on the mice testes, specifically you, Pietro. They're so small, you'll need a stereoscope to see them.
I don't know that I've ever been close enough to know magnitude of scale. Daylon? I'm going to take the fifth on that. I haven't looked too closely.
Great. My thesis had plenty of mice testes and ovaries, and they're small, but fun. All right, Blake, round out the heavy hitting science for us.
In reviews this month, we have a nice longitudinal view of what happens to childhood cancer survivors, specifically with an eye towards reproductive health. What do we need to know as we care for these patients? Thanks, Pietro. A rare segue between F&S science and F&S reviews because they do talk about tissue cryopreservation, so we'll get into that briefly here in a bit.
But this review is entitled Cancer Therapy and Reproductive Health in Childhood Cancer Survivors, a Systematic Review of Long-Term Health Effects by Yonatan Amir out of Spain. So, this article reviews a very important topic, discussing survival rates of cancer patients, how they have very fortunately improved dramatically over the past few decades. But the authors of this article want to talk specifically about life after cancer, more specifically, family building, fertility, and long-term reproductive health.
The authors cite that more than 80% of children diagnosed with cancer today will survive, which is great, but up to 75% of them will experience long-term health effects, and fertility is one of those that can be potentially life-altering, as we well know. So, this study was a large systematic review looking at the time frame between the year 2000 and 2025, focusing on childhood cancer survivors, both male and female, and how different treatments will impact reproductive outcomes. They looked at a number of different parameters in both male and female survivors, including timing of puberty initiation, hormone levels, sperm parameters, pregnancy rates, and live births.
The overall big picture takeaway that they will tease out, and we'll discuss that, is they look at cancer treatments, especially chemotherapy, radiation, and the long-term effects on fertility for both male and females, and also how these treatments are dose-dependent. So, higher exposure, greater the impact. So, first, we're going to talk briefly about what they found on female fertility.
For women, these effects can show up in several different ways. They can have puberty timing being much later, or some even show earlier, interestingly. A lot of these patients who have chemo and or radiation can have a significant lowering of their ovarian reserves, meaning fewer eggs, as evidenced by a lot of reduction of the AMH levels.
Therefore, these patients can have a high risk of primary ovarian insufficiency. When we see these patients in our clinic very commonly, we're talking about what life might look like after chemo, and how they may not have periods any longer, may have to be on hormone replacement therapy, and ultimately lower pregnancy and live birth rates. The authors discuss that abdominal, cranial, ovarian, and testicular radiation are particularly detrimental, and as you can probably assume, higher doses correlating with worse outcomes.
So, then they jump to male fertility, and the authors really stress that this is an issue that they feel is not as... People are not as vocal about this as they should be. It's not as well studied as it should be compared to female fertility, and they really make a push to pronounce that we need to focus on this and be more vocal about this amongst ourselves, amongst our colleagues, and be more proactive about this. But the authors discuss how, similarly, if you have radiation and or chemo, can have reduced sperm parameters, may even have azoospermia, erectile dysfunction, smaller testicular size, and therefore segue into lower rates of having children in the future.
The authors quote that male survivors have as high as about 50% infertility rates compared to the general public, and they discuss that there's, as I mentioned, a need for more data. So, when we look at why this happens in the body, a lot of this is pretty common knowledge to us, but just to reiterate a couple of things. So, we know that alkylating agents, in particular, are very damaging to the ovaries as well as the testes.
So, in addition to alkylating agents, the gonadal or cranial radiation treatment modalities are strongly associated with reproductive impairment in these cancer survivors. So, even relatively low doses, they discuss that there's not a safe dose necessarily. So, even low doses can have long-term effects, and there may not be a necessary safe threshold, so to speak.
And so, the authors will emphasize that this equates to lower chances of pregnancy, higher risk of daring pregnancy as well. These exposures of treatment can be associated with preterm birth or low birth weight, as well as even long-term sexual health issues in both men and women. And so, when we talk about fertility preservation, to segue from what we discussed with Daylon, they do emphasize ovarian tissue or testicular freezing in the prepubertal patients.
We do have a program here at OU in which we can offer that to patients and have performed testicular cryo or ovarian cryopreservation for an option in the future for these patients. And also, of course, egg freezing or sperm banking are going to be the easiest, most tried and true that we do commonly. So, one of the things that the authors really, really stress is that we need to be really vocal and discuss all of these options with our colleagues, particularly our onc colleagues, and make sure that they are aware that we are here for these patients and we can, in a very short amount of time, get tissue, whether it be sperm, eggs, testicular tissue, ovarian tissue.
So, not oftentimes we need like weeks and weeks and weeks. That's sometimes a misconception and they think that, well, we don't have time, we just need to go ahead and start treatment at this time. And then, that can obviously ruin their future family building options.
So, the authors really stress that we really want to address those gaps in care there. So, takeaway from the article, childhood cancer survivors face significant fertility risk. Both chemo and radiations have dose-dependent reproductive effects.
Male infertility, the author stresses, is an under-recognized and understudied area. And early fertility preservation counseling is critical. So, not a whole lot of new information in this study, more of just a public service announcement that is nonetheless extremely important.
But what are your thoughts about this review, takeaways from it? I really like that they talk about kind of the cranial radiation and the impact of that. I had a patient who had, you know, in like the 90s, we were giving people a lot more radiation than we are now as well. We had cranial and kind of lower dose full body radiation.
So, it was interesting as she presented with both DOR and her gonadotropins were not that high for how DOR she was with an undetectable AMH and probably would be POI, but didn't quite meet the FSH criteria. And so, you can see how those cases can be missed because they're a little bit more complicated or nuanced where her FSH isn't going to rise as high or as quickly because of the combined central and peripheral detriment. Yeah.
One of the authors didn't really discuss much doing GnRH agonist, which I personally, you know, if I'm counseling a patient in front of me, if I have the option to get the eggs and freeze them and get the eggs out of their body before radiation and or chemo, that's going to be my preference. But do you guys offer GnRH agonist therapy to patients often? Or what's your takeaway on that? I know there's even fertile battles we've had in the past and F&S and talked about that. Let's call a spade a spade.
It don't work. We want it to. Right.
But it just doesn't pass that whole rigorous body of evidence to suggest it does what we think it does. And even from a biologic plausibility, like these eggs are sensitive. They're better to preserve than they are to try to protect.
And I wish we had something better. And maybe it's not a GnRH agonist. Maybe it's a infusing AMH as a oocyte protectant.
But I don't hang my hat on that. What do you guys do, per se? Yeah, I agree. And unless if a patient's at risk of having thrombocytopenia and heavy vaginal bleeding, then of course, let's be on a GnRH agonist.
But I agree. I otherwise am not going to recommend that for fertility preservation. Yeah, I noticed sometimes people are a little bit overly positive about the, especially from oncology, about the impact of the GnRH agonist.
And sometimes I have to be very clear with my fellows and residents. Sometimes the patients are admitted they're too medically complex, even for ovarian tissue cryo, quite sick and starting chemo that night. And then fine, let's do the GnRH agonist.
And we can try and be positive about that. Hey, maybe there was one study that it might have some benefit. But for their knowledge base, and for kind of talking to the patients realistically about future options, the data is mixed or no effect, just as you said.
Yeah, I agree. So yeah, I've thought a lot about this. And there's so much involved.
One, yes, there's, I think a big debate is the prophylaxis. If you keep them in there and they're exposed to the chemo, then what's the egg quality, right? Preserving the quantity at the expense of the quality. And I think the jury is still out on that.
And really, in terms of the means of the fertility, it seems like these two agendas are opposed. You're trying to save the patient's life. You're trying to save their fertility.
I think less so. There's a lot more referral to OncoFER. But the science and the clinical practice, I think, is still quite young.
Even though cryopreservation is now no longer experimental, so it's in much wider practice, the autotransplantation is lagging way behind. So we have a latency where you have all this tissue piling up in these cancer survivors. Whether or not we're going to be able to get it back into those patients, whether or not we'll need to is the first question.
Some of them may not encounter any of the iatrogenic sequel egg. But for those who do, it's going to be many years before they come back. Particularly in the States, we don't have a very strong track record of transplanting back into patients relative to European groups.
And the bigger question, I would say, is it a moving target in some ways? Like it's still the first line, these gonadotoxic therapies. But nowadays, and the direction we're going with adaptive immune therapy and CAR-T, and even just garden variety, you know, PD-1 inhibitors, immunotherapy, that obviates the need for the carpet bombing approach. I think you wonder if maybe there's going to be such a need in 30, 40 years from now for this kind of further protective measure.
And by the same token, the means for preserving, like Kyle Orwig, for males, as you said, just to the last point, where I think there's a lot less consideration for males. But the good news there is that unlike the ovary, where you need to kind of preserve the whole unit of that primordial follicle with the oocyte and the granulosa cells surrounding it, with spermatogonia, they can be reduced down in mice, it's been shown. And I think in humans, there's a lot of progress being made that you can freeze in like a slurry of single cells almost, the spermatogonia, and then transplant back in and a single cell suspension to recolonize.
So many forces at work here, improvements in treatment, improvements in the restoration of fertility using that kind of cell and cryopreservation methods. You wonder where the both pharmacological, fertile protection, prophylaxis fits in there. And certainly, surgical transplantation, which is amazingly cumbersome, expensive, you know, with considerable risk and not very high efficacy.
So there, I just, you know, took my 10 minute monologue. But to say this is a very complicated issue with a lot of different interests moving along parallel tracks. I wish it was easier to get ovarian tissue without having general anesthesia and a laparoscopy.
Like why can't someone work on a transvaginal device with a wide bore where you can take cortical strips of ovary noninvasively in an outpatient setting and freeze big old chunks of tissue? Bleeding, a lot of bleeding. I don't do surgery, but wouldn't that be tough with the... There are devices that can help with bleeding. There are things that you could inject for bleeding.
There are medications to give for bleeding. I feel like it's probably because it's too niche. So no one's going to spend time, energy, and money developing it.
But we do so much transvaginally. Blake's program has a trial on using ablative devices to restore ovarian balance in PCOS patients transvaginally. We retrieve eggs transvaginally.
It seems like a really worthwhile thing to do to really maximize people's ability to freeze tissue. Yeah, well, then there's the freezing. The freezing is still another major obstacle, not to mention the reimplantation.
So it's just such a huge engineering problem. Science is just trying to catch up. Yeah, well, speaking of science trying to catch up, I'm going to end up with a podcast with just a palate cleanser.
I want to talk about the state of how we're training our next generation of women's health providers to have some of these nuanced discussions that we're all having. And this is an article entitled Closing the REI Education Gap in OBGYN Residency Training by first author Jennifer Law from Loyola University in Chicago. And our friend of the pod, Megan Sachs, who's now at Fertility Centers of Illinois in Chicago.
Molly, fun fact here for you. You are cited as an article in this paper, Cornfield et al. Strengthening Reproductive Endocrinology Curriculum Through Three Interactive Cases from 2023.
So I'm hoping that's our Molly Cornfield, but it could be someone else who knows. It's me. It's me.
Yeah, it is. So the whole gist of this paper is we are growing as a population. We're having kids at older and older ages.
And really the first line for having these conversations, screening and counseling patients is actually the bread and butter generalist OBGYN. It's not the reproductive endocrinologist, which are in short supply and located often in urban coastal areas and not in the middle of the country. This article is trying to point out that we need to really double down on how we train the average OBGYN and how we expose them to REI within their four years of training.
I'll ask you guys, Molly and Blake, how many weeks of REI training did you have in your OBGYN residency? Required four. But as most REI fellows do, I had a lot of elective time spent in REI facilities, but required just about four weeks. That's it.
Our residents here at OU do eight weeks. Yeah, our residents are doing eight weeks, or were doing eight weeks. So when I was a resident at OHSU, I did eight weeks.
But now I think it's down to six to seven weeks. And usually they're encouraged to take one or two weeks of their vacation on REI because then they don't need as much coverage. So I was about to say, I feel like most residents will automatically have vacation on our service too, because we're much more relaxed and chill compared to the other services.
Just, I mean, in terms of the demand of what is required of a resident. So when we survey programs that have and don't have REI fellowships, on average, if you do not have an REI fellowship, you get about seven and a half weeks of OBGYN exposure to REI. When there is an REI affiliated program within, it's actually less, it's six and a half weeks, which is interesting.
Kudos to the programs that don't have an in-house fellowship. They're doing more than we all were with in-house fellowships. The problem, of course, is that it's not nearly enough time to teach a resident about something that's so important.
They're going to become an increasingly large part of their practice in doing this counseling and evaluation. And unfortunately, that six into seven week time limit is actually often chipped into by vacation, being pulled for off-service rotations, taking board exams. It's really, on paper, it looks like a lot of weeks, but it's actually in practicality a lot less.
The problem here, of course, is that it's the patients that we all hope to cover and care for as we get out into practice that are going to suffer. There's a persistent knowledge gap amongst clinicians in core areas of fertility, infertility treatment, fertility preservation. And I think for us who are affiliated with the training of residents and medical students, it's a call to action for us to really double down on having something that's a bit more structured, trying to maximize the amount of hours spent doing some of that education.
And when we can, speaking to trainees about what it is we do, how successful it might be in giving them the tips and tools for counseling that might make their job a little easier and get patients into care a little sooner. So a really nice call to action. Hopefully it's resonating with the folks listening and for the people who have an opportunity to better expose themselves to OB-GYN trainees.
Let's all try to do a little bit better. Yeah, that's a really good message. It seems so simple, but it really is something that's so important.
I can't even begin to count the number of patients, and I'm sure you guys see similar scenarios where if a patient is trying to get pregnant, their provider, whether it be a primary care doctor or even a general OB-GYN, that means you should just take Clomid or you should take progesterone. But because it's a hormone, that means it's a fertility agent. And I'll have patients come to my office that are taking daily progesterone.
And I have to go over graphs and charts. And then at the end of it, I'll say, so what we call this is birth control. And they're like, what? Are you serious? They've been on it for months.
Same thing with Clomid. And this is a patient that has clearly unexplained infertility. They've even had a workup done by an outside provider.
And just because they're wanting to get pregnant, that means in their mind, just take Clomid and do timed intercourse. But then I have to tell them, well, you've unfortunately wasted months of your life. And so these are very, very simple things that I just it needs to be shouted from the rooftops and just say, just send them on to an REI.
Don't don't retain these patients and treat them inappropriately and waste time a lot of months of their life. But on the flip side, let's educate them a little bit better to do more of the workup, more of the counseling and avoid having MCS, because we are pretty limited resource. There's 1300 practicing REIs for a lot more patients than we can handle.
And if we empowered them with like, these are the bread and butter things you should check. This is an algorithmic way to start to manage PCO. To start to manage unexplained infertility.
I'd like to see patients who really stand to benefit from subspecialized level care. I think all of us are unfortunately seeing patients that don't need subspecialty level care. If the generalist just did a little bit more and felt a little bit more comfortable doing it.
And I think it's on us to educate them, teach them, empower them so that we see the ones who really need us. Yeah. Testosterone.
Don't prescribe testosterone to a male or female. I see men and women. It's like, who are these people putting these reproductive age people or patients on testosterone? Blows my mind how often it happens.
It must feel amazing. We're always joking about like, should we start microdosing testosterone? I bet it gives you a nice boost to your day. I'm sure.
Elon, comments, thoughts? Big testosterone guy these days? I could use some. I would say I'm not low T, but I'm circling the drain. Yeah, well, you got a full head of hair.
You're probably fine. Great head of hair. Guys, that's all the time we have for today's discussion.
It's a real treat being back with all of you guys and listeners until we see each other next time. Continue listening to our F&S OnAir, F&S Roundtable offerings and the occasional Journal Club Global that we're managing to put together and share with the world. We'll see you next time.
Bye-bye. 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.
