Fertility and Sterility On Air - Live from AAGL 2024: Joint AAGL/ASRM Podcast

Fertility & Sterility on Air brings you a panel discussion from AAGL 2024 in New Orleans, LA! We bring you a joint episode with ASRM and the American Association of Gynecologic Laparoscopists. Join Pietro Bortoletto, Rebecca Flyckt, Zaraq Khan, and Charles Miller discussing management of endometriosis and adenomyosis from the eyes of the reproductive surgeon.

View Fertility and Sterility at https://www.fertstert.org/

Welcome to Fertility and Sterility On Air, the podcast where you can stay current on the latest global research in the field of reproductive medicine. This podcast brings you an overview of this month's journal, in-depth discussion with authors and other special features. F&S On Air is brought to you by Fertility and Sterility family of journals in conjunction with the American Society for Reproductive Medicine and is hosted by Dr. Kurt Barnhart, Editor-in-Chief, Dr. Eve Feinberg, Editorial Editor, Dr. Micah Hill, Media Editor, and Dr. Pietro Bortoletto, Interactive Associate-in-Chief.

Hi everybody, there's no use in waiting one additional minute. I think we can go ahead and get started since we have a quorum. Welcome to an unusual event at the AAGL.

This is the third annual joint ASRM-AAGL live podcast recording. We have been coming to the meeting for the last three years and have had folks from the AAGL coming to the ASRM meeting for the last three years to talk about topics that overlap. There are still a couple of people at the ASRM who do surgery, despite what others say, so we're delighted to continue to be invited and be present at this meeting.

And Peter, there are still a couple of us MIGS people who do IVFs. That's true. Not a lot, but we have a couple of them here on the stage.

Like Dr. Miller was saying, my name is Pietro Bortoletto, I'm a reproductive surgeon and reproductive endocrinologist at Boston IVF, Beth Israel in Boston, Massachusetts. I'm also one of the media editors for Fertility and Sterility. On the panel today, we have three illustrious REIs who also do reproductive surgery, and I'm not sure that that's the correct order they would introduce themselves in, but from left to right here, we have Dr. Rebecca Flyckt, who's the division director at the University Hospitals in Cleveland, Ohio, Dr. Zaraq Khan, division director at Mayo Clinic in Rochester, Minnesota, and a man who needs no introduction, Dr. Chuck Miller, former president of the AAGL and a reproductive endocrinologist and reproductive surgeon.

Thank you guys for being here on a Monday morning in New Orleans. Great to be here. Thank you for having us.

So our topic today is we're going to talk about endometriosis and adenomyosis in the eyes of the reproductive surgeon, because we know that if you're a hammer, everything's a nail, but sometimes there's a slightly nuanced approach that one needs to take to diagnostic evaluation, counseling, and even surgical management for the patient who's actively trying to conceive, depending on kind of where they are over the arc of that journey. I wanted to kind of take this in a stepwise fashion, first start talking about diagnosis. We talk about endo, we talk about adeno, but we know that there's a significant diagnostic delay for our patients with pelvic pain.

Zaraq, I want to start with you, because you happen to be at the Mayo Clinic, where you have such a strong imaging department. Give us a little bit of how you view the role of imaging, specifically MRI and ultrasound, both for the diagnostic evaluation and surgical planning for endo and adeno. Yeah, that's an excellent question.

I think one of the nuances of endometriosis care and diagnosis is that the age-old diagnosis of pathology is now being challenged in basically diagnosing disease with imaging, because we've gotten so much better. I think that imaging has a very, very important integral role for the surgeon and for people that manage endometriosis, because it really gives you sort of a guideline and almost a roadmap of how you are going to decide to do your surgery. Not just imaging, but collaborative efforts and collaborative research, and also multidisciplinary conferences with your radiology department are extensively important.

And I'll give you an example of our program. When we started the advanced endometriosis program in 2015, we have started doing multidisciplinary care conferences with our radiologists. And in the process, not just for us as the surgeons, but also for our trainees, we have through these years trained our own eyes in identifying disease, learning from our radiology colleagues, to the point where now there's sometimes where us gynecologists can sort of pick up on subtle things that maybe the non-endo radiologist is missing, and that at our conferences that continues to come up.

So it's exceedingly important to have collaborative efforts with radiology. Of course, it depends on if you're an MRI or an ultrasound heavy program, and I think we now know that both have a very important role in identifying endometriosis preoperatively and adenomyosis for that matter. And it just depends on what kind of efforts are being held in your institution.

The ultrasound is a little bit tricky because it's not your usual conventional ultrasound. Usually these ultrasounds require time, dedicated radiologists or an operator that's knowing how to do things. And there's a whole checklist of things and also a bowel prep actually for the ultrasound is exceedingly important for DE into the bowel.

So those sort of protocols, and then having a standardized protocol and approach to all endometriosis when it comes to your institution's own protocols. So for example, we use a 3.0 Tesla MRI for all our MRs for endo. We give glucagon to slow down bowel motility, we use vaginal gel for every single patient to delineate the fornices and vaginal disease better.

So I think those efforts of standardizing and then of course studying it in an academic fashion and looking at research is going to be really important as well. Can you, I think we've had this conversation offline before. Talk to me a little bit about the role of having a radiologist in the operating room with the ultrasound probe themselves, real time, kind of correlating what they see with what you see.

Absolutely. Teaching opportunity and opportunity for them and for you. Totally.

I think that's really important as well. I think we continue, we want to be lifelong learners and I think that's the beauty of what we do. We continue to learn and evolve and we right now are learning how to do intraoperative ultrasounds for deeply infiltrating lesions into the bowel and also trying to look at margins and where do we take the staple line compared to just viewing it and feeling it with a robot or an instrument that's not as tactile.

The radiologists are having a new perspective and a newfound appreciation of what happens in the operating room and I think it's symbiotic for both because we're learning a lot from them and they're in turn learning from us too. So I think it just generates a very wonderful learning environment and also generates ideas for research questions even in the operating room when you're working on a day to day basis. That's the ideal.

That's the ideal. I know the people that he's working with at Mayo Clinic and they are an exceptional team. I mean Xerox with radiology spells success but many of us do not have that luxury.

I'm a private practitioner. I work at tertiary hospitals but I'm a private practitioner. For me it's very difficult as much as I talk with my radiologists for me to get the type of response with MRI that I would like to get, the types of reading.

We rely a lot on ultrasound. The way we do that is I'm working with my ultrasound tech and looking at that in real time. So while I would love to have Mayo Clinic at my back and I've actually talked to his people to come down to Chicago, the reality is you have to work out for yourselves how you can best define the disease.

Only say one more thing. Someone at this meeting, a well-known endometriosis surgeon, made the comment that I don't believe that much in imaging. I just get into the case and decide what I'm going to do.

To me that is surgical heresy. It makes no sense. You don't have an opportunity to set your goals, to define the goals for the patient and it is really wrong.

You have to be able to define the disease and understand what you're going to do so you can better talk to your patients both ahead of time and then have her understand when you're talking post-surgery. Yeah, I just want to jump onto that too. I think we're all in agreement here.

And you know, Zaraq and I published with a bunch of collaborators in fertility and sterility last year how do different gynecologic subspecialties approach a patient with advanced endometriosis. And one of the things that we all agreed on, GynOnc, MIGS, REI, was detailed preoperative imaging. And I think everybody here that's done this at different institutions, you just have to identify that champion.

There are people out there who are excited to do these, do these kinds of MRIs. I've done it now at two institutions, Cleveland Clinic and University Hospitals, and in each case I had to find a radiologist buddy who was really excited about it. My most recent hospital, we were lucky to have an MRI radiologist from Brazil, which is one of the big areas where they pioneered this work.

And once you have that person that has a special interest and can develop your protocol, you can take it far. But the other thing I was going to comment about the IDEA consensus guidelines for dynamic imaging for endometriosis is when you read about it, don't go for all four necessarily right from the beginning. Like if you look at it going to the third step, maybe you're not going to see two millimeters of endometriosis on the rectal sigmoid, but you can do a sliding sign and you can really start to practice your skills.

And I basically have replaced, you know, every one of us that does fertility, they get a pelvic ultrasound and some of us still do physical exams. So I kind of do it back as like a two for one. As part of their initial intake, they're going to get this scan with me.

I can map out where their pain points are. I can do parts one through three of the dynamic ultrasound for endometriosis, and I'm starting there as I build my skills towards like the full, the full four parts that have been described. I think one thing I was going to say is we often underestimate our ability to learn new things once we're done with training.

And I've been surprised by how much I personally have learned how to read MRIs and do detailed ultrasounds when I was on faculty and staff. So I think we can continue to learn these things with the help of our radiologists. Well, I couldn't, I couldn't hearken that more.

As someone my age, I'm still learning and I'm enjoying it. I think that that's the fun, in part so that I can continue to take the best care I possibly can of my patients and, and in fact, to still be relevant to all of you, to be able to talk. And many of you have been with me for many years discussing, et cetera.

And I think I owe it to all of you to still be that educator. And it's important because this is an area that is so important both to pain, both to fertility, really it sets, it sets the family. We know imaging is not the only way to diagnose endometriosis and adenomyosis and both at this meeting at the ASRM that we all attend, there are an increasing number of groups that are working on biomarkers, serum biomarkers, endometrial tissue biomarkers.

I feel like there's often a disconnect between what the REIs have in their armamentarium for diagnostic tools and what the average minimally invasive surgeon has. By a show of hands, how many have heard of the Receptiva test? Yeah, a very small number of folks. Receptiva test in ASRM REI land is a ubiquitous test for folks who have implantation failure or having pelvic pain, failure to implant good high quality embryos.

And it's an example of a test where you're not looking for direct signs of endometriosis but you're looking for indirect markers of inflammation. So this is a biopsy collected in the luteal phase of the cycle that's looking for presence or absence of BCL6 which has been studied and shown to be associated with either hydrosalpinges or endometriosis but is a tool that sometimes we have available to us to encourage or to at least broach the conversation with that patient who has unexplained infertility, hey, you might have endometriosis. I'd love to hear from you all who both do surgery, appreciate the value of imaging.

How are these other biomarkers, both serum and tissue biomarkers, fitting into your practice and specifically where over the arc of the patient journey are you discussing them? Are you waiting for failures to happen? Are you doing it to help them understand, like, I think you have endo. I have now tissue or serum evidence to suggest that you have an associated inflammatory marker with endo. Maybe we should talk about treatment.

So I can start us off. I think it's fascinating to see how few people have heard of these tests because certainly in our world of REI, I mean, it's being marketed directly to patients and they're asking for it. And even my friends who are general gynecologists are, you know, calling me up on the phone, like, what is this test? I had a patient ask for an endometrial biopsy.

So it will, I'm sure, make its way to you. I'm at an academic center. I mean, we're all academicians and so I'm a late adopter for some of these things.

I mean, I think there still is a burden of proof that needs to be satisfied for us to use it routinely. But just to step back a little bit, you know, it's a protein that we're looking at that is associated in some studies as an inflammatory marker that may signal endometriosis or hydrosalpinx. And you can do an endometrial biopsy, send it off, and it can give you a level that is supposedly indicative of disease.

I think my concern with it, and I'm curious if you guys share this, is, you know, I can do a laparoscopy and find endometriosis on almost anyone. And so, you know, you get a positive BCL-6 and then you go in and do your laparoscopy and you take out the endometriosis, but I'm just not sure whether the kind of endometriosis that we find with a positive BCL-6 is clinically significant, and then also whether removing it actually improves outcomes. And I think that's really the next step in the research around this and other non-invasive biomarkers.

I mean, there was a review recently. There's literally hundreds of salivary, urinary, serum, endometrial biomarkers. Like, this is the holy grail that everybody is looking for.

And even on the exhibit hall here, you'll see, you know, plenty of non-invasive detective methods that are being marketed. So I think we just need more and better research. That's kind of my takeaway.

But is that part of the problem, that we're still talking about endometriosis as one disease without the level of nuance and detail that we see in breast cancer, where we have estrogen receptor positive, we have genetic versus not hereditary versus non-hereditary breast cancers. We have so much more detailed information about the pathology in front of us, and we're still talking about endo. Yes, no.

Yeah, because it's, I just want to add one thing, is that, you know, we think about it, implantation failure and mild endometriosis, and you're sitting there saying, how does that work? How does that work? Well, the fact is, is that, remember, that endometriosis is, even in its mild state, is an inflammatory condition. And that inflammatory condition sends or increases estrogen locally. And that endometriosis talks back to the endometrium.

So you get an estrogen-like dominant endometrium. So I looked at this study with Receptiva. There is a large difference between pregnancy rates and non-pregnancy rates with treatment of the disease when the inflammatory marker, the Bcl-6, is noted.

So that is- And for the audience, Chuck, what do they prescribe as treatment for endometriosis? So then the treatment is either to proceed with surgery or to proceed with a GnRH agonist. In the United States, it would be Lupron. And I'm surprised that they talk about two months of Lupron, because that never worked for me.

But that's what they talk about, and they show the success both with surgery and with medical treatment. My point is two. Is number one, I look at it from a standpoint, if I have someone 40 years old with two euploid embryos, two normal embryos, and they're getting ready to put back one of the embryos, I'm going to try to create that endometrium to be as great as it possibly can.

So I do look at timing. I do look at infection. And I do look at the possibility of endometria or inflammation.

I always explain it as inflammation. We find very, very similar success rates between the medical treatment, surgical treatment, and we advise our patients on that. Many people will choose the surgical treatment, because obviously it is a faster time to be able to implant the embryo.

And secondly, we have found in working with this that not only is the inflammation related to endometriosis, but as you guys said, related to tubal disease, and we've even seen inflammation via adhesions. We've had a couple patients with subacute appendicitis that all is a factor. So we think that it is an important marker, at least at this point.

So I think this is a really interesting conversation, right? Because I feel like I am somewhere in between. Because when I do, full disclosure, we don't do receptiva testing in our practice at this point, because we just don't feel like the evidence is as compelling, even though there are some studies, as Dr. Miller described as well. I have yet to give you a formal percentage, but I can tell you more than half of my patients with positive BCL end up having minimal to no disease.

So I always wonder as well what the role of excision of disease there is. And just so we can understand this, I love what you said, Pietro, which is we are probably thinking of a disease that is very, very different in different areas or different organ types that it affects. And a little bit of that is some of the work that I do with my translational scientist group, who are immunologists.

And we're looking at the molecular signature of endometriosis, depending on what organ system it involves, whether it's peritoneal, ovarian, colorectal, bowel, ureteric or bladder. And it's fascinating the differences we're finding. So like for the colorectal endometriosis, the molecular signature that the disease leaves behind is very similar, or your immune response to the disease is very similar to that of colorectal cancer.

You have a huge uptick in your T helper cells in that pathway, whereas a peritoneal disease does not rev up the immune system as much as colorectal disease does. Well, that's great in theory, but I think we have to translate that into pregnancy and pregnancy outcomes. Because if you truly take that philosophy of inflammation equals bad, then colorectal resection should really enhance pregnancy rates, which we are yet to see.

So I think that we're just scratching the surface of this when it comes to biomarkers. And I'm really excited where the field will take us, because there's a lot of potential with diagnostics, especially in the messenger RNA area, with the Nobel Prize going to that area as well. I think there's going to get more attention there.

And it's interesting. So that comes back to the way we view the literature, the way we view the literature. Because in my, I'll acknowledge virtually all the studies on bowel disease and pregnancy are single site studies.

They are generally case studies that you have a number of patients, you look back at pregnancy, they are not controlled at all. Many of these people end up getting GnRH agonists as part of their study. Many of them are trying on their own versus immediately to IVF.

So there's a lot, a lot of wrong in the studies. But when I look at the body of work, I think that working on deep infiltrative endometriosis, bowel endometriosis, can certainly enhance pregnancy rate. So it's the way you look at the literature.

And I actually completely agree with that, because that's what we do as well, but it's just a deficiency of the literature and issues with the literature. Agreed. Agreed.

And just one more quick point, because all of you are going to hear from patients who are interested in this kind of testing, and they're going to ask you to interpret it. So I will say, wearing my fertility hat, I do use it. I use it for patients who have recurrent implantation failure, which you can define as implantation of two to three healthy, often PGT-tested embryos.

I also have started to use it in some of my patients with recurrent pregnancy loss outside of an ART context. So I think all of us have to take our best guess at what the literature is telling us now. There are studies, as Chuck alluded to, that are supportive of BCL-6.

However, a lot of those were published by the people who are making the test. And then there was a randomized study that showed lack of benefit. So again, this is just sort of an appeal for good and unbiased, better quality research, because I think this is a fascinating topic.

Well said. I will tell you that I order it. I have ordered, I think, 11 or 12 of them over the last two years.

My hit rate is 100%, because I only order it when I know someone has endometriosis. But I need an additional piece of evidence to suggest that their endometriosis is real and worthy of treatment, because there's so much apprehension about two months of Lupron and what that does to ovarian stimulation response for patients who don't have frozen embryos. Waiting two to three months to get on a surgical schedule with recovery before transferring embryos.

So for me, I use it as a way of really driving home the point, I think this is what's going on, and I think we can make a couple of things better, and here's an additional piece of proof for it. But if you're a MIG surgeon and your REI friend asks you to look because the patient has a positive BCL-6 and she chose surgery, make sure not only are you looking for endometriosis, but you're looking for other potential causes of inflammation, and make sure you check the tubes. Make sure you check those tubes, because that's one of the other factors too.

One question I'll pose to the group that we haven't really discussed about, and just a quick yes-no, CA-125. There's an overwhelming amount of literature about the role of CA-125 as a marker for endometriosis, specifically endometrioma. Is that something you have ever used in your practice as a diagnostic tool, or is that something that you let the oncologist take care of? I mean, I think with the imaging we have right now, that is, I believe in advanced imaging really being a better guide than CA-125.

I don't know about you guys. Yeah, I agree. History, physical, imaging, I think CA-125 is too nonspecific.

Yeah, agreed. Now, we've talked a lot about endometriosis. We know adenomyosis is, we think, likely on the same spectrum of disease, just located differently and acting in a slightly different way, but fundamentally kind of the same biologic process.

How does the co-occurrence of adenomyosis in patients with endo, specifically deep infiltrating endo, complicate our ability to diagnose, treat, and most importantly, study the individual impacts of these diseases? Should we really be segregating them as different disease processes, or should we have a better way of conceptualizing this full-spectrum disease in the pelvis? Well, I'd be most curious to see what my other panel members say, but to me, I think it's still a very interesting phenomenon, because when I talk with my radiology colleagues, and I think I heard Chuck mention it yesterday as well, that adenomyosis and endometriosis, they're almost, there's two variants, if you look at disease in the uterus. So there's disease that goes from out to in, and that typically is considered endometriosis that's infiltrating into usually the torus uterinus, or the posterior retrocervical area, or where the uterus acryls meet. And then there's disease that sort of is almost coming from the cavity out into the wall, which is our classic adenomyosis.

And I think that we, at least in our practice, we think of them as two different things and treat them differently, but I'm curious to see what others think here, too. I think that's a really, really good point, because when we talk about bowel studies, deep infiltrative endometriosis, we talk about the fact that, well, that patient had adenomyosis. But what Zarak is saying is that adenomyosis is really out to in, it's as part of the deep infiltrative endometriosis, it's an extension into the uterus as well as into out.

So I think that if I were doing studies, if we were doing a multicenter study, I would include those patients who have adenomyosis that is next to the deep infiltrative bowel disease. Saying that, I think that too much of the time, too much of the time, and my friend Keith Isaacson will say this, that we look at infertility as basis of endometriosis when in fact, because there is such a big correlation with adenomyosis, that it's really the uterus that is failing as opposed to the pelvis. And I'd like to hear you, what you're feeling about that, Rebecca.

No, I think these are great points. I mean, I will say, yes, I think of them as cousins, but I do think that the pathobiology is actually distinct, and there are some interesting molecular studies that it is distinct as a disease, maybe along the same spectrum as endometriosis, but not exactly the same. And I think that there are studies emerging that how we can and should manage it in a fertility patient may also differ.

So I think I would be directed a little bit more towards surgery or excisional surgery, you know, for someone with endometriosis, either before IVF or after implantation failure with IVF, whereas adenomyosis, you know, I think in my practice, at least, I'm going to favor a suppression protocol. And I think there's some really exciting studies coming out of how we can manage adenomyosis histroscopically, because historically, those surgeries, at least for me, you know, if you've got a big adenomyoma, I mean, those are big, morbid surgeries, especially for the pre-pregnant uterus, you know, you're cutting into it and doing a complete home makeover. So I think that, you know, we need to be very cautious about how we intervene surgically on adenomyosis, because I think sometimes we can do a little bit more harm than good with some of these big surgeries for people who are doing IVF.

Well, let's talk about that specifically. With the 15 minutes we have left, let's move on to treatment. And I think treatment for endometriosis, I don't think there's much in the way of innovation, probably tools, but we kind of understand the major paradigm of how to do it.

I think adenomyosis is where we probably have the most amount of distance to travel. And specifically, I want to talk about the role of radiofrequency ablation for adenomyosis, be it diffuse or focal. I want to talk about sclerotherapy as a tool for adenomyoma treatment.

And finally, what Rebecca said, is hystroscopic approach for the treatment of adenomyosis in patients, all who are desiring future fertility. Chuck, tell me a little bit about how you view radiofrequency ablation as a tool, in the context of having a real paucity of evidence on long-term reproductive outcomes for these patients. There really is a paucity of evidence, I totally agree with you, and especially in the United States.

We have, there are limited numbers of studies. Most of the studies actually come out of China, come out of Asia, and does show actually a very, very good subsequent pregnancy rate, similar, about 40%, similar to what we have with a surgical approach. There is a higher recurrence rate, but it is less than 10%.

And obviously, to go back to what Rebecca said, you don't fillet the uterus like you do when you do a surgery, in a very extensive adenomyosis surgery. So I do think that that will have a place with focal disease, with adenomyomas. I certainly do not feel that it has a place with diffuse endometriosis throughout the uterus, adenomyosis.

I think that's one of the best and most important takeaways, which is not all adenomyosis is created equal, and it used to be that adenomyosis was a pathologic diagnosis, but getting back to our imaging, I mean, you can absolutely detect adenomyosis now with advanced ultrasound and MRI. And so I think the key concept in how we're going to manage is really, like, is there just a big chunk of it that's an adenomyoma, or is it just diffuse disease? And you can really see those different phenotypes, similar to how we have different phenotypes with endometriosis. There's peritoneal disease, ovarian disease, deep disease.

So same with adenomyosis. You can really start to categorize it, and then that categorization is going to be what guides your treatment. Let me make one more point about using RF frequency.

Before you start doing assessment sonata in your patients with adenomyosis, I think you better make sure you're doing this under investigation, because at this point, we really have no indication for either of those in the United States. Yeah, I have to say, in speaking with a lot of my MIGS colleagues, I'm not sure that there's a lot of awareness that, like, even on the website, it says this is not indicated for women who want to become pregnant. Actually, the pregnancy rate data is very reassuring.

I will absolutely go with that. There's plenty of women who have gotten pregnant after radiofrequency ablation. However, like, it is on the manufacturer website that we don't really know what the risks are.

And so I think, at least just from an awareness standpoint, we have to know that if you do it, there's some special counseling that probably should go into that. And also, if you have the ability to do it under an IRB, that gives you that extra protection should something unfortunate happen, you know, and you've used this device in a way that it is not indicated. Rebecca, tell the audience a little bit about the hysteroscopic approach for the management of adenomyosis.

You had talked a little bit about how there's some interesting techniques and approaches to this. How do you view hysteroscopy as a tool for this disease that has now left the cavity and is now in the muscle? Yeah, I mean, I'm curious what my co-presenters say. First of all, just because I know we're wrapping up soon and this is a podcast, I just have to say that there is, like, standing room only here right now, which is just so exciting that people are this engaged about reproductive surgery.

Chuck and I were commenting about this with our session yesterday. That's great. We've been doing the reproductive surgery session together for the last, I don't know, seven years.

And I remember a time where, you know, it was us and the 12 people in the room. Echo's in the hall. We're so back, baby.

So I just love that you guys are all here and your engagement and that ASRM and AAGL are doing this podcast together. I just think it's a bright new day. So I just wanted to say thank you for coming and for coming to the session yesterday.

But in any case, there was a video I think we published recently on FNS for our surgical videos. And people are doing some really cool things with hystroscopic treatment of adenomyosis. I think that just kind of like with isthmus seal, this may be part of our evolution for the reproductive patient.

And you know, you will probably have to go back to learning how to use a resectoscope. I do think that resectoscopy is not dead. That's one of the sessions for today.

But there's some real artistry in carving out those crypts that you see in the uterus. And Chuck had a great video on that that we shared. So I think that that may be what's next.

We need to make sure, and this goes back to the very beginning of this talk, this session. We need to image. It all is dependent on image.

The case that I showed, I initially thought I was in bowel. I was so deep. It was the endometrioma.

It was the adenomyoma that was cystic. Well, I knew that. I'm just kidding.

I knew that I was there because I had imaged before. I knew exactly where I was going. But had I done this without imaging, I would have stopped and I wouldn't have treated that patient.

So imaging, imaging, imaging is so important with these disease states. I couldn't disagree more. And I think as one of the things as I think about adenomyosis and bringing it forward is a plea for some form of a staging criteria for adenomyosis, because as we have been talking about, it is a very varied disease.

So you can have that patient with a thick and junctional zone and an otherwise completely normal looking uterus. It's not even soft and boggy on laparoscopy, but that person still has adeno and has all the symptoms of adeno, versus you could have localized adenomyomas, which our favoring is to surgically excise that, versus I saw a patient with a 28-week uterus, that in my opinion, not much is going to help that patient. And so how we talk to patients about their fertility goals then becomes really important as well, because you're constantly walking this tightrope of making sure you're catering to their GYN needs of pain, dysmenorrhea, and menorrhagia, but also talking to them about their fertility.

And if we have a little bit more of breaking down this disease in an organized manner, then you could say, yep, you get surgery for X and gestational carrier for Y, because your uterus is 30-week size, for example, whereas the thick and junctional zone patients could go on Lupron and possibly an embryo transfer. So I think that's where we need to start putting our efforts, and a forum like this where the minimally invasive surgeons and the ASRM is coming together, I think it's a really nice opportunity to start talking about that. You couldn't agree more.

I couldn't agree more. We need that. I was waiting.

Imaging, imaging, imaging. Oh wow, the gauntlet has been thrown. So one big question, and we're running at the end of our time, is you all care for these patients surgically, but they are often also seeing us to talk about their fertility goals.

And one of the questions that we get a lot is, should I freeze my eggs? I don't have any endometriomas, but I have endometriosis, or I have a small 2-centimeter endometriosis not trying to get pregnant any time soon. How do we conceptualize that conversation for the patient who's not ready to get pregnant yet, but we know has a disease that will speed up ovarian aging, decrease oocyte quality and reduce their reproductive potential as this disease progresses over the many, many years before they're ready to conceive. How do you talk to them with and without data, Rebecca, about freezing eggs ahead of laparoscopy? Yeah, I mean, I think that's the fun part for all of us that can do the ART and do the surgery is talking about if and when somebody should freeze their eggs.

And this has been a hot topic for a while that is, I think, understudied. I don't think we have good data. And as Pietro said, we're in the process of trying to complete a cost-effectiveness study to see, OK, at what age is it actually cost-effective to freeze your eggs? And Pietro and I were saying it's probably going to be in our early 30s, not spoiler alert for when we get our publication going.

But we'll see. And on the one side, I don't think I've ever managed a patient who's like, oh, I really regret freezing those eggs. But I think that we do know that the cost is significant for a lot of patients.

And so we're trying to figure out that tipping point. There's a sort of flow diagram that my surgical mentor, Tommaso Falcone, and I put together that's been widely adopted. I've seen it in a bunch of talks that basically triage is based on age.

Have you had previous surgery? What's your AMH? Do you have bilateral OMAs, or is it just unilocular disease? And that's really the worst quality of evidence, even as someone who helped put it together. I think they call it BOGSAT, like a bunch of guys sitting around talking. And that was us.

You were sitting around talking. We were like, oh, that makes sense. But I think we actually need some kind of data to inform when and whether people should freeze their eggs.

Can I pivot a second? Sure. Just a second. Give the old man a thought here.

You know, when you're working with your patient who's newly been diagnosed with breast cancer or Hodgkin's disease, whatever, you would not be happy with going to the oncologist and the oncologist does not talk about freezing eggs if she's going to get adjuvant chemotherapy. We know, especially in the case of bilateral endometriomas, but even with large endometriomas, that you can significantly impact AMH and the ovarian reserve. What I'm saying to all of you is, and I'm passionate about this, I think we are wrong if we do not have the discussion with our patients about potentially freezing eggs at that time in a situation where we are going in and doing a surgery that could negatively impact her chances of successful pregnancy.

Now, I certainly understand someone who has to have an emergent procedure. But there are plenty of patients who have discomfort, know they want and need surgery that are willing to do egg freezing. And we know that stimulating an endometrioma is going to be very, very, there's going to be very little with our protocols, with our few days of giving them gonadotropins.

So my take home is please, please, please, please, when you're going to do an endometrioma, have the talk about the patient with freezing eggs if you can. Particularly if you're going to take them back for that second cystectomy on that same side. That truly is the kiss of death from an ART outcome perspective.

That ovary, when you're trying to stimulate it after a second cystectomy on the same side, doesn't do much. I'm going to try this one more time. I couldn't agree more with Chuck this time, and I actually have a very similar conversation about dermoids as well.

We see them bilaterally quite often. I can't tell you the number of times I see a patient with a previous oophorectomy for a dermoid, and now they have a recurrence on that side. So we know 15% will be bilateral.

Just like other inherent risk to fertility, endometriosis is a risk to fertility. We've done a study within our population of about 500 patients, and oftentimes it's eye-opening because we feel we can't make decisions for patients. Just because we feel like she may not want to do oocyte freezing or she may not be able to afford it is not the right thing because about 28% of patients that said to the surgeon that I'm not going to freeze eggs, but just met with an REI, actually did freezing in our cohort.

And so it speaks volumes, and there's a lot of literature from Scandinavia about regret and fertility preservation, but just by talking to an REI and explaining the process to the patient, a lot of patients will actually do that and do the right thing for themselves and get some insurance on their fertility. And just to piggyback on that, for folks that are not in the REI world, I mean I think it would be very important to order a preoperative AMH in any patient that you plan ovarian surgery, endometriosis or otherwise. It's easy to order.

You don't have to get it at any specific part of the menstrual cycle. It's steady state. And like any sort of tumor marker, you know, it can give you like a pre and a post value.

I do not check an AMH for three months after an endometriosis surgery because there's clear data that it's going to bottom out and then do some recovery. So don't freak your patients out by checking it too soon. But I do think checking that AMH is critical.

And then just to kind of give a window of like what's now and what's next, there's a grant that we put in to look at endometrioma excision. And when you actually look at it under the microscope, like there's always ooze sites that come out with your endometrioma, usually like closest to kind of the hilum where it's very sticky. And we can actually now with these biphasic protocols in vitro mature those ooze sites and freeze them.

So I think that's really like the best crosstalk between MIG surgeons and REIs, which is, you know, if you're the ones that are getting these endometriomas out, maybe we can take them in the lab and do some elective egg freezing at the time of their endometrioma excision. So I think that's really exciting. And just a word on AMH since we get asked about it a lot.

You absolutely can check an AMH while someone is on hormonal contraception. The data suggests that the value is typically about 15 to 20% lower than if they were off hormonal contraception. But if you have a reassuring AMH on hormonal contraception, it's only going to be better off.

The tricky part becomes when you have a low AMH, then that discussion of is this real, is this artificial from the hormonal suppression and just have to prepare patients ahead of time for it. Another thing that you can also do is on ultrasound as you're looking at your endometriomas, look at the follicles. Look at the number of cystic structures below 10 millimeters and that can tell us that someone has a lot of antral follicles and that's a good surgical candidate without potentially needing to do egg freezing.

And that again, if you don't feel comfortable with that, consultation with your local reproductive endocrinologist I think is worthwhile for that patient. And I just think we're moving beyond like see a cyst, take out a cyst. I have had patients where I check their AMH and if it's really low, we might talk about whether it really makes sense to go in for that second endometrioma surgery.

Maybe not if it's two centimeters, three centimeters. There's other ways to manage pain now medically. So I think we just have to get more thoughtful and when we operate on the ovary of reproductive women.

Or even when you see it the first time, that age old question of do you do surgery first, do you do IVF first or fertility treatment first? And I think that's a really important conversation that is multifaceted but primarily based on the patient's age, infertility history, their ovarian reserve and their desired family size. I think those are all really important questions to have prior to going in for that disease which is also important. I wish we had another 45 minutes but we don't.

I wanted to thank our panelists for being here early on a Monday morning at the Expo Hall and thank our audience which as Rebecca noted, full audience sitting, full audience standing. Thank you for your interest in this topic. We'll be around for questions if there are any afterwards.

But thank you all. Bye. Thanks, Pietro.

Thanks, guys. This concludes our episode of Fertility and Sterility On Air, brought to you by the Fertility and Sterility Family of Journals in conjunction with the American Society for Reproductive Medicine. 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 hosts, it is not intended to be the only approved standard of practice or to direct an exclusive course of treatment. The opinions expressed are those of the discussants and do not reflect Fertility and Sterility or the American Society for Reproductive Medicine.