You're listening to the fertility docs, uncensored podcast, featuring insight on all things, fertility from some of the top rated doctors around America, whether you're struggling to conceive or just planning for your future family, we're here to guide you every step of the way.
Speaker 2Hello? Again, this is Dr. Susan Hudson with fertility and accents censored. We are going to have an exciting talk today with Dr. Kaylen Silverberg from Texas fertility center about endometriosis. We again have Dr. Carrie BDN from fertility center of Las Vegas. Hello and Dr. Abby Evelyn from Nashville fertility center. Hi everybody. Hey Katelyn , how are you doing today?
Speaker 3Well, I'm kind of shut into my house. Like everybody else here. It's, it's a , you know, it's the beginning of April and I think that we're all wishing we were outside doing a lot of other things in what we're doing right now, but otherwise
Speaker 2Good stuff. Good stuff. So I have a question for each of you, if you had your crystal ball and you could predict one positive thing, that's going to come out of COVID-19 what would it be?
Speaker 4I think that the over-scheduling of kids and activities is going to drop way back, because I think that the going to baseball practice, you know, every other day in games, all weekends or soccer, soccer practice or whatever, and the drive to push, push, push, push, push, I think that's going to get dropped back considerably because even though most of our kids are not in school right now , um, for those of us who are fortunate enough to have them and, and so many other activities have been put on hold, I think people are going to realize that it's okay not to be scheduled every minute of your life and that it is not necessarily a virtue to be scheduled every second of your life. That's my production.
Speaker 5I think many, I think many people will think a lot more about hygiene issues and go into large crowded environments with a lot of people. I think, I think some people probably have a little bit of almost PTSD post-traumatic stress disorder just for being in large groups. And I think it'll take a while for some of us to kind of get used to being back in large groups. Again,
Speaker 4I totally agree. I went to the grocery store and waited an hour and a half in line to get into Costco on Friday because they had , I mean, they had a beautiful system set up outside. It was a gorgeous day. Everybody was easily six feet or more apart from each other. Um, and the store itself was pretty empty because they were keeping it so empty. But I , I found myself getting more and more anxious the longer I was in there and around all these people that I didn't know, didn't have the same sense of protection I do in my own, my own really clean house right now.
Speaker 2I always think of it as like in dirty dancing when it's like, this is my dance space and this is your dance space. We've all extended our dance space a little bit. Absolutely. What do you think Kaylyn ?
Speaker 3I think from a, from a business perspective, I think that businesses are going to realize that maybe you can get a whole lot done with technologies that allow you to telecommute , uh , that you can have a lot of your people working from home. If they want to, that you don't have to have all these face-to-face meetings. Um, I feel bad for the airlines because I think there's going to take a long time for them to recover. But I think that a lot of business people are really going to rethink. I mean, I know I travel almost every week , um, and , uh, I'm certainly be thinking how I approach that. And I think that a lot of companies are going to rethink that as well, that they can get a lot done over the internet. And , uh , you know, you're, you're almost face-to-face , I mean, you know, we're doing this now with the technology that allows me to see you guys and, and , uh, you know, yet we're not in the same room, but it feels like we're in the same room,
Speaker 5Our own medical practices, have we, as we've all discussed, you know, it's just amazing. I never thought I'd see the day when I would be working from home. I just didn't think that was a possible thing to do as a physician, but yet it's worked and it's actually worked pretty well.
Speaker 3What kind of visits are you all seeing from home now? Uh ,
Speaker 5Basically new, I mean, new patient visits, consult visits, you know, the only downside for the patients is that at some point they will have to come in for an exam and they will have to come in for an ultrasound and blood work, but you know, really a lot can be accomplished without, you know , having, having to be in the same office together.
Speaker 3Yeah. And I agree with that too. We're even doing pre-ops and post-ops over a , over this technology as well
Speaker 4For us, I will be really interested to see, and I've , I have started to see it in some platforms of how do you do an eye exam? How do you do an ear exam? And more importantly, for us, especially with our pre-ops, how do you do a heart and lung exam remotely? And what is your patient need to have in order for you to get the information you need and then expanding? I mean, so much of what we do is based on touch, especially with our abdominal exams, but , um, but how do you, how you get at least some of that information remotely?
Speaker 2I think it's amazing though, how , um, how much of us we have avoided going to tele medicine and things like that for so many years, because quite frankly, you know, a lot of this has been available for many years, but many of us , um, I think all four of us included have kind of avoided it until we needed to do it. And we were able to relatively spend on a dime to ramp everything up and get everything moving so quickly that really the ease of being able to do it was like, oh my goodness, why didn't I do this earlier?
Speaker 5Well, I think part of it is insurers are willing to cover it. Now that was the other, we did telephone consults for a while early on when I was in our practice and then insurance providers stopped covering it and they wouldn't do it. And patients really wanted it, particularly some of the patients that we have that are two or three hours away, but it wasn't covered by insurance. I think that's going to change after this.
Speaker 3I hope that the changes that we're putting in place now or are long lasting, because I think that everybody benefits. I mean, you know, I , I kind of joke with my patients the other day about this. And when I was talking to several of them that, you know, you're going to have to give up that long drive to the office, you're gonna have to give up looking for a parking place. You're going to have to give up sitting in the waiting room, reading old magazines, you're going to have to give up waiting on me, you know, until, you know, till I'm ready to see you and can get you in, you know, you're just going to have to sit at home or sit at the
Speaker 2Office and, you know, just pick up the phone and call me or I'll call you. And, you know, it's, it's just, I mean, everybody was laughing about it because it's incredible. But I think the insurance company issue is a big one because they've been forced now by government to pay for these things that they should have been paying for all along. And I'm just hoping that they don't find other ways to take advantage of the current situation to their benefit because that's what they specialize in. And hopefully they won't. Yeah. We're all hoping that the positive things stick around for sure . Yeah. Yeah. So kind of on the positive , um, Kayla, we've asked you to come here today because you have so much experience dealing with endometriosis in so many different ways. You've had patients that have had so many unusual presentations with endometriosis. We wanted to kind of get your perspective on what used to be done. What's done now, you know, where do you see things going in the future?
Speaker 3Well, you've been doing this for so long. Oh my God. Tell us what it was like in the horse and buggy days. But , um, endometriosis is an interesting disease. Uh, it's an unfortunate disease because the severity of the disease and the symptoms, severity decisions really have nothing to do with each other. And that's something we don't like in medicine. You know, we love it in medicine. When the line goes from the Southwest to the Northeast, we like it when the severity of the symptoms as they get worse and worse, it means that the disease is worse and worse. And we can predict what we're going to find. We can predict how we're going to treat people. We can predict how they're going to respond, what their prognosis is going to be. It's all great. But the problem now is , is that with endometriosis, it just, unfortunately doesn't work that way. So because okay, with you, I'd like to kind of start off with, you know , a description of what endometriosis is and what I tell them. Well, what I tell my patients is endometriosis is basically normal uterine lining in an abnormal location. Okay. So uterine lining should be inside the uterus. And my patients know I've got stupid analogies for everything. And my analogy for the uterus is the uterus is like a jelly donut. Okay. The muscular walls of the uterus are like the dough and the donut and the cavity where the baby goes is like the jelly and the inside. Okay. And so when you talk about that, you understand that the jelly belongs on the inside of the donut. Okay. It doesn't belong anywhere else on the outside of the donut . So even it's like with add no meiosis , when we talk about add no meiosis, which is where the uterine lining invades the wall of the uterus, I say, okay, it's like somebody comes along now and they step on that jelly donut. And so now you've got jelly in the middle of the dough. You got dough in the middle of the jelly. And just like you can't put back together a jelly donut that's been stepped on and make it perfect. You really can't ever completely get rid of add new miosis . And that's part of the problem with it . So stupid Silverberg analogy. Sorry.
Speaker 4I may use it Caitlin , as long as we're ruining foods that I love. Tell us how you describe endometriomas.
Speaker 3Oh boy. And an endometrioma I guess is like, you know, jelly in the middle of the ovary. So, you know, what happens when you think about the pathophysiology of endometriosis? In other words, how does it occur? Well, so there are a lot of theories about how it occurred, but the big theory that really caught hold is something called retro grade or backward menstruation . So we know that when women have periods, 95% of that fluid goes forward because through the cervix, into the uterus and out, but we know that 95% of the time, some of that fluid goes backward as well. And some of those cells, some of that jelly from the inside of the uterus, when those cells enter the abdominal cavity through the fallopian tube, those cells are alive and they can attach to the ovaries, the bowel, the bladder, the sidewall of the pelvis, and they grow. And every month as that normal uterine lining cycles, those abnormal uterine cells cycle as well. So every month when a woman is bleeding forward and she's bleeding backward, those implants of endometriosis that she has in her pelvis or bleeding as well. And that leads to scarring that leads to production of chemicals called cytokines and cytokines can do a lot of different things. And there's several different types of cytokines that have been identified with endometriosis. One of them , um, people may not recognize what it is, but they know how to treat it. One of them is called prostaglandin and prostoglandin is a hormone that makes the uterus really contract. And it's responsible for those nasty cramps that women get sometimes with their period. And they may not know about prostate gland, but they sure know how to get rid of prostate gland in because they raced to the store and they get a non-sterile Laney , inflammatory, they get Advil, they get a leave, they get, you know , other types of ibuprofen derivatives, and that interferes with prostate gland and production. And that's why cramping goes away. So, you know, I think that that's one of the cytokines, but there's two other categories of cytokines that I talk about my patients all the time. And one of those is a class of cytokines that can interfere with fertilization. And the other one is the class of cytokines that can actually interfere with implantation, with the ability of an embryo to attach to the uterus. And so those are all very, very important. And that's part of the mechanism of how this causes, how this nasty disease causes infertility. So as far as symptoms, I don't want to make this a monologue. You guys feel free to jump in. You want to, but as far as symptoms go, you know, people will tell me all the time. Well, I don't think I have endometriosis because I really don't have much cramping with my period, or they'll say to me, I know I have endometriosis because I have pain with sex or because I've got Televic pain in general. And granted, those are three of the most common symptoms of endometriosis, but the other most common symptom, at least in our practices is infertility. So, you know , about 75% of women who walk in the door with complaints of , of infertility are going to have suspicions that lead you to think that they may very well have endometriosis. And they may very well benefit from an evaluation for that
Speaker 2Katelyn . Um, there have been some changes over time about how a fertility doctor deals with endometriosis 20 years ago, you walked into a fertility doctor's office. You pretty much were signed up for a laparoscopy. What are your thoughts on that?
Speaker 3Well, so you're exactly right. You know, when I was in training, we were taught that that the evaluation of enemy of a , of infertility was a six step process. One step was something called a post-coital test, which has been relegated to the Ash bin of history. We're not doing that anymore. And another of those six steps was laparoscopy. We would laparoscope everybody who walked in the door. Well, Thomas Vaughn , our senior partner and I years ago looked at this and we tried to come up with something called limited laparoscopy. And so what we did was we developed an algorithm that we used in our practice for a while . Then we actually published it in clinics of north infertility clinics in north America. And what we did was we would look at patient's symptoms and history to determine who needed a laparoscopy and who didn't. So for example, if you have increasingly severe cramping with your period, increasingly severe pain was sex, previous history of sexually transmitted disease with an infection that we know can affect the fallopian tube, a history of a ruptured appendix, a history of previous abdominal or pelvic surgery, any abnormal finding on ultrasound, suggesting an endometrioma in the ovary or suggesting scarring. Okay. A really abnormal vaginal exam. Those were patients that we would take to laparoscopy. And what we found was was that the incidence of a negative laparoscopy fell to almost zero. So, you know, in the old days we would scope everybody, but some percentage of patients would have absolutely nothing. Everything would look perfect. And now that we've applied this new limited laparoscopy protocol or algorithm, we rarely, if ever, I can't think of it's been years since I've scoped somebody who didn't have something, whether it's a cyst , whether it's endometriosis, whether it's pelvic adhesions, whether it's something. So by doing that and ratcheting it down, we've been able to still find patients with disease without having to , to operate on everybody. So that's the scientific side. The cynical side is that, you know, years ago, insurance companies paid pretty well for laparoscopies for endometriosis. And you had all these people writing all these articles about how every speck of endometriosis is bad and every speck needs to be treated immediately. And if you can't get rid of it surgically, oh my gosh, patients are going to be in trouble. And then the insurance companies came along. Pre-existing conditions came along and then kind of the wheels started to turn a little bit and people started to say, well, wow, do you really want a laparoscope, everybody with endometriosis? Because then if you do that and you diagnose them, now they've got this pre-existing condition. And now when they change jobs or they change insurance, they're not going to be able to be covered anymore for treatment of endometriosis. So then the paradigm started to shift a little bit more towards medical treatment. And then when insurance companies ratcheted down on reimbursement for laparoscopy, for endometriosis, this is the real cynical side of me, people who used to write and lecture about the need to laparoscope everybody for endometriosis, realize maybe a dome , you know, maybe go ahead and treat these people medically. Well, why is that, you know, did the disease change? No. Did the real , did the treatments change ? Was there some new panacea that arose and now we can treat endometriosis successfully medically and everybody know , you know, did the side effects of the treatments that we have go away? No. So, you know, that's that super cynical side of me that thinks maybe there's another reason
Speaker 5On a related topic. And can you speak to what the different stages of endometriosis mean in terms of fertility and in terms of possible procedures that might need to be done based on those?
Speaker 3Sure, sure. So there , there really four different stages of endometriosis. Okay. 1, 2, 3, and four minimal, mild, moderate, and severe. And in the old days, it was more like, you know, you like your finger, you hold your finger up to the wind and you say, okay, boy, that looks like stage two endometriosis that patient's got mild disease, but there really is a scoring system. And the scoring system was developed years ago by the American society for reproductive medicine called the American fertility society at that time. And the scoring system was initially developed and then it was revised. And there is a point system where if you go in and you look at lesions, you look at the location, you look at the size, you look at the presence or absence of pelvic adhesions. You can actually assign patients a particular score. So one to five points to stage one disease, six to 15 points to stage two 16 to 40 is stage three and 40 , uh , 40 or above is stage four. And unfortunately in every study that's looked at it. The severity of the disease does not necessarily agree or predict infertility, but what it does predict is recurrence. So what I tell my patients, and this is an oversimplification of the literature, but it really does work. I tell my patients in stage one and stage two disease. This means really, if you don't get pregnant within four years, there is a 75 per I'm sorry. There is a 50% recurrence of your endometriosis. Whereas with stage three and stage four disease, if you don't get pregnant within two years, there's a 75% incidence of recurrence. So we know that stage three and stage four disease are much more likely to come back, much more likely to be aggressive. We know that stage one stage two disease are less likely to come back. And we know that the best treatment of offering Dimitrios, this is not medicine. It's not surgery it's pregnancy. So if we can help patients get pregnant, especially with stage one or stage two disease, there's a substantial likelihood they'll never hear from that disease. Again,
Speaker 2Kaylin , do you use that staging and advising your patients, how aggressive or not aggressive they should be in there ?
Speaker 3We do. We'd at least I do. And so, you know, we , uh , published a study with bill Schoolcraft and Eric Surrey and mark Surrey several years ago, because what we wanted to do was reevaluate the recommendation that right after surgery is the patient's most fertile time. And she should immediately try and get pregnant. And we looked at the data and we looked at the literature and we realized this is kind of an urban legend that had really grown over time. And wasn't really supportable by the literature. So what we did was we designed a prospective randomized multi-center trial, and we took patients who had stage three and stage four endometriosis. And we randomized them. Everybody had surgery and after surgery, half of those women went on to depo Lupron for three to six months. And the other half went immediately to fertility therapy , uh , either with gonadotropin therapy, combined with IUI or in vitro fertilization. And what we found out was was that actually patients who had stage three and stage four disease after surgery, if we treated them with depo Lupron for three to six months, they actually had statistically significantly higher pregnancy rates than patients who went right into therapy immediately. So this really contradicted kind of the dogma that we had all been taught in training. And when we were looking through the literature, we couldn't really find the source of where this all came from originally. It was just kind of, somebody kind of threw it out there. It just kind of got generally accepted. And that was it that, you know, you treat somebody surgically and immediately help them conceive. And while that may work for stage one and stage two disease, there's a lot of evidence including our study and a couple of others that followed this suggested that it may not be the case.
Speaker 5If you have a patient with stage three or stage four disease, you've just operated on them, what would you recommend then? Would you recommend a bull Lupron or would you recommend going to therapy in some time ?
Speaker 3Sure. So, yeah, so it depends on other things, for example, is this patient 33 or is she 39? Does she have an AMH of two? Does she have an AMH of 0.1? So, you know, if she is an older patient with low ovarian reserve, in other words, fewer eggs left than other women, her age, I would encourage her to ignore what we published. Okay. And, you know, vigorously, ignore it and proceed right away with aggressive fertility treatment. Whereas on the other hand, if she's younger, you know what I want to do. And I tell, I talk to all my patients about this. I want to keep them off of the proverbial rollercoaster, where they come in, you know, every two years for breast exam, pap smear and laparoscopy, that's not good for anybody. And know we really want to avoid that . So if we can take them from surgery, put them on Lupron, then help them conceive or put them on something. You know, there's a, there's another treatment now called oral Alyssa that we'll talk about in a few minutes, but if we can put them on something, you know, to try and really get their disease to regressed, because I mean, you know, you know, face it, we're all surgeons. Nobody wants to go to a surgeon who says, well, I don't know if I can get rid of this disease or not. Everybody wants to go to a surgeon who says, you know what, I've seen this a thousand times, I've taken care of it a thousand times. And we're going to get you an excellent result. You know, whether that makes us cocky, arrogant, you know, or just confident. I don't, I like to choose confident other people made she's cocky, arrogant. But , um, anyway, I think that, that , um, you know, even though we all think that we're really good surgeons, the bottom line is endometriosis is a slippery animal and it's impossible to get rid of all of it. You know, when you got stage four disease, you've got an endometrioma in the ovary. You can make a beautiful incision in the ovary. You can strip out that endometrioma, you can vaporize the base. You can suture the capsule. It can look textbook, you know, beautiful, you know, people are in showroom, new condition when they walk out of the operating room, but you know, that we've left disease behind. And that's why I think it's so important to make sure we eradicate it. We bomb it back to the stone age and then help them try and get pregnant very aggressively and very quickly
Speaker 5Thoughts on patients who have endometriosis . I have no reason to be triplets and ovaries. We know that they've got advanced disease and they're interested in getting pregnant quickly. You know, there's a big debate now, should we take them to IVF immediately and get eggs from them ? Or should we operate on them ? What are your thoughts?
Speaker 3Well, so again, another stupid Silverberg analogy. Okay. The ovary is like real estate. Okay. And you know, to some degree it's location, location, location, right. So, you know, if you've got a big endometrioma, that's taking up most of the real estate in that right. Ovary, I have a hard time saying it's okay to go ahead and stimulate that patient. And , uh , you know, an aggressively trying to stimulate her to get a bunch of eggs to develop, because I know that no eggs are going to develop where those endometriomas are. Now, on the other hand, I could make a pretty good logical scientific based argument that if you go in and you take a patient to surgery and you strip out those endometriomas by definition, a hundred percent of the time you're taking out some normal ovarian tissue in addition to those endometriomas okay. And the question has always been, and it's totally unresolved. The question has always been, is it better to resect that endometrioma and then get the patient, give the patient a couple of months to recover and then stimulate a really aggressively, or is it better just to stimulate around the enemy Triomphe ? And I will tell you anybody who says definitively it's one way or the other has no idea what they're talking about, because there is no definitive data that says one way is superior to the other. So at the moment, you can really make a good argument either way. And I tell patients, I don't want to sound like I'm on the fence, but I'm on the fence. And the reason I'm on the fence is because there is just no definitive data. So here's what I think in your particular case, with your particular numbers in your particular situation, this is what we need to do.
Speaker 4So Kaylynn going back to the earlier part of the discussion, where we were talking about who to take to surgery versus not. And if you have someone who's got symptoms that lead you to think, okay, they've got endometriosis because they have pain with menses or pain with sex or whatever it is. How do you approach that? Subset of people where their infertility is unexplained, they don't have anything that makes you say we need to take them to surgery, but the rest of their testing, their teeth look fine. Their egg count is reasonable. The sperm looks fine. And they're unexplained because all of us have had patients where we've taken them to the, or for whatever reason, unrelated to endometriosis. We get in there. And it looks like someone has poured rubber cement in there because the scar tissue is everywhere and it's just a disaster zone. And nobody knew it going in because she felt totally fine.
Speaker 3That's exactly right. And again, this is part of the frustration. That's a great question. This is part of the frustration of the fact that the severity of the disease and the severity of the symptoms have nothing to do with each other. So, you know, I tell all my patients look, I'm old enough to remember when we used to make medical decisions based on medical issues, right. We don't make medical decisions based on medical issues very much anymore. Now we make them on insurance issues or we make them on , uh, other, you know , psychosocial issues or I've got, you know, I'm a teacher and I'm going to be off for the summer. Or, you know, I've got a big business trip coming up and I can't do anything right now. You know, that's how we make decisions these days. And most often they're insurance-based . So, you know, a question that I would, I would ask the patient is, okay, what's the situation here? And what's the ultimate goal. So if she has unexplained infertility, and she has otherwise normal ovarian reserve, then my preference in that particular patient that you're describing, if pain is really not debilitating is going to be, let's try three cycles of something. You know, let's give her a clomiphene for three cycles. Let's give her Letrozole for three cycles. Let's do something like that. Maybe move on to an injectable cycle or two . Okay. But my typical algorithm, the way I treat my patients, I'm happy to try Clomid for a few cycles or, or from our , for a few cycles. But before we really go deep into the world of injectables and IUI, or in vitro fertilization, if they're not getting pregnant, I'll let them do one cycle of injections and IUI and no more, because at that point in time, we're going to laparoscope them . Because exactly as you're describing Carey , you know, frequently, we're going to find something that we're not expecting. And because of this cytokine issue, we know that endometriosis really is a systemic disease. And even within vitro fertilization, it's clearly been demonstrated that if you do embryo transfers on women who have active endometriosis compared to those who don't as measured, for example, by integral levels , um, then you're going to get a lower pregnancy rate. And so even if you've already got the egg outside the body, you've already fertilized that you've already got the embryo to develop. You know, if you go ahead and you do that transfer in somebody, who's got significant disease, lower integral levels, you know , uh , so to speak , um, then your chance for implantation is going to be lower. And so I think that there is a good argument for trying to suppress the disease first. And whether you suppress it medically, whether you suppress it surgically, you know, it doesn't, it's six of one, half dozen, the other to me, I just want that disease suppressed. Okay. Now I'm
Speaker 5Going to really put you on the spot controversial topic. Oh
Speaker 3Good. Cause the other ones were really , uh , you know, those were really straightforward, right ?
Speaker 5So w well , the reason I asked this question is personally I go back and forth. I, you know, I don't know whether to do integrant biopsies or not. It seems like lately many of the ones that we have done myself and my partners always come back positive. So we're almost at the point where it's like, well, why should we really do them? Because they're going to come back positive.
Speaker 3Well, I mean, it may seem like that, but in fact, this, this whole biopsy and the whole asset of the BCL six asset is still new. And there's not a whole lot of data yet that really correlates, you know what I'd like to see, you know, in my perfect world where, you know, everybody's agreeable to everything, right? And insurance companies cover everything we have . It's not the world that we live in. Unfortunately, I would really like to see a well-designed trial where you take patients who don't have disease. I mean, how are you gonna , you're never going to be able to get it through an ethics committee because they're not going to let you scope people who have no disease, no symptoms, but yet, on the other hand to answer the question, you really need to know the incidence of false positivity and the instance of false negativity. And this is why, you know, people are critical sometimes of surgical data, but you got to think about how do you design a surgical study? You can't operate on people who don't have symptoms and they give you no other indication for surgery in order to be able to validate a thought. I mean, you just can't do things like that. And so it's really a problem. And the way I look at the BCL six is is that if I've, you know, I've had patients like we all have where you go through, you know , treatment, they don't get pregnant. You go to IVF, you develop euploid embryos. You may or may not do an endometrial receptivity essay. If you depend on, if you believe in that, or if you don't believe in that, we happen to believe in it. But you do that, or you don't, you get the lining ready, you've gotten an HSG or you've done a hysteroscopy or a Celine stone or something. You know, the cavity is beautiful and you put in a euploid embryo and they don't get pregnant. And so then they come to you and they say, okay, are we going to do this time? What are we going to do different? All right . Because everybody expects that it didn't work because we didn't do something. It can't be because, you know, maybe the embryo isn't entirely normal otherwise, or maybe it was just, it didn't do a good job surviving freeze or surviving thought . Maybe it was injured when we did exi , maybe it was injured and we did a biopsy. You know, it can't be those things. So it's gotta be something with the stimulation, right. So we have to tweak the stimulation. So we make a minor tweak in the stimulation. And then we put in another beautiful embryo that's euploid and they still don't get pregnant. All right. So what do we do then? You know, and the answer is we're grasping, we're trying to figure out what, what could have gone wrong. And the way I explained it to my patients, is there five possibilities that I can come up with now. And that's because I'm not smart enough to think of the a hundred thousand that you know, that we're not talking about. So the five that we come up with now, two of them are embryonic. Three of them are uterine. One, embryonic is structural. You know, sometimes there's a baby, that's born with a huge structural defect, but it's euploid as Kerry typically normal. And maybe that interfered with implantation, that explained why the baby didn't get pregnant. There's never going to be a test for that because you can't test for structures on the fifth or sixth day of embryonic life. There are no structures. The second thing is could there be a genetic abnormality? So even though we tell patients near Breo is euploid, that just says that we've got the right number of chromosomes, but there could be defects within those numbers. They still could preclude implantation. All right , well, one day, hopefully not too far in the distant future, we'll be able to ask for those things, but we don't have that yet. So now let's look at the things we can control. One thing is the Intech integrity of the cavity. So I joke with my partners that if I get to come back next time to be king and make the rules, I'm going to history scope every single woman before every single embryo transfer, because we routinely find polyps, fibroids, little scar tissue, little things that are problematic. And so that's one thing as we evaluate the cavity. The second thing is I am a believer in the endometrial receptivity essay. So we would do that. And then the third thing is this assay for BCL six, to find out if in fact patients have , uh , the lower likelihood of implantation, but those are the only tools in the toolbox that I'm aware of, that we can really crack out and use to try and improve pregnancy rates.
Speaker 5You find that a patient does have an abnormal BC L six level. Then what would you do with that?
Speaker 3I would either scope her or put her on medicine, one of the other. Okay. And I would not. So if we can kind of transition to medical therapy, all right. So if you look at endometriosis as a progressive disease, which is how I look at endometriosis and granted, some people, their endometriosis will go away just because of luck, I guess, or just randomness. But the overwhelming majority of people I've seen in , you know, the 150 years I've been practicing medicine. Now the majority of people have progressive disease. And so sometimes the progress is quickly. Sometimes it progresses more slowly. It's not predictable. And what I'm trying to do is the , the, you know, the fashionable phrase now is I'm trying to flatten the curve, right? So, you know, when you look at treatment with birth control pills or with progestins, those will help lower the slope of the line of progression. And what I mean by that non-scientific terms is it will give patients a longer period of time before their disease progresses and becomes more severe. Nobody's born with severe endometriosis. It all starts as minimal disease and then progress as to mild and moderate and severe, right. Nobody's ever starting off with stage four. When you move up the chain of what there are for treatments, and you move into the GnRH analogs. Now you finally got treatment that can actually not only slow the rate of progression, but actually cause disease to regress. So, you know, the literature is very clear that if you have a patient who has an endometrioma in her ovary, and it's smaller than three centimeters, almost all of those patients will respond to medical therapy with a GnRH analog. Tell me what you mean by
Speaker 5The GnRH analog
Speaker 3For our listeners. You know , I know it's not for you. So there's two types of right . There's two types of analogs. There is an agonist and there is an antagonist. Okay? So in English, what this means is there are drugs that will stimulate a receptor so much that the receptor becomes really resistant to stimulation anymore and stops doing what it should do. And there are other drugs antagonists that will bind to that receptor and occupy it and turn it off immediately. So what I mean here is public enemy. Number one, when it comes to endometriosis is estrogen, right? So if we can suck the estrogen out of the system, endometriosis will regress. That's why after menopause, you only have about 6% of women who have endometriosis before menopause will continue to have it afterwards. 94% of women who don't, who have endometriosis before menopause will not have it afterwards. Right? And so, and even that's even true with hysterectomy . And so long story, a little bit shorter. If we go ahead and we can treat women with either depo, Lupron, which is a GnRH at a GnRH agonist, or treat them with a pill form called oral Alyssa , which is a GnRH antagonist, we can turn off the pituitary gland from stimulating the ovaries to make estrogen, and we can shut off estrogen production. Okay. Now that's a great concept, but the problem is women love estrogen. And because women love estrogen because it makes them feel better. It makes them livable. It makes, you know, it makes their
Speaker 5Testosterone. Let me point out to no , you guys were thinking that too , right ? Carrie and Susan.
Speaker 3Correct. But women don't like anything that interferes with estrogen. I mean, for example, menopause, right? I mean, who signs up for that voluntarily? Nobody. And so the bottom line is, is that , um, if we could suck all the estrogen out of the room, it would be great, but we have to do it in such a way that women can still function. Okay. Because estrogen does a whole lot of stuff. Besides making you feel sexy and making you feel pretty and making your face clear up and you know, all those things. I mean, it also does a lot of good for your heart. It does a lot of good for your bones does a lot of good for other things that you may not even realize. So what, what has to happen in when we give these medicines that can actually reverse endometriosis, we have to do things like put them on, add back therapy or give them other types of treatment to make them be able to tolerate the otherwise sometimes intolerable side effects of these medicines, but the medicines do work and they work really well. So we do have more tools these days in our toolbox. I mean the advent of this new of oral Alyssa, I mean, and I'm not here to do in rural . This is a commercial, but the advent of this medicine, it's really the first new thing that we've had the first new tool we've had in over 10 years. And that's why it's so exciting because it's a pill. It's not a shot. It makes the incidence of side effects of hot flashes. Vaginal dryness, bone mineral density loss are far lower than with the injectable form with depo Lupron. So with Lupron, you know, 95% of women are going to get a hot flashes and vaginal dryness with , um , you know , with the pill form. Now with oral Alyssa, if you give it the higher dose, 50% will have a side effects. And if you give the lower dose, only 25% will . So they really work very well with fewer side effects. Just on a side
Speaker 2Note, do you give estrogen add back with or
Speaker 3Alyssa ? I don't yet. I don't yet. I mean, if I , when I give any kind of add back, what I do is I start off with progesterone. So I love mark Hornstein study where, you know , they had four groups. Uh, they had , uh, randomized patients into four different groups. Um , they had all had surgery for their disease and one group went on and they all went on depo Lupron. So group one went on placebo, estrogen and placebo progesterone. And those patients dropped out because they just couldn't stay in the hot flashes group. Two went on , um , low dose progesterone and went on a jest and five milligrams a day and a placebo estrogen. And those patients did really well. And they did not have any statistically significant increase in bone mineral density loss that had fewer side effects of hot flashes. Vaginal dryness group three were patients who were given low dose progesterone, five milligrams of ed . And they were given very low dose estrogen as well. And they did very well just like group two did, but then group four was given low dose. They just , and five milligrams a day and they were given 1.2, five milligrams of estrogen. And unfortunately those patients dropped out because their symptoms recur because now they were getting too much estrogen. So when I give, add back, I start everybody off on five milligrams, a day of adjusted and that's it. And if they do well, great, I'll see them back every three months for the first year. And we'll see how we're doing. If on the other hand, they can't tolerate that five milligrams. I'll add back one milligram of the Estrace . And if they do okay with that, great, we're done. If not, I'll argue with them, I'll try, first of all, giving them one milligram of Estrace vaginally. And if that didn't work, I'll reluctantly go to two milligrams of Estrace, but I'll never go above that.
Speaker 2If you had to give our listeners who are probably mostly patients to words of advice, if they're concerned about having endometriosis, for whatever reason, whether it's, you know, my mom had endometriosis or I have pelvic pain, I've been reading them. This might be endometriosis. What are the two top two things you would want to share with them?
Speaker 3The first thing is, go see somebody, okay. And it's go see somebody qualified. Um, and the second thing is, is if they tell you to go away and take a nonsteroidal anti-inflammatory and you say to them, look, I've been doing that already for, you know, six months a year. And it hasn't helped me go see somebody else. Those are the two things. Those are the two words of advice because endometriosis a chronic disease. And it is unfortunately difficult to diagnose, but it's a real disease that affects 25% of all women of reproductive age. It is a very common, very prevalent disease. And you , there are no extra points that you get for having cramping with your period. That's debilitating. I mean, there's no benefit to that. There's no special place in heaven. That's going to be carved out for you. There is no, you know , no benefit in this life or next life for anything else. And there's no reason to suffer like that. So if you are not getting pregnant after six months, if you're over 35 or after a year, if you're under 35, go see a fertility specialist. If you're having pain worse than your friend's pain within a meter with a , with your periods, go see somebody. And if the doctor that you see, or the nurse practitioner that you see, or the physician's assistant that you see says, you know what cramping with your period is normal. Okay. And you feel like this is not normal. Go see somebody else. Okay. Don't accept that first diagnosis, go see somebody else.
Speaker 2That's really good advice. That's really good advice. So on that, I would like to thank you so much for joining us today. Katelyn it's really been as always amazing listening to you. Talk about endometriosis, even though it's , it's nothing we ever wanted to talk about, but unfortunately, like you said, it affects so many of the women that we see in our clinics.
Speaker 3Well, you guys are fantastic. I can't thank you enough for having me on. And I just congratulate you on the success you're having with your show because it's really taken off like a rocket and it's providing so many people, so much information. And especially now, when we're all kind of shuttered in our homes and people are struggling with how do they deal with life and how do they deal with everything to be able to provide the information that you're providing to them and make them feel like they can still make progress even from home is it's a godsend and I congratulate you on what you all are all doing.
Speaker 2Again, this is Dr. Susan Hudson from Texas fertility center, Dr. Carrie BDN from the fertility center of Las Vegas and Dr. Abby Ablin from Nashville. Fertility. We'll see you guys soon.
Speaker 6[inaudible] .