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Endometriosis: Contemporary Care and a Look to the Future
Originally broadcast March 30th 2021 | 10:00 am CET/5:00 pm Singapore and 3:00 pm PDT/6:00 pm EDT
Learning objectives:
Identify the symptomatology of endometriosis as it pertains to infertility and pain
Recognize the diagnostic indications for individualized patient care
Discuss the areas of innovation in endometriosis diagnosis and treatment
Speakers:
Anate Brauer, M.D.
Erica Fletcher Robinson, M.D.
Valerie Flores, M.D.
Host:
Vrunda B. Desai, M.D.
To view this presentation on-demand after April 1 and to access other multi-media educational content, please visit www.Cooperinsights.com
welcome to our webinar today endometriosis, contemporary hair to look into the future. I'm so pleased that we are joined today by some of the leaders in this field as we work together to raise the clinical awareness of endometriosis during this endometriosis marinus month. I've had the pleasure to work with all these speakers personally, and I wanted to tell you a little bit more about them. Dr Are not Brower is the I. D. F. Director of SDF New York. She's a reproductive endocrinologist who trained at New York Presbyterian Weill Cornell. Next we'll have Doctor Erika Robinson, who is a minimally invasive Julian surgeon and an assistant professor of O B G. Y n at Wake Forest University School of Medicine. Dr. Robinson trained at Emory University and completed her minimally invasive Joanne Surgery Fellowship at Vanderbilt University. And finally, we're joined by Dr Valerie Flores. Dr. Flores is a reproductive endocrinologist, an assistant professor in the Department of obstetrics, gynecology and reproductive sciences at Yale School of Medicine. Dr. Flores completed your residency at Brown and her Ari fellowship at Yale. So why don't we go ahead and get started with this Webinar by having Dr Brauer speak to us about endometriosis and infertility. Thank you so much, Doctor Dizzy and Cooper for having me in this very important session, especially during this month. Endometriosis Awareness Month. I will be covering the topic of endometriosis and infertility, which is something that I see pretty much everyday in my practice. So we'll start with the definition of endometriosis, which I know some of my colleagues will also cover. But briefly, endometriosis happens when the lining of the uterus or the endometrial glands and Strama are growing outside of the uterus. It's a benign disease. It causes mostly and presents mostly with pelvic pain and infertility, and we know that it's hormonally reactive, which leads to some of the symptoms, pathology and the timelines of symptoms we see in our patients. Let's speak a little bit about prevalence of enemy truces, which is actually very difficult to assess because it's diagnosed. The definitive diagnosis is made laparoscopically, and there's a long time lag between when a woman presents with symptoms and actually gets diagnosed. So we say that there is an estimated of about 3 to 10% of reproductive age. Women actually have enemies. Cirrhosis the mean age of diagnosis ranges from 25 to 35. And, as I said, there's an average of about eight years from the time of one represents the symptoms to the time that she's given a diagnosis. And that's because these women sometimes present in their teenage years and even in their early twenties, and they end up getting bounced from doctor to doctor trying to get a diagnosis. Um, it's pretty rare. And pre monarchical women, usually under age 17 presentations, are associated with McLaren anomalies. Fewer than 5% of women with endometriosis are present in the postmenopausal population. In patients who have actually had surgery where you see direct visualization. About 1% of women with that are taken to the O. R for any gynecologic indication. Have endometriosis. 127% of women undergoing tubal sterilization About 12 to 32% of women taken to the art for pelvic pain get diagnosed with endometriosis 9 to 50% of women with infertility, So up to 50% of women with infertility who are taken for diagnostic laparoscopy are found to have endometriosis and about 50% of teenagers that present with pelvic pain or Desmond area. So risk factors for endometriosis include factors that increase your risk and factors that may decrease your risk factors. They may increase the patient's risk. Are increased population demonstration so women with very early menarche or very late menopause may be at higher risk for endometriosis. Women with menstrual outflow, obstructions from uterine anomalies or, um, cervical or vaginal anomalies or reproductive system anomalies? In general, heavy alcohol and caffeine consumption has been shown to be associated with endometriosis as well as smoking, um, in utero exposure to D. E s, which we haven't seen so much in recent years. Decreased risk are women who have had pregnancies, and obviously that goes along with less populations for lifetime. Also lactation for the same reasons. Regular exercise, um, as well. So a little bit about the pathogenesis. I know some of my colleagues will review this as well, but there is no generally accepted method or thesis regarding the origin of endometriosis, but we know there are a few mechanisms that have been highlighted or outlined. One of the most popular theories is retrograde administration and implantation. So endometrial tissue actually back flowing from the uterus and implanting at various places in the pelvis. But we know that that doesn't describe all or explain all forms of endometriosis because we have distant sites such as the lungs and such as even limb. You can have lymphedema, trio sis and so other theories include Solomonic, Meta Play Asia, where, UM, there's actually met a plastic changes, whether spontaneous or induced, and mesothelioma cells that are derived from Slavic epithelium, Islamic epithelium can be found in the peritoneum. It can also be found in the pleura so that maybe one explanation direct transplantation from C section scars or even episiotomy repairs have been described more distant vascular and lymphatic dissemination, which will be described a little bit more by my colleagues later, genetics, which we know play role in endometriosis Studies have been done, and in Mona's idiotic zygomatic twinning um, in following pedigrees of families and following patterns of endometriosis. There's definitely a huge immune factor here as well. Um, and I'll describe that a little bit in my following slides. So definitive diagnosis is made through laparoscopy with direct visualization and pathology, and here you see some examples of what endometriosis might look like, which we've all seen in our in our surgical practices. It can be powder burn lesions on surfaces of the peritoneum. It can be, um, scarring that we see very often. It can be darker, red, more, um, beefy looking lesions. You can also see it in the vagina. You can see it on the cervix, and these are just some examples of photos of that. Next, we'll look at pathology, and this is kind of a classic pathologic diagnosis. And this is really the gold standard of of diagnosing endometriosis is histological evidence the topic into mutual glands and Strama in tissues, whether or not supposed to be. And you see here very nice h and e stain of that. So how do these patients present? We see them in our office every day, the present in lots of different ways. So most patients present in our case, they present with infertility. But to our surgical colleagues in our Joanne colleagues, they usually present with pain. This is usually cyclical pain. So with their period a lot of times with population as well pain with intercourse specifically deep penetration, many women will complain of sai click bowel or bladder symptoms, so pain on urination pain on defecation. Um, to us women present with infertility, many present with abnormal bleeding, many present with fatigue or accompanied by mood disorder. And physical exam findings are consistent with this, So pelvic ultrasounds and pelvic exams are a lot more comfortable uncomfortable for these patients. You can also, you can't diagnose endometriosis on imaging. But there are things on imaging that you can see that kind of give you a hint towards enemy towards the diagnosis of endometriosis on ultrasound. Really, ultrasound is more useful for advanced disease, so you can't really pick up mild or moderate disease. On ultrasound. You can pick up large endometrium, ast or large implants. You can actually sometimes see Blatter implants, for example, which I'll show you. Some pictures of MRI is helpful for differentiation of ovarian enemy troops from other masses. So sometimes we see something that because of the way it's positioned, we're not sure if it's a my OMA or some kind of other ovarian mass or an endometrium. A. And that's where M R M R. I can kind of help us differentiate that Short of going to the operating room, um, you cannot reliably image small peritoneal lesion. So there are many out there that believe that they can diagnose and reduce on MRI. But direct visualization is still always the gold standard. So these are some images of what endometriosis might look like on ultrasound. So the top two images are endometrium. Azan, enemies. Room is present as, um with an agent with an exogenous it on ultrasound. Kind of a great out, very homogeneous pattern. Um, on the ovary, the bottom two images you can see bladder images with endometriosis implants within them, which is actually very interesting to see. And you can pick that up on ultrasound. Not definitely not a definitive diagnosis. You still need direct visualization through sista Skopje or through laparoscopy, but still can give you a hint of Okay, this might be the disease that we're dealing with. And these are images of what enemy troops just might look like on MRI. And you see here that there's a very intense t one weighted images where you can see endometrium Aziz, and you can even see here these same kind of implants in the bladder. These very intense t one weighted images on MRI again. Not a definitive diagnosis. They can definitely help you differentiate between other types of pelvic masses and what may potentially be endometriosis. So what are the mechanisms of endometriosis within infertility? So these are associated mechanisms, right? So they're very well established. But there's not necessarily a causal relationship. And there's a very big difference, as we know from a statistical perspective between association and causation. So some proposed mechanisms that all go through clearly distorted pelvic anatomy from scarring, where the tubes just can't pick up the egg from the ovary that's been inoculated, altered peritoneal functions, altered hormonal and cell mediated functions. Endocrine and regulatory abnormalities. Impaired implantation with progesterone resistance, which I'll briefly mention. Oocyte and embryo quality. And abnormal uterine suitable transport, which also is related to distorted pelvic anatomy and peristalsis of the uterus. So one of the hallmarks that we see an enemy trio sis is really the state of chronic inflammation, and this chronic inter peritoneal inflammation is really a characteristic feature of endometriosis. We see these animatronic implants that tend to induce an acute inflammatory response which recruit um T cells helper T cells, which then recruit monos sides, and macrophages, which maintain the chronic inflammation which then contributes to a kind of personal restructuring and adhesions, which leads to scarring. And this restructuring is very distorting to anatomy, and it makes it harder for tubes to pick up eggs from the ovary. So there are other mechanisms of chronic inflammation. Other short of obstructing tubes are leading to distortions. In anatomy, we see that there is an increased concentration circulation of cytokines such as interleukin one B, I, L a, T I, l 10 TNF alpha and follicles that are adjacent to enemy traumas that may be associated with a reduced ovarian response. In our patients, we see this very frequently with with with trying, you know, ovulation, induction with medicated I us. We also see in our IVF patients, they tend to be poor responders. There's been studies showing that elevated I'll six in the peritoneal fluid from women with endometriosis may inhibit sperm motility and contribute to sperm DNA fragmentation. We also know that prostaglandins and cytokines may interfere with the oocyte sperm interactions. It can impair embryo development and hinder implantation and keep all of these things in the back of your head. When you're talking about treating a patient with surgery versus IBF. So not only is there a milieu of chronic inflammation that may affect both for sperm transport, fertilization, embryo development, but we also see impaired implantation in these patients. So there are many studies looking at progesterone resistance. In these patients, there's a reduced expression of progestin receptors and endometrium of women with endometriosis. Progesterone is not only important for implantation, but it also progesterone itself, but it also induces expression of 17. Beta hydroxy serra de hydrogen is Type two, which metabolizes estradiol to the less potent estrogen. And we know that estradiol is also important for implantation. So it's kind of a double whammy to the story of implantation. Um, we also see altered hormonal milieu that may jeopardize implantation in these cases with the progesterone and estrogen. Um, we also see impaired you during contract ill itty. So there's a lot of di Paris dialysis. The tubes and the uterus have to move in concert together, as we know, in order to bring the egg and the sperm together, create an embryo and then bring the embryo from the tube into the uterus to implant. So if all of that is not working and that kind of goes along with this idea of retrograde administration is this Die Paracelsus of the uterus? It's everything's kind of beating and flowing the wrong way. That can also definitely impact implantation. This is all a natural conception, not in a R T conception. So we also see that it can affect in vivo oocyte development and quality. We see that women with endometriosis have regulatory dysfunction. They tend to accumulate it much smaller follicle sizes. We see that women with endometriosis have lower Roma taste activity and less progesterone production by Granny Lusa cells, um, which which can also impact, you know, implantation as well. We see that these women, generally both in and out of the lab, have core oocyte quality. So you have altered progesterone and cytokine concentrations in the follicular fluid of these patients. Um, and we also see higher incidence of a pop topic bodies in granule Asus cells from women with endometriosis. So what is the treatment for our patients with infertility and endometriosis? Obviously, it's a very, very frustrating disease. The mainstays of treatment have pretty much remained the same. Today we'll be hearing a little bit about more medical innovations, but for us as reproductive endocrinologist. Really, There's two questions. One. You see a patient with endometriosis, you think okay, are retreating the pelvic pain or the infertility and treatments for pelvic pain? There are several, right? So there's medical, their surgical conservative versus definitive um, there's combinations of medical and surgical and or you can just do nothing. Expectant management with pain control. But really, for infertility patients, the mainstays of treatment are surgery or a R T. So first talk about the surgical aspect, which has kind of evolved over the years. So this is a very controversial topic in our fields. And unfortunately, most of the studies specifically looking at the benefits of surgery for minimal to moderate disease really came from the late nineties. So there aren't a lot of great current randomized control trials when we talk to our patients about the idea of surgery versus going directly to IVF for a R T. We basically talk about the Canadian study in the Italian study, right? So the Canadian study was published in the late nineties in the New England Journal. The Italian study was published in the late nineties, also in human reproduction, and these studies are very much opposed to each other, one of them favoring surgery, one of them not. So let's just go through those studies, although all of us have heard about these studies and million times before. But it's always good to refresh our memory and how we cancel our patients. So the Canadian study was published in 1997. Quite a long time ago, it was a multi center study involving 25 centers. Women were ages 20 to 39 presenting with one year of infertility and no prior surgical treatment. Laparoscopy was done on all patients. Diagnosis was made visually, so not pathology was not required. It had to be made visually. Um, these women were followed for 36 weeks post op, Um for those who got pregnant, they were followed up to 20 weeks of gestation, which is actually a ding on the trial because they did not follow them to term. There are 348 women in total 176 in the operative group, 172. In the diagnostic group, the diagnostic group, the fecundity rate went from 2.7% of baseline prior to surgery to 17.7% posts up and and the operative group. So by diagnostic, I mean, they took a look with the scope, and they did nothing. They did not fall great or excise endometriosis, an operative group which had federation or excision. The Kennedy rate increased from 4.7% of baseline to 30.7 post operatively. So their argument is, we have seen this, what, statistically significant increase in pregnancy rates. Miscarriages occurred in the same rate with both groups. Um, and from this study, you can take that you need to operate on nine women according to the to the statistics of this study, in order to achieve one additional pregnancy. You know these. This was a relatively small sample size. Again, the women were not followed two term, although the miscarriages rates for the same in both groups. But but practitioners who kind of tout surgeries the first line therapy, rather than going straight to IVF commonly quote this study. Um, And then there's the opposing study, which is the Italian study. So the Italian study was published in 1999 in human reproduction as a rebuttal to the Canadian study. It involved seven centers, 100 women with stage 1 to 2 endometriosis again under age 36. These women had no prior therapy for endometriosis. They were randomized to ablation or resection, versus no treatment. They were followed for one year. Um, pretty small sample size 51 women in the reception ablation Group 45 in the new treatment group. And this study showed that there was no significant, uh, noticing any difference at all in pregnancy rates 24% versus 29% in both groups. Um, the one year birth rate was 20% in the treatment group and 22% in a non treatment group. So this study did follow the patients to turn birth. Um, there were no significant differences in the miscarriage group. And again, a ding on this study is that it was underpowered. So it was a small sample size. So there is a controversy revolving minimal to moderate disease. Based on those two studies, I think now that a R T has gone to a point where it is with IVF, most practitioners well, um, move forward with IVF sooner rather than later. Um, with severe disease. It's not as controversial. So the goal with severe disease and again most men with severe disease will present with pain, not just infertility. So they do have another indication to go to the O. R. But the goal of surgery with severe disease is really to restore normal anatomy. There is no randomized controlled trials looking at the effect of surgery for moderate to severe disease and infertility observation studies suggest that surgery is superior to medical treatment or no treatment at all in this, um, in this specific category of patients. But none of these studies really stage out disease, so you don't know if they're talking about moderate disease or very severe disease. Stage four stage three etcetera excision of the endometrium Aziz in women with Infertility is controversial. So you really have to weigh the risks of taking out the enemy Troma and what that's going to do for the patient's pregnancy rate, whether they're doing IVF or not, versus the risk of taking with the endometrium a healthy tissue. And this is a conversation we have with our patients every day, Um, and counseling them of whether or not they should take out the enemy Troma, I'll tell you that in our patients who present with enemy trio HMAS, we are more likely to talk to them about if they're going for endometriosis surgery. They have an enemy, Troma, for pain reasons. Then they may be better off retrieving eggs before they have that surgery to either freeze them or create embryos and freeze embryos. Um, just in case in that surgery, the surgeon takes along some healthy ovarian tissue along with the endometrium. A. As we know, endometriosis can be very sticky or if, God forbid, they lose an ovary during that surgery. So definitive surgical treatment is reserved for patients who have intractable pain from endometriosis they don't want. They don't want to conceive on their own or carry on their own. Um, and this is more appropriate for women who have completed childbearing. Although I have had patients who have require definitive surgical treatment even though they haven't completed childbearing and those patients, we create embryos and then they end up using a gestational carrier to have their babies. Um, it is for definitive surgical treatment. You really have to remove both the uterus and the ovaries, which for a young woman for many different reasons for long term health is a very difficult decision to make their studies that show that just removing the uterus, believing the ovaries in have a very high recurrence rate. Um, specifically with enemy Drusus and pain, um, from endometriosis lesions. So now let's talk a little bit about a R T options. So we have many treatment options in our arsenal, but pretty much the mainstays. Are you expecting Management versus II versus IBF? So there have been some studies done on, um, success rates with I u I and patients with endometriosis. We know that women with moderate to severe disease who have severe scarring and distortion of anatomy um, do not have good successors to the I. I generally would not recommend that patient waste their time with, uh I I before moving on to IVF. But really in women with more mild to moderate disease is where the question lies, right? If they have an HSG and they have open tubes, they have relatively normal anatomy. Do you offer them IOS? Um, there was a multi center cohort study from the Netherlands. It looked at over 14,000 cycles. That compared um, at presence of endometriosis and and other aspects and looking at treatment failure in these patients and found that endometriosis was a risk factor for treatment failure, which is not a big surprise. Other cohort studies. I have a table here of several cohort studies. Um, that compared, um, success rates of I u I in women with endometriosis versus unexplained infertility. And we see that five of the nine studies show that the enemy Drusus patients that had proven enemy troops is actually a much lower success rate with I o I having said that if a patient of mine, if everything else is normal on their work up, if they're, you know, an appropriate age and have an appropriate ovarian reserve where I don't think they're wasting too much time if they have a normal HSG with open tubes, of course, if I can get a patient pregnant without I d f, I would always much prefer it. Um and so I do offer it to my patients. But just like our unexplained infertility population after three Medicaid II cycles, I would usually pretty efficiently move on to IVF. So then there's the question of okay, IVF is probably presents the most efficient path to pregnancy for our patients with endometriosis. But should we be counseling our patients with endometriosis that they actually have a lower success rate with IVF, um, than than patients with, for example, unexplained infertility or tubal factor infertility? And there have been several studies looking at this mostly meta analyses, and they kind of have conflicting results. So there was a meta analysis done by our colleague Dr Barnhart out of Penn in 2000 and two, that show that infertility patients with endometriosis have a lower success rate in comparison with patients with tubal factor. Infertility, which is kind of the gold standard of of taking out variables are patients that have to do IVF with tubal factor infertility. There's a 2013 meta analysis that showed no difference in pregnancy rates between patients with mild to moderate endometriosis in comparison with patients with other ideologies and the fertility. And if you look at star data from 2010 to 2013, which is which is kind of looking at what Dr Barnhart did, and you look at success rates between on the left side. Patients with endometriosis underwent IVF in patients with tubal factor that underwent IVF. You'll see that the success rates that pregnancy rates are really very similar. The only, um, the only two categories that had reached statistical significance, but I wouldn't really call it clinical significance are the cancellation rate and how many embryos were put back into the uterus. If you really look at the numbers, you're comparing a cancellation rate, for example, and are under 35 category of of 6.9% versus 5.6%. Is that really clinical? Clinically significant, even though statistically significant and the same with the number of embryos transferred to M 2.0 embryos transferred versus 1.9. So I think this is a really important study. Um, you know, and look at a lot of data a large data set, which would make us feel comfortable offering our patients with endometriosis. IVF is the most efficient route to pregnancy, so the question that we face every day's practitioners and I think the answer to this question has gotten a lot easier over time, as as our IVF labs have become so much more efficient is surgery versus a R T. Right, so what really is the answer here. We know that IVF is likely is probably most likely the most efficient round to pregnancy in women with endometriosis. But in women with mild disease, there's still consideration for less invasive treatments, right? Not everybody has to get pregnant through IVF. Many of these women will get pregnant with expectant management. Many of these women will get pregnant without you. I it's just important to take into account that specific patient situation. So do they have other indications to go to surgery such as pain? Do they not have insurance coverage for IVF, and can they not afford it? And those cases, or do they not want to do IVF for religious reasons? Those are the patients were more likely to try less invasive options or even send them to surgery prior to doing IVF if they've exhausted their expectant management options. If they have exhausted their IOS then before going to IVF, if they can't do it for whatever reason, that's an indication in cases of mild to moderate disease. Maybe trying surgery first in Visualize Karen counseling is always the name of the game, right, with all of our patients, you have to see how well dissipation, What is there a very reserve? Can they afford to wait before going to IBF and any patient you look at? The question is always at one point, while the idea of success rates start to decrease, and if you see that you doing otherwise, you're sending them to surgery and the time required recovering from surgery, etcetera is going to hit that decreased success rate. Then I would move me personally to IVF sooner rather than later. Thank you so much for giving me this opportunity to review some of the literature regarding infertility and endometriosis. Um, myself and my colleagues I know we all feel very privileged to be taking care of this very specific pain population of patients who are often in pain and struggle with infertility. I think it's very important for our field in general to really, um, kind of bolster these voices of these patients and advocate for coverage for IVF and specifically for egg freezing for our patients, um, much like we do for our cancer population, Um, as this is a disease that that significantly affects our patients and their reproductive lives down the line. Thank you so much for having me. Thank you so much, Doctor Brower. It was really wonderful to hear about how endometriosis really affects infertility in our patients. Next, we'll have Dr Robinson speak to us about how endometriosis presents its pain in the clinical presentation of endometriosis. I thank you so much for the kind introduction, Dr Desai. My one disclosure is that I do consult for Hologic periodically, so I'm going to talk a little bit about chronic public pain from a gynecologic perspective. In general, the definition of chronic public pain is pain that has been present for at least six months or longer. It must impact your the daily life of the patient, often with a negative impact on their quality of life. Chronic public pain tends to be a cyclic, not lining up with their menstrual cycles. It can include both g, y, n or gynecologic and non gynecologic causes, and the other part is that the chronic public pain is not associated with the pregnancy. One thing that is often missed is that pelvic pain in chronic public pain is a very common problem for women and according to our literature, it can affect between 6 to 25% of our female patients. So why is it that finished physicians and clinicians run from pelvic pain? It's multi factorial. We've all heard these things. We've all thought these at some point when we think about chronic pelvic pain, sometimes we'll think it's too complicated. I don't have time. I have, however many other patients today or I don't know where to start, right? It sounds like everything is wrong, and I don't have a good starting point. Like I said, you may not have the time in clinic. A lot of places don't have the resources to manage them chronically over a long period of time. There's the perception sometimes that chronic pelvic pain patients are all drug seeking. Um, there are some people who may say, I don't really believe in chronic pelvic pain. There are other things that we can do to help you out or not believing that the patient's pain is truly that bad, that it's truly inhibiting their, um, their quality of life. And it's having a negative impact on them. So there are lots of reasons, but at the end of the day, it's chronic pelvic pain and it can be quite complex. One thing to keep in mind is that not all chronic pelvic pain is endometriosis. Endometriosis is a very common cause of it, but there is substantial overlap between the symptoms of endometriosis and other conditions that can cause pelvic pain, both gynecologic and non gynecological gynecologic causes. Um, this, combined with the fact that the limitations of the physical exam in the pelvic exam in detecting endometriosis can really make a clinical diagnosis challenging. So a lot of times we do know that endometriosis gets blamed for the majority of pelvic pain. But the reasoning is is because a good 70 plus percent of these women actually may have it. But what are the other things that could be going on? You could have uterine pathology such as adenoma, aosis or fibroids that could be contributing. There are GI problems such as irritable bowel syndrome, which can contribute to this pain. Painful bladder syndrome or interstitial cystitis is, uh, urologic cause of pain. There could be historic reasons like pelvic inflammatory disease or chronic and detritus, neuropathic pain, nerve pain, the psychiatric components of pain and then even the tubes. The tubes can be quite sensitive, so things like a hydra style pinks or chronic hydra style pinks can be sources of pain as well. So here is a relatively exhaustive list of several different factors and several different systems that can cause pelvic pain. So listed you'll see multiple gastrointestinal causes of pelvic pain. I. B S and I B D are often the most commonly seen in this in this group of women, um IBD with Crohn's and ulcerative colitis. A lot of times these patients will have abdominal pain or bloody diarrhea, and usually it's not related to their Menzies. And so people don't confuse these symptoms with their painful cycles. The gynecologic problems will come back to in just a second, but I usually think about them as being problems that are outside the uterus, uterine problems and then problems that we can create high estrogenic lee. For these patients, the musculoskeletal system as a gynecologist is one that I don't feel like was always harp done as a source of pain. But it can truly be a contributing factor. Patients have abdominal wall strains. Maybe they have a deist Asus from prior pregnancies. They could have degenerative joints and their hips that could be contributing to this chronic back pain, um, strains and sprains and muscles. And then, of course, we get into things like pelvic floor biologist and pure form a syndromes which can all contribute and create a very mixed picture of pain for these women that they just defined as being in their pelvis. Other things, such as the psychiatric or psychosocial components of this, with depression, neurologic dysfunction, PTSD, anxiety, all those things can contribute. And we know that when when people are stressed that pain perception changes dramatically. So those are all factors. And then we briefly touched about the urologic causes such as cystitis or painful bladder syndrome. Um, urethra, diverticular. Those can all be on the differential as well. And one thing to keep in mind is, a lot of times chronic pelvic pain doesn't fit just into one of these categories are often multiple things going on. So here I want to focus a little bit more on some of the gynecologic causes of pelvic pain. As mentioned, there are uterine causes. Um, sometimes things like endometriosis, chronic and detritus um, al positioned I u D fibroids. Those things can all contribute to pain, syndromes and pain symptoms, And a lot of times the history can help us differentiate those things. But things outside the uterus, things like a chronic salpingidis and inflamed You're angry tube endometriosis falls in this category. Patients who have had prior surgeries and maybe they have a ovarian remnant they can get sick like pain as well. Pelvic congestion is one that is debatable by several physicians, but it can also create a significant pain picture with the correct story with high debt. The correct history. The eye androgenic causes are ones that we don't talk about as much, but to keep on the on the plate. For these patients who have had a lot of surgeries, they could have adhesive disease. They sometimes we can have a post ablation tubal sterilization syndrome, also known as pets. And those are the women who have had an ablation of the endometrium lining but have also had some sort of tuba ligation. Um, mesh can also be a source of pain, so understanding their history and the things that could have happened to them from our end that could cause pain is important as well. So the important part here is to always think about things in a very systematic way. Um, and over time I have developed what my system is, but it's important to think about what would work for you. As one of my mentors always told me, You have two ears and one mouth for a reason. So you have to listen to the patient. This goes back to the very beginning of our training and education, which is you really have to take the time to let the patient talk. This can't be one of the really quick visits that we have scheduled through the day. You need the patient to tell you when it started, what were they doing the first time they felt this pain? Did they fall off a ladder? Were they in a car accident or was just happening when they were sitting in their living room watching TV? Is there any kind of discernible pattern to their pain? Is there anything that makes this pain worse and not just kind of activities, but time of day, certain, certain stressors, what makes their pain better and worse? And I asked them very directly about a lot of things that I know women try besides heat and all the over the counter pain medications. But do certain activities help? Does stretching help? Does yoga help? Does breathing help? What have they tried? And you know, And I say, if you're honest with me, then we can figure all this out. So I want to know what has what have they tried what's worked. And then the most important question that I think, is to ask the patient directly. Where do you think this pain is coming from? And they will tell you what they think, and that provides me with two things. One, it provides me an idea of where they're coming from and what obstacles I may have to overcome when we're discussing what the source of the pain is. But also, it helps me think about their differential diagnosis and where this pain truly might be coming from, and sometimes a good portion of time that patients are right. So this is the what my what my training is called the Are you listening? Slide? So there are some very clear descriptors that patients will use, um, quite frequently that can help you narrow things down in your mind from the very beginning, So the endometriosis related pain is typically going to be the pain that is worse when their cycles, they have pain. With intercourse, the pain is deep or sharp. It's better with birth control or depot. Lupron lied and things like that. That's oftentimes your endometriosis type of description. For patients who have had prior surgeries and the pain starts relatively soon after that, or if they've had a severe public infection, they might describe a pulling sensation in nature that is pretty focal or localized on their abdomen. And they can a lot of times make this pain happen, and sometimes you have bowel symptoms with it as well. And those are usually your pelvic adhesive disease patients. When the patient says, You know, I'm just after a really busy day, I have a lot of pain. It's all central I feel is that everything is just going to fall out of my body. I have pain with intercourse, and it can be worse with my stand for too long or when I sit for too long. Those are the patients I start thinking about pelvic floor, my algebra, pelvic floor pain, the bladder symptoms are often a little bit easier for us to think about, which is the painful urination having to get frequently to go the bathroom at night. We're going frequently with small voids during the day. Um, if there's certain foods that seem to make the pain worse, a lot of times that can be a bladder factor. The neuropathic pain are the pains that have this electric sharp quality that often radiate, Um, and those patients have sometimes had prior surgeries or injuries to take you to a nerve source from a bowel perspective constipation, diarrhea, bloating, pain that is getting better when they have a bowel movement. And then the other important thing is if the pain wakes him up in the middle tonight, it's most likely not their bowels. So because the bowels sleep when we sleep. So that's one of the other distinguishing factors. Help with some of the bowel factors. And then finally, the central, heavy cramping pain. That's worse, right? When the cycle is starting Dull Central. A lot of those things are gonna be more of your uterine sources of pain. So while we're talking about all these other sources of chronic pelvic pain. I am going to circle back to endometriosis because it is quite common, and it's a very common source of pain for women. Here you can see the endometriosis can be quite variable in appearance, and some of it can be very distinguishable, very easy to recognize, especially the chocolate cysts. And when you have the staining, the hemostat and staining of the pelvis. But in other instances, it can be quite difficult to identify it. If you're not looking closely and you're not thinking endometriosis in the back of your mind, things like those clear vesicular lesions can be really hard to pick up on. That would be very close to them microscopically so a quick review of endometriosis, um so endometriosis is a viable estrogen sensitive um, disease, where you have endometrial glands, which is the lining of the uterus associated with an inflammatory response outside of the uterus. So this is a very common picture of some endometriosis with an obscured passage called a sack. Endometriosis is one of the most common causes of pelvic pain. It is extremely common, with an average age of diagnosis being 28 years of age, and when we think about the average age of monarchy versus the average age of diagnosis of endometriosis. That's a big gap. There's a delay of at least nine years for many women who have symptoms before they are definitively diagnosed with endometriosis. Endometriosis also has a can have a very significant financial impact on us as a society, both an indirect and direct costs. Um, and one paper. They talked about at least $12,000 per woman per year. Um, perfected women per year as a thing. You have decreased quality of life. You have women taking time off of work, women who are unable to care for their families. Um, and it said that people can. Women can lose approximately almost 11 hours of work weekly due to their just not being able. They're being just fully disabled by this pain. And the last thing that I always want people to know is that remembers, endometriosis is a chronic disease, and it needs to be treated as one for a lot of us who do the endometrium. Two surgeries. We discussed three subtypes of endometriosis, which is a little bit different from the SRM staging system. Um so the most common one that you will see is that superficial geometry optic implant. Those are kind of like the pictures that I showed a few slides ago. Then you get to the endometrium is, as you can see on the screen, which is the larger, very insist, filled with endometriosis, also known as a chocolate cyst. And then the last portion is the more debilitating one oftentimes, which is a deep infiltrating endometriosis. So as endometriosis is a chronic disease, there are medical search and surgical options, and it's almost this never ending circuit of how we manage endometriosis these days. Most of the time, we recommend to start with something like a medical therapy before you begin surgical therapies. If you are well controlled with your symptoms on a medical therapy, and it's not counterproductive to your family planning goals at the time and you're tolerating the medication as well, a lot of us will not rock the boat and maintain you on those medical therapies for as long as possible. Surgery becomes an option, as you can see when you have poor symptom control, or if we can't find that right fit, or if you aren't tolerating those hormones very Well, then we start moving more towards the surgery, and the surgery should have several goals. The first one is to confirm the diagnosis. If you've not had a surgery before, the second one is to stage it. Some people will still use the SRM staging guidelines, but just to even categorize it as primarily superficial, primarily ovarian, within to be traumas or deep infiltrated into vitreous is present can be quite helpful for yourself to come back to or for other surgeons in the future. And then the goal in the end, is obviously symptom control until you are ready to begin your family or until menopause, and then we continue through the circuit. After surgery, you go back back into medical management to buy as much time as possible before you possibly may need another surgery. So the key points of medical management. So historically, we do know that progestin is in the combined hormonal contraceptives are effective in relieving their pain, and they tend to be well tolerated. So it's it's oftentimes a really good starting point for women that you suspect have endometriosis, preferably using them in a continuous fashion, um, and preventing those menstrual cycles from occurring can often be the most helpful. Projections are now emerging a little bit more as the as the new first line of treatment. It's the safest for long term control of symptoms of endometriosis, and more women are appropriate for progestin use when you may have some contraindications to use of estrogen. The other thing is, is that infant incense are commonly used, and we recommend them to help with some of the inflammatory discomfort and pain and the muscle discomfort. But it it hasn't really been shown to be an extremely effective source of pain control for endometriosis, although it is preferable to things like narcotics, um, they can help, but it's usually not enough. They usually need something else to help with their with their endometriosis pain. So say, you have gone through your medical management, and now you're moving into your surgical management options. So in patients who undergo a diagnostic laparoscopy who don't have any excision at all, the studies show that the natural progression of disease in a in a randomized controlled trial and a second look laparoscopy 30% should disease progression. 30% showed regression, but in the randomized controlled trial you had about 60% of people who stayed the same when nothing is done to manage the endometriosis. And from from that perspective, what we do know is that excision of endometriosis, an enemy traumatic lesions is vastly preferred over just an ablation treatment of the endometriosis at the time of laparoscopy. Now, when you think about your stage one Stage two or your superficial endometriosis, there's probably not a whole lot of difference between an excision and an ablation except excision can provide you with that pathologic diagnosis. But when you get to Stage three or Stage four, when you get to some of those endometrium Aziz and the deep infiltrating endometriosis, it really is excision of all the viable and Demetrius system that makes the biggest difference for these patients to improve their symptoms. A lot of the surgeons will also recommend if you have a lot of very superficial, Demetrius is present to do peritoneal resection or peritoneal stripping term of any endometriosis and as much visible endometriosis as possible. The goal of the surgery again is removed and treat all visible disease. Restore the normal anatomy, meaning cleaning up any adhesive disease you may find and then make sure you're using good surgical technique to try to prevent adhesions from reforming again. So when considering conservative surgery such as a laproscopic evaluation and treatment of endometriosis versus a hysterectomy, the other component to consider is whether or not to take the ovaries at the same time. So even with an O for ectomy at the time of the hysterectomy. For patients with endometriosis, there's still about a 10 to 15% risk of persistent pain and about 2 to 5% risk of worsening pain. So as long as you're having the conversation with the patient and you discuss that the surgery may not treat all of your pain, that's new is really reasonable to proceed If the patient has known bad endometriosis, if they're refractory to your medical treatment options, um, and if they understand that the removal of the ovaries going to render them surgically menopausal, then it's okay to proceed with that age is a factor in this and per several papers and data that we have available to us. The recommendation is often times above the age of 40 or 45 a lot of times over to me at the time of hysterectomy, meaning an extra operative procedure is often recommended for best management. For the younger patients who are having their hysterectomies early on for endometriosis, there is definitely a risk and benefit about taking their ovaries at the time of an early hysterectomy versus coming back for their ovaries a little bit later if they have persistence in pain just to allow them to have their ovaries endogenous estrogen for a longer period of time. For patients who want the excision or resection surgery again, those are ones that you would recommend for patients who desire preservation of their fertility. They have not completed their their family planning goals. Um, maybe they have a history of significant pain relief after the last surgery. There are managed for quite a while medically, but that medical management is not working for them at this point. Then it's a reasonable thing to go on and perform the next cleanup surgery or the next excision surgery always keep in mind. There's other factors, though, as to why their pain is under, well, control is well controlled for a good while, and then it becomes uncontrolled. So thinking about other factors that may be playing a role, and after those things are considered the moving forward, the surgery is definitely a reasonable option. So again, as my recurring theme, endometriosis is really never cured. It is a chronic disease. It is becoming known as a systemic disease because of the impact it has across the human body. And it does require most likely lifelong management following the reception of the hysterectomy. Consider suppressive therapy For these patients, suppressive therapy with something like a progestin can improve their postoperative pain. It decreases their recurrence rate by controlling those microscopic lesions. It prolongs the intervals between their surgeries. And there are lots of medications that you can use, whether they're oral medications, larks, um, or other medications that are coming to market now. But the key is that you want to try to suppress their ovulation and really suppress um, those endometriosis lesions, the ones that you may not have been able to see at the time of surgery. I want to thank you for surgical for asking me to join you today. I think it's very important to make sure that we bring to light a lot of the concerns about public pain. Chronic pelvic pain and endometriosis for women. And so I'm very excited to be here and thank you very much. Thank you so much, Doctor Robinson, for that wonderful review of pain and endometriosis which, as we know, affects so many of our endometriosis patients. Now that we've reviewed the two main clinical areas of endometriosis, let's move on to thinking about the future of endometriosis, both the diagnosis and treatment. But Dr Flores, thank you, Doctor, decide for that introduction before I get started. I just wanted to go through my one disclosure, which was for Abby, where I received speaking honorarium. I first wanted to start with the definition in terms of what endometriosis is. I know it's been introduced before, but it is endometrial tissue outside of the uterus, commonly ascribed to retrograde menstruation, with lesions implanting either superficially on the peritoneum, deep infiltrating or ovarian endometriosis. It affects one in 10 reproductive aged women, 50 to 80% of women with pelvic pain, up to 50% of women with infertility and over 176 million women suffer from endometriosis worldwide. In terms of health care dollar costs, it's over $22 billion in annual health care costs. And I think what's also important to recognize that the true cost of the disease includes the 100 potential affected women. The clinical presentation can be quite varied. Although women frequently complained of pelvic pain and can suffer from infertility many times, it can actually be completely asymptomatic. And what I'm hoping to get across throughout this presentation is the fact that this disease really does extend beyond the pelvis. It's not just limited to its pelvic manifestations, but instead is a systemic disease. Before I do that, however, I did want to go through the current limitations and endometriosis treatment. There are currently no noninvasive diagnosis, diagnostic tests for endometriosis, nor their disease specific treatments. And unfortunately, treatment failures are common. And even after surgical resection, recurrent rates are up to 50% at 2 to 5 years. So why are the symptoms non specific? And why is endometriosis is difficult to diagnose, and the answer, really is that endometriosis is complex and has actually many systemic features associated with it now. While several theories exist in terms of what causes endometriosis, the most well accepted is that of Sampson's theory of retrograde menstruation. however, it does not account for all forms of endometriosis. For example, endometriosis can be seen in postmenopausal women and can even be seen in men. So that suggests that the disease really goes beyond retrograde menstruation and instead probably involves stem cell trafficking. Um, stem cells can actually come from either the bone marrow or can actually come from the base Alice layer of the uterus. And when that happens, essentially what these stem cells do is they can travel throughout the circulation. They can either contribute to lesion growth themselves, or they can go from lesions and then re implant into the endometrium butt implant improperly, which affects inter cellular communications. In addition to the role of stem cells and endometriosis, other circulating factors have been found to contribute to the systemic manifestations of the disease. One of these factors are micro RNAs. My cronies are small, non coding RNA molecules that bind to and modulate mRNA translation. It has been previously demonstrated that microorganisms are differentially expressed in women with and without endometriosis, and that these microorganisms can travel to different organs within the body, including the liver, brain, spleen, lung and adipose tissue. In addition, they have also been previously demonstrated to contribute to inflammation, which likely also explains the chronic systemic inflammation that is frequently noted in the disease. To discuss a little more about the systemic effects of endometriosis, I did want to comment on some features that we commonly encounter in women with the disease. Women with endometriosis tend to have a lower body mass index and tend to have altered metabolism in a measuring model of endometriosis. Our lab has actually previously demonstrated that in mice who have endometriosis induced, there is induction of hepatic or an anorexia genic gene expression. And we have also found alterations and adipose site gene expression. Systemic inflammation is also commonly noted. This is due not only to estradiol mediated increases in prostaglandin e two, but is also related to apparent micro RNA function, apparent immune cell function and increased production of inflammatory cytokines. In addition, mood disorders are frequently noted women with endometriosis, including anxiety and depression, and in a different mirroring model. We have also demonstrated that in mice who have endometriosis induced, there's alter gene expression region of the brain associated with anxiety and depression, and other groups have also noted decreased volumes and areas of the brain associated with emotional and sensory nerve processing. As previously mentioned, microorganisms have been differential e expressed in women with endometriosis compared to women without the disease. And it may actually be that circulating micro grenades can serve as a biomarker of endometriosis. We have previously demonstrated in a retrospective study. Alterations in the following Micro RNA is specifically increased expression of micro in a 1 25 1 53 42 31 45 1 43 504 51 A and 18 A. With decreased expression of micro in a 6755 and 3613 Following this in a prospective study, we utilize a total of six of these microorganisms and found that when incorporating them into a receiver operating characteristics curve and then testing it on a training model with almost 100% accuracy, these six my cronies were able to diagnose endometriosis and women who had undergone surgery for the disease. And so they represent really a novel biomarker for women suffering from this disorder. And so what I hope to have gotten across is that endometriosis is a chronic systemic disease affecting multiple organs. The lesions in the pelvis are just a small component of the disease, and the systemic nature of the disease may explain the extensive symptoms often associated with endometriosis. Furthermore, stem cells, my cronies and inflammation are some of the mechanisms that likely mediate these long range effects. Now, well, I've gone through endometriosis, a systemic disorder, and also discuss some of the pathogenesis related to the disease. I next wanted to discuss treatment of endometriosis. While we frequently note that progestin based therapy is first line. Unfortunately, up to a third of women do not respond, and this is what we term progesterone resistance. We have previously demonstrated in our lab that progesterone resistance is mediated by altered progesterone receptor expression. In a retrospective cohort study utilizing 52 women who had undergone surgery for endometriosis, it was found that in women who did not respond to first line progestin based therapy there, lesions actually had decreased expression of the progesterone receptor. Furthermore, we were actually able to further characterize women into those who had high response to progestin based therapy and in fact, had high PR expression compared to those who had low PR expression and had nearly 94% chance of not responding to progestin based therapy. There, interestingly, was a group that had medium PR expression. But even then, if women did not have high PR expression, even with medium PR expression, their response rate to progestin based therapy was only 21%. Now the question becomes, and women who do not respond to first line progestin based therapy, what are alternative options for them? And typically we will look towards utilizing estrogen deprivation therapy. More frequently would have been used in the past was a January 2 receptor agonist, however, that was associated with significant side effects, namely the potential for a flare effect in that because it's a January 2 receptor agonist, there's initial release of FSH and LH, which can cause an initial increase in extra dial production. Um, in the past two years, Ella Golic's has been used now for the treatment of endometriosis associated pain. It is a generation analog, however, it's actually a generate receptor antagonist. And so what this means is that once women take this medication, which is actually, um, oral non peptide pill women, um, within 24 hours actually have a decreased production not only of FSH and LH, but also ultimately an extra dial levels. They're actually two doses available of the medication. There's a low dose and a high dose, and it allows really for tailoring of therapy for a given patient. The low dose of medication allows for a decrease in S to dial of on average 42 pictograms, whereas the high dose results in a estradiol level of 12 pictograms. And the end result really is hormonal suppression that is rapid and women who are failing progestin based therapy. This may serve as the next good next step in terms of adequately treating their pain. Now there is a big push towards developing non hormonal therapy because, as I mentioned earlier, women with endometriosis not only suffer from pelvic pain but also frequently suffer from infertility. And many of our existing regiments really don't allow for fertility because their end goal is really suppression of ovulation. As I had mentioned also previously, we have shown that micro needs are differentially expressed in women with endometriosis. One in particular is micro RNA. Let seven B, which is found which has been found to be decreased in women with endometriosis, and what this ultimately leads to is increases in inflammation, so inflammation is allowed to run unchecked in the disease process. In a mirroring model of endometriosis, we were actually able to demonstrate that if we replace micro RNA, let 70 there's actually a decrease in lesion size, and it also looking at this from a cell culture model. We have also been able to demonstrate decreases inflammation following treatment with Let's 70. So ultimately, there's decrease inflammatory cytokines, decrease in estrogen receptors and decreased aroma taste, which normally allows for the conversion of androgen to estrogen so well, not currently available. Although it does need to be studied prospectively in women, it does represent a novel non hormonal therapy option for women suffering from the disease. And so what I would like to end with is a quote, actually, which notes that a focus exclusively on pain underestimates the true extent of the consequence of endometriosis and the patient's full disability. One of the questions we just got was why is it important to classify endometriosis as a systemic disease? How will that even actually happen? Um, through society guidelines or what other kinds of changes we need to drive this disease to be more of a systemic disease instead of a more focal disease. That's a great question. I think. Many times women are often misdiagnosed or ultimately are seeing up to 45 providers before ultimately reaching the diagnosis of endometriosis. And I think it's because of the fact that, given its systemic nature, there are so many varied presentations. And so what I'm hoping is that by focusing on more of a clinical diagnosis and taking into consideration, the systemic effects of the disease will really ultimately help to diagnose women sooner and also hopefully develop novel therapies that can target not just again the lesions in the pelvis, but really the whole body effects of the disease can have on women. And sorry to get to your second point, which is how are we actually going to implement this? I think one of the biggest ways is increased education. So both from the perspective of our society guidelines changing how we think about the disease and really also focusing not so much on requiring the gold standard surgical diagnosis, but in fact shifting the paradigm and saying we can actually diagnosis disease clinically start treatment sooner and hopefully really avoid all of the long term sick quality of the disease. So you talked about a little bit about education. And, you know, right now I feel like there is so much education available online or in person, what are some really good resources for women's health care providers so that they can learn more about endometriosis? That's a great question. I think some great go to resources would include the American Society for Reproductive Medicine as well as the American College of Obstetrics and Gynecology. And even more recently, there was a publication and lands at that. I was fortunate enough to participate in where we focus a lot on the clinical diagnosis of endometriosis and really taking into consideration the systemic effects of the disease and using that as a way to be better equipped to diagnose the disease and ultimately treat the different manifestations of the disease as well. So here's an interesting question. Why is it important to classify this disease as a systemic disease? And how will that happen as we move forward? Well, that require society guidelines? Or what other ways can we get this endometriosis disease to become more of a systemic disease instead of just a vocal pelvic disease. That's a great question, Dr Desai. I think, really, in order to be the importance of diagnosing it and thinking about it as a systemic disorder, is really to help with diagnosis in and of itself. It's really common for these women to be misdiagnosed, and I think part of the problem is because a lot of these symptoms can seem so varied and so different from just a G y n pelvic disorder. And so if we can think about it as a cyst as its systemic nature, causing chronic inflammation affecting regions of the brain, the liver, adipose tissue causing infertility, I think that will hopefully help in terms of ultimately solidifying the diagnosis. I think the other thing that's important is in addition to our society guidelines which are great looking at other resources. I was fortunate enough to be involved in a new paper from Lancet where we review not only just the current information that we have about the path of physiology of the disease, but also really targeting the fact that it is a systemic disorder and really going into the fact that we need a paradigm shift instead of saying that the gold standard is surgical treatment or rather, surgical diagnosis, really thinking about it as a clinical diagnosis and then from there deciding on treatment based off of that. I also think if I can chime in, um, but a lot of the push is really not only coming from physicians and researchers and society guidelines, but it's also more and more coming from patients and patient advocates. And so there's currently just a whole world out there, whether it's on social media or whether it's, you know, groups that are going to lobby for insurance coverage. For example, in New York, the mandate now covers egg freezing. Um, in a lot of cases for an amateur is this is a medical diagnosis, and a lot of that is a push by patients and patient advocates. I think we do really also need to obviously continue doing the research but also encourage our patients to use their voices because they are, you know, a big, big part of this. I agree with both of you, and I think that a lot of the push is is that the patients are now finding resources, and they're much more available for them to come together and share resources and share information. And then they're also able to provide information about physicians who specialize in endometriosis who see a lot of endometriosis. And so I think I agree. I think patients are pushing a lot of this. And as physicians, I think we need to take it back to our societies and say we have good evidence that this really is a chronic systemic disease. And as Doctor Flores says, we have to stop the whole straight to surgery right away when we can actually be treating a lot of these patients before they go to surgery and start this ongoing surgical cycle that we often see for them. Thank you. That was a really great overview, not just from a clinical point of view, but also a patient point of view. The next question that we have is what kind of women's health provider do if they suspect a patient with possible endometriosis. I think the most important thing the provider can do is listen to their patient. So I think the reason that so many of these young girls and women are kind of being pushed from from doctor to doctor is because pelvic pain is hard to treat, and it requires a lot of patients and requires a lot of time. And a lot of General Ogun just don't have that time, not because they don't want to have that time. They're just very, very busy. Their offices are just overloaded, and so if, as a general is, you don't have the time to really sit and talk to the patient. If it's something that you do suspect, rather than sending them to someone else or a G I or their interns or what have you? It does behoove you to send them to someone who who specializes in Endo, whether they're dealing with pain or infertility, who has the time to really sit down and counsel them and listen to them? I think listening to the patient is a key part of all of this of treating the patient. There are more and more physicians out there, insurgents in gynecology and reproductive endocrinology and infertility, specifically who do focus very heavily on endometriosis. So there are a lot of resources that are coming out, and sometimes for somebody who suspects endometriosis but isn't sure where you're not comfortable with. Maybe what you may find in surgery. Then you know, there are a lot of resources to at least start something, some sort of treatment for them, and then help your patient be their advocate to find somebody close to you who really does have a passion for it. And, um, I guarantee you that most of those physicians are very interested in helping. We want to help. We want to help these patients out, um, and get these patients back to you with a good plan. Yeah, No, I think that those are the key principles we all learned in medical school. You're one history and physical. Listen to our patients. Help that guide your diagnosis because you can learn so much just by listening to our patients. Um, the next question is when infertility workout should be considered as part of the differential. And does this change when you refer that patient out to an r E? I You know, I think because it's such it can be such an insidious disease. Um, sometimes because because we have the same weapons in our arsenal, right? Really, I mean to treat our patients with unexplained infertility versus or end of patients. And at the end of the day, from an infertility perspective, you have the options of expectant management. Are you I, IVF, or surgery? I mean, that's really what we have. And so I don't treat my under patients that differently. Where difference coming into play if they're having concomitant symptoms such as pain. And there's a very different two very different patients, the patients coming to me where maybe some time in their history, I suspect endometriosis is maybe a cause for their unexplained infertility is not explained. Maybe Endo is a factor there, but that doesn't have debilitating pain and can tolerate the pain versus a patient. I saw a patient last week who actually got She has severe endo. She's been operated on multiple times. She got pregnant pretty easily with her first one. Her tubes are open. Surprisingly, she has a normal HSG, and then she just She had another surgery in 2018. She went on Lupron suppression and continues OCP, and now she wants to have a second child, and she's went off of her meds and is now having debilitating pain, and she came to me and said, I just want to get pregnant as efficiently as possible. And so the weapons in my arsenal are the same for her as they would be with someone with unexplained infertility. Someone who didn't have endo, which is we can either really be efficient and go straight to IVF. But is that really the answer in a 33 year old with a normal, very reserve who just had a spontaneous pregnancy? Not that long ago? Or do we start with us and efficiently move through that? Try three I us you're not successful. Move onto IVF. So a lot of times it's a little bit of a gray area of does the actual diagnosis of endometriosis really matter if we're treating it in a very similar way? Same with pain management. You don't necessarily have to take someone to the O. R. Two actually diagnosed them before you try different modalities, even starting with a continuous OCP or Lupron or Alyssa or some of these other things. And my colleagues are talking about today, the end of the day, our arsenal is our arsenal. So, um, that's kind of how I view my patients. Even if I do suspect it, I'm more likely to just give them the treatment option because the end of the day that's what's going to get them pregnant, not necessarily the actual diagnosis itself. And I would also add to that as a reproductive endocrinologist as well that it is tricky sometimes because they come in. It's very common to have infertility as an endometriosis patient, but just because you have infertility, then on the flip side does not mean that you have endometriosis. But if that's the diagnosis that I suspect, I think like you had mentioned, what I would do differently is efficiency, because for them we know if they're not on a suppressive therapy that obviously also prevents pregnancy, then they're Endo and their estrogen is going up, and that's allowing their end of to grow. And then they have pain. And then we're more likely to have to do a surgery before we can treat them for their infertility. And so I think just that efficiency approaches key rather than letting them try naturally for a few months and then see what happens, I would go at least immediately to either ovulation induction with I u i or I you. I know more than three cycles because again we're allowing their estrogen to go up and their disease can get worse. And then if after three cycles it doesn't work, then we move on to IVF, And then, in terms of how we maximize those options, I think it just becomes a little bit different. If let's say someone had a failed IVF cycle, for example, or has issues with implantation, then we can look at newer ways to treat these women, which is, you know, GN Rh analog suppression and seeing if that will ultimately maximize their chances from an IVF perspective. And then I guess, the final question. You know, what are some resources that women's health providers can access to learn more about endometriosis? I mean, this has been a great Webinar and will be available on Cooper. Insights are eight CP only website. But where else can providers learn more about endometriosis? What are some reputable sources that you would recommend from an infertility perspective? I think a srm, um, has a great website with where all the committee opinions are, Um and you know, all the pertinent papers regarding to Endo. I think a stream is a great option even for General g y n those who are interested for just surgical education and self training as well. Um, a g l has surgery you with lots of videos of endometriosis surgeries, Um, and similarly a G often, um, works with SRM and some of our, um, friendly peer groups to optimize this treatment. Because sometimes it is a very good collaboration between your minimum invasive surgeons and your r E I teams and, um so there is precedent out there and there are lots of resources to help facilitate that. Great. And I think other resources. ACOG is a great general resource. A serum is a great resource. Spear off was just recently updated, and I was fortunate to be a part of helping to edit the endometriosis chapter. So I think that helps get again at the mechanistic aspects of it, looking at as a systemic disease. And then the review that came out and landed really trying to change the clinical paradigm. Well, thank you all again. I'm so honored that you were able to join me on this webinar. I've had the pleasure of working with all of you personally as a colleague. And so I know how you treat your patients. And we're all lucky to have you seeing patients every day and helping on a one on one basis with them to help their lives with this horrible speed. So thank you again and in celebration of endometriosis Awareness month. I'm really, really happy that we were able to do this, so thank you.
