I am thrilled to have famed fertility doctor, Dr. Geoffrey Sher on today’s show. We’re going to talk about the rational basis for treating endometriosis related infertility.
Dr. Sher is founder of Sher Fertility Solutions (SFS), and is an internationally renowned expert in the field of Assisted Reproductive Technology (ART). Dr Sher has been influential in the births of more than 17,000 IVF babies, and over the last 36 years, he has helped fashion the field of ART. After training under the fathers of IVF (Dr. Patrick Steptoe and Dr. Robert Edwards), he established the third IVF program and the 1st private IVF center in the United States in 1982. Dr. Sher has authored over 200 scientific articles and abstracts and has authored several books, including his most recent, “From In Vitro Fertilization to Family” written with his partner, Dr. Drew Tortoriello MD. It will be available soon.
Dr. Aimee: Thank you for joining us again, Geoff. First, what is “rational” about treating endometriosis related infertility?
Dr. Geoffrey Sher: Endometriosis is a condition where the lining of the uterus (endometrium) grows outside of the uterus, predominantly in the pelvic cavity. It occurs in about 10% of all women and can be symptom free or present with a wide spectrum of manifestations. About 25% -40% of all female infertility is in one way or another linked to endometriosis. Endometriosis is a condition for life. It cannot be completely eradicated. Infertility can often predate clinical manifestations of endometriosis.
While clinical and anatomical progression of endometriosis can usually be controlled (medically or surgically), the condition itself is not curable. Whether you eradicate visible/accessible lesions through medical or surgical intervention, it will not resolve the problem of associated infertility, treatment of which must take into account the underlying causative mechanism(s).
Dr. Aimee: What do patients need to know about it if they suspect they have it? How do they talk to their doctor about it?
Dr. Geoffrey Sher: First, this requires a working understanding of the pathogenesis of endometriosis.
There are many theories on how endometriotic nodules and deposits appear in the pelvis. The most popular of these theories relates to what we refer to as “retrograde menstruation” which refers to the fact that aside from menstruating outward through the vagina, most women who have one or both Fallopian tubes that are open also commonly and frequently menstruate backwards through their tubes sand into their pelvic cavities. This menstrual blood contains live endometrial cells that have a predilection for growing on the surface of the membranous envelopment of all the pelvic organs known and the “peritoneum”. Thereupon, under the influence of estrogen, the endometrial cells attach to and then proliferate on, the peritoneal surface in small clusters (or “islets”). The deposits are at first not visible to the naked eye.
The moment the woman ovulates her ovaries start to produce progesterone. This sends a signal to her immune system to dispatch “janitorial cells” (macrophages) to the areas of implants to remove them by engulfing them…much like the old-fashioned game of Pac-Man. So, by the time the next menstrual period begins, all of the deposits are gone, and the process starts over again.
In some women, this clearance mechanism is partially suppressed, allowing the deposits to perpetuate and continue to grow. As they grow, they thicken progressively. Ultimately, since they are composed primarily of endometrial cells, when the woman menstruates, she menstruates into this tissue.
Blood contains “red stuff” known as hemoglobin which is an iron compound. So it is that when the next menstrual period comes, bleeding occurs into the deposits and when her period subsides, the blood begins to absorb. Depending on the size of the deposits and the amount of bleeding into them, some blood and hemoglobin might remain in the deposits. The residual “iron-pigment” (hemosiderin) leaves a tell-tale sign such that when you do a laparoscopy or you open the abdomen and look inside, it will appear as little “pigeon eyes” or as “gunpowder burns”. At this point the doctor makes a diagnosis of endometriosis, often being oblivious to the reality that the process has probably been ongoing for several years already.
These endometriotic lesions can become confluent, they can grow, they can eventually bleed more and more with each ensuing menstruation. If a collection of blood occurs in or on the ovary, the blood might collect, decompose, and present as a cystic lesion (an ovarian endometrioma). The decomposed blood looks like “melted chocolate,” hence the name “chocolate cyst”.
Given the likely genesis of endometriosis it follows that for every “endometriotic lesion” visualized and/or ablated/removed surgically, there are likely to be numerous others that are in the process of developing but are not yet visible/detectable. For this reason, endometriosis is something that you probably develop from a rather early age, but which only becomes clinically manifest later in life…usually in the second half of a woman’s reproductive lifespan.
The endometriotic deposits release “toxins” into the secretions of the pelvis. These toxins attach to little receptors (ZP-receptors) on the egg envelopment (zona pellucida) where sperm attach, compromising fertilization potential. As a consequence, the ability of a woman to get pregnant is reduced five- or six-fold per month of trying.
Importantly, it is not only the visible endometriotic lesions that produce these “toxins”. They can and are indeed produced by evolving, non-visible endometriotic lesions. This also serves to explain why failure to conceive often occurs in women with early endometriosis as well as in those that present with so no visible lesions (“unexplained infertility”) often well before endometriosis becomes clinically recognizable. It also explains why surgical ablation of visible endometriotic deposits, the use of fertility drugs or intrauterine insemination (IUI) will not significantly enhance the ability to conceive and is often no better than “no treatment at all”, when it comes to “infertility” due to endometriosis. The only treatment that improves the chance of having a baby is IVF, because here, the eggs are removed from the woman’s ovaries before they are exposed to the peritoneal “toxins”.
So, the woman’s ability to conceive is not improved through using fertility drugs, nor is it improved by surgical ablation of endometriotic lesions. The only way you can improve the chance of a woman getting pregnant is really to extract her eggs t before they’re released into the “toxic peritoneal environment” that exists in all cases of endometriosis (regardless of severity), fertilize them in the laboratory (IVF) and thereupon, transfer them to the woman’s uterus (embryo transfer-ET). I am not suggesting that all women with endometriosis need IVF. They can still get pregnant if they have the time to wait…because it will usually take much longer. Therefore, for younger women who have normal ovarian reserve, a wait and see approach is acceptable. But for women over 35y and/or women who have diminished ovarian reserve (DOR) for whom time may be an issue, a – 3% chance of conceiving per month of trying on their own or following ovarian stimulation/IUI or surgery might pose too great a risk.
Whether you do surgery, whether you do intrauterine insemination, whether you give fertility drugs, the chance of conception in a woman with endometriosis, even in its mildest form, is no better than no treatment at all. Surgery and medications can and usually will alleviate symptoms and reduce the risk of medical complications, but IVF is the only way to enhance fertility in such cases. The rest are all “temporizing measures”. I will go so far as to say that if any alternatives to IVF does result in a pregnancy, this likely occurred “in spite of”, rather than “due to” such treatments. In my opinion, the only time surgery is indicated is if there is endometrioma, or if there are dense adhesions that are preventing the tube (s) from functioning.
Dr. Aimee: How do you diagnose endometriosis?
Dr. Geoffrey Sher: It can only really be diagnosed definitively by doing a laparoscopy or making an incision in the abdomen and seeing these little gunpowder burns or little pigeon eyes looking at you. Or if you detect an ovarian endometrioma (“chocolate cyst” at ultrasound or MRI.
There are certain newer tests such as the BCL6 test where you do a biopsy of the endometrium, and you look for beta integrins, but these are not conclusive.
Dr. Aimee: Do you have any favorite IVF protocols that you use for patients if you know that they have endometriosis?
Dr. Geoffrey Sher: Not really. But the ovarian stimulation protocol used MUST be individualized to fit the woman’s profile. In my opinion, all ovarian endometriomas (greater than 1.5cm) should be removed by surgery or sclerotherapy well in advance of undertaking ovarian stimulation for IVF. These endometriomas act as “space occupying, misfit tumors” that activate the surrounding connective tissue (stroma) in the ovary, causing overproduction of the male hormone testosterone. While testosterone and other ovarian male hormones) are essential for follicle growth and egg development, too much testosterone can have the reverse effect. It gets into the fluid of the follicle and interferes with egg development. Thereupon, when you “trigger “egg maturation (meiosis) with hCG (or equivalent) the eggs in the affected ovary (with the endometrioma) are more likely to be chromosomally abnormal (aneuploid and “incompetent”)
Dr. Aimee: I think what you’re saying as in women who have endometriomas, they should be at least counseled about the benefit of surgery and be told that they might have lower egg quality, lower number of blastocysts, and if they get blastocysts, there is a higher rate to be genetically abnormal. Is that right?
Dr. Geoffrey Sher: That is absolutely correct. It’s important to make people understand that it is only the ovary that contains the endometrioma (s) that is so affected.
Dr. Aimee: When you’re making a fertility plan with a patient and you know that they have endometriosis, how many cycles? This is a question that I get all of the time. Do you tell them that they need more embryos than someone else who doesn’t have endometriosis to reach their family size goals, or at the outset tell them that they might need more cycles from the beginning?
Dr. Geoffrey Sher: I don’t think that the presence of mild endometriosis in the pelvis, or even moderately severe endometriosis, will affect egg quality. However, if an ovary has a sizeable endometrioma or in cases with advanced endometriosis where the blood supply to the ovary is compromised such that DOR develops, the egg quality can be affected.
Dr. Aimee: When you have a patient who is preparing for their IVF cycle and you know they have endometriosis, is there a special diet or supplement regimen or exercise regimen that you ask them to follow?
Dr. Geoffrey Sher: Not really. To my knowledge at least, I don’t believe there are any supplements that directly impact egg quality. I know all sorts of things have been suggested, like DHEA, and ovarian PRP. To me, that’s “window dressing”. I don’t believe there is any real evidence that it does anything. We do, however, offer it to patients who absolutely insist upon trying.
The big issue is to get the eggs out before they run out which might well happen with advanced endometriosis, to treat the ovary(ies) affected by endometriomas, to make sure that ovary isn’t compromised, and then give eight to twelve weeks of a break to allow the ovary to recover before doing another egg retrieval. But I don’t think that there is any evidence whatsoever that any of these drugs or approaches really impact egg quality.
Dr. Aimee: What I would love to get into more is about endometriosis impact on implantation and what your favorite transfer protocols are, or your approach when it comes to that.
Dr. Geoffrey Sher: We’ve been through this in previous discussions. What we’ve found unequivocally, is that about one-third of women who have endometriosis, regardless of severity (including women with preclinical endometriosis) there is an increased risk of an immunologic implantation dysfunction (IID), Here, immune cells in the uterine lining called natural killer (NK) cells and T-cells become activated and overproduce TH1 cytokines that attack the embryo’s trophoblast (“root system”), so the woman loses the pregnancy, often before she knows she’s pregnant or she gets pregnant and then the embryo runs out of steam and she has a “chemical pregnancy” or early miscarriage.
As I implied earlier on in this presentation, women with endometriosis have somewhat “dumbed down” immunologic responses. This probably contributes to the development of endometriosis, in the 1st place.
Dr. Aimee: What about the role of Depot Lupron, Orlissa in your practice? Do you use that when you’re preparing someone for an embryo transfer?
Dr. Geoffrey Sher: I do not personally use long-term agonist treatment, such as Lupron, or Decapeptyl, or Superfact. My reasoning is that if you give a woman Depot Lupron, you end up suppressing estrogen production by the ovary. For the uterine lining to respond adequately to estrogen, the endometrial estrogen receptors have to be attuned. If you starve the endometrium of estrogen over a protracted period of time, you’ll end up with the uterine lining being unable to respond optimally to estrogen and end up with an endometrial lining issue.
I’m not a big fan of using Depot Lupron or Depot Progesterone. It’s a different matter if you’re using it for symptomatic relief of endometriosis. But I don’t think it adds anything to the infertility treatment equation. There are others that might disagree, and I’m not always right, as my wife often reminds me. The truth of the matter is, one has to accept that you’re really not going to do much to improve the quality of the eggs. When you stop the Depot Lupron, the problem comes back within four weeks and you’re right back where you started from. So, I’m not a big believer in it. Again, it’s never the doctor’s right to tell people what to do. It’s our responsibility to give information so that they can make their own choices, and then to execute based on those choices. I’m never going to turn down a patient that says, “I want to use something to suppress the endometriosis for a few months,” but I’ll warn her that she is likely to be wasting valuable time on the “biological clock”
Dr. Aimee: I agree. Using them first can be extremely detrimental.
Dr. Aimee: I couldn’t agree more with you. I feel like endometriosis is definitely a fertility-threatening condition, and women who are diagnosed with it, especially when they’re teenagers, whoever is making that diagnosis should also encourage them to freeze their eggs. Don’t wait, freeze your eggs. If you had surgery for endometriosis when you were 20, the next thing you should do, or even before surgery, is freeze your eggs.
I’m also pretty passionate about requiring, and I wish I could do this, that every OBGYN for endometriosis surgeon out there, a lot of them are pretty good about this, before you do
surgery on a patient with endometriosis, it should be a requirement to talk to that patient about her fertility so that at least she is educated about it.
Dr. Geoffrey Sher: I applaud you. That is probably the most important point that has been made in this entire presentation. I should have launched with it. Indeed, any woman with endometriosis must realize that it’s only going to get worse. The earlier it is diagnosed, the more likely it is that it’s going to get bad by the time they want to have a family.
It’s very important that doctors refer patients with early endometriosis who don’t have children or who want to have more children later on to people like us for Fertility Preservation (FP-egg banking) to extract their eggs and freeze them for future dispensation. If you do nothing about it in a timely manner, by the time the woman reaches 35y her egg quality might start to decline rapidly and the likelihood of DOR increases because “Time waits for no one”
While no one wants to waste time and money there is also the matter of emotional stress. People often ignore how emotionally debilitating infertility can be. To put someone on a course which is not going to benefit their end point objective, in my opinion, is not good medicine. So, I agree with you, and I applaud that statement. All doctors who detect endometriosis in young women should at least talk to them about infertility or refer them to people like us where we can talk to them and explain these realities so that they can prepare themselves and avert the disaster that will follow.
Please don’t believe people who tell you, “I’ll go in and do a laparoscopy and “zap” the endometriotic deposits, and then you’re going to be fine,” because for every lesion they zap and remove, there are probably another 20 or 30 coming up already doing their disaster. The bottom line is you’re not improving your chances by just doing surgery, or doing fertility drugs or IUI, unless you have an ovulation problem that you’re treating in the hope of getting pregnant on your own before you get too old or before you run out of eggs.
Dr. Aimee: Then there’s something else that I’ve been also telling my patients who have endometriosis, probably in the last five years or so. I’ve been reminding them about the connection between endometriosis and ovarian cancer.
Dr. Geoffrey Sher: I think that’s good because endometrioid cancer can occur in women with endometriosis. Yes, the doctor has to be on the lookout for it and do whatever testing is necessary. Unfortunately, as you know, ovarian cancer is not easy to diagnose. But you have to be on the lookout for it. Oftentimes, doing paracentesis flushing of the cul-de-sac, taking the fluid to look for ovarian cancer cells is a way to go.
But I agree with you, patients need to be aware that endometrioid ovarian cancer is actually something that you need to be on the lookout for.
Dr. Aimee: Geoff, thank you for the wisdom that you’ve shared with us today. I will never forget the piranha cells, the janitor cells, the pantheon cells, the misfit tumor, I love it all and I’ll be using them. Tell us what you’re up to lately.
Dr. Geoffrey Sher: I just want your listeners to be made aware that there is a book they can get for free as a download or they can read it online that I’ve just written with my partner in New York, Dr. Drew Tortoriello. The book is called From In Vitro Fertilization to Family. It’s like an “operational manual”, it’s about 180 pages long, and it goes into virtually all aspects of the IVF experience, at least from our perspective as what we think needs to be considered. There’s a whole chapter in the book on endometriosis and infertility, as well as on immunology and infertility.
The book is not going to be available commercially for a couple of months. In the meanwhile, anybody interested in gaining access to this ebook can call my assistant, Patti Converse at 702-533-2691 or can go to Patti’s email at [email protected] and ask her to forward you the link (free of charge), then you’ll be able to look at this particular book. I think it will be helpful to you and you should take advantage of that.
Dr. Aimee: I agree. All of the books that you’ve written, my patients have really enjoyed reading. Like I said earlier, your shows have always had the highest downloads, especially our episode on How to Avoid Implantation Failure During IVF. I think this episode will also be very helpful for women who are suffering with infertility, especially those with endometriosis.
Geoff, before we end our show today, where can patients find you if they want to work with you as their fertility doctor?
Dr. Geoffrey Sher: Firstly, let me explain something that is really important. I do consultations out of my home base in Las Vegas. I don’t do procedures here. When I do procedures, it’s at our clinic, SFS-New York in Midtown Manhattan. My patients come there for a week, I do their egg retrieval, we do the testing, they come back for frozen transfers as needed.
But Aimee, when they have a doctor like you, they usually won’t need me. You are the best. I often tell my patients that if my daughter lived in your area and needed IVF, there’s only one place that I would send her, and that would be to you. That’s really a feather in your cap because I don’t say that often or glibly.
The truth of the matter is if anybody for some reason, needs me to become their treating doctor. I will be happy to help you. The consultation is done online. Simply call my assistant Patti Converse (702-533-2691) or email her at [email protected] or go to my website, sherivf.com address that I gave for her, or by going to my website www.SherIVF.com and book a consultation with me, online and I will give you my best advice.
Dr. Aimee: You certainly do. I send so many patients to you for those second opinions, and we greatly appreciate the advice that you’ve given them.
Dr. Geoffrey Sher: It’s always a pleasure.
Dr. Aimee: Thank you, Geoff. I hope that you’ll come back again soon. We’ll talk about more topics, and I’ll just continue to learn more from you. Thank you so much.
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You can find Dr. Geoffrey Sher at Sher Fertility Solutions, or call 702-533-2691 and Patti can help answer your questions.
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