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Fertility specialist Oluyemisi Famuyiwa discusses her article, “Endometriosis and fertility: What every woman should know.” She explores how endometriosis, an inflammatory condition affecting 10 percent of reproductive-age women, disrupts fertility through pelvic adhesions, ovarian damage, and chronic inflammation. Yemi breaks down treatment strategies, from laparoscopic surgery and hormonal therapy to assisted reproductive technologies like IVF. She also highlights the role of dietary and lifestyle changes in reducing inflammation and improving reproductive outcomes. Tune in to learn about cutting-edge fertility treatments, diagnostic advancements, and personalized approaches to overcoming endometriosis-related infertility.
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Transcript
Kevin Pho: Hi, and welcome to the show. Subscribe at KevinMD.com/podcast. Today, we welcome back Oluyemisi Famuyiwa. She’s a fertility specialist. Today’s KevinMD article is “Endometriosis and fertility, what every woman should know.” Yemi, welcome back to the show.
Oluyemisi Famuyiwa: Thank you. Thank you so much. Always a pleasure.
Kevin Pho: All right. Tell us what your latest article is about.
Oluyemisi Famuyiwa: Well, my latest article is about endometriosis because it’s so prevalent and people always asking me or, you know, I have this diagnosis or I think I may have it, and I just wanted to do a little something about it just to shed some light on it.
Kevin Pho: All right, and let’s get everyone to the same page. For those who aren’t familiar with endometriosis, tell us exactly what that is.
Oluyemisi Famuyiwa: So endometriosis is when what’s supposed to come out with the menstrual fluid—you know, when people have their fluid period, the lining sheds and comes out, right? That’s what’s supposed to happen.
Now imagine this fluid that’s supposed to shed out, the lining that comes out is not coming out the right way, or it’s either going backwards, or you’re finding it in places where you’re not supposed to find it, like, you know, on top of the ovary, in the ovary, inside the muscle of the uterus, around the pelvic tissue, and in weird places like the lungs.
So it’s endometrial tissue that’s not behaving the way it should be.
Kevin Pho: And how does that normally typically present in patients?
Oluyemisi Famuyiwa: It’s very difficult to diagnose, right? It could be present in up to 50 percent of infertile patients, probably about 10 percent of reproductive-age women. It’s difficult to diagnose because typically patients will complain of pain with menstrual cycles.
And you might have someone having a history of painful periods for so many years, and it’s like, oh, you ruptured a cyst or, you know, you’re just having a rough cramp. So there’s always that latency before the proper diagnosis, sometimes six years or more.
Kevin Pho: And as it relates to infertility, what are the connections between the two?
Oluyemisi Famuyiwa: So because this tissue is behaving in an aberrant manner, it’s located where it shouldn’t be. So imagine if you have menstrual fluid in your pelvic cavity, in your abdomen. It’s not supposed to be there. It releases certain factors—we call them cytokines sometimes—that are inflammatory, and they just, like, it’s like putting jalapeño pepper inside your belly. It just tears things up, causes severe inflammation. That’s where the problem comes.
And then things start to get stuck together, and that could cause fertility issues down the line.
Kevin Pho: And do we have any data that kind of quantifies that connection?
Oluyemisi Famuyiwa: I don’t think there’s—you know, one of the things with endometriosis is there may not be a one-to-one correlation, right? It depends on where it’s located. Some people have it, a very small amount, but if it’s located, say, on a nerve fiber or produces neurotoxin, neurocytokines, or something like that, will have severe pain, and other people have an extensive amount and barely know it, until maybe they go in for surgery or something else and it’s incidentally caught.
So it’s not sometimes a one to one. I think sometimes the scary part is if it happens to be in the ovary and it tries to shed as if it’s a period, it has nowhere to shed to. There’s no cervix, no vagina to come out. It sheds within itself, and it expands as a system, forms what is called the chocolate cysts. And sometimes it may not have symptoms when it first starts at the early stages. It’s only much later that you might have symptoms. And some people don’t have symptoms. And you find out when you’re doing an ultrasound for something else: Wait a minute, you have this thing here. What’s going on here?
Kevin Pho: And what are some of the risk factors for someone developing endometriosis?
Oluyemisi Famuyiwa: Well, we know that it’s inflammatory caused. We think part of it could be either genetic, right? Nature, nurture. We know that there are some studies now looking at individuals who may be experiencing extraordinary stress may be at risk for it. But I don’t think that we have the one goal thing that says, here, this is what causes endometriosis.
Kevin Pho: And you mentioned also in your article that endometriosis also impacts egg quality as well.
Oluyemisi Famuyiwa: Yes, because it releases cytokines. Well, first off, just the pressure effect of it being in the ovary—if it’s not removed, it continues to produce direct effect on the eggs, but also the inflammatory reaction that it induces can affect the eggs and lead to oxidative stress. So just that excess inflammation is not good for the eggs.
Kevin Pho: Now if someone comes to you for fertility treatment and they have a history of endometriosis, does that change what you do from a fertility lens?
Oluyemisi Famuyiwa: Well, so the first thing I want to know is how extensive was the diagnosis, how was it made, and what is it involving? Is it in the uterus, in the muscle of the uterus—which is adenomyosis, right—or is it in the ovary, or is it mostly in the pelvic cavity? That will give you an idea of what you need to start approaching them with. If it’s just in the peritoneal cavity around and in nothing else, very mild cases, they may do things like intrauterine insemination and still get pregnant. It’s the more extensive cases that you may need to do IVF for them and try to get eggs and fertilize the eggs and put it back in the uterus.
Kevin Pho: Now, if someone has a history of endometriosis, are there some things they need to consider if they’re also infertile? What are some of the things that they need to consider?
Oluyemisi Famuyiwa: Yeah, so my thing is, at the time of diagnosis, how was it treated? How extensive was it? And that matters a lot, because there are studies that have come out that have shown that at the time of diagnosis, especially for people with extensive endometriosis, if they got a GnRH antagonist, for instance, like Lupron, or the antagonist—the recent one is Aurelisa, which is orally taken—if they got treated with those remedies, it puts off any recurrence, sometimes by as much as five years.
And also, if they had extensive endometriosis, who did their surgery? Was it completely excised, or was it something where they saw, oh my gosh, you have endometriosis, let’s get out of here, you know. So if it was completely excised, the peritoneum involved was stripped and removed versus it was burnt and the peritoneal surface where it was was left in situ, then those patients are at much higher risk for recurrence.
If it was adequately treated at the very beginning, it does buy them a lot of time to try and get pregnant or preserve their fertility. So it all depends on how was it initially treated. I know one of my friends who does endometriosis surgery up in New York always has this mantra: Look, you know what? I prefer to see you first before you get surgery done halfway, and then I have to come back and clean up. That’s a lot harder.
Kevin Pho: And in terms of the general treatment approaches to endometriosis, you mentioned surgery. Are there any other options?
Oluyemisi Famuyiwa: Yes. Yeah, we talked about hormonal suppression, such as the GnRH agonists, antagonists, except you can’t use those long term because you get bone loss with them. You can do something like a low-dose birth control pill continuously. And now there’s some evidence that even things like Mirena, which is actually local—it has an IUD that releases progesterone locally—but even that too has some benefit in some patients with endometriosis to provide that long-term suppression.
The ones that are having the hardest times that I’ve seen, and also in the literature, they had surgery, had an endometrioma removed, extensive endometriosis debulked, excised, and they weren’t given anything, right? And I had a patient who came from overseas that had a large endometrioma removed, and she said it was done, I think, around September or October, and I saw her in February. And I’m like, are you sure it was removed? Because here, look, you know, this thing is there, you know. I don’t see if it was removed. It’s just four months out of surgery, and I’m seeing this nine, eight-centimeter thing that could be a problem.
Kevin Pho: Now, if you have a patient who has a history of endometriosis and is interested in fertility treatments, anything from a dietary or lifestyle standpoint that they can do, anything that they could do on their end?
Oluyemisi Famuyiwa: Yes. So we know that endometriosis is a very, very high inflammatory process, right? And some people have even looked at even your gut microbiome could be deranged when you have endometriosis. So try to live the best anti-inflammatory lifestyle possible is probably the route to go.
And now I know there are ongoing randomized clinical trials, ongoing now, that are looking at diet and outcome to see if you can abide by a Mediterranean-type diet that has a very low inflammatory intake—would you have a better outcome? So in terms of what I tell my patients for lifestyle, you want to make sure that you’re eating a lot of vegetables, a lot of fruits. The same anti-inflammatory type diet that has been shown to help Alzheimer’s, has been shown to help heart problems. If you listen to Dr. Fisher, he talks about it all the time. That same lifestyle is also helpful when you have endometriosis. Avoiding excess alcohol, because that just may just, you know, make things flare up. Avoiding smoking is not good for you. So watching what comes in contact with your body and trying to live a more holistic lifestyle is the best that we have at the present time, right, short of medication.
Kevin Pho: In your article, you talk about some advanced treatments like stem cell therapy and immunotherapy. So talk about those potential approaches going forward.
Oluyemisi Famuyiwa: Those are probably in the trial phase. They’re not out there for everyone. And that’s, you know, first the things that are out there right now is looking at biomarkers. We talked about how difficult this thing is to diagnose early. So there are tests out there, there are studies out there looking at biomarkers that may be able to maybe pick it up in the bloodstream or even in menstrual effluent. We know that the menstrual effluent has some stem cells in it.
And if some of those stem cells may actually induce endometriosis because they’re not behaving normally, and when they get into the peritoneal cavity, they also recruit bone stem cells that add insult to injury. There are other studies saying that different types of stem cells may help to correct that regulation. It’s not prime time yet.
They’re looking at immunomodulators targeting tumor necrosis factor agents. Those are under investigation. Another thing that’s under investigation is your angiogenesis inhibitors, right—anti-VEGF—again to try to disrupt the blood supply that starts with this lesion. It’s very common for it to have what we call angiogenesis, meaning development of new blood vessels. So maybe if you can disrupt that development, you might be able to inhibit it.
You know, the funny part is when I was reading this, a lot of the newer therapy that they’re using, again not prime time yet, are the same kinds of medication they use for people with leukemias, lymphomas, myelomas. You know, so is it a blood disorder thing that’s happening in the pelvic cavity and uterus? And is that why these new agents are being used to target them? Again, those studies are not prime time yet.
And then one of the fascinating ones I saw was looking at—it’s called HDAC inhibitors. These are things—histone and methylation—and, you know, they disrupt DNA methylation, or DNMT inhibitors. So can you disrupt the methylation process that’s happening in this aberrant tissue? Because we know that excess methylation may compound it. So they’re looking at trials to see if we can disrupt that or even remove the methyl groups—would it help in actually treating endometriosis? That would be so nice, wouldn’t it?
And another thing I looked at, I mentioned mesenchymal stem cells that may help to repair damaged endometrium and maybe modulate the immune response, again under clinical trials. So I think data is ongoing, and stay tuned in a couple of years, we may be able to really do some damage to this very terrible process.
Kevin Pho: Now taking a step back, overall, how successful are women with a diagnosis of endometriosis in terms of getting pregnant? And I know that it certainly depends on the severity of the endometriosis. But in general, how successful are they?
Oluyemisi Famuyiwa: I think that they’re very successful if they’re appropriately treated. Let me give you an example of a case that I had several years ago. Actually, the insurance company reached out to me and said, can you please help this lady who was diagnosed with breast cancer and had to freeze her eggs?
And when you looked at her ovary, it was one giant endometrial cyst. It was like nine centimeters, and all the normal tissue had been pressed and pushed aside. I saw no antral follicle. Her antimüllerian hormone level was, might as well not be existent. And so what we did, we worked as a team with a GYN, with the oncology team treating her breast cancer, with her GYN oncology team working with the mass. And I said, I can’t stimulate this woman because this mass is there, right? Either we decompress it or remove it, but we don’t have time to do like a straight-up surgery where you strip the cyst wall, let her recover. She had to do chemo in a few weeks.
So what they did was they decompressed this thing, laparoscopically sucked it out, didn’t strip it. They didn’t have time for that. And then she came back to see me like a week after this. And just by decompressing that cyst, a lot of the ovarian cortex was able to start responding, and I treated her with letrozole, which is a medication that will keep her estradiol levels down, both for her breast cancer as well as the endometriosis, and we were able to get 13 eggs on someone that we ordinarily would not have been able to. We would have said, call it quits, go just get the cancer treated, you’re done.
So there are success stories like that, that with adequate, prompt management—the correct management—the success is very good. It’s when it’s not managed correctly, you know, like someone who had an endometrioma picked up and they placed her on a high-dose birth control pill, that’s not going to help you. That’s actually defeating the purpose because the high dose estrogen is going to feed into that.
Kevin Pho: We’re talking to Yemi Famuyiwa. She’s a fertility specialist. Today’s KevinMD article is “Endometriosis and fertility, what every woman should know.” Yemi, let’s end with some take-home messages that you want to leave with the KevinMD audience.
Oluyemisi Famuyiwa: If you’re having any symptoms, if you’ve been having cyclic pain, you know, let’s say you were told you had a cyst rupture, you went to the ER and they say, oh, you just had a cyst rupture. If you have all these recurring problems, feel free and bold to ask your doctor, please, you know, can we investigate this further? Can we maybe get an ultrasound? That’s the first line of, you know, initial scanning. And sometimes you need to do a pelvic MRI, and sometimes you need to advocate and speak up. You know, this is not going away, it’s recurring, and then we as physicians, if our patients are coming back to us and they’re having this repeated complaint, we should kind of take a step back a minute and say, let’s look into this just in case something else is going on.
Kevin Pho: Amy, thank you so much for sharing your perspective and insight. Thanks for coming back on the show.
Oluyemisi Famuyiwa: Thank you very much. Thanks for having me.