Adenomyosis: What is it, and why should we care?
We are told that the rate limiting step in IVF is usually embryo creation. However, we are also learning that the uterine environment needs to be optimal to allow for an embryo to implant and thrive.
In this episode, I cover the following:
the definition of adenomyosis
why we should care as pertains to fertility treatment
imaging findings suggestive of adenomyosis
clinical situations in which lupron suppression could be considered
My goal is to empower you with knowledge and for you to have the most efficient and successful fertility journey possible.
As always, please keep in mind that this is my perspective and nothing in this podcast is medical advice.
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Please don’t let infertility have the final word. We are here to take the burden from you so that you can achieve your goal of building your family with confidence and compassion.
I’m rooting for you always.
In Gratitude,
Dr. Erica Bove
Transcript:
Hello, my loves, and welcome back to the Love and Science podcast. Today, we're going to talk about something that I recently did a deep dive into the literature about because I, as part of my clinical role, I actually work in GY and ultrasound. And sometimes that includes seeing ultrasounds for patients with infertility or current loss. Other times it involves actually like 85 year old women with ovarian masses or postmenopausal or perimenopausal women with abnormal bleeding.
And so, you know, one thing I enjoy as a double board certified OBGYN is that I get to keep my hand in a lot of the more sort of general OBGYN stuff as well as the infertility. And that sort of lens of ultrasound and like what's normal, what's pathological, I think that I see a lot more of that than the general REI. So what I want to talk about today is really what we call adenomyosis and what is it? Why do we care? And could this be affecting the fertility journey for you?
I will just add a disclaimer in this role. My sort of comments are medical sort of perspective and not advice. You know, this is sort of my summation of the medical literature, even though I am a doctor, I'm not your doctor. But I do think that sort of giving you the result of my hours and hours and hours pouring over the medical literature and looking at images and putting together a talk recently for my group, I wanted to share some of that wisdom because I learned a ton during that talk. I learned a ton that I think is going to help all the people in my spheres. And, you know, I feel like why would I not share that information with you, wonderful smart humans who do your very best every single day for people in all the various disciplines. So what we're going to do is I'm going to sort of give you the highlights of that talk on adenomyosis. And hopefully you can take some nuggets of wisdom away with you. I will start by saying I will never forget that about seven years ago, as I was preparing to do my REI oral boards, the main journal that we have in our field, which is fertility and sterility came out with an entire episode or not, I guess the episode is not the right one, an entire journal full of every single article related to adenomyosis. It was like basically a typical issue right that month. But the theme that month was adenomyosis. And up until that point, adenomyosis had not really been thought to be anything of concern for people with infertility. It was thought like this is sort of something we see in quote unquote fertile women in their mid 40s. You know, we notice it sometimes it causes some kind of collagical symptoms, but it's not really pertinent for the fertility world. But then, you know, the people started to study this and it does seem that some adenomyosis actually might make infertility and recurrent loss worse. So then the question becomes like, if you see it on ultrasound, like who does it matter for?
Who does it not matter for? And how can you ultimately sort of guide people in the right direction?
So what is adenomyosis? So adenomyosis is defined as a disorder in which endometrial glands and stroma are present within the myometrium. The pathologist, of course, will appreciate that sort of pathological definition, but it really is actually a pathological definition. Really, we can only truly diagnose it with a hysterectomy specimen, which for most of the people that I help in my various roles, most people are going to still have a uterus, not everybody, but most people.
And so the diagnosis of adenomyosis would necessarily be presumptive based on imaging studies such as ultrasound or MRI or even HSG sometimes. So what happens at adenomyosis is that you can get hypertrophy and hyperplasia of the surrounding myometrium.
And, you know, that can result in abnormal uterine bleeding, which can be super pesky if you're trying to start an IVF cycle, especially with a transfer. It can result in dysmetorrhea.
It can result in dyspareunia, actually, and even infertility, we think. And, you know, because the adenomyosis has hormone receptors, this actually can vary over the course of a menstrual cycle. It also can be comorbid with endometriosis and fibroids.
So why do women have it? We really don't know why. I mean, we think that perhaps there's this endometrial endometrial endometrium. It might be de novo from U.L.A. and remnants.
There might be a sort of a role of microtrauma of the endometrium and the myometrial interface. Think about maybe like a myomectomy or something that might open a portal for that growth. And also some people talk about retrograde menstruation, which is kind of what we think about endometriosis. The endometriosis is endometrium outside of the uterus and the uterine cavity kind of in the pelvis. But what we're really talking about here is like endometrium that it's made its way into the wall of the uterine muscle. We know that the hormone receptors are upregulated, specifically estrogen progesterone receptors. And we also know that estrogen makes it worse. So I can, you know, whenever I see an impressive ultrasound, it kind of becomes burned in my brain. I feel like my brain is like a library of different things I've seen over the years. And I'm very visual, too. So specifically, like I have a mind I can close my eyes and truly see various people's ultrasounds over the years. And I'll never forget I was taking care of this patient who had a long fertility journey. We're trying to get her to a transfer frozen number of transfer. And we put her on estrogen and all of a sudden her uterus just went from this like very calm looking typical uterus. It just it just transformed like over the course of a few weeks.
I remember seeing like it looked much bigger. It looked much more heterogeneous. There were sort of these lacunar spaces and myometrial cysts. And the distinction between the endometrium and the myometrium was very indistinct. And she's somebody who actually already had uterine lining issues to begin with. The whole uterus just looked really not like a good home for a baby. I can't describe it any other way. It just looked very pathological. And so, you know, that was OK. Well, we have embryos frozen. Like we're not going to take those precious embryos and put them in.
Let's see if we can suppress the uterine, you know, sort of adenomyosis with Lupron for a few months and then get her to a transfer. But given that we just tried to do a program cycle like this probably isn't going to go over too well if we reintroduce estrogen to the situation.
So what we decided to do was we decided to do Lupron for a few months then with the plan to do a natural cycle frozen embryo transfer because hopefully the natural cycle estrogen would not be sort of quite as much of an amount as the medicated cycle with, you know, with the estradiol.
And that actually works. So after this woman had several year journey of long standing infertility was able to transfer, you know, two beautiful untested embryos into her uterine lining, which looked a lot better after this process. And she ended up remarkably having a child.
But, you know, the point is that adenomyosis can change over time. It can respond to hormones and you can take what looks like a seemingly normal uterus and it can then all of a sudden look very abnormal. And even though we don't have the best quality data, we do, you know, I do believe and we do have some preliminary data that the reproductive outcomes are not as good when you see these changes present. And it makes sense, right? We know that there is growth factors, there are cytokines. It's just a very inflamed environment. In addition, we know that women with adenomyosis have increased rates of miscarriage, increased rates of preterm delivery, and also small for gestational age infants. So whenever I'm meeting with, you know, a patient or a couple, I say, my role as an RAI is not just to get you pregnant, it's to help you get pregnant and stay pregnant.
And ultimately 10 months later, walk home with a healthy baby from the hospital. Right. So, you know, I've not really done my job if I, you know, don't think about all the factors ahead of time and somebody has an outcome that might've been able to be prevented if we had been a little bit more thoughtful or patient. So, you know, thinking about what are the data for infertility, there was actually a review by Junes et al. in FNS in 2017, FNS means fertility and sterility, that showed for people with adenomyosis, there were lower implantation rates, lower clinical pregnancy rates per cycle, lower clinical pregnancy rates per embryo transfer, lower rates of ongoing pregnancy, and even a lower live birth rate. So in our studies in infertility, like sometimes we don't have that live birth data. We have just surrogate markers up until then, but this study actually looked at like, what are the live birth rates for women with adenomyosis? And there actually was a lower live birth rate. So, you know, that question, why should we care? I think we should care a whole awful lot, especially if the whole point is to help people walk home with a healthy baby at the end of the day. Also, sometimes when there's not a ton of embryos to work with as well. Right. I also looked at the data because like I said, I learned an awful lot. There's like focal adenomyosis and there was diffuse adenomyosis. And I kind of knew that intuitively, but I'd never quite put it into those categories, my brain. And, you know, focal adenomyosis is when you see an adenomyoma. Like I've known that term since my residency, when I remember going in thinking there was a fibroid and then just like, you know, fibroids shell out very nicely. You can sort of take them apart from the myometrium. There's a plane at the pseudo capsule. Sometimes there's a little bit of bleeding, but you kind of sew up the uterus back in layers and all as well.
But with an adenomyoma, there's just not that same plane of distinction. And so it's really unclear, like, where does the abnormal tissue end? Where does the normal tissue begin?
And sometimes it feels like you're truly just like searching for that plane, which never really comes. And it can be very hard to know which tissue to remove and which to leave. So this focal adenomyoma adenomyosis does seem to be worse than this sort of more diffuse globular adenomyosis that we can see on the imaging. And, you know, one person described it to me recently. In some ways, it's almost like having an endometrioma of the, you know, of the uterus. And again, endometriosis and adenomyosis are two distinct entities. Even like on molecular levels, they do appear to be different. But I think it's actually kind of interesting to think about it that way, that there's actually like a cystic structure within the myometrium kind of similar to what we see on, you know, in the ovary, which we call an endometrioma, which is associated with the worst forms of endometriosis, the worst stages. So, you know, what's better MRI or ultrasound?
I will say based on my reading, they both have comparable sensitivity around 78, 79% to pick it up. But the MRI does seem to be a little bit more specific. So the MRI has 93% specificity versus the ultrasound, which has 80% specificity. Although, you know, as we all know, G-1 ultrasound is a lot more readily available compared to MRI. It's more cost effective. And so I think, and a lot of people are already getting ultrasounds for their fertility care and monitoring and planning. And so I think most of us would say that ultrasound, transnational ultrasound is a very reasonable place to start. And if there's any ambiguity, or if people are thinking about surgical planning for fibroids or endometriosis, or have another reason to do an MRI, then that might make sense. But ultrasound is actually extremely good at looking at adenomyosis.
And now with the advent of three-dimensional ultrasonography, we can actually get a much better look at the junctional zone. And so that's a zone between the endometrium and the myometrium. So that has further enhanced our understanding of adenomyosis through the view of ultrasonography. So what might we see? You know, that's a question I get from a lot of my clients, a lot of, you know, sometimes my patients too, like, you know, I saw that my uterus is a little bit heterogeneous. Like, does that really mean anything? Do I have any other findings of adenomyosis? And so, you know, one thing to sort of understand is that when you think about ultrasound findings, there's direct findings, which mean that you can actually see the adenomyosis and its surrounding effects, like directly. And then there's indirect signs, which are kind of what, what does that then induce in the uterus? So like, for instance, an indirect sign might be a globular uterus because the cumulative net effect of all that adenomyosis in the wall is that the area is a lot bigger and kind of looks a little bit more like a pair, like a bulbless pair compared to something that looks like a little bit more like a light bulb, I guess you could say, in terms of shape. So myometrial cysts are one of the sort of hallmark direct signs of adenomyosis because you actually have the glands in the stroma in the myometrium. And so you can actually see these cystic structures. And sometimes they can actually be very close to the endometrium to the point where you're wondering, like, is there something I have to worry about with this endometrium? Like, is this, you know, gonna relate to inflammation or like, you know, sometimes it's like I said, super like these truly sub endometriosis. And other times they're like sort of farther away in the myometrium. But I think it's just important to like, call them out and we see them. And also to like notice them on your ultrasound reports, because that can be evidence of adenomyosis.
What else? So another telltale sign, which is a direct sign is these hypercoic islands in the endometrium. You know, I see these all the time on ultrasound. Again, that's that question of is this pathological or is it not? In a patient with infertility, if they're asymptomatic, otherwise, I definitely would have a higher level of suspicion to call this out and, you know, potentially think about treating some of these areas. Again, you can't treat them directly, you can treat them with hormone suppression. But you can see like these sort of hypercoic areas that are outside of the endometrium itself. And that's the hypercoic endometrium that has migrated. And like I said before, like you can see this very differently in different parts of the cycle. Even a couple of weeks ago, I saw somebody who was actively menstruating, you know, like an older lady who didn't necessarily have infertility, but like her endometrial islands were super prominent.
And so obviously I commented on them, but like it's just sort of something to note because it doesn't look like that pretty picture in the textbook. There's definitely something that is out of place there, so to speak. What else can you see? You can see these echogenics, sub-endometrial lines and buds with a poorly defined junctional zone. Basically, those are like outpouchings of endometrium that are truly growing into the uterine wall. And then what happens when you see those is it casts them shadowing. So you actually it kind of creates this fantail like appearance in the myometrium, especially posteriorly as you look at your ultrasound. And in large globular uterus, I feel like we all learned about that in medical school. That's sort of one of the more classic things, which like I said, is an indirect sign. Sometimes it's symmetric, sometimes it's asymmetric.
One thing I found really interesting in my lit search was that the sort of symmetry is not all that objective. So if one side of the uterus, like anterior versus posterior in a sagittal plane is more than five millimeters different than the other side, then they can call that asymmetric.
Or if that ratio is like much greater than one or much less than one, of course you have to be looking in the same plane. So it's apples to apples, but you can kind of see it when you look at the ultrasound, but it is a little bit subjective. And you can also get sort of this asymmetric thickening of the my, my, my, either from diffuse adenomyosis or an adenomyoma.
So sometimes it's helpful to then put some color flow on to see what that looks like, because there's often vascularity that flows through the adenomyoma. A fibroid tends to have a little bit more peripheral vascularity versus the adenomyoma itself, which has like a little bit more diffuse vascularity throughout, which if you think about the pathophysiology, that makes a lot of sense. What else? So three-dimensional ultrasound, I'm so fortunate that I have regular access to three-dimensional ultrasound in my medical practice. You can really see that junctional zone well when you look at the renderings and there's different sort of post-imaging processing that you can use also to get further clarification on that as well.
So what you want to see in a junctional zone is like a nice thin smooth junctional zone. You can see the whole thing all the way around where the endometrium and the myometrium meet each other.
And there really shouldn't be any like interrupted areas. But as we know, many people have adenomyosis and you can actually see these interruptions. They don't look the prettiest, but you're, you know, especially when you train your eye to see them, you can definitely catch them.
And also like when you look at the different, you know, views, the different planes of the uterus, looking at coronal, looking at transverse, looking at sagittal, you can really start to put together the three-dimensional view of what is there. And, you know, it's kind of interesting. I was actually talking to somebody recently who's planning surgery for endometriosis. And the kind of curious thing is even with surgery, even though you can see the outside of the uterus on laparoscopy, it might look bulbous or you might see a fiber or something. You really, the only way to beam into the myometrium itself is actually to do some sort of imaging where something passes through.
So like an MRI or an ultrasound, like that's really the only way to see that even a hysteroscopy is truly just going to show you the endometrium for the most part and the two openings, but that sort of what does the myometrium look like? That's really going to be an imaging diagnosis, unless you are doing like a myomectomy and are cutting into it for some reason. So just a thought, like somebody said, well, I'm having surgery, that doesn't necessarily mean that the myometrium can be directly evaluated. And sometimes these imaging studies can be very helpful, both for preoperative planning, as well as to figure out if maybe like a course of Depo-Lupron might make a difference before a transfer. What else? So, you know, there are different sort of categorization schemas. So the ones that we use in the ultrasound world, we use the Morphological Uteras Sonographic Assessment. And that was published in 2015. And then it was actually updated in 2022. So we're actually looking at fairly recent categorizations. Interestingly, there was a prospective study using 2D and 3D ultrasound, looking not at infertility, but looking at like symptomatic women with abnormal uterine bleeding and dysphelia. And the junctional zone did seem to matter. So when the junctional zone was thicker, those women tended to be more symptomatic. And also, in a different study, it actually suggested that women whose onset of adenine was earlier than the 40s, those people tended to have more clinically significant adenomyosis, which again, that does make sense. MRI is also a very useful tool. So there are certain MRI findings that you can see.
You can see thick and junctional zone, you can see heterotopic endometrial tissue, you can actually see different sort of perspectives on T1 versus T1, excuse me, T1 versus T2 imaging.
You can see focal adenomyoma pretty well, you can see diffuse adenomyosis pretty well.
And even HSG, I have appreciated for a while on HSG how sometimes that border of the outline of the uterine cavity is not quite crisp and distinct like it should be. Sometimes you see these little microdiverticulae that out pouch into the myometrium. I mean, sometimes that's just menstrual blood and that sort of area is a little bit irregular and that can be very normal. But sometimes it can be pathological. And even recently, I saw images from a patient where she had pretty intensely deep diverticula and sort of group consensus indicated that perhaps the best way to help her was long-term Lebron suppression. So I think we really need to use our thinking caps when we think about sort of adenomyosis and what somebody's clinical story and does this or does this not need to be treated.
Now, in terms of actual clinical pearls, what do I think about adenomyosis? Because we see it, I mean, I pretty much see it every single day. When I am in the ultrasound suite, whether it's fertility specific or more broad in terms of GYN, I truly do see adenomyosis and features of it every single day. And so when does it matter and when doesn't it if somebody's on the fertility journey? I would say certainly if somebody has abnormal uterine bleeding, that can't be stopped to try to get them to a fertility cycle that obviously needs to be addressed. I also think that if somebody has like very limited number of embryos or limited time, say somebody is like 44 and they froze eggs at the age of 33 and they're finally using those and they don't know what they're able to work with at this point in time from their own eggs in 2025, that might be a consideration to really suppress the adenomyosis before using embryos that were more may not be able to be generated or generated easily. I think if people have had several unsuccessful cycles and there's really nothing else, but the uterus just doesn't look quite ideal. Maybe the borders of the endometrium and the myometrium are a little bit indistinct. Maybe there was like a small adenomyoma. I do think it's reasonable in those situations to take a pause. I always say sometimes we got to be patient to make progress. And so two to three months of Lupron suppression, looking with ultrasound to kind of assess if it's getting better, which I mean, in my experience over 95% of the time it does and then rolling right into ideally a natural cycle, frozen embryo transfer.
So as not to flood the system with more estrogen, but to get a good uterine lining to be able to do a transfer. And I can think of three patients in my career that had very, very long fertility journeys. And that's exactly what we did for those people. One woman was even on Lupron for six months because everything was so severe, but now she's a mom. And it's like, okay, like not that she wanted to be on Lupron for six months of her life. I mean, I know that was a very long wait.
A lot of IVF has hurry up and wait, but I truly don't think that she would be a mom today if she had not invested that time in the Lupron suppression. So, you know, in conclusion, what I would say, adenomyosis is super common. A lot of times people have symptoms like pain, abnormal uterine bleeding, dyspareunia, but sometimes they don't. Sometimes all we can do is see it on ultrasound.
Ultrasound and MRI can pick it up with pretty comparable sensitivity. MRI has slightly better specificity. Three-dimensional ultrasound has really aided in our ability to see the junctional zone and sort of other endometrium that's out of place. And I went through the typical findings, which I won't go through again for the sake of time, but I do think it's worth the question.
You know, it's hard because if you're 43 and on this journey, you know, somebody might say, well, of course you have adenomyosis. Pretty much most women at your age have adenomyosis.
But I always say like, I'd hate to look back and say that there was a variable that we had just not addressed. And if that address, that variable had been addressed, it might have changed the outcome. Well, you never know to try, but gosh, there's so many things in life that we can't control, right? You know, especially like I say, like if it comes to substances we put in our body or sometimes weight optimization or sometimes like stress reduction and all those things, like adenomyosis is one of those things that we actually can get a handle on with a little bit of time. And if it is a variable and you've had either a long journey or you have very limited embryos and want to give them the best shot, I do think that, you know, addressing the adeno as you also think about your fertility care is, you know, a very potentially useful thing to do. So again, this is not medical advice, but it's me as an RAI/coach having poured over the literature over the last few weeks in preparation for a talk I gave last week to my team. And I learned a lot and wanted to share it because I had some insights, new insights for people that I take care of in various capacities. And, you know, if this then empowers you to ask better questions or maybe invest a little bit of time in suppression yourself, if that again, talk with your doctors, see if that's relevant. I think sometimes these little adjustments can actually, especially when you add them up together can make huge difference. So I will record more science episodes. I know that that is what the people are asking for. And I'm very grateful for my education. I'm grateful for all my training. I'm grateful that I continue to get to take care of patients and that this lifelong learning that we all talk about, like this is truly this in action and the science evolves. Right. Like I said, in 2018, all of this stuff came out and now we're starting to think about acting on it. I want you to be the beneficiaries of some of this newer data so that you can have the best possible fertility journey possible. With that, I love you until the next time and talk to you soon. Bye.
