Why Your Embryo Isn’t Implanting: The Truth About Endometrial Thickness & Uterine Lining

Today we’re diving into one of the most important and often confusing topics in fertility care: endometrial thickness and uterine lining quality.

As embryo selection continues to improve, many patients are left asking the same question:

Why aren’t my high-quality embryos implanting?

In this episode, we walk through what the science actually says about endometrial thickness, what we know (and don’t know) about uterine lining quality, and how to think about your individual situation when preparing for transfer.

We cover:

• What endometrial thickness really means and why it matters

• Is there a “minimum” thickness needed for implantation?

• Does a thicker lining always lead to better outcomes?

• The role of trilaminar (patterned) vs non-trilaminar linings

• Why “normal” doesn’t always mean optimal

• How protocols (medicated vs natural cycles) can impact lining

• What to consider if your lining is consistently thin

• Current evidence on blood flow, ultrasound findings, and newer technologies

Most importantly, this episode is about helping you move from confusion → clarity.

Because fertility is not one-size-fits-all, and understanding your own patterns, history, and physiology is what leads to better outcomes.

If this is something you’ve been navigating, you’re not alone — and there are thoughtful, individualized ways to approach it.

This episode is part of Season 1 of The Love & Science Fertility Framework: The Biology Beneath the Surface — a clinical series examining the physiology that drives reproductive outcomes.

If you found this conversation valuable, book a consult call with me using this link:

https://calendly.com/loveandsciencefertility/discovery-call

Also, be sure to check out our website: loveandsciencefertility.com

Follow us on social media:

IG: www.instagram.com/loveandsciencefertility

FB: www.facebook.com/profile.php?id=61553692167183

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:

Welcome back to the Love and Science podcast. Today, we're going to talk about a very important
and controversial topic, which is endometrial thickness and quality as well. Because as our embryo
quality has gotten better and better, we are perplexed by this question of why are my high quality
embryos not taking? I think in the setting of the very thin endometrium, many of us are like,
okay, well, it's probably the fact that the endometrium isn't thick enough to, you know, hold an
embryo and plant an embryo. But I think especially in the face of like thicker endometriums where
the embryos just aren't taking, it becomes a very, very important question as to are there features
other than endometrial thickness that are important and how can we help understand even ahead of
time, whether a person is likely to have a successful transfer or not. So let's talk a little bit
about history here. So we've been having these conversations really since the advent of IVF.
Even since the 1980s, we've been asking this question about like, does the appearance and thickness
of the endometrium matter? Interestingly, our machines were a lot worse back then. And so now our
machines are much more fancy and we can detect a lot more detail and blood flow and things,
three-dimensional ultrasound, et cetera. And so just noticing that we've always been asking this
question is important. But it wasn't until 1995 when there was a paper published that suggested a
higher pregnancy rate when the uterine lining was trilaminar. And then there was this other
researcher in 2000 who also affirmed that, Dr. Kim, and then also Dr.
Zhang in 2005 as well. And so that is a question that we actually don't have a ton of data on to
this day, and I'll review some of it in a few minutes. But the question of... quantitative
measurements and qualitative aspects as well are the questions that we're still asking.
Of course, we know that it's really hard to isolate these variables because we have no two patients
who are alike, right? So we have patients who have a multitude of diagnoses. For most fertility
patients, it's not just one diagnosis. It's usually a few little diagnoses that tend to add up. So
it's really hard to... you know, keep things clean when, you know, each patient is truly their own
situation. And also age matters too,
right? We look at how endometrial quality can decline in women over the age of 40. And we're also
asking those questions now, even with euploid embryos, is the implantation rate a little bit
different in older women? Most data say no, but there was actually a study published not too long
ago that suggests that that may in fact be true. So really trying to understand not for just
academic purposes, but to say, you know, if you are the one listening to this podcast and your
embryo transfers haven't worked yet, like what is actually going to help you get to that point of
having a successful outcome, especially in the face of, you know, some sort of suggestion of a
uterine factor where maybe the lining is indistinct or maybe it's not getting thick enough or.
Maybe, you know, it's irregular. There's something that doesn't look quite right. Say your
hysteroscopy is normal, like what to do here? So those are the things I'm hoping to talk about. So
let's talk about thickness. I think the best study that looks at this is actually a Canadian study
looking at databases over 12,000 frozen embryo transfer cycles. And they looked at it and they
stratified. very granularly, right? Endometrium less than five millimeters. And then from five to 5
.9, six to 6.9, seven to 7.9 and so on. And they found that in their group of an endometrium less
than five millimeters, they actually had no pregnancies. And that was, you know, the N was over a
hundred in that study. Interestingly, when they looked at the subgroup five to 5.9 millimeters,
they had a 16% live birth rate in the subgroup that was six to 6.9 millimeters.
it was a 31.7% pregnancy rate, excuse me, live birth rate. These data are for live birth rates.
From seven to 7.9%, excuse me, seven to 7.9 millimeters, the live birth rate was 33.3%.
And then over eight millimeters, the live birth rate was 40.6%. And so interestingly,
I think most of us tend to look for a cutoff of seven millimeters. You know, this would argue that
maybe there's not too much difference between six. the group in the six to 6.9 versus the seven to
7.9, but there may be a benefit of over eight millimeters, which is interesting. Most of the other
data actually looks at like under seven millimeters or over seven millimeters.
I've seen some that uses 7.5 millimeters as a cutoff. So it does seem like, I will tell you when I
was a fellow, we pretty much did not do any embryo transfers unless the uterine lining was 7.0
millimeters or above. And we know there's some subjectivity, right? It's like you've got to measure
in the mid-sagittal plane when you can see ideally the endometrium going all the way to the cervix
so you're not getting an oblique angle. There can be differences in opinion as to where the
endometrium starts and ends in that sagittal plane. And so,
yes, I do think that we have to have objective standards, but just to call out that there can be
some subjectivity, sometimes I remeasure an endometrium that's already been measured and I might
get a different measurement then. what was presented to me initially. And also the CINES matter.
Like when you scan through in two dimensions as well, like you scan through in the sagittal plane,
you scan through in the axial plane. Sometimes you can see things that you don't necessarily see in
a still image, such as like maybe the endometrium tapers at the top, which is not really a good
sign. Say there is an area of irregularity, maybe focal adenomyosis that wasn't appreciated in a
different plane. And so a comprehensive view is always going to be the best. But interestingly,
you know, most of the data suggests that the endometrial thickness is not associated with
miscarriage rates, which, you know, I think intuitively we're like, oh, is it thinner endometrium?
It's probably going to have a lower, you know, or a higher miscarriage rate. But I don't think the
data would suggest that once people do get pregnant, the endometrium itself does not seem to matter
in terms of the thickness and miscarriage rate. Let's see. Interestingly, there was another paper
that showed that uterine endometrial thickness of less than seven millimeters versus over seven
millimeters. There was an odds ratio of 0.47 for the people in the under seven millimeter group.
And so just noticing that, you know, this does seem to, the thickness does seem to matter.
And the, the point though, is I think each person probably has their maximum thickness that their
endometrium will get to. And so really trying to understand what that is for that person.
And so I do want to comment on, you know, appearance as well, but I will tell you,
like, if I'm doing the ultrasound monitoring for IVF or even, even a natural cycle,
actually even like an ovulation induction cycle, but any sort of cycle where I need to make a
decision that's going to help somebody either proceed or not proceed. I painstakingly go through
and click on every single ultrasound that person's ever had, because I want to know, you know, in
their IVF cycles, what was their uterine lining on the day that they triggered in their frozen
embryo transfer cycles with each different protocol that they had? What was their, you know, max
thickness? Like, when did they do the best? There are data that in thin linings that the actual
protocol type doesn't matter, but that's like all things being equal. You know, sometimes you see
that somebody. does a modified natural cycle with letrozole and their lining gets to like 7.8
millimeters versus, you know, a medicated cycle at hovered in the mid fives. Like to me, that's,
that's important to know. And so I always like try to understand the context I go through and I
look at every single ultrasound for comparison so that I can, I try to understand when did this
person do the best? Did they do best with like a fully? medicated cycle? Do they do best with their
own endogenous estrogen? Sometimes it's even like a purely natural cycle where somebody's own body
does everything on its own. And then we track that as well. But I think, you know, seeing each
person as an individual, yes, of course, we can look at these large data sets and they are
important. But again, thinking about each person in the context of their history, their diagnosis
and their situation, their pregnancy history, that's really important as well. So let's talk about
the appearance. I did a deep dive into literature. I did this also as a fellow, interestingly,
because my attending was telling me about type A endometrium, which is trilaminar, and type B,
which is sort of intermediate, and then type C, which is homogeneous. I'd never heard of those
letters before, but it doesn't seem to be a lot more data than when I was a fellow,
sadly. There was one study published by Flores, which looked at these A versus B versus C patterns
and found that the type A or trilaminar endometrium, and this is not even in PGS tested embryos,
this is PGA, this was in untested embryos, that in a trilaminar frozen embryo transfer cycle,
there was a 65.9%. I believe this was pregnancy rate.
Yes, pregnancy rate. And then looking at the type B and type C, type B was 48%,
type C was 44%. You know, those were not different from each other statistically,
but definitely different from the trilaminar pattern. And, you know, I really tried to find a
decent amount of data, but I really couldn't. And I think maybe because there's more subjectivity
as well to whether an endometrium is trilaminar or not. I mean, sometimes you can see an extremely
beautiful pattern where you see like the gray, white, gray, and it's a textbook,
beautiful endometrium. Sometimes you scan through and you really do. see that it's like vaguely
trilaminar which i mean maybe they would call it a type b in the studies i'm not sure um but it's
it's a lot harder to put these characteristics into buckets for studies when the there's not like a
numerical measurement that you can put on the quality of the endometrium and so i do think that we
have a ways to go um i did look at like is there such a thing as a an endometrium that's too thick
and most people would define that as like 14 millimeters or above is a thick endometrium.
And interestingly, like the thicker endometriums did not seem to have worse outcomes. Of course,
you know, my, my gynecology brain would want to make sure that somebody didn't have a polyp or
hyperplasia or things like that. But, you know, a thick endometrium,
all other things being equal does not seem to have a negative effect. Now, there are people who
have looked at some of the newer data, and I thank Dr. Jen Dadi, who is my partner,
who did a lot of this research for a recent ultrasound talk we had on ultrasound appearance and
endometrium. She looked actually at three-dimensional ultrasound and if that's useful for
conferring prognosis. And interestingly, like a lot of the studies that you look at will have a
high. negative predictive value, but they don't really have a good positive predictive value.
And so it gets tricky when you're looking at it because what you really want to know is like, okay,
like how can we risk stratify this person ahead of time? Or how can we either maybe even cancel a
cycle ahead of time if it's not going to be the best possible outcome? But there is not a ton of
great predictors other than what we've already talked about. So three-dimensional ultrasound, not
particularly helpful. They've done actually a lot of studies, which Dr. Dundee very nicely
characterized in her presentation. about uterine artery blood flow and different resistance indices
as well. Uterine artery blood flow, even though it sounds like biologically plausible,
it does not seem to have borne out in the data in terms of being something that is useful for
predictions. Also, I mean, there are some subtle data that maybe three-dimensional power Doppler
of the subendometrium might be helpful, especially in people of advanced reproductive age.
diminished brain reserve and so they actually designate the endometrium into zones in this
particular study and the sub endometrium is like the area right underneath if you think about it
too it makes sense because you have the you know the uterine arteries and then there's all these
different branch points and you have the radial arteries and then um all the way down to the like
the spiral arteries that go right into the endometrium and so it really is like a tree. And so the
farther you get down, you can sort of see what's going on. And if the subendometrium is not being
fed appropriately, then most likely that's going to affect the overall blood flow to the area
that's most critical. And so thinking about that, that's kind of an interesting place where we need
more data, but again, not to the point where we can use that meaningfully right now in a clinical
scenario. Of note, some of these studies actually did show that high gonadotropins and high
estrogen levels weren't great for outcome, which is interesting because we also can correlate that
to IVF data where we know that like super high estrogen in a fresh cycle, that those people have
worse outcomes. So anyway, so I think what we've sort of figured out thus far is that a thicker
endometrium tends to be better for prognosis. There's a question about where that line in the sand
is seems to be like seven and greater does seem to be to hold true. You know,
my own experience would argue that maybe six and above, especially in the face of a trilaminar
lining is sufficient. But again, it's really hard to get a study that shows all the combination of
factors and then trying to figure out for each particular person, like when their lining looked the
best and replicating that as much as possible in their frozen embryo transfer cycle. Or maybe it's
a fresh embryo transfer cycle too. I mean, I think sometimes we've gotten so focused on FETs that
we don't give enough credit to fresh embryo transfers, but many people get pregnant with a day
three fresh embryo transfer into a beautiful lining. And then that's the end of the story for them.
So I just wanted to say there's many different ways to think about it. So what can be done? Okay.
So let's talk about it. So say somebody is on a medicated FET protocol, which is typically like
estrogen pills. Once the lining gets thick enough, we add in some progesterone and oil. Um, what if
the lining is really just like not getting thick? It's like five, five, two millimeters.
We bring somebody back and it's like not looking optimistic. My first go-to in that scenario is to
add some vaginal estrogen. And one of the benefits of vaginal estrogen, and it's actually the same
as esterase. It's the same as the oral estrogen, but it's just placed vaginally. The vagina is a
very, um, it's like a very spongy tissue. So it absorbs the estradiol very quickly. And unlike the
oral route where you have the first pass metabolism through the liver, like there's actually a
first pass effect, right? Right. Cause there's a local absorption right to the uterus itself. And
so I have even seen people across that seven millimeter threshold, even after just two days of
vaginal estrogen, when their endometrium had been stuck for like a couple of weeks. And so just to
say, I'm a big believer in vaginal estrogen. Usually what I do is if somebody is already on oral
estrogen, I add the vaginal estrogen and then I divide the dose. So half is oral, half is vaginal.
And that really can help a lot of people.
Other times like people can add like a estradiol patch, which, you know, can be helpful too.
It's like a different route of administration with steady levels. And so that can help people as
well.
And, you know, I think that in a medicated cycle, another route of estradiol that can be tried is
IM estradiol. Well, it's really estradiol valerate is the formulation.
In my experience, I don't love that protocol as much because there does seem to be like a
Goldilocks effect on the endometrium. You don't want it like too, you know,
you don't want the estrogen to be too high because it gets too exciting. And my experience is over
time. that the endometrium then starts to develop fluid and sometimes less is more or like a
slower, gentler approach. Estradiol, Valerie, is like a pretty heavy hitter. And so sometimes we
can use it with good success, but I do find that like the endometrium is a little bit gentler and
sometimes does better with like a more gradual, slow approach. But hey, I've had people had success
with it. So if that works for them in particular. it's the best route for them, then by all means,
then, you know, we would do that as well in our practice.
Sometimes, like I said before, you know, a natural cycle is where people have the best endometrium,
whether that's a purely natural cycle where they grow the follicle on their own with their own
body's hormones. And then we track the endometrium and then oftentimes we'll either wait for a
surge or have somebody take a trigger shot to then give them the luteal phase. That can be a really
nice method. I know I will say I don't tend to trust people's ovaries. And so I tend to do some
sort of modified natural cycle, either with like letrozole or FSH, sometimes men appear depending
on the situation. And, you know, sometimes we can get a really nice endometrium because the
estrogen is coming from the follicles, not from the outside world. And there seems to be a subset
of women for whom that is beneficial to them and that their uterine lining does much better under
those circumstances. If we do those gonadotropin FET cycles, there can be ovarian hyperstimulation
on the other side because we're not doing a retrieval. I've seen people have like IVF-like scans
and then we do a transfer and then those people can feel pretty nauseous, pretty bloated. But
again, if that's the only way that somebody is going to get pregnant, then it's weighing the
benefits and the risks. There's also been some like adjuncts that have been tried.
I want to mention those as well in terms of like Viagra, Sildenafil. There's a tiny bit of data.
It may make a difference, but just like the uterine ultrasound studies looking at the blood flow
doesn't seem to make a tremendous difference with outcomes. That's really how the sildenafil works,
right? Is to increase the blood flow to the uterus. And if that doesn't seem to really matter, then
maybe that's why those data really haven't borne out so much. There's also some data for like
vitamin E, which is a pretty low hanging fruit, but again, not really enough to use it routinely.
Some people are trying like intrauterine agents like GCSF or even like PRP inside the uterus.
There's also some other agents that are being used for people who had Ashermans before, because as
all things, you have to think about, okay, well, why does the person have thin lining in the first
place? Is it because it used to be thick and then they had some instrumentation and then maybe the
layers of the endometrium have been damaged and that's where the struggle is? Is it maybe somebody
whose body has never seen a ton of estrogen in the first place? Maybe somebody would like...
syndrome or somebody with hypothalamic amenorrhea and we have to get their endometrium used to
endometrium over time kind of like a priming of the endometrium like we're taking them through
puberty i also think that there's a huge number of women these days who have had iud exposure for a
long time. I mean, most of us were trained, like IUDs are God's gift to women is what I was told
when I was a fellow. I had one myself and I'm just going to be very transparent. I did not like my
IUD and I pulled it out myself after a year. Don't recommend that, right? Unless you're trained and
know what you're doing. But I always say that we're seeing more and more women who their only risk
factor for thin lining is that they had long-term IUD use. And so I don't think they're as
harmless as we once thought they were. Of course, we have to weigh that against the risks of an
unintended pregnancy. And especially if somebody is on, you know, teratogenic medications or, you
know, has a underlying heart condition where it's really dangerous to carry a child. Like those are
all very important reasons to have reliable contraception. But I think so many of us were like the
good girls and we were always saying, just don't get pregnant, do everything you can not to get
pregnant. And then on the other side, end up being surprised when it's a lot harder than we
thought. Think about that too in your own practices as you're thinking about counseling people
about IUDs. Again, I don't think that they are entirely benign. And I do think I've even seen some
people need gestational carriers because I think what was caused from long-term IUDs. But again,
always asking about the why of things, like why does somebody have thin lining? If it's Ashermans,
you got to treat the Ashermans, right? Or if it's hypothalamic amenorrhea, you got to feed
somebody's endometrium like weeks and weeks and weeks of estrogen. But I think that this sort of
stepwise approach of, you know, adding a little bit of vaginal estrogen, even in this, you can even
do that in the setting of a modified natural cycle too, as long as you don't give too much and it
shuts the process down, that can be a really nice way to augment somebody's endogenous estrogen in
those sorts of cycles is you can add in a baby dose of exogenous vaginal estrogen as well to get
people over that hump. So a lot of times it just takes some experience and some outside of the box
thinking. But I think what's clear is that there's some things we know and some things that are not
yet certain. And I really, really hope over the next 20 years or so that we can make some really
big advances in the field of the endometrium, because I think as our technologies have gotten
better and better with embryo selection, we really need to look a little bit more and actually a
lot more at what's going on on the uterine receptivity side of things and have better ways of
assessing with our imaging studies, who's going to be a good candidate for a transfer. And if
there's anything we can do between now and the point of transfer, that's going to give people a
better outcome. So I hope you enjoyed this talk. Stay tuned for more. You know, I love you.
Bye.