Episode 137: Fertility 101: Endometrial Receptivity Test
The Fertility 101 Series, because there’s no shortage of daunting terms to keep your mind running, is a quick and dirty breakdown on a specific topic with insights from a fertility expert.
In today’s episode, we explore Endometrial Receptivity Testing, a clinical aspect of embryo transfer and implantation. Mike Large, from CooperSurgical, walks us through the process and breaks down some of the complicated language and mechanics that go with it.
Mike explains the proper window of implantation, how it isn’t the same for everyone, and how a test called ERPeak can help determine this timing. He provides a step-by-step description of the process women go through to pinpoint the most valuable time to implant an embryo, shedding light on a process commonly discussed by doctors and embryologists, but not always talked about with patients.
Guest: Mike Large, Senior Director of Life Sciences Innovation at CooperSurgical
Host: Dan Bulger, Progyny
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Here are some highlights from this episode:
Understanding the Basics
04:58 – 06:33
Mike Large: It’s about seven days after ovulation. That’s the time when the endometrium will actually be ready and prepared and willing to receive an embryo that will implant and begin establishing a placenta. And that’s really the interface between the fetus and mom. So, classically, the textbooks we follow think that all patients are the same. And if we just looked at seven days after ovulation, that would be when the endometrium is ready. But evidence over — I would say the last decade or so maybe a little bit longer, we’ve come to find that for some women, particularly women who have a history of embryo implantation failure, their timing is a little bit different than what we would expect. And so, in some women, the actual window occurs a little bit faster.
In other women, as you might predict, the time was a little bit delayed. So, if you look, when we classically thought the window should reopen, you’d see that it’s not prepared to receive and implant an embryo.
And so we can look at the genes that are driven by estrogen, for example, or we can look at genes that are driven by progesterone. And based on the gene signature that’s there, we can actually infer when a patient’s window of implantation is, and where she is compared to that time.
How ERPeak Works
7:09 – 11:44
Mike Large: Instead of relying on the ovaries and a natural cycle in IVF, we generally have frozen embryos ready, and we want to put one of those embryos back at the exact right time. And so, in many circumstances in IVF, patients actually are administered these steroid hormones to prepare that endometrial lining.
There are ways to measure how the endometrium is progressing. You can look by ultrasound, for example. And you can see how thick that endometrial lining is. If you’ve seen the endometrial lining is not recovering, and it’s very thin, then you know that you’re in a circumstance where you need to reevaluate the treatments or the patient’s response to treatment. So, after five days of progesterone exposure, instead of replacing an embryo, like you would in a normal IVF cycle, you would actually do an endometrial biopsy. A small bit of tissue is taken from the endometrium. And that’s sent to us at CooperSurgical, where we isolate it from the tissue. And then we’re able to, through a technique called qPCR, really measure very sensitively and very accurately the key genes that we think are involved in this process.
And then those go into a bioinformatics algorithm, which builds and predicts where the patient’s window is receptive, then that’s the expected timing. But there are a couple of other categories of results which are pre-receptive and post-receptive. So, if you were to get pre-receptive results, for example, that would mean that under that five-day exposure, the endometrium is not ready yet. The recommendation would be to give the endometrium more time before you do the procedure. And so, for some patients, they elect the recommendation to give it that one extra day. And the physician would do an embryo transfer based on that timing.
So, all of that’s done in what we call a mock cycle, because we’re not actually placing an embryo, but we’re giving the same exact hormones. Then you get those results, and the physician will make their adjustments accordingly.
Why Might Someone Opt to Use ERPeak?
17:10 – 19:12
Mike Large: Maybe you don’t have a great success rate of producing many embryos. If you only have one good embryo, it’s really precious and important, which makes timing the transfer even more important. You would really hate to transfer that embryo at the wrong time. Because we know that if you’re outside of the window of implantation, you’re not going to have a successful implantation.
We know that the older patients get, the more likely the appropriate number of chromosomes is abnormal. So, we should get one copy of DNA from mom. And we should get one copy of DNA from dad. And we have actually 22 chromosomes plus our sex chromosomes x and y. So, we should get one copy from each. And if we get no copies from one parent of a certain chromosome, or we get an extra copy from one of the parents. That’s called a Trisomy. And Trisomy 21, is also an unsound situation. It’s something that some people may be more familiar with already. But we know that you have an abnormal number of chromosomes, it’s called aneuploidy. And those embryos are more often than not, not compatible with life. And you have a miscarriage and other sorts of unfortunate adverse outcomes. So, if you’ve done the genetic testing on a few of your embryos and identified the euploid embryo, the one that has the right number of chromosomes, and you only have one of those many patients who are really trying to do their best and find out everything that they can about their fertility, they will do an ERPeak test to make sure that they’re putting that embryo back at the right time.
Dan has been in the healthcare industry for the last six years as a multimedia content producer. Better known as ‘Video Dan’ he has interviewed numerous doctors, patients and other experts in the world of fertility. He’s also the producer for this podcast, This is Infertility. On a personal note, Dan’s parents started fostering kids when he was four years old, and he considers himself a proud older brother to over 100 foster children.
Mike earned his PhD from Baylor College of Medicine where he focused on the intersection of progesterone and growth factor signalling and their role in endometrial receptivity. While finishing his work there, he was recruited by Mark Hughes of Genesis Genetics to open a Research and Development PGS laboratory in Houston, Texas. Mike quickly rose to prominence as a technical expert and was instrumental in the adoption and implementation of Next Generation. Shortly after being acquired by CooperSurgical, he was promoted to Director of Genomic Laboratories, overseeing multiple PGT-A labs. He then took on a role leading research efforts in Genomics where his team developed our state-of-the-art analytical methods for interrogating Reproductive Genetics. His current focus is on strategy and innovation.