ERA Was Supposed to Improve Embryo Transfers—Could It Actually Make Them Worse?

Does the ERA test actually improve your chance of pregnancy with IVF—or has endometrial receptivity testing been oversold?

Patients often receive completely different advice. Some fertility specialists say the Endometrial Receptivity Analysis, or ERA, can identify a personalized window of implantation. Others say research has proven the test does not work. The truth is more complicated.

In this episode, Dr. Mark Amols revisits ERA in light of newer randomized trials, meta-analyses, and research on recurrent implantation failure. He also examines statements from his earlier episodes—including why he would no longer confidently tell patients that an ERA “cannot hurt.”

Topics include:

• How ERA attempts to identify the window of implantation
• Whether ERA improves live-birth rates during routine IVF treatment
• What the major randomized trial actually found
• Whether that trial was adequately powered
• Why the data do not support ERA before a routine or first embryo transfer
• The unresolved role of ERA after recurrent implantation failure
• Why results differ between untested and euploid embryo transfers
• Whether changing transfer timing could potentially lower success
• Concerns about test accuracy and cycle-to-cycle endometrial variability
• When ERA might still be discussed as an optional, unproven intervention

The current evidence is reasonably clear for the average IVF patient: routine ERA testing does not improve live birth. For patients with repeated implantation failure—particularly after failed euploid embryo transfers—the answer remains uncertain because the adequately powered randomized trial needed to settle the question has not yet been completed.

This episode separates what ERA has been proven to do, what it has been proven not to do, and what fertility medicine still does not know.

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Join us next Tuesday for more discussions on fertility, where we blend medical expertise with a touch of humor to make complex topics accessible and engaging. Until then, keep the conversation going and remember: understanding your fertility is a journey we're on together.

Transcript

Dr. Mark Amols: 0:00

Today we talk about ERA and whether one of the most controversial tests in IVF actually helps, does nothing, or could even make your chances worse. I'm Dr. Mark Amols, and this is Taco Bout Fertility Tuesday. For years, patients have been told completely different things. Some doctors say the ERA does not work. Others say it can find your personal window of implantation, and some still recommend it after failed embryo transfers. I've even talked about ERA on this podcast before. And after looking at the newest evidence, there are things I would say different today. So what is actually true? Did the big randomized trial really prove ERA doesn't work? Does it still have a role after recurrent implantation failure? And could changing your transfer timing based on the test actually hurt your chances? Well, today we separate the claims from the evidence. Now, as I've mentioned, I've covered ERA before on this podcast. So if you want to learn a little bit about the test and some of the things in the past, go back and listen to those episodes. And some of that stuff I said still holds up today. But some of it I frame different today, and not because I was wrong, but because we simply have better data now than we did then. And that's not a contradiction. That's what's supposed to happen when the science moves forward. Because, as, I mentioned before, depending on which doctor you ask, you're going to hear very different things about ERA. You're going to hear it doesn't work. You're going to hear it does identify your personal window of implantation. And you're also going to hear, I don't use it routinely, but I do use it after failed transfers. And this leaves patients left wondering who's right. So today, I'm going to walk through what we actually know, what we think, and what we simply haven't studied well enough yet, and then let you take that into your conversation with, your doctor who knows your case far better than a podcast can. The first question is, what is ERA trying to solve? See, implantation requires two things to line up an embryo capable of implanting and an endometrium that's receptive at the right moment. This is the window of implantation. In a programmed frozen transfer, progesterone converts the lining into a receptive state. After a standard duration of exposure, most patients reach that state on a predictable timeline. The theory behind the ERA is that some patients don't. Their window is shifted either early or later, and that testing gene expression in the endometrium can identify that shift. So the transfer then can be timed around it. And that's a very reasonable hypothesis. But for it to actually help patients, several things all have to be true. Number one, an individualized implantation window exists in a clinically meaningful way. Number two, that the ERA actually identifies it. Number three, the result is reproducible between cycle to cycle. And number four, timing the transfer around it actually improves live birth. And that last point is the only one that really matters. Where did this ERA test come from and what made it popular? Well, early studies suggested a subset of women with recurrent implantation failure had a dysplace window and that personalized transfer timing improved the pregnancy rates. Early reproducible studies also reported consistent results on retesting. So that combination, this is your personal window and it's stable, was a compelling marketable idea. And that was the framework I was working on from the earlier episodes about this topic. But then there was a trial that changed the conversation. And this was a study of Doyle in 2022. This large multicenter randomized trial enrolled patients transferring a single euploid blastocyst, meaning aneuploidy, one of the biggest causes of implantation failure was already ruled out. And then the patients were randomized to either standard timing or receptivity-guided timing through the ERA. What they found is that the live birth rate was about 58.5% for the ERA guided transfers and 61.9% for the standard timing. Now, at first it sounds like, oh my goodness, it hurts your chances. Now, keep in mind, that's not statistically significant, meaning the difference could just be pure chance. But it wasn't what people expected. Was it underpowered? Well, not really. The trial was able to enroll the number of patients they needed to have a roughly 10 point absolute improvement in the live birth rate. And it didn't find one. And the numbers themselves didn't even trend that way. Basically, it was a flat line and technically slightly negative, but as I said, not statistically significant, meaning it. It could have just been chance. Well, what it did show was that there was no evidence of a routine benefit in good prognosis patients. What it did not show was that proof that the ERA has zero effect in every patient or in every situation. But the real question is what the Doyle study didn't study and why that matters both ways. See, Doyle excluded patients with recurrent implantation failure. So the strongest evidence against routine ERA doesn't directly answer whether ERA helps someone who has failed multiple good quality transfers. Now, it's important to keep both sides of that not studying. RIF doesn't mean ERA works for RIF patients, meaning recurrent implantation failure patients. It also means we don't know yet. Well, when it comes to the RIF patients, there was a recent 2026 meta-analysis and that pulled 44 studies together to come up with a decision. That decision doesn't make it fact. It just says this is what the current evidence is trending towards. That study used four randomized controlled trials, 40 cohort studies, and the answers it got basically depended on the population you're looking at. If you do not have recurrent implantation failure or minimal prior failures, essentially there was no effect. Basically supporting the original study that routine use isn't supported, and this finding was consistent. Now, if you had recurrent implantation failure, untested embryos, such as no PGT-A, there was a real statistical notable association of improved live births. Now, keep in mind, this was from observational cohort studies. This was not a randomized controlled trial. So again, this is something that says there might be a benefit in patients who didn't do PGT-A who also have recurrent implantation failure. The problem is, why would there be a difference between people who did euploid embryos? Possible that patients who received testing may differ from those who didn't in ways researchers can't fully control for, maybe clinical protocol, monitoring intensity and more. So it's associated with better outcomes, but doesn't prove to cause them. When they looked at patients with recurrent implantation failure with euploid embryos, what they found, it was a very wide range of results, from meaningful benefit to no effect to even harm. But the evidence was very low quality, so we can't use that. And I know what you're thinking, that's really strange. If you have normal embryos, wouldn't you expect that to be the best evidence that the ERA works? And yet that group is exactly where the evidence is least settled. So, in summary, what the 2026 meta analysis showed is that it is true if you do not have recurrent implantation failure, basically have no benefit by doing ERA, and that routine use isn't supported. If you have recurrent implantation failure and you have untested embryos, there may be some benefit by using the era, but we can't even say if the benefit came from the ERA. Now, if you have a recurrent implantation failure and have euploid embryos, it's basically unclear. Still. Now the question is, has anyone ever shown any positive effects of ERA? Well, they did in 2020. Simón found favorable outcomes for personalized transfer in their per protocol analysis, they found a 71.2 cumulative live birth rate versus 55.4 for conventional timing versus ERA adjusted. So the point is, not every randomized trial came back negative. But there was a problem with the study. Roughly half of the randomized participants didn't make it into that per protocol analysis. Unfortunately, with that much attrition, it weakens the randomized controlled trial. And so although it showed a positive, it's just not strong enough on its own to settle the question. But here's the real concern. Could timing ever work against you? And this is where there's a genuine update from where the evidence stood in my earlier episodes. An exploratory post-hoc analysis of Doyle's data. That was the research that showed that there was no benefit to people using it in general. empirically. The researchers looked specifically at patients whose results recommended shifting transfer timing by 24 hours. Essentially, they said, hey, if someone had more than 24 hours, that would be the ones affected most. Theoretically, that group would likely benefit the most. But in the post-hoc analysis, that group showed lower clinical pregnancy rates, more biochemical losses, and a numerically not statistically significant lower live birth rate. Now, keep in mind, this doesn't prove harm exploratory. That was not the trial's primary analysis. But it raises a real mechanism worth naming. And that is a test that's sometimes wrong, isn't automatically harmless once its results is used to change treatment. It could remove someone away from, from a window they would have hit correctly with the standard timing. Interestingly, a reanalysis by Richter and Richter looked at how well ERA classifications actually discriminate implantation from failure. Even ASRM's 2026 RIF opinion, cites that basically, it's essentially a coin flip. And basically what that means is not that there may not be an implantation window, but whether the test measures it accurately enough to act on. Now, here's where it gets a little bit more crazy. Does the window even stay put or does it change frequently? Well, a 2026 study biopsied 20 women across two consecutive cycles. And it looked at that broad endometrial gene expression. It found meaningful cycle to cycle variability. Samples from the same women weren't dramatically more consistent with each other than with other women's. Now, this doesn't directly prove ERA results shift month to month. The question here is, is it actually changing or is the test not even recognizing it? So where does this leave us? Well, when it comes to the American Society Reproductive Medicine, the Recurrent Implantation Failure Committee they do not recommend routine receptivity testing in recurrent implantation failure. They describe the evidence as insufficient to support routine use. Not that ERA has been definitively disproven. That's a meaningful distinction, one worth bringing to your own doctor if it comes up. So let's run through the claims. ERA works the verdict too broad. What about the claim of ERA doesn't work? Again, also too broad. What about the claim of everyone doing IVF should

get one? The verdict: 12:54

No, there is good randomized evidence that argues against routine use. What about the claim that the big trial was just underpowered? No, it hit its planned power and the trend didn't favor ERA anyway. What about the claim that ERA is proven to help recurrent implantation failure? No, there is observational data, but there is no adequately powered randomized controlled trial that proves that. What about the claim that ERA is proven not to help RIF? Also no; that trial hasn't really been done yet. Now, what about the claim that ERA can hurt? Well, this is a fair question, but the verdict is still we don't know. And it's a fair question to ask. What about the claim that your window is fixed after doing the ERA and changing it? Well, because there's the question of changes between cycles. It brings up the question that even if you make a change, did it fix it? Now, this episode was not to tell you that it's good or that it's bad. Matter of fact, I still do eras in very selective patients. I do think it's overused at times. And this podcast is also not meant to tell you what to do. That's a conversation for you and your physician, who has the full picture of your history, your embryos, and your prior workups, which this podcast cannot do. So when you talk to your doctor, because maybe you had failed transfers and you want to know if you should do ERA testing, the evidence that supports it is fairly clear. Routine ERA and a good prognosis. First transfer patient isn't backed by the data. Now, if you have recurrent implantation failure, the question is, are your embryos tested or not? If they're untested, there's encouraging observational data that shows there may be real benefit. But there's no randomized controlled trial, meaning the evidence is not strong. Now, if you're talking about recurrent implantation failure with euploid embryos, unfortunately, this is where there's a lot of uncertainty. And this is, one area I still use it in. But the one really big change is this idea that receptivity testing is automatically low risk, and that the only risk is to your wallet is not proven at this time. And in light of Doyle's subgroup analysis, it brought up the question could it be harmful? And unfortunately, until we have those studies, we just don't know. The answer is it could be, we just don't know. Now, when the transfer doesn't work, ERA comes in the conversation, especially after repeated failures. But it's worth having a workup that looks at more established possibilities first, such as embryo quality, such as the uterine cavity, things like polyps, or looking for fibroids or adhesions, looking for things like hydrosalpinx or even endometriosis, maybe things like chronic endometritis. What if maybe even the timing was off, meaning the patient took the things at the wrong time? Sometimes even look at the clinic you're at, the pregnancy rate is 15%. Well, yeah, of course it didn't work. You don't have to jump on the ERA train that fast. Unfortunately, the trial that would actually settle the euploid recurrent implantation failure question hasn't been done yet. The only thing we can truly say at this moment is using ERA as an empiric test on all patients is not needed, and that there could be harm. We just don't know it at this time. Unfortunately, until that study exists, this is a case of incomplete evidence. Not contradictory evidence, just unsettled. If you were interested in ERA, hopefully this episode helped you. If you want to learn more about how the test works, you can listen to some of my old podcasts about this topic. If you or someone you know is going through this and might benefit from this episode, tell them about this episode. If you love this podcast, keep supporting us. give us a five star review on your favorite medium. But most of all, keep coming back. I look forward to talking again next week on Taco Bout Fertility Tuesday.