What is an ERA test?
An ERA Test or Endometrial Receptivity Analysis is available to help women pursuing In Vitro Fertilization (IVF) determine whether their endometrium is receiving an embryo at the right time in an attempt to maximize their chances of a successful pregnancy and live birth.
Even outside of a fertility clinic, getting pregnant is a delicate science. It involves all the right pieces being in the right place at the right time.
One of the most important pieces in this reproductive orchestra is the relationship between a woman’s endometrium (uterine lining) and the embryo that is about to implant inside it.
Both in the bedroom and the fertility doctor’s office, the meeting of the embryo and the endometrium has to happen at just the right time for implantation, and pregnancy, to occur.
If the meeting doesn’t happen when it needs to, like ships in the night, the embryo and endometrium will just miss each other, and pregnancy will not occur.
This concept is known as ‘the window of receptivity,’ or ‘the window of implantation.’ An ERA helps women determine this window during an IVF treatment cycle.
But what exactly is this test? How is it performed? Does it work? And most importantly, should you do it? We’ve got simple answers to all those questions below. Let’s get started.
What is the window of receptivity, exactly?
The window of receptivity is a short amount of time when your uterus is ready to receive an embryo at the proper stage of development necessary for implantation, and therefore pregnancy, to occur.
In the case of the uterus, it’s the lining inside the uterus, the endometrium, that plays a major role.
In addition to being a certain thickness, the endometrium must be expressing the correct genes that tell a potential embryo it is ready for implantation, a process largely driven by the hormone progesterone.
As for the embryo, it must be mature enough to successfully implant (it must have reached the blastocyst stage, which is day 5 or 6 of growth).
If both the embryo and uterus are ready at the same time, implantation and pregnancy can occur; if the window is missed, however, and the embryo is not at the right developmental stage by the time it reaches the uterus, it doesn’t contain the right number of chromosomes or the endometrium is not expressing the correct genes, implantation and pregnancy will not occur.
This ‘window of receptivity’ exists in both natural conception and in IVF.
Is every woman’s window of receptivity the same?
Though doctors used to believe that this window existed sometime between 8 and 10 days following ovulation for all women, it is now understood that this window is not universal for all women, and can vary depending on the woman’s level of progesterone and the genes being expressed by her endometrium.
Do I need to worry about my window of receptivity?
Many women who pursue IVF don’t need to worry about their window of receptivity because they do indeed get pregnant, meaning successful implantation has occurred.
In fact, RMA research has shown that women with three normal embryos have a 95% of pregnancy.
In other words, almost all women will have success on their third IVF cycle with a normal, or euploid, or embryo, meaning the window of implantation was met.
For the small percentage of women who do not get pregnant after multiple attempts with normal embryos, fertility doctors may investigate whether the reason for their Recurrent Implantation Failure (RIF) – characterized as the inability to achieve pregnancy after the transfer of three or more normal embryos – is related to missing the window of receptivity.
So what is ERA testing?
ERA testing analyzes whether a woman’s uterus is in, is about to be, or has passed its window of receptivity. Most fertility clinics will offer this procedure.
ERA stands for Endometrial Receptivity Analysis or Endometrial Receptivity Analysis.
The aim of the test is to tell the IVF patient and her doctor whether their existing protocol (and embryo transfer timing) should remain as is, or be pushed forward or back.
This is known as a ‘personalized embryo transfer.’
How does the ERA test work?
The test consists of two parts:
- Taking a sample of a woman’s endometrium (a biopsy)
- Having that sample tested for its gene expression.
Based on what genes are being expressed in the biopsy, clinicians will be able to tell whether the endometrium is receptive or non-receptive to an embryo at the time of the biopsy.
How is the ERA biopsy performed on a patient?
In order to get the most accurate results, the biopsy should be performed at the exact moment when doctors would transfer an embryo into a patient’s uterus.
This means that patients will undergo a transfer cycle but not actually have the embryo transferred. This is because the objective is to test the endometrium for its gene expression right before a transfer.
This ‘prep’ cycle involves the same steps as a ‘real’ transfer cycle. – taking oral medications and self-injected medications to stimulate your uterine lining.
At the end of the prep cycle, a doctor will perform the biopsy. The biopsy is a two-minute procedure that may be slightly uncomfortable. The procedure does not require sedation.
The biopsy involves placing a flexible plastic tube into the woman’s uterus (with the help of a vaginal speculum) and moving it back and forth to collect tissue from the lining of the uterus.
Afterward, a doctor will send this sample for processing to a third party who will test the sample for the expressions of hundreds of genes and deliver a result to the doctor and her patient.
Depending on the result, a doctor may move the patient’s transfer timing (by modifying the patient’s exposure to progesterone) forward or back so the patient can meet her window of receptivity during her next cycle.
So patients who get an ERA will delay their fertility treatment?
Yes. Because no embryo will be transferred during the prep cycle when the test is performed, a patient will be delaying treatment (in the form of a real transfer).
The delay will likely be about a month for those who have embryos to transfer. It can take up to two months for those who must undergo an egg retrieval cycle to make embryos prior to transfer.
Does the ERA test actually work?
The ERA test holds promise, and some women have seen success with it, but there is simply not enough research on the topic or the efficacy of the test to say for sure. This is why patients should discuss the topic with their reproductive endocrinologists and decide together whether pursuing the ERA test is a good route.
There are three reasons why it’s hard to know whether the test works.
- First, the complex interplay between the embryo and the uterus – and especially the genetic expression that occurs inside the endometrium in preparation for pregnancy – is still poorly understood, with scientists just beginning to scratch the surface of this field.
- Second, the ERA tests on the market today have not undergone rigorous scientific validation (like a non-selection study to determine the predictive value of the test) prior to their commercial launch and clinical application.
- Third, the one Randomized Controlled Trial (RCT) conducted on the effectiveness of the ERA showed no benefit based on the intention to treat analysis.
For these reasons, the jury is still out on whether altered timing of embryo transfer based on the implantation window improves pregnancy rates, and whether the commercially available ERA tests accurately predict the ideal timing for implantation.
Having said this, however, several studies have shown improved pregnancy outcomes for women who received the test and altered their transfer protocol accordingly, which is why the test continues to be an option.
So who should get an Endometrial Receptivity Analysis?
The group with the best chance of success from an ERA is women with recurrent pregnancy loss (RIF), or the failure to achieve pregnancy after three or more euploid embryo transfers.
In these women, missing the window of implantation may be the reason behind their inability to achieve pregnancy, and understanding the exact timing of their window would be beneficial.
Most doctors do not offer this test to patients prior to beginning treatment. Some may not even offer it after one failed IVF cycle with a euploid embryo.
Once the patient has failed two or more IVF cycles with euploid embryos, a doctor may discuss the possibility of the test with a patient.
Does RMA offer the ERA test?
Yes, RMA does offer the ERA test. many of our physicians recommend it for interested patients with recurrent pregnancy loss. Your physician will speak about their plan of care in-depth before making any decisions.
Is the ERA test the same as the DEFENTS study at RMA?
No, these are two different things, but they are related.
As a research clinic, RMA is currently conducting much-needed research on endometrial gene expression. Our current research is looking at the window of receptivity.
This research study, which is called DEFENTS and is currently enrolling patients, will help RMA clinicians understand the differences in gene expression between fertile, infertile and recurrent pregnancy loss patient populations, a critical step in understanding differences in the window of receptivity among women and the efficacy of commercially-available ERA tests, which RMA also uses.
Is the ERA test covered by insurance? If not, how much does it cost?
An ERA test may or may not be covered by insurance. The test usually costs around $1,000 out of pocket.
What’s the bottom line?
The ERA test can be a good option for IVF patients with a history of implantation failure. Although the efficacy of the test is still uncertain. If you think you might want the test, talk to your fertility doctor.