Endometrial Receptivity and ERA Testing: What Is It For and What Does the Evidence Say?

Endometrial receptivity is the limited period in which the lining of the uterus can accept the embryo. ERA (Endometrial Receptivity Analysis) is the name of a commercial test aimed at measuring this period; similar tests are generally referred to as endometrial receptivity tests. Current guidelines on this subject do not recommend the existing tests. The information below offers a general framework and does not replace a diagnosis or treatment recommendation specific to you.

What is endometrial receptivity?

For the embryo to be able to attach to the uterus, the lining of the uterus (the endometrium) needs to be in a suitable state. This layer changes throughout the cycle, and the time interval in which it can accept the embryo is limited; this interval is often called the "implantation window". This concept rests on the idea that the embryo and the lining must be in step with each other.

How does a receptivity test work?

The logic of endometrial receptivity tests is as follows: in a small tissue sample taken from the lining of the uterus, the extent to which certain genes are working is examined. The result is interpreted as whether the lining is ready for the embryo at that moment, and gives an idea of whether the time of the transfer should be shifted. The sample is taken by endometrial biopsy. Depending on the type of test, an additional cycle may be needed.

Are the existing receptivity tests recommended?

According to a current assessment of add-on procedures on this subject, the existing endometrial receptivity tests are not recommended. In the same assessment, other add-on practices aimed at the lining of the uterus were dealt with with similar caution. A practice not being recommended does not mean that it is harmful in every individual; in such classifications, safety concerns, a lack of effectiveness or a lack of biological justification are counted as reasons.

Does a transfer time determined by the test increase live birth?

In the largest randomised study in this area, frozen embryo transfer timed according to receptivity was compared with transfer timed in the standard way. In the end, it was not shown that the timing guided by the test significantly improved live birth.

Does the test result provide a definite prediction?

Robust data on the effectiveness of the test are lacking. The methodological limits of the test and the reproducibility of the result are also discussed in some publications. Because of this uncertainty, just as an "appropriate" result does not mean success, a result of "not appropriate" does not mean definite failure. Interpretation of the result lies with the doctor.

What questions should you ask if the test is recommended to you?

The situations in which the test is applied are generally earlier transfers having been unsuccessful, or a concern about the match between the embryo and the uterus. Even so, because current guidelines do not recommend the existing tests, it is sensible to ask the following questions when a test is offered to you:

• Why is this test being recommended?
• What evidence does the recommendation rest on?
• How will the result change my treatment plan?
• Will an additional cycle or wait be needed for the test?

How can the biopsy and the testing process affect you?

The test has its own burdens. Cramp and light spotting may be seen when the tissue sample is taken; infection is rare. Waiting for the test result and leaving the transfer to a separate cycle can cause treatment to lengthen; this matters more if your age is advancing. The additional cost is also taken into account in the decision.

Mild cramp or light spotting for a time after the biopsy is usual. If a hormone medicine is used in the test cycle, the risk of clotting should also be kept in mind. This risk exists, although it is rare.

What are EMMA, ALICE and endometrial scratching?

There are also other assessments that can be offered together with ERA or on their own. EMMA (Endometrial Microbiome Metagenomic Analysis) is a test aimed at examining the balance of the microbial community in the lining of the uterus. ALICE (Analysis of Infectious Chronic Endometritis), on the other hand, investigates the presence of certain bacteria linked to chronic endometritis. These two tests are generally offered as a panel with ERA from the same tissue sample; however, their state of evidence differs from each other and from ERA.

In a current assessment aimed at recurrent implantation failure, profiling of the intrauterine/vaginal microbiota is among the practices that are not recommended; the data in this area are regarded as dynamic, and whether an unbalanced microbiota directly disturbs implantation is not yet clear. Assessment for chronic endometritis, on the other hand, appears in the same document in a more cautious framework, as an option that can be considered depending on the situation; no common threshold has yet been defined for the methods used in diagnosis, and studies on the benefit of antibiotic treatment when chronic endometritis is detected contradict one another. For this reason EMMA and ALICE are not at the same level of evidence; when a test is offered to you, it is sensible to ask what it rests on and how the result will change treatment.

Endometrial scratching is the procedure of lightly injuring the lining of the uterus with a fine instrument; it is sometimes recommended in recurrent implantation failure, and the idea behind it is that the mild inflammatory response that results may contribute to attachment in the next cycle. A current assessment of add-on procedures does not recommend this procedure for routine use; the mechanism has not been confirmed by data, the study results remain uncertain, and no particular group of patients who benefit from the procedure has been identified. Mild bleeding and pain related to the procedure have been reported.