Endometrial Receptivity Array (ERA): Procedure and Success Rates

The endometrial receptivity test, also known as the ERA test or Endometrial Receptivity Array, is a molecular diagnostic test used to determine the receptivity of the endometrium.

Thanks to this test, implantation failures are less likely to occur in in vitro fertilization (IVF) treatments. It allows us to determine the most appropriate day to perform the embryo transfer, increasing the probability of pregnancy.

As such, the endometrial receptivity test is recommended in patients with embryo implantation failure even if they have mainly good quality embryos. However, this test is not available in all cases.

Basic concept and meaning of ERA

Before explaining what the ERA test is, it is advisable to introduce some concepts that are necessary to better understand the purpose of the test.

Endometrial receptivity

The endometrium is the mucous layer that lines the internal walls of the uterus. Thanks to the action of the female sex hormones, estradiol and progesterone, it thickens as the menstrual cycle progresses and acquires numerous glands that secrete substances to promote the implantation of the embryo.

Endometrial receptivity, therefore, refers to the ability of the endometrium to interact with the embryo so that implantation can take place. This property of the endometrium varies throughout the menstrual cycle.

What is endometrial receptivity?

Because of this, embryo implantation can not take place at any time during the woman's cycle, but is restricted to a specific period of the cycle known as the implantation window.

Implantation window

The implantation window refers to the time period in which the endometrium is receptive. During this period, the endometrium has already acquired the morphological and functional characteristics necessary for the embryo to adhere to it and implant.

This phenomenon usually starts 5-7 days after ovulation has occurred. However, there may be cases in which the implantation window is displaced and does not occur on those specific days, resulting in infertility.

What is the implantation window?

Endometrial receptivity is essential to achieve pregnancy because even if we get very good quality embryos should they be transferred at an inappropriate time during the cycle, implantation failure is likely to occur.

Endometrial receptivity test

The endometrial receptivity test or ERA test is a test that involves analyzing the gene expression of the endometrium to determine whether or not it is in a receptive state.

This type of study has been developed with the purpose of coordinating the embryo transfer as much as possible with the moment of greatest endometrial receptivity. This way the chance of pregnancy is much higher.

When is the ERA test recommended?

Mainly, women who will benefit from the ERA test are those who have had repeated implantation failures after IVF despite having good quality embryos.

It should be noted that in the case of IVF with donor eggs, the patient may also fail to achieve pregnancy if her endometrium is not receptive at the time of the embryo transfer.

When is the ERA test recommended?

The same occurs with patients who perform an IVF cycle with preimplantation genetic diagnosis (PGD) to genetically analyze the embryos. Despite transferring healthy embryos, implantation failure can occur if the endometrium is not receptive.

For these reasons, patients who had egg donation with PGD could also be candidates for the ERA test.

How is the ERA test done?

To perform the endometrial receptivity test, the woman must undergo an endometrial biopsy and a sample of endometrial tissue obtained.

Although taking the biopsy is simple, it may cause some discomfort during its procedure. Despite this, it is not necessary to enter the operating room or apply anesthesia, as it can be done in the consultation room.

What is the procedure for an ERA test?

Once the endometrial tissue has been collected, it is placed in a suitable, sterile container and kept at low temperatures until it is processed.

When is the best moment to do the ERA?

When the first ERA test is performed, it is appropriate to perform the endometrial biopsy at the time when the implantation window period should theoretically begin.

In a natural cycle, this period begins on the 21st day, which is known as the day LH+7.

This expression has its origin from the moment in which it occurs during the menstrual cycle, the so-called LH peak. This hormone triggers ovulation and with it, the levels of progesterone begin to increase which will allow the endometrium to change from a non-receptive to a receptive state.

Therefore, to obtain the biopsy, 7 days will be allowed to pass from the peak of LH, at which time, in theory, the endometrium would already be receptive.

When to perform endometrial biopsy for ERA

However, in a substituted cycle where the woman is taking hormonal medication for endometrial preparation, the biopsy will be performed 5 days after starting the administration of progesterone, i.e. on day P+5.

What is analyzed?

The characteristics that differentiate a receptive from a non-receptive endometrium can be identified by ultrasound or by analyzing the tissue itself under the microscope.

These characteristic details that denote that the endometrium is in a state of receptivity are as follows:

Endometrial thickening

the endometrium measures between 7 and 10 mm when it is receptive. This can also be measured by ultrasound.

Presence of pinopods

these are cytoplasmic projections that arise from endometrial cells.

Glands

the presence of glands in the endometrial tissue is characteristic of the period of receptivity.

Cell growth

endometrial thickening is caused by a massive increase in endometrial cells.

However, the determination of endometrial receptivity by direct observation of the tissue may not be entirely accurate. Therefore, molecular tools such as the ERA test have been developed to obtain more reliable results.

Thanks to scientific and technological advances in the field of genetics, it has been possible to identify the expression of certain key genes for an endometrium to reach the receptive state.

Among the many genes analyzed, the expression of 248 genes has been found to be vital for qualifying an endometrium as receptive.

Comparison of gene expression in the ERA Test

Therefore, the ERA Test consists of identifying which genes are being expressed in the patient's endometrial sample and comparing them with the 238 genes that have been identified as markers of endometrial receptivity.

ERA test results

Once the endometrial sample has been analyzed by genetic comparison, the result of the ERA test can be as follows:

Receptive

the endometrial sample is expressing the receptivity genes, so the implantation window corresponds to the day the biopsy was performed. That moment of the cycle is optimal to perform the embryo transfer and it would not be necessary to repeat the ERA Test.

Non-receptive

the endometrial sample is not expressing the receptivity genes, so the implantation window does not corresponds to the day the biopsy was performed. In this case it would be necessary to repeat the test on another day of the menstrual cycle until finding the location of the implantation window.

Embryo transfer after ERA test

Whether or not the endometrial receptivity test shows a receptive result, the embryo transfer should be postponed until at least the next cycle. Processing the sample and obtaining the results may take a few days, so the implantation window period of the same cycle would be lost.

This makes it necessary to freeze the embryos obtained during the IVF cycle until the transfer is carried out.

Should the endometrium be receptive, the frozen embryo transfer (FET) will be planned for the next cycle, exactly on the same day the endometrial biopsy was performed.

Displaced implantation window and embryo transfer

If, however, the result obtained from the ERA test is unreceptive, the endometrial biopsy will be rescheduled on a different day than the one on which the test was first performed to repeat the test. This means keeping the embryos frozen for a longer period of time and postponing the transfer again for a later date.

Success rates with the ERA test

The endometrial receptivity test has proven to be a very useful tool in increasing success rates in assisted reproduction cycles.

As we have already indicated, its high benefit has been proven in women with repeated implantation failure in IVF treatments. In many cases, both the endometrial thickness and the quality of the embryos to be transferred are optimal, but implantation does not occur because they are not transferred at the right time in the cycle.

When are embryos transferred after an ERA test?

As such, the ERA test allows us to identify with precision, the best moment to perform the embryo transfer in order to achieve pregnancy.

FAQs from users

What is the purpose of the ERA test?

The Endometrial Receptivity Array (ERA) is a novel diagnostic test that allows the study of the endometrium to determine if it is in adequate conditions for embryo implantation. In this way, we can personalize the transfer of the embryos, performing it at the most appropriate time for each woman.
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Does it make sense to do an endometrial receptivity test even if I have had children in the past?

The endometrial receptivity test informs us when the exact moment the embryo transfer should be performed (number of specific hours of progesterone administration). The window of implantation may be altered despite having had a normal pregnancy in the past.
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How much does the ERA test cost?

The cost of this diagnostic technique varies from clinic to clinic. The approximate costs are $800 in which costs for fertility medication and endometrial biopsy are not included.

Can the implantation window be displaced? Why?

The window of implantation is the period of time in which the endometrium presents the optimal conditions for embryo implantation to be possible. This period is usually between days 20 and 24 of a 28-day menstrual cycle.

To maximize the chances of pregnancy, embryo transfer in an assisted reproduction treatment should be performed at the optimal time within the implantation window, when the endometrium is most receptive.
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Can endometrial receptivity be improved?

A good rest, a balanced diet and moderate sport practice help to improve stress levels. If we find ourselves in times of many nerves, we can see altered blood circulation and hormonal function that are so important for good endometrial development.

On a pharmacological level, the growth of the endometrium can also be improved by applying hormones. However, this treatment must always be supervised by a specialist.

Does the ERA Test fix implantation failure?

No, unfortunately, the endometrial receptivity test is not always the solution to cases of implantation failure.

On certain occasions it is discovered, thanks to the ERA test, that the patient's implantation window is displaced and therefore a poor endometrial receptivity was the cause of the failure. However, there are many other cases that are not due to the fact that the transfer is being performed at an inappropriate time in the cycle.

The causes of implantation failure can be very different, and not all of them can be identified with the endometrial receptivity test.

Recommended reading

If you want to learn more about the endometrium and its role in achieving pregnancy, the following article has lots of useful information: What is the endometrium?

To learn more about implantation, its phases, and other interesting facts in the following post: What is embryo implantation and when does it happen?