Endometrial Receptivity Array (ERA): Procedure and Success Rates

By (gynecologist), MD, PhD (gynecologist), BSc, MSc (embryologist), BSc, MSc (embryologist) and (invitra staff).
Last Update: 11/06/2020

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, as it allows us to determine the most appropriate day to perform the embryo transfer.

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 what the purpose of the test is.

Endometrial receptivity

The endometrium is the mucous layer that lines the uterus internally. 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.

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.

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.

Dr. Pilar Alamá tells us that ERA allows us to know if the genes involved in endometrial receptivity are present, that is, it goes beyond. Not only does it allow us to know the uterine morphology, but it also allows us to know if that endometrium is capable of implanting the embryos.

Indications

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.

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.

Numerous studies have shown that 3 out of 10 fertility patients have a displaced implantation window.

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.

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 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.

On the other hand, 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.

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 expressing the receptivity genes, so the implantation window 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.

If, on the other hand, 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 frozen embryos frozen for a longer period of time and postponing the transfer again for a later date.

ERA test success rates

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

As we have already commented, its high benefit has been proven in women with repetitive 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 take place because it is not transferred at the right time in the cycle.

The ERA test, therefore, makes it possible to precisely identify the moment in the cycle when it is most appropriate to transfer the embryos in order to achieve pregnancy.

According to Igenomix, pregnancy rates after the ERA test in patients with implantation failure are up to 73%.

FAQs from users

What is the purpose of the ERA test?

By Dr. Luis Rodríguez Tabernero (gynecologist).

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.
Read more

How much does the ERA test cost?

By Victoria Moliner BSc, MSc (embryologist).

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 endometrial receptivity be improved?

By Victoria Moliner BSc, MSc (embryologist).

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?

By Victoria Moliner BSc, MSc (embryologist).

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.

Suggested for you

If you want to learn more about the endometrium and its role in achieving pregnancy, don’t miss this article: What is the endometrium?

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

Our editors have made great efforts to create this content for you. By sharing this post, you are helping us to keep ourselves motivated to work even harder.

References

Bassil R, Casper R, Samara N, Hsieh TB, Barzilay E, Orvieto R, Haas J. Does the endometrial receptivity array really provide personalized embryo transfer? J Assist Reprod Genet. 2018 Jul;35(7):1301-1305.

Díaz-Gimeno P, Horcajadas JA, Martínez-Conejero JA, Esteban FJ, Alamá P, Pellicer A, Simón C. A genomic diagnostic tool for human endometrial receptivity based on the transcriptomic signature. Fertil Steril. 2011 Jan;95(1):50-60, 60.e1-15.

Garrido-Gómez T, Ruiz-Alonso M, Blesa D, Diaz-Gimeno P, Vilella F, Simón C. Profiling the gene signature of endometrial receptivity: clinical results. Fertil Steril. 2013 Mar 15;99(4):1078-85.

Miravet-Valenciano JA, Rincon-Bertolin A, Vilella F, Simon C. Understanding and improving endometrial receptivity. Curr Opin Obstet Gynecol. 2015 Jun;27(3):187-92.

Neves AR, Devesa M, Martínez F, Garcia-Martinez S, Rodriguez I, Polyzos NP, Coroleu B. What is the clinical impact of the endometrial receptivity array in PGT-A and oocyte donation cycles? J Assist Reprod Genet. 2019 Sep;36(9):1901-1908.

Ruiz-Alonso M, Blesa D, Díaz-Gimeno P, Gómez E, Fernández-Sánchez M, Carranza F, Carrera J, Vilella F, Pellicer A, Simón C. The endometrial receptivity array for diagnosis and personalized embryo transfer as a treatment for patients with repeated implantation failure. Fertil Steril. 2013 Sep;100(3):818-24.

Tan J, Kan A, Hitkari J, Taylor B, Tallon N, Warraich G, Yuzpe A, Nakhuda G. The role of the endometrial receptivity array (ERA) in patients who have failed euploid embryo transfers. J Assist Reprod Genet. 2018 Apr;35(4):683-692.

FAQs from users: 'What is the purpose of the ERA test?', 'How much does the ERA test cost?', 'Can endometrial receptivity be improved?' and 'Does the ERA Test fix implantation failure?'.

Read more

Authors and contributors

Dr. Luis Rodríguez Tabernero
Dr. Luis Rodríguez Tabernero
Gynecologist
Degree in Medicine and Surgery from the University of Salamanca and Specialist in Obstetrics and Gynaecology via MIR. Dr. Rodríguez Tabernero is responsible for the Human Assisted Reproduction Unit of the Gyaecology and Obstetrics Department of the Hospital Clínico Universitario de Valladolid since 2013 and has also been working in the field of reproductive medicine since 2000. More information about Dr. Luis Rodríguez Tabernero
Licence number:474705276
Dr. Pilar Alamá Faubel
Dr. Pilar Alamá Faubel
MD, PhD
Gynecologist
Bachelor's Degree in Medicine from the University of Valencia (UV). PhD in Medicine and Surgery with the highest qualification from the University of Valencia. She works as an OB/GYN specialized in Reproductive Medicine at IVI Valencia, where she is the Director of the Egg Donation Program as well. As regards her experience as a teacher, she is a professor at the Biotechnology of Reproduction course of IVI and the Master's Degree in Human Reproduction. More information about Dr. Pilar Alamá Faubel
License: 464619335
 Victoria Moliner
Victoria Moliner
BSc, MSc
Embryologist
Degree in Biochemistry and Biomedical Sciences from the University of Valencia (UV). Master's Degree in Biotechnology of Human Assisted Reproduction from the UV and the Valencian Infertility Institute (IVI). Presently, she works as a Research Biologist. More information about Victoria Moliner
 Zaira Salvador
Zaira Salvador
BSc, MSc
Embryologist
Bachelor's Degree in Biotechnology from the Technical University of Valencia (UPV). Biotechnology Degree from the National University of Ireland en Galway (NUIG) and embryologist specializing in Assisted Reproduction, with a Master's Degree in Biotechnology of Human Reproduction from the University of Valencia (UV) and the Valencian Infertility Institute (IVI) More information about Zaira Salvador
License: 3185-CV
Adapted into english by:
 Romina Packan
Romina Packan
inviTRA Staff
Editor and translator for the English and German edition of inviTRA. More information about Romina Packan

Find the latest news on assisted reproduction in our channels.