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If you have had implantation failure, we can help you

1. Introduction. What is it?

ERA endometrial receptivity test : implantation failure


ERA is a state-of-the-art diagnostic method, which was developed and patented by IGENOMIX after more than 10 years of research. This technique enables the evaluation, from a molecular point of view, of the status of endometrial receptivity.

ERA indicates the window of implantation (WOI), increasing your chances of successful transfer.
Endometrial receptivity is the state at which the endometrium is ready for embryo implantation to take place. This occurs around days 19-21 in each menstrual cycle of a fertile woman. Until now, the only study done on the endometrium was an ultrasound scan, and there was no analysis method available to help doctors in their clinical practice.

Now, during the process to treat an infertile couple, the ERA test (Endometrial Receptivity Analysis) leads to the evaluation, at the molecular level, of the endometrial factor. This molecular tool allows us to diagnose whether the endometrium is receptive or not by analyzing the expression of a group of genes related to endometrial receptivity. For that, an endometrial biopsy must be performed at P+5 (hormone replacement therapy cycle) or at LH+7 (natural cycle) and, after its shipment to one of our locations, the expression of 238 genes is analyzed. According to these expression values, the endometrium is classified as receptive or not receptive by a computational predictor.

More Info:
The ERA is a personalized genetic test to diagnose the state of endometrial receptivity in the window of implantation.

This molecular diagnostic tool is used to analyze the expression levels of 238 genes related to the status of endometrial receptivity. For that, RNA obtained from an endometrial tissue sample is hybridized in a custom microarray with probes for those genes. After hybridization, a computational predictor classifies the sample as receptive or non receptive according to its specific expression profile. The Endometrial Receptivity Analysis and the computational predictor (ERA®) were designed, developed, and patented by IGENOMIX (PCT/ES2009/000386).

2. Goal. What is ERA for?

More than 10 years of research support this test.
The ERA test is used to assess endometrial status and to determine whether or not the patient’s endometrium had a receptive gene profile at the time of biopsy.

The analysis reveals the timing of the implantation window and leads to a personalized embryo transfer (pET) timing based on the individual results obtained.

The result from the test will determine if a woman is receptive or not on the day and in the kind of cycle when the biopsy was performed. If she is receptive, it means that her window of implantation falls on the day of the cycle during which the biopsy was performed and, therefore, the blastocyst could implant on this day during the same kind of cycle.

A non-receptive result could imply a displaced window of implantation. Therefore, a second biopsy would be needed to validate this displacement. For that, a specific day for the second biopsy will be suggested according to the first result obtained. This will allow the implantation in a subsequent cycle with a personalized embryo transfer (pET).

3. Uses. Who is it for and why?

Before starting an assisted reproduction treatment, the ERA
can identify if the patient will require a personalized window of implantation.
The ERA has been tested in patients who have had implantation failure with embryos of good morphological quality (at least 3 failed embryo transfers for younger women or two in patients 37 years or older). This test is recommended for patients with apparently normal uterus and with normal endometrial thickness (≤6mm), in which no problems are apparent.

A displaced implantation window is detected in approximately 20% of these patients.

This analysis allows the implantation window to be located, enabling personalized embryo transfer (pET) to be performed based on these individual results.This test must be prescribed by a physician and the result will be sent to the doctor. It will never be sent to the patient. The physician who prescribes the test will be responsible of sending the report to the patient.

4. Advantages. What are its advantages over the other tests?

As an endometrial receptivity diagnostic method, the ERA determines the personalized window of implantation for each patient before she begins an assisted reproductive treatment.

The ERA test has shown high sensitivity and specificity for detecting gene expression profiles associated with receptivity.

Endometrial status dating has been classically determined based on histological criteria. However, this method has been shown not to discriminate between fertile and infertile patients and involves a high degree of subjectivity, meaning these results cannot be applied in the clinic. The ERA test overcomes these problems.

5. FAQs

1. In which kind of cycle could the ERA test be performed?

The ERA test should be performed in an HRT or a natural cycle. The receptivity diagnosis is valid just for the type of cycle in which the test is performed. Therefore, the embryo transfer must be done in the same kind of cycle in which a receptive result is obtained.

2. How is the endometrial biopsy taken?

Biopsy of the uterine fundus is performed according to a standard procedure with a Pipelle catheter or similar. About 30 milligrams of tissue is enough. For illustration purposes, this equates to a cube of approximately 3 millimeters by side.

3. How is the timing of the endometrial biopsy calculated?

Hormone Replacement Therapy cycle
Upon initiation of an HRT cycle, the biopsy is taken after five full days with progesterone impregnation (approximately 120 hours). The day for the first intake of progesterone is considered as P+0 and the day of the biopsy is P+5. If you refer to the first day as P+1, the day of the biopsy will be P+6.

Check that progesterone level in blood is <1ng/mL before starting the progesterone intake.

Natural cycle
The biopsy is taken 7 days after the LH surge. The day of the LH surge is considered as LH+0, and the biopsy will be taken at LH+7 (approximately 168 hours). If the ovulation is determined by ultrasound, the day of ovulation is taken as Ov+0, and the biopsy will be taken six days later (approximately 144 hours) at Ov+6.

4. How is ovulation detected in a natural cycle?

The time of ovulation in natural cycles can be measured using LH test strips in urine, by direct measurement of luteinizing hormone (LH) in blood serum, or by monitoring follicle rupture by ultrasonography.

5. Which is the strategy to follow according to the ERA result obtained?

An endometrial biopsy is taken in an HRT cycle or in a natural cycle to perform the ERA test.

Result: ‘Receptive’
If the patient has frozen eggs or embryos, or has fresh OvoDon eggs or embryos, these can be transferred within the same type of cycle (HRT or natural) in which a receptive result has been obtained. If a blastocyst is going to be transferred, it would be performed in a subsequent cycle in the same day in which the biopsy was performed, but if a day-3 embryo is going to be transferred, then it should be done two days earlier than the day of the biopsy.

If the patient does NOT have frozen eggs or embryos and wants to use their own eggs, a cycle of ovarian stimulation for egg or embryo cryopreservation will be performed. Embryo transfer will be performed in a subsequent cycle of the same type (HRT or natural) in which a receptive ERA test result was obtained.

Result: ‘Non receptive’ (with a recommendation of a new window of implantation)
If the result of the first ERA test is non-receptive and the expression profile analysis suggests that the window of implantation may be displaced, it is necessary to validate this displacement with a second ERA test. This second analysis will identify the day when the endometrium shows a receptive status, and therefore the thawing of eggs or embryos and their transfer must be scheduled to coincide with the day for which the receptive result has been obtained.

Result: ‘Non receptive’ (without a recommendation for a new implantation window)
If the result of the first ERA test is non-receptive and the expression profile analysis does not suggest a displaced window of implantation, unfortunately we are unable to offer a therapeutic solution. This happens in less of 1% of patients.

6. Other scientific documents

Endometrial receptivity array: Clinical application.

Mahajan N.
J Hum Reprod Sci.2015 Jul-Sep;8(3):121-9. doi: 10.4103/0974-1208.165153. PMID: 26538853 [PubMed] PMCID: PMC4601169. [Epub ahead of print]

Human Endometrial Transcriptomics: Implications for Embryonic Implantation.

Gómez E, Ruíz-Alonso M, Miravet J, Simón C.
Cold Spring Harb Perspect Med. 2015 Mar 27. pii: a022996. doi: 10.1101/cshperspect.a022996. [Epub ahead of print]

The genomics of the human endometrium.

Ruiz-Alonso M, Blesa D, Simón C.
Biochim Biophys Acta. 2012 Dec;1822(12):1931-42.

Profiling the gene signature of endometrial receptivity: clinical results.

Garrido-Gómez T, Ruiz-Alonso M, Blesa D, Diaz-Gimeno P, Vilella F, Simón C.
Fertil Steril. 2013 Mar 15;99(4):1078-85.

Impact of final oocyte maturation using gonadotropin-releasing hormone agonist triggering and different luteal support protocols on endometrial gene expression.

Bermejo A, Cerrillo M, Ruiz-Alonso M, Blesa D, Simón C, Pellicer A, Garcia-Velasco JA.
Fertil Steril. 2014 Jan;101(1):138-146.e3.

The impact of using the combined oral contraceptive pill for cycle scheduling on gene expression related to endometrial receptivity.

Bermejo A, Iglesias C, Ruiz-Alonso M, Blesa D, Simón C, Pellicer A, García-Velasco J.
Hum Reprod. 2014 Jun;29(6):1271-8. doi: 10.1093/humrep/deu065. Epub 2014 Apr 4.

Clinical management of endometrial receptivity.

Blesa D, Ruiz-Alonso M, Simón C.
Semin Reprod Med. 2014 Sep;32(5):410-3. doi: 10.1055/s-0034-1376360. Epub 2014 Jun 24.

Transcriptomics of the human endometrium.

Díaz-Gimeno P, Ruíz-Alonso M, Blesa D, Simón C.
Int J Dev Biol. 2014;58(2-4):127-37. doi: 10.1387/ijdb.130340pd.

Timing the window of implantation by nucleolar channel system prevalence matches the accuracy of the endometrial receptivity analysis.

Nejat EJ, Ruiz-Alonso M, Simón C, Meier UT.
Fertil Steril. 2014 Sep 17. pii: S0015-0282(14)02025-1. doi: 10.1016/j.fertnstert.2014.07.1254.

Deciphering the proteomic signature of human endometrial receptivity

Hum Reprod. 2014 Sep;29(9):1957-67. doi: 10.1093/humrep/deu171. Epub 2014 Aug 8