ERA TEST DIAGNOSTIC METHOD

Personalized embryo transfer

1. What is the ERA test?

The ERA test for the endometrial implantation window is an innovative diagnostic method developed and patented by IGENOMIX R&D after more than 10 years of research. This technique allows the evaluation of endometrial receptivity from a molecular point of view.

The ERA test for the endometrial implantation window is an innovative diagnostic method developed and patented by IGENOMIX R&D after more than 10 years of research. This technique allows the evaluation of endometrial receptivity from a molecular point of view.

Now, during the treatment process of an infertile couple, the ERA test provides an assessment of the endometrium at the molecular level and is a personalized genetic test to assess the state of endometrial receptivity in the implantation window. Whether the endometrium is receptive or not is determined after analyzing the expression of a group of genes. Endometrial biopsy should be performed on day P+5 (5 days after initiation of progesterone in a cycle with hormone replacement therapy) or on day LH+7 (7 days after the luteinizing hormone peak in a spontaneous cycle). Once the sample is delivered, the expression of 238 genes is analyzed. RNA from the endometrial tissue sample is hybridized with samples of these genes. After hybridization, computer analysis classifies the sample as receptive or non-receptive according to specific gene expression.

2.Why is an ERA test done?

Over 10 years of research and 3,000 clinical trials support this diagnostic method. The ERA test is used to assess the state of the endometrium and determine whether or not a patient's endometrium is receptive according to the genetic profile at the time the biopsy is performed.

The analysis reveals the timing of the implantation window and leads to personalized embryo transfer (PET) and synchronization based on the individually obtained results.

The test result determines whether or not a woman's endometrium is receptive on the particular day and type of cycle in which the biopsy is performed. If she is receptive, this means that the implantation window is on the day the biopsy is performed, and therefore the blastocyst can implant on that day in this type of cycle.

If non-receptive, the result may indicate a displaced implantation window. Therefore, a second biopsy will be required to determine this shift. According to the first result obtained, a specific day will be suggested for the second biopsy. This gives a greater opportunity to carry out implantation in the next cycle, through personalized embryo transfer (PET).

3. In what cases is the ERA test used?

The ERA test can determine whether a patient needs to customize the implantation window before starting treatment. This diagnostic method has been tested in patients who have failed to implant embryos with good morphological characteristics and quality (at least three embryos in younger women or two in patients over 37). This test is recommended for women with normal parameters of the uterus and with a normal thickness of the endometrium (≤6mm), as well as the absence of reasons for infertility found during the examination. Displacement of the implantation window is found in about 20% of these patients.

4. What are the advantages of the test?

As a diagnostic method to determine the receptivity of the endometrium, the ERA test determines the window of implantation personalized for each individual patient before starting in vitro treatment.

The ERA test shows high sensitivity and specificity in determining gene expression profiles associated with receptivity.

The classic method for determining the state of the endometrium is based on histological criteria. This previous diagnostic technique has been shown not to differentiate between fertile and infertile patients and is associated with a high degree of subjectivity, meaning that these results cannot be applied in clinical practice. The ERA test provides a solution to these problems.

5.Frequently Asked Questions:

• At what cycle can the ERA test be performed?
  The ERA test should be performed in either a stimulated or spontaneous cycle. The diagnosis of endometrial receptivity is valid only for the type of cycle in which the test is performed. Embryo transfer should therefore be performed in the same cycle type for which a positive receptivity result was obtained.

• How is an endometrial biopsy taken?
  A biopsy of the uterine fundus is performed according to a standard procedure with a PipeIle catheter or similar. A sample of about 30 mg of tissue is sufficient (approximately the size of a cube with a side of 3 millimeters).

• How is it determined when to do the biopsy?
  Stimulated cycle: When starting a stimulated cycle, the biopsy is taken after five full days of progesterone (about 120 hours). The day of the first dose of progesterone is considered day P+0, and the biopsy is done on day P+5.
  Spontaneous cycle: The biopsy is taken 7 days after the LH (luteinizing hormone) peak. The day of the LH peak is considered LH+0, the biopsy is done on day LH +7 (after about 168 hours). If ovulation is determined by ultrasound, the day of ovulation is taken as day Ov+0, then the biopsy is done six days later (approximately 144 hours) on Ov+6.

• How is it determined when ovulation is in a spontaneous cycle?
  The time of ovulation in spontaneous cycles can be determined using test strips for LH (luteinizing hormone) in urine, by direct measurement of LH in blood serum, or by observing follicular rupture on ultrasound examination.

• What actions are taken according to the result obtained?
  Result: "receptive"
  If the patient has frozen embryos or has fresh donor embryos, they can be transferred in a cycle of the same type (stimulated or natural) for which a receptivity result was obtained. If blastocysts are to be transferred in a subsequent cycle, this is done on the same ordinal day on which the biopsy was performed in the previous cycle. If day 3 embryos are to be transferred, this should be done two days before the biopsy from the previous cycle.
  If the patient does not have frozen eggs or embryos and wants to use her own eggs, one cycle of ovarian stimulation should be performed to cryopreserve eggs or embryos. Embryo transfer is performed in a subsequent cycle of the same type (stimulated or spontaneous) for which an ERA test receptivity result is obtained.Result: "Non-receptive" (with recommendation for a new implantation window)
  If the result of the first ERA test is not positive and the analysis of the genetic profile indicates that the implantation window may be shifted, it is necessary to confirm this shift with a second ERA test. This second analysis will determine the day on which the endometrium is receptive and, therefore, the thawing of embryos and their transfer should be planned according to this result.Result: "Non-receptive" (no recommendation for a new implantation window)
  If the result of the first ERA test is not positive and the genetic profile analysis does not suggest a shifted implantation window, unfortunately, no therapeutic approach can be offered. This happens in less than 1% of patients.