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Thursday 22nd September 2016

Endometrial Receptivity Array (ERA)


ERA in the news

Alex Jones show 'Fertility & Me' recently discussed the 'Endometrial Receptivity Array' (ERA). As CRGW has offered the test to patients for some time we have received a lot of phone calls and emails asking for more information about the test and have produced the following web page in response to those questions to explain the test in more detail below. If you would like to watch the BBC show, click on the image below which will take you to BBC iPlayer.

What is an ERA?

Endometrial receptivity is the state at which the endometrium (the lining of your uterus) is ready for an embryo to implantant. 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, the ERA test (Endometrial Receptivity Analysis) allows the evaluation, at the microscopic molecular level, of the endometrial factor. This molecular tool allows us to diagnose whether the endometrium is receptive or not to an embryo by analyzing the expression of a group of genes (these are made of DNA and act as instructions to make proteins) related to endometrial receptivity. For that, an endometrial biopsy must be performed and the 'expression' of 238 of these genes involved in implantation is analyzed. According to these results, the endometrium is classified as receptive or not receptive by a computer driven 'assay'.

The Science

Each cell in the uterine lining has a nucleus which contains the genetic material known as DNA. DNA is the coded blueprint for the instructions that a cell needs to carry out its function. For example, if a cell’s purpose is to make a certain protein, the DNA contains the code for how to make the protein. The code is “translated” into a slightly different form called RNA and the RNA tells the cell which amino acids to combine to make the protein.

DNA is converted to RNA which makes proteins

 
 
 
 
 
 
 
 
 
 
 
 
 
 
The uterine lining cells make more of a certain type of RNA at one time of the cycle and less in another time of the cycle. Powerful computer chips can look at the amount of RNA produced at different times of the cycle. Then, using computer algorithms, we can detect patterns in the RNA production. Some RNA levels may not correlate with the window of implantation at all. Other types of RNA may be present in higher amounts and some may be present in lower amounts. The computer will see this RNA production in coloured bands and can analyse which patterns are associated with implantation: 
 
 
This endometrial receptivity array is very powerful. First, it is very accurate at determining when the window of implantation is “open”. Second, it is very reproducible. Studies were done on patients where they took two samples at the same time of the cycle several months apart. Most often, the results of the tests were the same.
 
The most interesting part of the endometrial receptivity assay is that it has identified that some women might have a receptive uterus at an earlier time than expected and some might be receptive at a later time! The CRGW team can then use this information to change the time that embryos are placed into the uterus so that it matches up better with the window of implantation!

What is ERA for?

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).

Who is it for an why?

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, 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.

FAQ's

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

The ERA test should be performed in medicated or a natural cycle. The 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 endometrium is performed according to a standard procedure with a catheter. About 30 milligrams of tissue is enough. This equates to a cube of approximately 3 millimeters on each side.

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

Hormone Replacement Therapy cycle
Upon initiation of an HRT (medicated) cycle, the biopsy is taken after five full days with progesterone (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.

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 you have frozen eggs or embryos, or fresh 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 you do NOT have frozen eggs or embryos and want to use your 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 there is currently no therapeutic solution. This happens in less of 1% of patients.

I have further questions. Where can I ask these?

Please click on the question mark if you have further questions or telephone the clinic on 01443 443999.