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Specialized Services | Endometrial Receptivity Array (ERA)

Endometrial Receptivity Array

If you or someone you care about has struggled with failed IVF cycles which are unexplained, consider fertility physician about ERA.

At times in cases of recurrent implantation failure, it can be a tricky and frustrating situation for the fertility experts as well trying to track down a cause, in addition to the anxious couple. Patients need answers, and doctors want to help. Happily, new tests are constantly being added and technologies are getting advanced and more refined.  The ERA test is one of these new scientific inventions, which is offering information & diagnostics to patients coping with implantation failure from a specialized molecular perspective. Anmol Fertility & IVF Centre uses this novel technique in selective cases to help evaluate the woman’s endometrial receptivity and thus we can plan a ‘personalized embryo transfer ‘( PET), a timing based heavily upon the test, carried out in a person. A cross-talk between endometrium and embryo gets well established and brings success to the vital process, Implantation.

Recurrent or repeated implantation failure (RIF) can be devastating. Some patients undergo three or more rounds of IVF and everything seems to go well: a good number of eggs at retrieval, a good fertilization rate, the embryos appear to be healthy and high quality, the uterine lining looks good, the transfer goes smoothly, but the pregnancy never “sticks.” After so much emotional, physical, and financial investment, the disappointment and distress caused by repeated implantation failure is often severe. There are several possible factors which can cause implantation to fail.  Once genetic and all other factors are ruled out& the focus is narrowed down to the endometrial lining itself being a probable cause, there arises need of more specialized tests which can help reproductive experts provide some of these answers and help patients find the right path to pregnancy. The ERA test is one of the latest tool to identify the point in time, of endometrial receptivity, optimal at the genetic level.

Concept of Window of Implantation (Endometrial receptivity)

Receptivity of the endometrium is a condition in which the endometrium (uterine lining) is most ready for implantation (nesting) of the embryo. Each woman has an “implantation window” in her cycle which is a few days long, generally occurring from the 19-23 days of the menstrual cycle. During this time, proteins are created which make the lining thicker and more receptive. In about 84% of women this small window occurs at the expected time. About 16% of women have a unique window which can be earlier or later than expected. For IVF cycles, this could mean that the embryo transfer is happening on the wrong day, when the window hasn’t opened yet or has already closed, thereby causing implantation failure.

What is the ERA test?

ERA stands for Endometrial Receptivity Analysis (or Array). It is a genetic diagnostic test to investigate the receptivity of endometrium, using a small sample of a woman’s endometrial tissue to evaluate whether or not the endometrial lining is prepared at molecular level to accept an implanting embryo. ERA is a personalized genetic test to diagnose receptivity in the window of implantation. ERA determines the exact time period during which an embryo needs to be transferred into the woman’s uterus to achieve a successful pregnancy.

Who are the best candidates for ERA?

It is advised for patients who have had repeated implantation failure with embryos of good morphological quality( at least 3 failed embryo transfers for young women or two in patients of age 37 years or more) for patients with apparently normal uterus and with normal endometrial thickness(>-6 mm), in which no problems are apparent.

How does the ERA test work?

When the endometrial lining is receptive, the genetic material of the endometrial cells have a unique “expression,” which means that they may be making more or less of certain specific types of RNA( ribonucleic acids ). In ERA test at the molecular level  , the researchers determine& analyze the expression of 236 genes that will participate in endometrial receptivity per sample and built up a database of more than 12,000 samples of endometrial tissue to see the levels of RNA produced at different times of the cycle. They then used advanced computer algorithms to look for patterns until they could reliably classify a sample as “Receptive” or “Non-Receptive” according to its specific expression profiles.It will therefore make it possible to evaluate whether the endometrium is properly receptive for embryo transfer in peculiar days or whether the so called “window of implantation” is shifted. Thus, using ERA, doctors can identify whether a woman’s “implantation window” is happening as per expectation or whether they need to move the transfer date to ensure the best “sync” between the embryo and the uterine lining.

How is the ERA test performed?

Endometrial Receptivity Analysis requires a sample of the uterine lining obtained at a very specific time in the cycle. It is also possible to use fertility medications to prepare the uterine lining, using supplemental estrogen and progesterone. This like mimicking the frozen thawed cycle of embryo transfer. But during the test cycle, there will be no transfers, we only do the test. The day the progesterone is started is Day Zero, and the test is done five days after that.

The tissue sample is taken in a procedure known as endometrial biopsy. A thin catheter is inserted through the cervix into the uterine cavity, and a plunger in the catheter is used to create suction and draw a tiny sample of the endometrial lining into the catheter. Some women may find this part of the process uncomfortable, but it is a very quick procedure and the pain is momentary. The sample is then sent to the lab for analysis using Next Generation Sequencing technology. Results are available in around three weeks. If the results come back that the tissue was “Non-Receptive” then the test should be repeated earlier or later, until the optimal time is identified. Once the patient’s receptive window has been identified, personalized embryo transfer (pET) timing can be used . ERA test is carried out optimally during the cycle preceding the one in which the embryo transfer is planned. The result will therefore enable us to set the appropriate date of embryo transfer individually for each client.

Cautions:   

Avoid intercourse on the day of ERA test.

Short general anaesthesia/local anaesthesia may be required if there is excessive pain.

Beware that, rarely it may be necessary to retest due to an inadequate sample ( <6 mm thickness).

Advantages: 

It helps to determine which is the optimal time to do embryo transfer.ERA test is highly sensitive and enables detection of the receptivity of endometrium and is a good choice for women with repeated unsuccessful embryo transfers.

This test is highly reproducible, which means that when samples are tested at the same time of the cycle but months apart, the results remain the same.

It is usually done in Frozen thawed transfer cases, but can also be carried out in natural cycles on the 5th day of confirmed ovulation.

Relatively simple procedure, no major procedure related risks except momentary pain.

Interpretation of the test: If she is receptive, it means that her window of implantation falls on the day of the cycle during which the biopsy was performed. A different result could imply a displaced window of implantation, Pre or post receptive. Accordingly the transfer date can be scheduled and displaced, sooner or later than the standard 5 day progesterone therapy.

 

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