More research is indicating that IVF implantation failure can be caused not only by problems with the quality of the embryo (most often genetic errors), but because of problems with the endometrial lining - the tissue on the inside of the uterus that prepares each month for the arrival and implantation of an embryo. This can lead to an unsuccessful in vitro fertilization (IVF) due to implantation failure, even with a genetically healthy embryo.
Endometrial Receptivity Assessment (ERA®)
In my fertility practice during the past several years, I have been using a new cutting-edge test called the Endometrial Receptivity Assessment (ERA®) to improve the chances of a successful embryo transfer in patients who have experienced unsuccessful IVF due to several implantation failures. This ERA test helps reproductive endocrinologists determine the right time to transfer an embryo, and we have experienced wonderful results.
What Is ERA®?
In general, in a natural cycle, the endometrium (lining) is receptive to the implantation of embryos (endometrial receptivity) between days 19 and 21 of the menstrual cycle (five to seven days post ovulation). However, if the endometrium is not receptive during this proper time frame, the embryo may be 'out of sync' with the uterine lining and transferred at the wrong time during IVF, thus missing the female's fertility window of implantation.The Endometrial Receptivity Assessment is an advanced, personalized, genetic diagnostic method developed by IVIGEN that evaluates a woman's endometrial receptivity (the status in which the endometrium is ready for embryo implantation) from a molecular point of view. In the endometrium, numerous proteins are produced under the influence of estrogen and progesterone. These proteins are involved in preparing the endometrium in terms of its thickness and receptivity for implantation. Protein production in all cells is regulated by "gene expression" (gene activation or inactivation). The ERA test analyzes the genetic expression levels of 238 genes related to the status of endometrial receptivity, assessing the activity of genes in the endometrial lining in order to pinpoint a woman's optimum time for transfer of a frozen embryo. For 75-80% of women, day 5 (5 full days of progesterone then thaw and transfer the next day) is the optimal ‘window for implantation’.
The test assesses the status of the endometrium and determines whether the patient's womb has a receptive gene profile on day 5 or not at the time of the biopsy.
How Is the ERA Test Done?
In the past, the only study that was done to assess endometrial receptivity was an ultrasound scan, which was performed to assess uterine lining thickness. For the ERA test, an endometrial biopsy must be performed by the reproductive endocrinologist at LH+7 (LH surge + 7 days) during a woman's natural cycle or at P+5 (start of progesterone + 5 days) in a woman's hormone replacement therapy cycle. The biopsy is sent off to the IVIGEN lab for analysis of the expression of 238 genes involved in the endometrial receptivity.
The analysis results determine whether the patient's endometrium is classified as receptive or non-receptive by a computational predictor
- If the patient is classified as receptive, then the window of implantation is defined as the day on which the biopsy was taken, which means the embryo is capable of implanting during this period.
- If the patient is classified as non-receptive, it means the window of implantation is displaced. Once this personalized window of implantation is identified, the embryo may successfully implant in a subsequent cycle called the Personalized Embryo Transfer.
Who Should Consider the ERA Test?
The ERA test has been tested in many patients who have had two or three implantation failures with frozen embryos of good morphological quality. In a pilot study, researchers gave the test to 85 women who had each experienced on average five rounds of IVF that had failed at the implantation stage. They found that the fertile window was more likely to be shifted early or late; in some cases they were completely missing the day when the embryo is transferred in standard IVF protocols. With the ERA test as a guide, the study found that 33 percent of those treated had a successful implantation, much higher than would typically be seen for such a group of patients.
The ERA test has now been shown to be helpful in several studies, involving thousands of patients who have experienced two to three implantation failures, despite good quality embryos. A displaced "non-receptive" window of implantation has been detected in 20 to 25 percent of these patients.
ERA testing is often recommended for my patients who have had several frozen IVF implantation failures, despite a normal uterus and endometrial thickness (6 mm or more), and apparently healthy looking embryos. It allows the personalized window of implantation to be detected. To date, I have been very impressed by this novel diagnostic tool, which has helped many of my patients.
ERA® Fertility Specialist
I will occasionally even offer it to couples who only have a few frozen embryos, even if they haven’t failed a frozen transfer yet. In addition, for couples who have done Pre-Implantation Genetic Screening (PGS) on their embryos, I will often offer the ERA test before doing a frozen transfer. If you would like more information about the ERA test and whether it is right for you, please contact me at email@example.com or go to www.ivigen.com.
By Laurence A. Jacobs M.D. revised 12/17