ERA Diagnostics

ERA is a diagnostic method to determine the cause of implantation failure.


Should the repeated transfer of well-developed embryos not result in pregnancy, it is necessary to examine why it has not been successful. In recent years, significant improvements have been made, especially in the laboratory. However, the influence of the uterine mucous membrane on the success of IVF-ICSI remains largely unknown. For a long time, people looked for an examination method to determine the correct time for embryo transfer. Until now, the only methods available to the physician were thickness measurement and assessment of the “echo structure” of the uterine mucous membrane to try to identify whether embryo transfer could be carried out successfully. Histological examination of the uterine mucous membrane does not assist with this process.

With the arrival of the era of molecular genetic testing, we now have a method that actually enables us to predict whether or not the mucous membrane will be receptive during the implantation window. During the search for a conclusive, safe, reproducible, and non-subjective method, testing of gene expression in the endometrium was discovered.

ERA is an array test that enables the examination of the endometrium gene expression during the implantation window. Numerous comprehensive studies have shown that 238 genes have a predictive significance in the classification of the receptivity status of the endometrium.

This allows the endometrium to be classified as either pre-receptive, receptive, or post-receptive. It has been shown that the gene signatures found, which depend on the cycle day, can be reproduced in women for at least 20 months. This means that the results provide a measurement that can be used for the timing of the embryo transfer over a period of 20 months. Thanks to this method, we now know that 80% of women have a receptive endometrium during the implantation window and the remaining 20% have a non-receptive (mostly pre-receptive) endometrium. (*current information following personal communication with IVInomics – May 2013 – 26% of women non-receptive, and 74% receptive).

However, the results presented up until now only apply to natural and HRT cycles (known as artificial cycles with mucous membrane building up via the implementation of oestrogen). Endometrium receptivity examinations relating to controlled ovarian stimulation (COS) as part of IVF-ICSI cycles are not yet available. Globally, these examinations are currently only carried out in IVIOMICS laboratories, e.g., in Spain.

Procedure


For natural cycles:

The biopsy must be collected on LH day +7, the assumed optimal receptivity day (problem: repeated blood and urine testing is required to determine the LH increase. This information provides a definitive biopsy date. This is difficult to implement for both working women as well as the practice (weekends/public holidays). Because the results can also affect the spontaneous cryocycle, this creates a logistical problem.  ERA is therefore most commonly used for HRT cycles.

For HRT cycles (known as an “artificial cycle”):

Oestrogen is administered according to a predefined schema to build up the mucous membrane. After 12 to 15 days, the mucous membrane is sufficiently built up so that the administration of additional corpus luteum hormone can begin. The very flexible starting time can be chosen. This enables the biopsy to be scheduled on the optimal weekday for both patient and practice. The biopsy is carried out on day 6 following the beginning of the administration of progesterone.

Procedure:

Usually carried out with ultrasound monitoring (with a full bladder), the cervical canal is probed and slightly dilated. This can be rather uncomfortable for the patient. However, anaesthesia is usually not necessary. Subsequently, a plastic tube (pipette) is inserted into the uterine cavity. Suction is then used to collect 1 or 2 biopsy samples.

Examination Results and Consequences:


If the endometrium is classified as being receptive on the day of the biopsy, then the transfer can take place on this same day during the next cycle. If the endometrium is classified as being pre-receptive, then a new examination should/could be carried out a later day, e.g., P+7.
In the event of a post-receptive status, the 2nd biopsy should take place based on the recommendation of the IVInomics laboratory, e.g., P+5.

Results:


The embryo transfers carried out following a “time correction” of the implantation window, showed very good implantation success and pregnancy rates that correspond to “normal” age-appropriate rates.
We have been using this diagnostic process for approx. 10 years and we are able to confirm the numbers reported in the presented studies on our patients. The total cost is approx. €1000-1100, including ultrasound and medication.