Endometrial Receptivity Analysis (ERA)

The implantation window is a short time during a menstrual or treatment cycle when the lining of the uterus, called the endometrium, is receptive to the implantation of an embryo.

The implantation window is usually active at around 7-9 days after either the hormone surge that triggers ovulation, or after injection with fertility drugs that mimics the surge.

Some studies have shown that the implantation window may open and close earlier or later in some individuals. The endometrium is less receptive to embryos outside of the

implantation window, potentially inhibiting implantation and pregnancy.

We can carry out ERA testing either during your natural menstrual cycle, or during a stimulated cycle.

During the test, which is similar to a smear, we’ll take a biopsy of the womb lining then analyse the tissue to monitor 248 genes which studies show to regulate when the implantation window is open. This will determine when your endometrium will be most receptive and we can use these findings to determine the timing of your embryo transfer, which could increase the chance of successful implantation.

The results are usually returned to the clinic within 2-4 weeks which means the optimal timing

of your next embryo transfer will be known before your next cycle (unless we recommend a

second biopsy).

If your ERA test shows an unusual implantation window, we would not perform your embryo transfer in a fresh IVF treatment cycle. Any embryos created will need to be frozen and transferred in a frozen embryo transfer cycle.

We might recommend ERA if you are under 37, and had unsuccessful treatment following a transfer of a good quality day five embryo.

The test may also be helpful if you have limited opportunities for future treatments, maybe due to costs, or concerns over the availability of viable embryos in the future.

For example,

• where you only have a single embryo available for transfer
• you are using donated gametes where the availability of future embryos is uncertain
• where embryos are being transferred to a surrogate.

Embryo transfer is one of the most important stages of your IVF treatment. If we think this could be an issue for you, we might suggest endometrial receptivity analysis. If you’re still unsure whether it might be an option, talk to your local clinic or contact us for support.

The endometrial biopsy is a low-risk procedure used in many aspects of gynaecology. You may experience cramping after the procedure, and there is a small risk of infection and bleeding. There is also a minimal chance of uterine perforation. In around 5% of cases, the biopsy may not be adequate, or the tissue is unsuitable for processing, in which case the test can be repeated at no extra charge in the next cycle. ERA does not have any additional known risks for the child born due to fertility treatment.

The independent regulator of fertility treatment, the Human Fertilisation and Embryology Authority (HFEA), has developed a 'red-amber-green' rating system and provides information on their website about treatments offered on top of your routine fertility treatment – known as treatment add-ons. They consider that the only way to be confident that a treatment is effective enough to be used routinely is to carry out a randomised controlled trial (RCT). Patients are assigned randomly to two groups in an RCT: a treatment group, given the new treatment and a control group, given either a well-tried treatment or a placebo.

One RCT has been performed to study the effectiveness of ERA in increasing the chances of having a baby. Although the study's outcomes were promising, the results did not prove that ERA made a genuine difference to the chances of having a baby. For this reason, the HFEA gives the use of ERA a red rating.

There have been over 20 peer reviewed studies published over the past 6 years looking at which groups of patients would benefit from having an ERA. Two studies1 published in March and April 2022, have given us further information about which group of patients will potentially benefit from testing.

The first study looked at the pregnancy rates for 281 patients who had a personalised embryo transfer once a displaced window of implantation was identified by ERA. Of those patients, 141 had a conventional frozen embryo transfer and 140 patients who had experienced recurrent implantation failure, 3 or more failed cycles of treatment, had a personalised transfer based on an ERA test.

In those who had an ERA, 70 out of 140 (50%) achieved a clinical pregnancy2 with their first transfer. In the group that had a conventional frozen embryo transfer 35 out of 141(25%) achieved a clinical pregnancy. Both groups had good quality embryos to replace. This was a significant finding. The number that sadly miscarried in both groups were the same, 8 patients.

The second study, reviewed the findings of 11 different studies all looking to define if there is a benefit and a place for ERA. This type of study is called a meta- analysis, and allows good quality studies to be compared to each other to increase the level of reliable data to help to make decision about the effectiveness of a test.

The review reached the following conclusions:

1. Approximately one third of sub-fertile women could suffer from a displaced implantation window
2. The ERA test has emerged as a promising tool.
3. Patients with an overall good-prognosis may not benefit from ERA
4. Personalised embryo transfer (pET) guided by ERA significantly increases the chances of pregnancy for non-receptive patients with recurrent implantation failure (RIF) of endometrial origin.

We performed a review of our own data in January 2022 at Care. Our results for 88 patients show similar findings to these larger studies. However, it is important that you know and understand that such new treatments remain unproven.