Medical

ERA testing and the ‘implantation window’: what the research really says

It’s an appealing idea: if embryos don’t implant, perhaps it’s because the transfer is taking place at the wrong time. Recent studies are far less enthusiastic than the publicity suggests.

Published on · 5-minute read · by Triada Baloukoudis

After two or three transfers without a pregnancy, almost all the patients I support are offered, at some point, an endometrial receptivity test, the best known of which is ERA (Endometrial Receptivity Analysis). They ask me whether they should have it done. My answer can be summed up in one sentence: first ask what the test will change for you, in light of what the studies show. Here are those studies.

The principle behind the test

The endometrium is only receptive to an embryo for a short period, known as the ‘implantation window’. In a standard transfer cycle, it is assumed that this window opens at a fixed time after the start of progesterone treatment. The ERA test is based on the hypothesis that, in some women, this window is shifted by a few hours or a day.

In practice, a ‘dummy’ cycle is carried out, prepared in the same way as a real transfer cycle with oestrogen followed by progesterone, but without an embryo. A small endometrial biopsy is taken at the time when a blastocyst transfer would have taken place, after five full days of progesterone, i.e. approximately 120 hours. In a natural cycle, this is carried out seven days after the LH surge. Analysis of the expression of numerous genes classifies the endometrium as receptive, pre-receptive or post-receptive. If the result is not ‘receptive’, the next transfer, during another cycle, is brought forward or delayed accordingly: this is known as a personalised transfer.

What the studies show

Three types of data exist, and none of them confirm the promise.

  • The most robust randomised trial, published in JAMA in 2022, included 767 patients across thirty US clinics, all with a single chromosomally normal embryo. The live birth rate was 58.5 per cent when the transfer was guided by the test, compared with 61.9 per cent with the usual schedule: no benefit, and a figure that was even slightly lower.
  • The multi-site trial published in 2020, led by the team that developed the test, showed a benefit in patients who had followed the protocol to completion. However, the intention-to-treat analysis – which provides the best protection against bias – found no difference, and nearly half of the participants had withdrawn from the study before it was completed.
  • Meta-analyses and large cohorts also fail to find any benefit. A 2023 meta-analysis, covering eight studies and 2,784 patients, showed no significant improvement in live births. A large retrospective study from 2022 even found poorer outcomes with personalised transfer following a first failure.

Not all the patients included in these studies were in your situation, and research is ongoing. However, to date, no robust comparative study has shown that the test increases the number of babies.

The view of professional bodies

The European Society of Human Reproduction and Embryology (ESHRE), in its 2023 guidelines on complementary options to IVF, is clear: the endometrial receptivity tests currently available are not recommended, due to a lack of robust data on their effectiveness.

The UK’s Human Fertilisation and Embryology Authority (HFEA), which classifies these options using a colour-coded system, has assigned the test the colour red, its most unfavourable rating: for most patients, the available high-quality evidence suggests that it may reduce the effectiveness of treatment rather than improve it. These options are discussed in greater detail in the article on add-ons.

Why the idea remains appealing, and what it overlooks

The mechanism is plausible, and research into the endometrium is an active field. However, the most common cause of transfer failure remains the embryo itself, in particular a chromosomal abnormality, the frequency of which increases with the age of the woman who produced the egg. A test focusing on endometrial timing cannot do anything to address this. This is why the assessment of repeated failures begins elsewhere: see the assessment of implantation failures and PGT-A.

What the test really costs when you’re coming from abroad

On top of the cost of the test itself, there is a full cycle without a transfer, meaning at least one extra month. For a patient travelling from abroad, this may also mean an additional stay, or organising a biopsy at home and sending a sample, depending on what the clinic allows. Before agreeing, ask for the total cost in writing and the exact timetable: biopsy, results, then transfer.

Questions to ask before saying yes

  • Why is this test recommended in my specific case, and what makes me think the endometrium is the issue rather than the embryos?
  • Have my embryos been genetically tested, or does my age make a chromosomal abnormality likely?
  • What will actually change if the result is not ‘receptive’?
  • Which studies does the clinic cite, and are they comparative?
  • What is the total cost, including the preparation cycle?

If you would like us to go through the report of your previous transfers together before making a decision, please write to me.

Frequently asked questions

Does the ERA test increase the chances of pregnancy?

Not according to the most robust studies. In the randomised trial published in 2022, involving 767 patients and a chromosomally normal embryo, the live birth rate was 58.5 per cent with the test compared to 61.9 per cent without it.

How long after the ERA test does the embryo transfer take place?

The test is carried out during a cycle prepared without a transfer. The transfer takes place during a subsequent cycle, prepared in the same way, with the duration of progesterone treatment adjusted according to the result.

Does the ESHRE recommend the ERA test?

No. In its 2023 recommendations on complementary options, the ESHRE states that the endometrial receptivity tests currently available are not recommended.

Can the ERA test explain repeated failures?

Rarely on its own. The most common cause of failure remains the embryo, particularly a chromosomal abnormality. The assessment of repeated failures begins with other investigations.

This article provides general practical and administrative information. It does not constitute medical or legal advice. Rules and costs are subject to change: always check for the latest information with your health insurance provider, the clinic treating you and your doctor.
Triada Baloukoudis

Triada Baloukoudis
Independent IVF patient coordinator in Thessaloniki, with 24 years of experience supporting patients travelling from abroad. More · Contact · Facebook

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