Recurrent Implantation Failure: What the 2023 Definition Changed

Recurrent implantation failure describes the situation where embryos judged viable have repeatedly failed to produce a positive pregnancy test in a particular patient, often enough to justify further investigation. ESHRE published good practice recommendations on it in Human Reproduction Open in 2023.

Their wording matters, because it is deliberately not a fixed count. RIF, in their phrasing, is the scenario in which the transfer of embryos considered to be viable has failed to result in a positive pregnancy test sufficiently often in a specific patient to warrant consideration of further investigations or interventions.

• It is defined per patient, not by a universal number of cycles.
• It depends on how likely each transferred embryo was to implant.
• It is a trigger for investigation, not a diagnosis in itself.
• Two people with the same number of failed transfers can differ.

That is a real change from the definition still quoted on most fertility sites, including the earlier version of this page.

Because three transfers can mean very different things. Three transfers of untested embryos in a woman of 41 and three transfers of euploid blastocysts in a woman of 31 carry different cumulative odds, and treating them as the same situation produces both over-investigation and under-investigation.

ESHRE's answer was to define the threshold in terms of the odds rather than the count. The recommended threshold for the cumulative predicted chance of implantation, for the purpose of starting further investigation, is 60%.

In practice that means adding up the estimated implantation probability of each embryo transferred so far. Where the running total passes 60% without a positive test, the failures have become unlikely enough to warrant looking further.

Below that threshold, the more probable explanation is ordinary chance. Two failed transfers of embryos with a 25% chance each is a common outcome, not a signal, and investigating it tends to find things that were never causing the problem.

• After a Failed IVF Cycle: What Is Worth Investigating
• IVF Add-Ons: What the Randomized Trials Actually Found
• PGT-A in IVF: What the Evidence Shows About Testing Embryos
• Fertility Myths vs Facts: Ten Claims Checked Against the Evidence
• IVF Success Rates: How to Read the Numbers You Are Quoted
• Egg Quality and Age — What You Can Change, and What You Cannot (2026)
• Endometrial Scratching: What the 1,364-Woman Trial Found

The evidence does not currently support routine use. ESHRE's 2023 position is that there are insufficient data to recommend the routine use of any commercially available test of endometrial receptivity to diagnose the cause of RIF.

The largest trial is the reason. Simón and colleagues ran a five-year multicentre randomized controlled trial comparing personalised embryo transfer guided by endometrial receptivity testing against fresh and frozen transfer without it, published in Reproductive BioMedicine Online in 2020.

Outcomes per transfer were comparable across the arms. A higher cumulative live birth rate appeared only in the per-protocol analysis — that is, among those who completed the protocol as intended rather than everyone randomized, which is the weaker of the two ways to read a trial.

• Per-transfer outcomes were comparable in the randomized comparison.
• The benefit appeared only in per-protocol analysis, not intention-to-treat.
• ESHRE assessed the data as insufficient for routine use.
• Testing specific aspects of endometrial function can still be considered case by case.

ESHRE does leave a door open: assessment of specific aspects of endometrial function by testing can be considered. That is a narrower statement than the marketing around these tests suggests.

The 2023 document is unusually direct about immunological testing, which is where much of the money spent on unexplained implantation failure goes. Four of its recommendations are stated flatly, without the hedging that usually accompanies this area of practice.

• Peripheral NK cell testing is not recommended.
• Uterine NK cell testing is not recommended.
• Uterine T lymphocyte assessment is not recommended.
• The assessment of blood cytokine levels is not recommended.

One test is recommended in defined circumstances. Assessment of antiphospholipid antibodies and antiphospholipid syndrome is recommended in women with RIF who have additional risk factors for thrombophilia, and can be considered in women without such risk factors.

Being told a test is not recommended is not the same as being told nothing is wrong. It means the test has not been shown to identify the problem or to change what happens next. Where a treatment follows automatically from a test that cannot do either, the cost is not only financial.

Structural and embryonic factors remain the ones with the clearest evidence behind them, and they are usually cheaper to check than the immune panels. That combination is why they come first in any sensible order of investigation.

• Uterine cavity assessment, since structural findings are treatable.
• Embryo quality and, where appropriate, chromosomal status.
• Thyroid function, which is straightforward to test and to correct.
• Antiphospholipid antibodies where thrombophilia risk factors are present.

Our article on endometrial polyps and IVF covers what the evidence shows for one of the commonest cavity findings, and TSH levels and fertility covers where the thyroid thresholds actually sit.

It is also worth saying plainly that a proportion of repeated implantation failure has no identified cause after full investigation. That is an uncomfortable answer and it is more honest than the alternative, which is attaching a diagnosis to a test that ESHRE does not recommend.