Recurrent implantation failure (RIF): the facts

Few situations in assisted reproduction cause as much distress as embryos repeatedly failing to implant, despite the transfer of good-quality embryos.

A whole industry of tests and treatments has grown around “recurrent implantation failure” (RIF). Let us look calmly at what the evidence says.

What is RIF?

There is no universally accepted definition. A practical approach defines it as failure to achieve clinical pregnancy after the transfer of several good-quality embryos — usually at least three — or after the transfer of a set number of euploid embryos.

The key point is that true RIF is rare, affecting fewer than 5% of couples. Many “failures” are simply due to chance — each transfer has a certain success rate, and a few failures in a row are statistically expected.

Is it a real diagnosis or a statistical artefact?

Often it is the latter. If each embryo transfer has, say, a 35% chance of success, then a proportion of couples will have, purely by chance, three failed transfers in a row — without any underlying “implantation problem”.

This does not mean we should not investigate; it means we should avoid over-pathologizing a situation that is often just bad luck.

What is the role of aneuploidy?

The most important one. The majority of implantation failures are due to chromosomal abnormalities of the embryo — which are not always visible in the morphology. When a tested euploid (chromosomally normal) embryo is transferred, the implantation rate is high, regardless of age.

Data show that the cumulative implantation rate after transferring euploid embryos in women with previous failures remains very high — most couples eventually achieve pregnancy.

Which work-up makes sense?

A sensible work-up focuses on correctable things: assessment of the uterine cavity (for polyps, fibroids, adhesions, hydrosalpinx), thyroid function, and re-evaluation of embryo quality and the laboratory protocol.

The aim is to find something that can genuinely change the outcome, not to accumulate tests without therapeutic consequence.

Which treatments lack evidence?

Many popular “RIF treatments” have no proven benefit: immunological therapies (intralipids, corticosteroids, intravenous immunoglobulin, treatments for NK cells), endometrial scratching, PRP injections, and the general use of endometrial receptivity testing (ERA).

These interventions add cost, anxiety and sometimes risk, without evidence of increasing births. Attention should focus on embryo quality and a normal uterine cavity.

What is the realistic approach?

The best-supported strategy is patient continuation: transferring one good (ideally euploid) embryo at a time, correcting what can be corrected in the uterus, and optimizing the protocol.

Clear, honest information that most women eventually succeed is part of the treatment — it lowers anxiety and prevents spending on ineffective interventions.

Summary

“Recurrent implantation failure” is often statistical chance more than a distinct disease; true RIF affects fewer than 5% of couples. The chief cause is embryo chromosomal abnormality — euploid embryos implant at a high rate. The work-up should be targeted (uterine cavity, thyroid, embryo quality). Immunotherapies, scratching, PRP and routine ERA lack evidence. The realistic path is patient transfer of good embryos — and most women eventually succeed.

Sources: ESHRE Good Practice Recommendations on the diagnosis and management of recurrent implantation failure; euploid-embryo implantation data (Fertil Steril / Hum Reprod).

⚕ Medically reviewed by Prof. Stratis Kolibianakis · Thessaloniki Medical Association Reg. No. 16340

ARTICLE 9 · FERTILITY PRESERVATION