Recurrent implantation failure: what is established, what is controversial, and why the add-on menu gets dangerous

After two or three embryo transfers without a pregnancy, many patients hear the phrase "recurrent implantation failure," or RIF. It can sound like a diagnosis. In reality it is a description of what has happened, and the reasons behind it vary widely from one person to the next.

It is also the point in IVF where patients are most likely to be offered tests and treatments with little evidence behind them. This article sets out what the European Society of Human Reproduction and Embryology (ESHRE) recommends, what it advises against, and how to keep the investigation focused.

What RIF means, according to ESHRE

In 2023, an ESHRE working group published the society's first good practice recommendations on RIF (ESHRE Working Group on RIF, Human Reproduction Open, 2023). It describes RIF as something seen only in IVF and ICSI patients: the transfer of embryos considered viable has not led to a positive pregnancy test often enough to warrant further investigation.

Instead of a fixed number of failed transfers, ESHRE proposes a threshold based on probability. When a patient's cumulative predicted chance of implantation across their transfers has passed 60%, and no implantation has happened, they should be counselled about further investigation or treatment.

The working group's broader message is to challenge RIF as a one-size-fits-all concept and recognise it individually for each patient (ESHRE, 2023).

Why a probability threshold makes sense

The 60% threshold reflects something simple: different embryos carry very different chances. Three failed transfers of embryos with a high individual chance of implanting is more surprising, and more worth investigating, than three failed transfers of embryos with a low chance.

An illustrative calculation only, with made-up numbers:

The arithmetic is 1 minus the chance of failing every time. For Patient A, 1 − (0.6 × 0.6) = 0.64. Under ESHRE's approach, Patient A would reach the point of further investigation after two failed transfers, while Patient B would not reach it even after four. Real per-transfer chances depend on age, embryo stage, quality and testing, and your clinic should explain how it estimates yours.

The same arithmetic is a reminder that even good embryos fail by chance. A run of negative tests is painful, but it does not by itself prove something is wrong.

Embryo, uterus, or chance?

Implantation needs two things to work together: an embryo capable of developing, and a uterus ready to receive it. When transfers keep failing, it helps to ask which side of that partnership is more likely to be involved.

On the embryo side, the biggest influences are the age at which the eggs were collected and whether the embryos had the right number of chromosomes. An embryo's appearance under the microscope does not show how many chromosomes it has, so a well-graded embryo can still carry a chromosome error. That is one reason the genetic-testing history of past transfers matters when RIF is being assessed. An embryo with a chromosome problem may fail to implant however healthy the uterus is.

On the uterine side, structural problems inside the cavity, inflammation of the lining, and how the lining was prepared all play a part. These are the areas ESHRE's suggested investigations focus on.

And then there is chance, which never goes away entirely. A good investigation tries to weigh all three rather than assuming the answer lies in whichever one is easiest to test.

What ESHRE recommends looking at

The 2023 recommendations separate a short list of steps that are recommended from a longer list that could be considered, depending on the patient.

Recommended

• Lifestyle review. Smoking, body mass index and drug use should be reviewed, because these are factors that can change.
• Genetic counselling where needed. If a chromosomal abnormality is found, genetic counselling is recommended, along with preimplantation genetic testing where relevant.

Could be considered

• Chromosome testing (karyotyping) of both partners
• A 3D transvaginal ultrasound of the uterus, if not done earlier
• Hysteroscopy, a camera look inside the uterus, especially if ultrasound suggests a problem
• Assessment of certain aspects of how the endometrium (lining) functions
• Testing for chronic endometritis, a low-grade inflammation of the lining, with antibiotics if it is diagnosed

Not recommended routinely

• Routine measurement of vitamin D, or treating vitamin D deficiency for this purpose, because data are insufficient
• Routine use of commercially available endometrial receptivity tests, because evidence is insufficient

The ESHRE summary page adds that many of the tests and treatments reviewed are not recommended until higher-quality studies confirm that they are effective and safe.

Where the add-on pressure comes in

When standard tests come back normal, it is natural to want an explanation. That is also when immune tests, endometrial tests and infusions tend to appear on the menu. The UK regulator's ratings give a useful independent check (HFEA, reviewed 2026):

A normal standard workup may simply mean that no treatable cause has been found. It does not prove that a hidden immune or lining problem must exist. Our wider guide to which IVF add-ons are evidence-based explains how to read these ratings.

A focused review, step by step

A disciplined approach looks at the whole chain before reaching for new tests:

1. Rebuild the transfer history. How many transfers, of what embryos, at what stage, after what preparation? Our article on embryo grading helps make sense of the quality descriptions.
2. Estimate the embryos' realistic chances. Age at egg collection is a major factor. Whether embryos were tested for chromosome number also changes the picture.
3. Check the uterus. Ultrasound, and hysteroscopy where indicated, look for problems inside the cavity.
4. Review how transfers were prepared and done. The way the lining was prepared for frozen transfers is part of this; see our comparison of natural and medicated frozen transfers.
5. Follow your history. Investigate specific conditions your history points to, such as signs of chronic endometritis.
6. Discuss uncertain options with clear limits. If you choose an unproven option, agree in advance what you will and will not try.

When reviewing the clinic itself is reasonable

Sometimes the most useful review is of the process rather than the patient. Unclear embryo reports, inconsistent transfer technique or poor communication are worth raising. If you are considering moving to another clinic, including one abroad, ask for full records of each transfer, not just the outcomes.

Pacing the next step

After repeated negative tests, there is a strong pull to start again as soon as possible, with as many changes as possible. Changing many things at once makes it hard to learn anything from the next transfer. It can be more useful to agree with your clinic on one or two well-reasoned changes, the reason for each, and when you will review the plan again. Taking a short pause to recover emotionally is also a legitimate choice, not lost time.

Questions to ask before any new test or treatment

• By your estimate, what was my cumulative chance of implantation across these transfers?
• What specific problem would this test or treatment address?
• Has it been shown in good-quality trials to increase live births?
• How does ESHRE or the HFEA view it?
• If the result is abnormal, what would we do differently? If normal, what then?
• What does it cost, and what are its risks and side effects?

Frequently asked questions