Study Summary
3 minute readRecurrent implantation failure, or RIF, is a diagnosis women are often given after only two or three euploid embryos fail to implant. It implies something is wrong that will keep stopping embryos from implanting. This study set out to test whether that's real. It followed women who kept transferring euploid embryos after three failures, from 26 clinics across four countries, screened from a population of 123,987 patients.
What they found was that continued failure isn't inevitable. The fourth euploid embryo led to a live birth 40% of the time and the fifth 53.3%, the same as the earlier transfers. Added together, that is a 98.1% cumulative live birth rate by the fifth euploid embryo. Once genetically normal embryos are being transferred, the female body is capable of carrying given enough attempts, and true recurrent implantation failure is rare.
- Hypothesis: that after three failed euploid transfers, the fourth and fifth would show a clear drop in success, which would identify a real group of women with recurrent implantation failure.
- Study Type: a large retrospective outcome analysis, assembled to have enough repeat euploid transfers to see whether success falls away with each attempt. It is well suited to that question. It cannot prove cause and effect, and only women with euploid embryos to spare reach a fourth transfer, so the group leans towards good prognosis.
- Conclusion: Their hypothesis was disproven. The fourth and fifth euploid transfers work as well as the first three. The prevalence of genuinely unexplained recurrent implantation failure is under 2%. If there is no known issue (such as an immune concern or thin uterine lining, etc.), then multiple failures with euploid embryos usually reflects chance, not a broken uterus.
Try it with a result
Select a transfer number to see the per-transfer and cumulative live birth rate, and how little the cumulative result changes across Day 7 embryos, higher BMI, donor sperm or double transfers.
The study
This study followed already-tested euploid blastocysts through transfer, recording positive test, clinical pregnancy and live birth.
Study population
The women were having IVF with genetically tested embryos across four countries, with a good ovarian reserve on average (AMH around 3 ng/ml or 21 pmol). The results were not broken down by age, so they describe what a euploid embryo does once you have it, rather than what happens to an older or younger woman specifically. However, we know from other studies that once a euploid embryo exists, the way it performs is generally age independent.
Anyone told they have recurrent implantation failure after two or three failed euploid transfers.
Anyone with a known, treatable factor that was excluded here (a hydrosalpinx, a polyp or fibroid in the cavity, adenomyosis, a thin lining, a karyotype problem). And a woman with only one or two euploid embryos cannot count on the averages the way this group could.
Methodology
- Every woman had already failed to conceive after three consecutive euploid transfers, with no known cause. Donor eggs, surrogates, uterine pathology, a thin lining, karyotype problems and mosaic embryos were all excluded.
- The researchers recorded the outcome of the fourth transfer, and the fifth where it happened: a positive test, a clinical pregnancy, and a live birth. They counted each euploid embryo transferred, not each cycle, so attempts could be compared directly.
- They repeated the analysis with several groups removed (Day 7 embryos, higher BMI, donor sperm, double transfers). The result held every time.
What they found
Failure doesn't become "more inevitable" each time you transfer
Live birth was 40% at the fourth attempt and 53.3% at the fifth, with no significant difference and no downward trend. Three failures in a row does not make the fourth more likely to fail.
The fourth performs like the first
In the group whose first three transfers were tracked at the same clinic, the fourth euploid embryo gave the same live birth rate as the first. Each euploid embryo is a fresh chance.
True recurrent implantation failure is rare
Because the rate never falls away, the researchers put the prevalence of unexplained RIF under 2%. An earlier study (Pirtea 2021) had put it under 5% after three transfers, while this study pushes it even lower.
A euploid embryo is still not a guarantee
Each euploid transfer fails 40 to 50% of the time, and not just because of chromosomal issues. This is the black box of implantation (Cimadomo 2023): the endometrium, timing and receptivity all play a part, and several of them can be influenced.
What it means for older women
The chance of making a euploid embryo falls steeply with age. The chance of a euploid embryo implanting, once you have it, does not. This study says: given enough euploid embryos, the large majority of women can successfully carry a baby, and repeated failures are usually chance rather than a fault in the body.
The challenge for older women is that they may not have enough euploid embryos for those averages to work in their favour. A single euploid may take several cycles to produce. When embryos are few, the answer is not to repeat the same transfer and hope, but to make each one count: optimise every evidence-based factor, from the cycle type to the lining to timing.
Evidence strength
This is large, multi-centre, real-world data, and every sensitivity analysis agreed. It is retrospective though, and the women who continued to a fourth transfer may differ from those who stopped. The evidence is strong enough to stop treating recurrent implantation failure as a common diagnosis and to stop chasing unproven fixes for it, but not to promise any individual a 98 to 99% outcome.
Things you can discuss with your doctor
- Do not accept recurrent implantation failure as a dead end after two or three failed euploid transfers. Based on this study, it is uncommon.
- Ask for the known, treatable factors to be checked before you even begin your first transfer: the lining, a hydrosalpinx, the uterine cavity, thyroid function, and parental karyotype where failures are unexplained.
- Where euploid embryos are limited, optimise everything you can before, during and after each transfer.
Source: Gill P, Ata B, Arnanz A, et al. Does recurrent implantation failure exist? Prevalence and outcomes of five consecutive euploid blastocyst transfers in 123,987 patients. Human Reproduction, 2024;39(5):974-980.
Written by
Michelle Bourke
Founder of Better IVF. I went through IVF over 38 myself, and I write these guides to be the clear, properly-sourced resource I wish I'd had, more honest than the forums and deeper than the clinic pages.