If several euploid embryo transfers do not result in pregnancy, can another transfer still work?

What did this research set out to answer?

When several embryo transfers do not result in pregnancy, patients may wonder whether there is an underlying problem preventing embryos from implanting. This is sometimes referred to as recurrent implantation failure.

Researchers wanted to understand what happens after three euploid embryo transfers have not resulted in pregnancy, when other known factors that could interfere with implantation have been ruled out.

Specifically, they looked at whether a fourth or fifth euploid embryo still had a meaningful chance of resulting in pregnancy and live birth.

What did the researchers do?

Researchers conducted an international, multicenter review of IVF treatment data collected between 2012 and 2022.

They screened data from 123,987 patients and identified 105 patients who had not achieved a positive pregnancy test after the transfer of three euploid blastocysts and then underwent at least one additional euploid embryo transfer.

Patients with known factors that could affect implantation, including certain uterine abnormalities, adenomyosis, and other clinical conditions, were excluded so researchers could focus on otherwise unexplained implantation failure.

The researchers then evaluated pregnancy and live birth outcomes after the fourth and fifth euploid blastocyst transfers.

What did the research find?

Even after three euploid embryos had failed to implant, later euploid embryos continued to have a meaningful chance of resulting in a live birth.

Researchers found:

• -40% live birth rate with the fourth euploid blastocyst
• -53.3% live birth rate with the fifth euploid blastocyst

The live birth rate did not significantly decrease with these later transfers.

When these results were combined with previously published outcomes for the first three transfers from the same center, the cumulative live birth rate after five euploid blastocyst transfers reached 98.1%.

Based on these findings, the researchers estimated that unexplained recurrent implantation failure may occur in fewer than 2% of patients once other known causes of implantation failure have been excluded.

What does this mean for patients?

Having several unsuccessful embryo transfers can make it feel as though another embryo is unlikely to work. This study suggests that this is not necessarily the case when chromosomally normal embryos are being transferred and other known causes of implantation failure have been ruled out. A fourth or even fifth euploid embryo may still have a meaningful chance of resulting in a live birth.

The results also suggest that recurrent implantation failure without an identifiable cause may be less common than previously thought.  

These findings should not be interpreted to mean that every patient should automatically continue with additional embryo transfers. The study was retrospective, and the patients who continued treatment after three unsuccessful transfers may differ from those who stopped treatment. The number of patients reaching later transfers was also relatively small.

Your care team can review whether there are factors that should be evaluated after unsuccessful transfers and discuss whether another embryo transfer makes sense for your individual situation.

Gill, P., Ata, B., Arnanz, A., Cimadomo, D., Vaiarelli, A., Fatemi, H. M., Ubaldi, F. M., Garcia-Velasco, J. A., & Seli, E. (2024). Does recurrent implantation failure exist? Prevalence and outcomes of five consecutive euploid blastocyst transfers in 123,987 patients. Human Reproduction, 39(5), 974-980. https://doi.org/10.1093/humrep/deae040