Elevated homocysteine linked to implantation failure in first embryo transfer

Women with elevated blood levels of homocysteine who had the amino acid measured more than a year before their first embryo transfer showed a higher rate of implantation failure, according to a retrospective study published in BMC Nutrition. The researchers emphasize that the findings are hypothesis-generating and require confirmation before any clinical application.

Homocysteine has previously been associated with adverse pregnancy outcomes, but its relationship with implantation failure in a first embryo transfer, and with endometrial characteristics, remained unclear. The study also examined whether nutritional supplementation was linked to these outcomes.

The analysis drew on 1770 participants undergoing their first embryo transfer between January 2015 and May 2025 who did not have established risk factors for implantation failure. Of these, 589 had homocysteine measured before transfer and were included in the analysis. The primary outcome was implantation failure.

In the overall cohort, and in patients whose homocysteine was measured within one year before transfer, implantation failure rates did not differ between patients with levels of 8 micromoles per liter or above and those below that threshold. The picture changed in the subgroup measured more than one year before transfer: patients with homocysteine at or above 8 micromoles per liter had an implantation failure rate of 53.4 percent, compared with 36.5 percent in those below the threshold, a difference the authors report as statistically significant.

In that same subgroup, elevated homocysteine was also associated with a lower prevalence of type A endometrium on the day of the hCG trigger, at 76.3 percent versus 93.8 percent, along with lower implantation rates of 32.8 percent versus 49.0 percent and lower clinical pregnancy rates of 46.6 percent versus 63.5 percent. The association with implantation failure remained significant after multivariable adjustment, with an adjusted odds ratio of 1.3 and a 95 percent confidence interval of 1.1 to 1.6.

Across the overall cohort, homocysteine at or above 8 micromoles per liter was also associated with a lower prevalence of type A endometrium on the hCG trigger day, with an adjusted odds ratio of 0.5 and a 95 percent confidence interval of 0.2 to 0.9.

Methylcobalamin supplementation was more common among patients with elevated homocysteine in the overall cohort and in the subgroup measured within one year of transfer, both after homocysteine measurement and before transfer, with all reported comparisons reaching statistical significance. This pattern was not observed in the subgroup measured more than one year before transfer. Among patients with homocysteine at or above 8 micromoles per liter, nutritional supplementation was positively linked to a type A endometrial pattern, with an adjusted odds ratio of 2.9 and a 95 percent confidence interval of 1.2 to 6.7.

The authors conclude that in patients whose homocysteine was measured more than one year before transfer, elevated levels were associated with implantation failure and a lower likelihood of a type A endometrium, while nutritional supplementation was associated with a higher prevalence of the type A endometrial pattern even among patients with elevated homocysteine. As a retrospective analysis of a single cohort, the study identifies associations rather than demonstrating causal effects, and the authors state explicitly that the findings require confirmation before clinical application.

Subject of Research: The association between homocysteine levels and implantation failure in first embryo transfer

Article Title: Associations of homocysteine levels and implantation failure in the first embryo transfer: a retrospective study

Article References: Li, Y., Wang, W., Lin, H., Ji, X., Fu, S., Zhu, L., Zhang, S., Zhang, Q., Chiu, P. C. N., Li, Y., & Chen, H. (2026). Associations of homocysteine levels and implantation failure in the first embryo transfer: a retrospective study. BMC Nutrition. https://doi.org/10.1186/s40795-026-01530-x

Image Credits: AI Generated

DOI: 10.1186/s40795-026-01530-x

Keywords: homocysteine, implantation failure, embryo transfer, endometrium, fertility, methylcobalamin, retrospective study, clinical pregnancy, BMC Nutrition, reproductive medicine, Associations, levels