Elevated maternal pre-transfer serum lipid peroxidation is associated with implantation failure and early pregnancy loss.

Abstract

Embryo implantation failure and early pregnancy loss remain significant challenges in assisted reproductive technology (ART). Lipid peroxidation is known to be involved in reproductive physiology. However, its role during the implantation window and its effects on post-embryo transfer outcomes remain incompletely understood. This translational study combined clinical and animal model research. Clinically, serum samples (n = 2040) and uterine fluid samples (n = 487) from patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles were analyzed using propensity score matching (PSM), univariate and multivariate logistic regression analysis, restricted cubic spline (RCS) analysis, and subgroup analysis. A murine model of lipid peroxidation was established by administering erastin during the implantation window to investigate its effects on endometrial receptivity and decidualization. Elevated serum levels of malondialdehyde (MDA) and non-heme iron were independently associated with recurrent implantation failure (RIF). Among patients without RIF, elevated pre-transfer serum levels of MDA, non-heme iron, 12-hydroxyeicosatetraenoic acid (12-HETE), and 15-HETE were associated with implantation failure and early pregnancy loss. Consistent with this, intrauterine MDA levels were significantly higher in patients with these pregnancy failures compared to those with ongoing pregnancy. Complementary murine studies supported these clinical observations, showing that elevated lipid peroxidation during the maternal implantation window was associated with impaired endometrial receptivity and decidualization. Elevated maternal lipid peroxidation is independently associated with RIF. In patients without RIF, it is similarly associated with implantation failure and early pregnancy loss. The endometrium appears particularly sensitive to this peroxidation, which may impair receptivity and decidualization. These support further investigation of redox-modulating strategies in ART.