Pre-pregnancy exposure to organophosphate esters was associated with adverse ovarian reserve and in vitro fertilization-embryo transfer outcomes in women of reproductive age

Organophosphate esters (OPEs) are classified as emerging environmental pollutants with reproductive and endocrine toxicities, whereas studies on the relationship between OPEs exposure and reproductive health in women of childbearing age are limited. This study investigates the relationship between serum OPEs exposure and in vitro fertilization-embryo transfer (IVF-ET) outcomes, along with the mediating role of ovarian reserve indicators from the cohort of women undergoing assisted reproductive treatment in Henan Province, China. We included 555 women undergoing IVF-ET treatment. Twelve OPEs in serum were measured using UPLC-MS/MS. Seven OPEs were detected in over 50 % of samples, with geometric mean concentrations ranging from 0.01 to 1.23 μg/g lw. Intermediate and clinical IVF-ET outcomes, along with ovarian reserve function, were ascertained by embryologists and clinicians following standardized protocols. Generalized Linear Model (GLM) indicated that EHDPP was negatively associated with two-pronuclear count (2PNC) ( β = −0.17, 95 % CI : −0.32, −0.03), metaphase II oocyte count (MIIC) ( β = −0.15, 95 % CI : −0.28, −0.01), fertilization count (FC) ( β = −0.17, 95 % CI : −0.30, −0.03), usable blastocyst count (UBC) ( β = −0.23, 95 % CI : −0.45, −0.00) and usable blastocyst rate (UBR) ( β = −0.59, 95 % CI : −1.07, −0.11). Bayesian Kernel Machine Regression (BKMR) identified EHDPP as the major contributor to the mixed exposure effect of OPEs. Serum EHDPP was positively correlated with progesterone and testosterone. Additionally, testosterone significantly mediated the associations between EHDPP and various IVF-ET outcomes, with mediation proportions ranging from 8.10 % to 18.70 %. Our findings demonstrate that pre-pregnancy exposure to OPEs may be associated with adverse IVF-ET outcomes in women of reproductive age. EHDPP is the major contributor to the mixed exposure effect. The testosterone mediates the adverse effects of EHDPP exposure on IVF-ET outcomes. • Reproductive-aged women in this study showed higher OPEs exposure than other regions. • Pre-pregnancy exposure to OPEs was associated with adverse IVF-ET outcomes. • EHDPP was the major contributor to the mixed exposure effect of OPEs. • Testosterone mediated the adverse effects of EHDPP on IVF-ET outcomes.