Associations of urinary metabolite concentrations of phthalates and their alternatives with reproductive outcomes among women receiving in vitro fertilization: A repeated measurement analysis.

Background: Studies suggest that phthalates (PAEs) may disrupt female reproductive health, but few have explored repeated measurements of PAE and their alternative exposure and their joint impact on reproductive outcomes.

Objectives: To evaluate the associations of repeatedly measured urinary levels of PAE and their alternative metabolites with reproductive outcomes in women receiving in vitro fertilization (IVF).

Methods: This study included 704 women undergoing IVF between February and October 2023 in Chongqing, China. Concentrations of 23 PAE and PAE alternative metabolites were determined in three urine samples of each participant collected at the IVF treatment appointment (visit 1) and during ovarian stimulation (visits 2 and 3). IVF outcomes were obtained from electronic medical records. Generalized linear models, generalized estimating equations, and quantile g computation (QGC) were applied to evaluate the relationships of individual metabolites and the mixture with the IVF outcomes.

Results: Health risk assessment indicated that 19.7 % of the participants had dibutyl phthalate exposure levels exceeding the safety threshold. Urinary concentrations of mono-(6-oxo-2-propylheptyl) phthalate [a metabolite of di-(2-propylheptyl) phthalate (DPHP)] and sum concentrations of DPHP metabolites (ΣDPHP) were related to decreased probability of good-quality embryos on day 3 (percent differences in each interquartile ratio-fold increase of the analyte concentrations ranged from -14.0 % to -15.2 %). These associations were more prominent during ovarian stimulation. QGC analyses also showed a negative association between the mixture and the probability of day 3 good-quality embryos, with ∑DPHP contributing the most.

Conclusions: Exposure to DPHP may impair embryo quality in women receiving IVF. The ovarian stimulation stage seems to be a sensitive period. Additional studies are needed to validate these results.