Background: Phthalate exposures have been shown to be inversely associated with reproductive success among women undergoing assisted reproductive technology (ART). However, the underlying mechanisms are unknown.
Objectives: To explore blood coagulation function as the mediating role of associations between exposure to phthalates and ART outcomes.
Methods: A total of 735 women from the Tongji Reproductive and Environmental (TREE) study were included. Urine samples collected at recruitment were quantified for 8 phthalate metabolites, and blood clotting time and platelet indices were also determined. Generalized linear regression, logistic regression, weighted quantile sum (WQS) regression, or Bayesian kernel machine regression (BKMR) models were applied to investigate the associations among individual and mixture of phthalate metabolites, blood coagulation parameters, and ART outcomes. The mediation role of blood coagulation parameters was estimated by mediation analysis.
Results: Mono-n-butyl phthalate (MBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), and molar sum of di(2-ethylhexyl) phthalate metabolites (∑DEHP) were positively associated with platelet indices. Phthalate metabolite mixture was also positively associated with platelet count (PLT), mean platelet volume (MPV), and plateletcrit (PCT), whereas inversely associated with international normalized ratio (INR). Meanwhile, PLT and PCT were inversely associated with the odds of implantation success and live birth, while prothrombin time and INR were positively associated with the odds of implantation success. Mediation analyses showed indirect effects of above-mentioned phthalate metabolites and phthalate mixture on the odds of implantation success and live birth through PLT or PCT, with the proportion mediated ranging from 3.44% to 8.96%.
Conclusions: Phthalates may increase the risks of ART failure through enhancing blood coagulation function. More studies are warranted to verify the findings.
Keywords: Assisted reproductive technology; Blood clotting time; Mediation analysis; Phthalate; Platelet indices.
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