Associations between Preconception Phthalate Exposure and Infertility Treatment Outcomes among Couples Undergoing In Vitro Fertilization

Abstract

Background/Aim: Phthalates are implicated as reproductive toxicants in animal models and human populations. We modeled associations between couples’ preconception phthalate exposures and in vitro fertilization (IVF) outcomes.Methods: Women (n=56) and their male partners (n=43) undergoing IVF were enrolled in a prospective cohort investigation of environmental exposures and reproductive outcomes. Participants provided urine samples (fasting for women) on the day of oocyte retrieval. Urine was analyzed for monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), mono-n-pentyl phthalate (MPP), mono-n-hexyl phthalate (MHxP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-isononyl phthalate (MiNP), mono-isodecyl phthalate (MiDP), monocyclohexyl phthalate (MCHP), and monobenzyl phthalate (MBzP) via liquid chromatography-tandem mass spectrometry (Agilent LC 1260-AB Sciex 5500). Modified Poisson regression models, were used to assess associations between IVF outcomes and individual urinary phthalates among women and men separately, and simultaneously in couples, adjusted for age, body mass index (for women), and cigarette smoking. Results: Individual partner models showed higher likelihoods of pregnancy and live birth associated with greater concentrations of several urinary phthalates, albeit without statistical significance, with the exception of men’s MEHP and pregnancy [RR=0.53 (95%CI: 0.24-1.17). However, most urinary phthalates were associated with lower chances of pregnancy and live birth among couples. A doubling in women’s MBP was associated with a 43% [RR=0.57 (95%CI: 0.36-0.91)] lower likelihood of a pregnancy and a 46% [RR=0.54 (95%CI: 0.27-1.08)] lower likelihood of a live birth, adjusted for the male partner. Doublings in men’s MEHP andMEP were associated with 66% [RR=0.34 (95% CI: 0.16-0.72)] and 28% [RR=0.72 (95% CI: 0.52-1.01)] lower likelihoods of a pregnancy, respectively, adjusted for the female partner. Conclusions: Greater urinary MEP, MBP, and MEHP were associated with lower probabilities of pregnancy and live birth among couples undergoing IVF. The results suggest that greater phthalate exposure in couples may be deleterious to IVF.