Preconception exposure to perfluoroalkyl and polyfluoroalkyl substances and couple fecundity: A couple-based exploration

Numerous studies have examined the adverse health effects of perfluoroalkyl and polyfluoroalkyl substances (PFAS) but it remains unclear whether preconception exposure to PFAS affects couple fecundity. This prospective preconception cohort study with 936 Chinese couples aimed to comprehensively assess the effects of PFAS on couple fecundity [measured by the time to pregnancy (TTP)] and infertility (i.e., TTP > 12 menstrual cycles) with a focus on the effects of partner-specific exposure and joint-effects of couple-based exposure. Twenty-five PFAS were quantified in plasma from each partner, including seven branched isomers, two chlorinated polyfluoroalkyl ether sulfonic acids, four emerging PFAS replacements [i.e., 6:2 fluorotelomer phosphate diester (6:2 diPAP) and three short-chain alternatives: perfluoro-n-butanoicacid, perfluorobutane sulfonate and perfluoroheptanoic acid (PFHpA)]. Using a two-phase regression approach composed of elastic net regression and principal component analysis, we found that exposure to 6:2 diPAP and PFHpA rather than legacy PFAS in women and the couple-based exposure patterns characterized by high level of female 6:2 diPAP were significantly associated with reduced couple fecundity, which was independent of the adjustment of co-exposed PFAS homogenous from both partners. For example, a ln unit increase in female 6:2 diPAP was associated with 15 % [fecundity odds ratio (FOR) = 0.85, 95 %CI: 0.76, 0.96)] lower odds of couple fecundability (i.e., longer TTP) and 45 % increased risk of infertility [OR = 1.45 (95 %CI: 1.16, 1.81)], respectively. While most PFAS in men were not associated with couple fecundity, certain PFAS (e.g., perfluorohexane sulfonic acid) in men were negatively associated with infertility risk. However, the combined effects of PFAS mixture in couples were nonsignificant. Our findings suggest that PFAS in men and women may exert different impacts on couple fecundity. Preconception exposure to 6:2 diPAP and PFHpA in women may have the potential to impair couple fecundity.