Urinary phthalates, serum omega-3 fatty acids and ovarian reserve among women seeking fertility treatment.

Exposure to phthalates is common and difficult to avoid. However, intake of long-chain n-3 polyunsaturated fatty acids (n3PUFAs) may ameliorate negative effects on ovarian reserve by exposure to phthalates as both are involved in key processes of ovarian function. Among 139 women attending a fertility center in the Environment and Reproductive Health (EARTH) Study (2004-2017), we evaluated whether associations between urinary phthalate biomarkers and antral follicle count (AFC) were modified by tertiles of serum α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We used Poisson regression (for individual phthalate biomarkers) and quantile Q-computation (for mixtures) models adjusted for age, body mass index, prior smoking, number of urine samples and urinary specific gravity. We found that serum EPA + DHA levels modified the negative association of urinary phthalate biomarkers mixture with mean AFC (P for interaction = 0.23); sum of di(2-ethylhexyl) phthalate metabolites (∑DEHP) had the strongest effect modification (P interaction = 0.01). Specifically, phthalate biomarkers mixture and ∑DEHP were inversely related with AFC only among women in the low (P trend = 0.03 and < 0.001, respectively) and middle (P trend = 0.07 and 0.002) tertiles of serum EPA + DHA, but not among women in the high tertile (P trend = 0.56 and 0.93). No effect modifications were found by serum ALA. These findings suggest certain serum n3PUFAs may attenuate effects of phthalate exposure on ovarian reserve marker. Such interaction points toward select n3PUFAs as key modifiers of phthalate toxicity on ovarian health with potential implications for other women's reproductive health endpoints.