The association of urinary phthalate monoester concentrations with measures of ovarian reserve among patients undergoing fertility treatments

Abstract

To determine the association of urinary phthalate metabolite concentrations with measures of ovarian reserve. Prospective cohort, 201 women undergoing fertility treatment. Urinary concentrations of 7 phthalate (P) metabolites [mono(2-ethylhexyl)-P (MEHP), monobutyl-P (MBP), monoethyl-P (MEP), monobenzyl-P (MBzP), mono(2-ethyl-5-hydroxyhexyl)-P (MEHHP), mono(2-ethyl-5-oxohexyl)-P (MEOHP), and mono(2-ethyl-5-carboxypentyl)-P (MECPP)] were measured using solid-phase extraction, high performance liquid chromatography, isotope dilution tandem mass spectrometry. Transvaginal ultrasonography was used to determine the ovarian volume and antral follicle count (AFC). Day-3 FSH was measured in the serum. Poisson, linear, and logistic regression were used to evaluate the association of urinary specific-gravity (SG) adjusted phthalate concentrations with measures of ovarian reserve, adjusted for age. SG-MEHP was negatively associated with the number of follicles (p-trend: 0.03), with an average decrease of 21% (95%CI:−37%,−2%; P=0.03) and 19% (95%CI:−34%,−1%; P=0.04) in the number of follicles for the highest and middle tertiles of SG-MEHP, respectively, compared to the lowest one. SG-MEOHP and SG-MEP were also negatively associated with the number of follicles (p-trend: 0.1). The middle and highest tertiles of SG-MEHP were associated with an increased odds of an AFC<15 (OR: 3.2, 95%CI:1.2-8.6, and OR: 4.2, CI:1.5-12.4, respectively). Similarly, the highest tertile of SG-MEOHP was associated with an increased odds of AFC<15 (OR: 13.1, 95%CI:1.1-8.8). Phthalate metabolites were detected in urine from >70% of participating women. There was a trend of lower AFC with higher levels of phthalates (mainly DEHP metabolites). Based on animal data showing that some phthalates are endocrine disruptors through altered endogenous steroid hormone signaling, there is potential concern in humans of an accelerated follicle loss and reproductive aging.