Phenol biomarker concentrations in human ovarian follicular fluid and the associations with in-vitro fertilization outcomes.

Background: Phenols are a family of short-lived endocrine disrupting chemicals found in a wide range of products and have drawn significant attention because of widespread human exposure and their potential adverse effects on reproductive health. Phenols have been widely detected in several human bodily fluids, particularly in urine and blood. However, there is limited data on phenols in human ovarian follicular fluid (FF). In addition, studies suggest associations between exposure to bisphenols and measures of infertility in humans. Nevertheless, the association of FF concentrations of bisphenols and female fertility has not been investigated.

Objectives: To quantify phenols in human ovarian FF, investigate correlations of phenol concentrations between FF and urine, evaluate trends over time, and explore any associations between FF concentrations of phenols and in-vitro fertilization (IVF) outcomes.

Methods: This analysis includes 143 women who enrolled in the Environment and Reproductive Health (EARTH) Study and underwent one IVF cycle between 2009 and 2015, with available, FF, urine and reproductive outcome data. FF concentrations of 2,4-dichloro-phenol (2,4DCP), 2,5-dichloro-phenol (2,5DCP), methyl-paraben (MPB), ethyl-paraben (EPB), propyl-paraben (PPB), butyl-paraben (BPB), bisphenol A (BPA), bisphenol S (BPS), bisphenol F (BPF), benzophenone-3 (BP3), triclosan (TCS) and triclorocarban (TCC) were quantified by isotope dilution tandem mass spectrometry. Generalized linear models were used to explore the associations between FF concentrations of bisphenols (in tertiles or dichotomized) and IVF outcomes, adjusting for confounders.

Results: Detection rates varied from high (79-95 %) for MPB, PPB and BPS, to moderate (44-65 %) for BPA, BP3 and TCS, to low (1-34 %) for 2,4DCP, 2,5DCP, EPB, BPB, BPF, TCC. Correlations between FF and urine were strong for BP3 (r = 0.86), moderate for MPB (r = 0.64) and PBP (r = 0.63), and weak for BPS (r = 0.21) and BPA (r = 0.12). FF BPA concentrations significantly decreased over time, whereas FF BPS concentrations increased. Most of the examined FF phenol biomarker concentrations were not related to early IVF outcomes (endometrial thickness, total and mature (MII) oocyte yield, fertilization rates). However, significant associations between PPB and endometrial thickness, and between BP3 and MII oocyte yield were noted, without these findings translating in any effects observed on pregnancy outcomes (implantation, clinical pregnancy and live birth).

Conclusions: We observed that most phenols were detected in FF and there were some correlations with urinary concentrations. We confirmed in FF that phenols such as BPA may be declining, while exposure to new replacements such as BPS are increasing. However, no overall associations were observed for the examined FF phenol biomarker concentrations with early IVF outcomes and pregnancy outcomes. Further research is needed to examine the potential associations of these phenols in FF, especially the newer ones that are on the rise.