Associations Between Levels Of Bisphenols Exposure And Diminished Ovarian Reserve Among Women From An Infertility Clinic

Objective: In recent years,the effect of environmental pollutants on female reproductive health has been raised concern by an increasing number of studies.Some studies have shown a global rise of infertility during the past years.The causes of infertility are complex,including sociodemographic risk factors such as older childbearing age and low education level,lifestyle risk factors such as smoking and excessive drinking,and pathological risk factors such as tubal factors and diminished ovarian reserve(DOR).DOR refers to the decrease in the number of follicles and / or oocyte quality retained in the ovary.DOR affects about 10 % of women seeking assisted reproductive technology(ART).Even though the etiology of DOR is still largely unknown,genetic and environmental factors interact in a way that contributes synergistically to its heterogeneity.Endocrine-disrupting chemicals(EDCs)may be one of important environmental factors.Bisphenol A(BPA)is one of the most common EDCs.As a raw material for polycarbonate plastics and epoxy resins,BPA is widely present in a variety of daily necessities.The general population can be inevitably exposed to BPA for a long time through ingestion,inhalation and dermal contact.Toxicology studies have demonstrated that BPA can cause ovarian toxicity,manifested as altered ovarian steroidogenesis,inhibited follicle growth,and disrupted oocyte maturation.As a result,BPA has been banned in many countries,leading to the increasing usage of its substitutes such as bisphenol F(BPF)and bisphenol S(BPS).Recently,both in vivo and in vitro studies have suggested that BPF and BPS have even stronger ovarian toxicity than BPA.However,existing human evidence on ovarian reserve have predominantly focused on BPA,with inconsistent results yield.Epidemiology studies on the effects of BPF and BPS exposure on ovarian reserve have not been reported.Therefore,we conducted a hospital-based cross-sectional study to examine the relationship between urinary levels of bisphenols exposure and ovarian reserve in women from a fertility clinic in Northern China.We measured BPA,BPF and BPS in urine,and examined the associations between urinary bisphenols(BPA,BPF and BPS)and indicators of ovarian reserve(AFC,AMH,FSH and E2)and DOR.The dose-response relationships were further explored by restricted cubic spline(RCS)models.Our results contributed to the evidence for adverse ovarian reserve exerted by exposure to environmental bisphenols in female population.Method: Hospital-based cross-sectional study was conducted.Women were recruited from a fertility clinic in Shenyang.Written informed consent was obtained from all participants.Trained staff used a pre-structured questionnaire to gather demographic characteristics and lifestyles from participants at recruitment.Urine samples of women were collected to measure BPA,BPF and BPS.Electronic medical records were used to obtained reproductive information including primary infertility diagnosis and indicators of ovarian reserve.Results: 1.A total of 111 women were included in this study.The detection rates of BPA,BPF and BPS were 100 %,91.1 % and 60.0 %,respectively.The median exposure levels of BPA,BPF and BPS in urine were 4.33,2.86 and 0.28μg / L,respectively.2.We observed inverse associations between urinary BPA and BPS level and AFC(BPA: β =-0.015,95% CI:-0.024,-0.005,P=0.003;BPS: β =-0.109,95% CI:-0.195,-0.022,P=0.014).And compared with the lower group,the AFC in the higher BPF group was significantly decreased(β =-0.108,95% CI:-0.209,-0.008,P=0.034).3.We found an inverse association between urinary BPS level and AMH(β =-0.287,95% CI:-0.505,-0.070,P=0.010),and the dose-response relationship was further confirmed in the RCS model.4.Higher levels of BPA and BPS exposures were associated with increased risk of DOR(BPA: OR=7.112,95%CI: 1.247-40.588,P=0.027;BPS: OR=6.851,95%CI:1.241-37.818,P=0.027).Conclusion: 1.Women from a fertility clinic can be generally exposed to bisphenols,especially BPA and BPF.2.The AFC of higher BPF group decreased,and BPS was negatively correlated with AMH.3.High levels of BPA and BPS can decrease AFC,which is a risk factor for DOR.