Follicular fluid and blood levels of persistent organic pollutants and reproductive outcomes among women undergoing assisted reproductive technologies

Richelle D Björvang,Ida Hallberg,Anne Pikki,Lars Berglund,Matteo Pedrelli,Hannu Kiviranta,Panu Rantakokko,Päivi Ruokojärvi,Christian H Lindh,Matts Olovsson,Sara Persson,Jan Holte,Ylva Sjunnesson,Pauliina Damdimopoulou

doi:10.1016/j.envres.2021.112626

Abstract

Persistent organic pollutants (POPs) are industrial chemicals resistant to degradation and have been shown to have adverse effects on reproductive health in wildlife and humans. Although regulations have reduced their levels, they are still ubiquitously present and pose a global concern. Here, we studied a cohort of 185 women aged 21–43 years with a median of 2 years of infertility who were seeking assisted reproductive technology (ART) treatment at the Carl von Linné Clinic in Uppsala, Sweden. We analyzed the levels of 9 organochlorine pesticides (OCPs), 10 polychlorinated biphenyls (PCBs), 3 polybrominated diphenyl ethers (PBDEs), and 8 perfluoroalkyl substances (PFASs) in the blood and follicular fluid (FF) samples collected during ovum pick-up. Impact of age on chemical transfer from blood to FF was analyzed. Associations of chemicals, both individually and as a mixture, to 10 ART endpoints were investigated using linear, logistic, and weighted quantile sum regression, adjusted for age, body mass index, parity, fatty fish intake and cause of infertility. Out of the 30 chemicals, 20 were detected in more than half of the blood samples and 15 in FF. Chemical transfer from blood to FF increased with age. Chemical groups in blood crossed the blood-follicle barrier at different rates: OCPs > PCBs > PFASs. Hexachlorobenzene, an OCP, was associated with lower anti-Müllerian hormone, clinical pregnancy, and live birth. PCBs and PFASs were associated with higher antral follicle count and ovarian response as measured by ovarian sensitivity index, but also with lower embryo quality. As a mixture, similar findings were seen for the sum of PCBs and PFASs. Our results suggest that age plays a role in the chemical transfer from blood to FF and that exposure to POPs significantly associates with ART outcomes. We strongly encourage further studies to elucidate the underlying mechanisms of reproductive effects of POPs in humans.

Highlights

Infertility is a global issue with one in six couples experiencing involuntary childlessness at some point in their life
Our results suggest that age plays a role in the chemical transfer from blood to follicular fluid (FF) and that exposure to persistent organic pollutant (POP) significantly associates with assisted reproductive technology (ART) outcomes
Despite decades since restrictions in Sweden, lipophilic POPs are still widely detected in blood and FF of women living in Sweden

Summary

Introduction

Infertility is a global issue with one in six couples experiencing involuntary childlessness at some point in their life. The current prev alence for this is 8–12% worldwide for women aged 20–44 (European Society of Human Reproduction and Embryology, 2020). In 10–20% of cases, it cannot be explained by currently known factors (European Society of Human Reproduction and Embryology, 2020). In addition to biological factors, several lifestyle factors have been shown to be associated with infertility including age (Crawford and Steiner, 2015; Nugent and Balen, 2001; Society of Obstreticians and Gynecologists of Canada, 2012), smoking (American Society for Reproductive Medicine, 2006), and body mass index (Gesink Law et al, 2007). We and others have shown that persistent organic pollutants (POPs) are associated with lower biomarkers of ovarian reserve, longer time-to-pregnancy, and higher odds for infertility (Bjorvang et al, 2020, 2021a; Buck Louis et al, 2013; Cohn et al, 2011; Pan et al, 2019)

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