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Research article - Peer-reviewed, 2022

Association between chemical mixtures and female fertility in women undergoing assisted reproduction in Sweden and Estonia

Bellavia, Andrea; Björvang, Richelle D.; Roos, Kristine; Sjunnesson, Ylva; Hallberg, Ida; Holte, Jan; Pikki, Anne; Lenters, Virissa; Portengen, Lützen; Koekkoek, Jacco; Lamoree, Marja; Van Duursen, Majorie; Vermeulen, Roel; Salumets, Andres; Velthut-Meikas, Agne; Damdimopoulou, Pauliina


Objective: Women of reproductive age are exposed to ubiquitous chemicals such as phthalates, parabens, and per -and polyfluoroalkyl substances (PFAS), which have potential endocrine disrupting properties and might affect fertility. Our objective was to investigate associations between potential endocrine-disrupting chemicals (EDCs) and female fertility in two cohorts of women attending fertility clinics.Methods: In a total population of 333 women in Sweden and Estonia, we studied the associations between chemicals and female fertility, evaluating ovarian sensitivity index (OSI) as an indicator of ovarian response, as well as clinical pregnancy and live birth from fresh and frozen embryo transfers. We measured 59 chemicals in follicular fluid samples and detected 3 phthalate metabolites, di-2-ethylhexyl phthalate (DEHP) metabolites, 1 paraben, and 6 PFAS in > 90% of the women. Associations were evaluated using multivariable-adjusted linear or logistic regression, categorizing EDCs into quartiles of their distributions, as well as with Bayesian Kernel Ma-chine Regression.Results: We observed statistically significant lower OSI at higher concentrations of the sum of DEHP metabolites in the Swedish cohort (Q4 vs Q1, beta =-0.21, 95% CI:-0.38,-0.05) and methylparaben in the Estonian cohort (Q3 vs Q1, beta =-0.22, 95% CI:-0.44,-0.01). Signals of potential associations were also observed at higher concentrations of PFUnDA in both the combined population (Q2 vs. Q1,beta =-0.16, 95% CI-0.31,-0.02) and the Estonian population (Q2 vs. Q1,beta =-0.27, 95% CI-0.45,-0.08), and for PFOA in the Estonian population (Q4 vs. Q1, beta =-0.31, 95% CI-0.61,-0.01). Associations of chemicals with clinical pregnancy and live birth presented wide confidence intervals.Conclusions: Within a large chemical mixture, we observed significant inverse associations levels of DEHP me-tabolites and methylparaben, and possibly PFUnDA and PFOA, with OSI, suggesting that these chemicals may contribute to altered ovarian function and infertility in women.


Endocrine disruptors; parabens; phthalates; environmental mixtures; ovarian sensitivity index; female fertility

Published in

Environmental Research
2022, volume: 216, number: Part 1, article number: 114447

Authors' information

Bellavia, Andrea
Utrecht University
Björvang, Richelle D.
Karolinska Institute
Roos, Kristine
Tallinn University of Technology
Swedish University of Agricultural Sciences, Department of Clinical Sciences
Swedish University of Agricultural Sciences, Department of Clinical Sciences
Holte, Jan
Uppsala University
Pikki, Anne
Uppsala University
Lenters, Virissa
Utrecht University
Portengen, Lützen
Utrecht University
Koekkoek, Jacco
Vrije Universiteit Amsterdam
Lamoree, Marja
Vrije Universiteit Amsterdam
Van Duursen, Majorie
VU University Amsterdam
Vermeulen, Roel
Utrecht University
Salumets, Andres
University of Tartu
Velthut-Meikas, Agne
Tallinn University of Technology
Damdimopoulou, Pauliina
Karolinska Institute

UKÄ Subject classification

Environmental Sciences
Obstetrics, Gynecology and Reproductive Medicine

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