TY - JOUR
T1 - Association between chemical mixtures and female fertility in women undergoing assisted reproduction in Sweden and Estonia
AU - Bellavia, Andrea
AU - Zou, Runyu
AU - Björvang, Richelle D
AU - Roos, Kristine
AU - Sjunnesson, Ylva
AU - Hallberg, Ida
AU - Holte, Jan
AU - Pikki, Anne
AU - Lenters, Virissa
AU - Portengen, Lützen
AU - Koekkoek, Jacco
AU - Lamoree, Marja
AU - Van Duursen, Majorie
AU - Vermeulen, Roel
AU - Salumets, Andres
AU - Velthut-Meikas, Agne
AU - Damdimopoulou, Pauliina
N1 - Funding Information:
This project was funded by the European Union's Horizon 2020 research and innovation program (FREIA, grant no. 825100 ), the Estonian Research Council (grant PRG1076 and PSG608 ), Horizon 2020 innovation grant (ERIN, grant no. EU952516 ), and the Enterprise Estonia (grant no. EU48695 ). The project also received funding from Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS) (Grants No. 942-2015-476; 2015–00623 and 2013–01966 ) and the Dutch Research Council ( NWO ) (EXPOSOME-NL project number 024.004.017 ).
Funding Information:
This project was funded by the European Union's Horizon 2020 research and innovation program (FREIA, grant no. 825100), the Estonian Research Council (grant PRG1076 and PSG608), Horizon 2020 innovation grant (ERIN, grant no. EU952516), and the Enterprise Estonia (grant no. EU48695). The project also received funding from Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS) (Grants No. 942-2015-476; 2015–00623 and 2013–01966) and the Dutch Research Council (NWO) (EXPOSOME-NL project number 024.004.017). We thank Dr. Christian Lindh, from Lund University, for sharing the PFAS measurement data from the Swedish cohort. We are grateful to all study participants for donating their samples for research.
Publisher Copyright:
© 2022 The Authors
PY - 2023/1/1
Y1 - 2023/1/1
N2 - 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 Machine Regression.RESULTS: We observed statistically significant lower OSI at higher concentrations of the sum of DEHP metabolites in the Swedish cohort (Q4 vs Q1, β = -0.21, 95% CI: -0.38, -0.05) and methylparaben in the Estonian cohort (Q3 vs Q1, β = -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, β = -0.16, 95% CI -0.31, -0.02) and the Estonian population (Q2 vs. Q1, β = -0.27, 95% CI -0.45, -0.08), and for PFOA in the Estonian population (Q4 vs. Q1, β = -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 metabolites and methylparaben, and possibly PFUnDA and PFOA, with OSI, suggesting that these chemicals may contribute to altered ovarian function and infertility in women.
AB - 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 Machine Regression.RESULTS: We observed statistically significant lower OSI at higher concentrations of the sum of DEHP metabolites in the Swedish cohort (Q4 vs Q1, β = -0.21, 95% CI: -0.38, -0.05) and methylparaben in the Estonian cohort (Q3 vs Q1, β = -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, β = -0.16, 95% CI -0.31, -0.02) and the Estonian population (Q2 vs. Q1, β = -0.27, 95% CI -0.45, -0.08), and for PFOA in the Estonian population (Q4 vs. Q1, β = -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 metabolites and methylparaben, and possibly PFUnDA and PFOA, with OSI, suggesting that these chemicals may contribute to altered ovarian function and infertility in women.
KW - Endocrine disruptors
KW - environmental mixtures
KW - female fertility
KW - ovarian sensitivity index
KW - parabens
KW - phthalates
UR - https://www.scopus.com/pages/publications/85139834626
U2 - 10.1016/j.envres.2022.114447
DO - 10.1016/j.envres.2022.114447
M3 - Article
C2 - 36181890
SN - 0013-9351
VL - 216
SP - 1
EP - 14
JO - Environmental Research
JF - Environmental Research
IS - Part 1
M1 - 114447
ER -