Perfluoroalkyl and polyfluoroalkyl substances and measures of human fertility: a systematic review

Abstract

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are found widespread in the environment and humans. The relation of PFASs to fertility has now been examined in a relatively large number of epidemiologic studies and a synthesis is in order. The aim of this study was to assess the current human epidemiologic evidence on the association between exposure to PFASs and measures of human fertility, with particular emphasis on perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). Systematic literature searches were initially conducted in MEDLINE and EMBASE and subsequently in references and citations of included papers. Studies were included if they assessed exposure to PFASs in biological samples in relation to reproductive hormones, semen characteristics, or time to pregnancy (TTP). Study characteristics and results were abstracted to predefined forms, and the studies were assessed for the risk of bias and confounding. Sixteen studies investigated the association between PFAS exposure in men and semen parameters, reproductive hormone levels, or TTP. There was a lack of consistent results among the numerous investigated exposure-outcome combinations. However, subtle associations between higher PFOS and lower testosterone or abnormal semen morphology cannot be excluded. Eleven studies assessed the association between PFAS exposure in women and TTP or reproductive hormones levels. Four of eight studies found prolonged TTP with higher PFOS or PFOA, but only one study found an association when restricting to nulliparous women. In men, there is little evidence of an association between PFAS exposure and semen quality or levels of reproductive hormones. For PFOS and PFOA, the literature indicates an association with female fecundability in parous women, which is most likely not causal.

Keywords:

• Epidemiology
• fecundability
• fecundity
• fertility
• humans
• perfluorinated compounds
• perfluoroalkyl and polyfluoroalkyl substances
• perfluorooctane sulfonate
• perfluorooctanoate
• semen quality
• time to pregnancy

Acknowledgements

The authors gratefully acknowledge the comments offered by four reviewers selected by the editor and unknown to the authors. The comments were helpful in improving the manuscript.

Declaration of interest

The authors declare they have no actual or potential competing financial interests. The authors’ affiliations are as shown on the cover page, and the authors have sole responsibility for the writing and content of the paper. The work was supported by the Danish Council for Strategic Research (part of the FETOTOX: Interaction between mother-fetus exposure to environmental toxicants and abnormal development, grant 10-092818), the European Commission's 7th Framework program (CLEAR, project FP7-ENV-2008-1-226217) and the Danish Research Council (grant 0602-01511B).