Abstract Study question Are paternal occupational exposures associated with a higher risk of fetal loss in the unexposed female partner? Summary answer Significant positive associations between paternal occupational exposures and fetal loss were retrieved, for chemical and physical agents and for several occupations. What is known already Adverse pregnancy outcomes are frequent and, in its recently updated guidelines, the ESHRE reinforced the interest of exploring the father’s exposures. Nevertheless, causes of fetal loss are still most often investigated only in mothers. Paternal risk factors for fetal loss have been scarcely explored, particularly occupational exposures. Though, males appear to be more exposed to occupational reprotoxic agents than females and are not always aware or sufficiently informed of these exposures. Reprotoxic mechanisms of father’s occupational exposures may include sperm nucleus alteration, seminal fluid contamination and/or indirect exposure of the mother to paternal occupational environment (via linen, dust…). Study design, size, duration A systematic review of the literature using PRISMA 2020 methodology was performed for full text English and French language articles in the Pubmed MEDLINE, Google Scholar, Web of Science and Embase databases. Participants/materials, setting, methods We included only original studies published until December 2022, performed in humans, including a control group and performing a multivariate analysis. The fetal losses analysed were early and/or late and we did not exclude studies analysing stillbirths. We excluded studies in which the female partner was also occupationally exposed. The dose-response relationship and mechanisms of action were noted where described. Main results and the role of chance The 33 studies included analysed a total of 540,246 pregnancies from 8,183 couples or 114,093 exposed male workers, and were classified into 3 groups according to the occupational hazards studied. Regarding chemical agents, the risk of miscarriage was significantly increased in cases of paternal occupational exposure to Thiocarbamate(OR = 1.9, 95% CI 1.1-3.3), Carbaryl (OR = 1.9, 95% CI 1.9-3.1), Dichloro-Diphenyl-Trichloroethane (OR = 1.57, 95% CI 1.13-2.18), printing solvents (OR = 5.5, 95% CI 1.8-17.2), ethylene oxide (OR = 4.7, 95% CI 1.2-18.4), petroleum refinery solvents (OR = 2.2, 95% CI 1.3-3.8) and stainless steel welding fumes (RR = 3.5, 95% CI 1.3-9.1). Regarding physical agents, the risk of stillbirth or perinatal mortality was significantly increased with exposure to ionising (OR = 1.86, 95% CI 1.21-2.76) and nonionising radiation (RR = 2.23, 95% CI 1.08-4.62). Regarding the type of occupation, the risk of miscarriage or stillbirth was significantly increased among crushers, grinders and calenders (OR = 2.20, 95% CI 1.13-4.30), to seamstresses (OR = 2.54, 95% CI 1.29-5), sheet metal workers and commercial aircrew (OR = 2.85, 95% CI 1.30-6.23). The dose-response relationships showed divergent results. The mechanisms of action hypothesized were mainly germ cell mutations. Limitations, reasons for caution The publications selected were mostly published before 2010 and showed high variation in the population sizes, types of male occupational exposure, and in the nature and number of confounding factors used for the multivariate statistical analysis. Due to the various nature of exposures analysed, no meta-analysis could be performed. Wider implications of the findings Men should be made more aware of male-mediated occupational reproductive risks. Occupational health professionals should participate in the investigation of the causes of foetal loss and act on male occupational exposures that may impact pregnancy outcomes. Further high-powered prospective studies are needed, which should include paternal current occupational exposures. Trial registration number not applicable
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