Critical Windows of Air Pollution Exposure During Spermatogenesis and Intrauterine Insemination Outcomes

Background: Male preconception health remains a critically under-addressed area of family planning. While research suggests air pollution may harm semen quality, downstream impacts on pregnancy, particularly for more vulnerable infertility treatment populations, are understudied. Objectives: Among couples seeking infertility treatment, we examined the relationship between men's exposure to ambient air pollution and intrauterine insemination (IUI) cycle treatment outcomes. Methods: In the Folic Acid and Zinc Supplementation Trial (2013–2018), 592 male partners resided in the Salt Lake City area with at least one IUI cycle in 9 months of follow-up (n = 1223 cycles). Residential air pollution exposure was estimated using Community Multiscale Air Quality models and averaged across the 74-day window of spermatogenesis prior to the insemination date, as well as across developmental windows of mitosis, meiosis I-II, spermiogenesis, and spermiation. Treatment-cycle probabilities of hCG+ pregnancy, pregnancy loss, and livebirth were evaluated using generalised linear mixed models adjusted for age, season, income, and co-pollutants (fine particulate matter [PM_2.5], nitrogen dioxide [NO₂], ozone [O₃], and sulfur dioxide [SO₂]). Results: In multivariable models, we observed a lower probability of pregnancy per 5 ppb increase in O₃ and NO₂ across the 74-day spermatogenesis window (relative risk [RR] 0.71, 95% confidence interval [CI] 0.55, 0.93; RR 0.73, 95% CI 0.50, 1.05, respectively), with associations noted during mitosis and meiosis. PM_2.5 and SO₂ were less consistently associated with IUI outcomes. Findings from mixture models were similar, as were findings for air pollutants and a lower probability of live birth. No clear patterns emerged between air pollutants and pregnancy loss. Conclusions: Ambient air pollution during spermatogenesis, especially during mitosis and meiosis, was associated with a lower chance of pregnancy and live birth in an IUI treatment population. Further understanding pathways between men's air pollution exposure and pregnancy and live birth is an important future research need. Trial Registration: clinicaltrials.gov identifier: NCT01857310.