Abstract
BACKGROUND: Previous studies have focused on the effects of ambient air pollutant levels on assisted reproduction. This research focused on the combined effects of lower concentrations of air pollutants and multiple environmental factors on miscarriage following assisted reproductive technologies. METHODS: A retrospective cohort study involving 2654 women who received treatment at a local hospital between 2015 and 2022 and met the inclusion criteria was conducted. The daily average levels of six pollutants (PM(2.5), PM(10), NO(2), CO, SO(2), and O(3)) and six environmental factors (temperature, relative humidity, wind speed, surface pressure, UV intensity, normalized difference vegetation index (NDVI)) were collected from relevant public data platforms. We employed generalized linear regression models (logistic and linear), weighted quantile sum (WQS) regression, quantile g-computation (QGC) regression, and Bayesian kernel machine regression (BKMR) and sensitivity analysis to assess the impact of environmental factors on miscarriage. Finally, genes associated with environmental factors and miscarriage were screened for prediction via the Comparative Toxicogenomics Database and the GeneMANIA platform. RESULTS: A significant positive associations were observed between miscarriage and exposure to PM2.5 (aOR = 1.49, 95% CI: 1.08 ~ 2.06), temperature (aOR = 1.36, 95% CI: 1.25 ~ 1.48), UV intensity (aOR = 1.36, 95% CI: 1.21 ~ 1.54). The WQS model revealed a positive correlation between mixed-exposure environmental factors and miscarriage (aOR = 3.65, 95% CI: 1.74 ~ 7.69). The BKMR results indicate that the overall effect of mixed environmental factor exposure from the embryo transfer date on the outcome is positively correlated with the risk of miscarriage. The NDVI, wind speed, surface pressure and UV intensity presented relatively high PIPs. Gene prediction and enrichment revealed that genes associated with environmental factors and miscarriage are associated primarily with immune-inflammatory responses. CONCLUSIONS: Results revealed that mixed exposure to air pollutants and environmental factors increases the risk of miscarriage. The analysis further demonstrated that temperature, NDVI, UV intensity, and wind speed could mitigate the impact of air pollutants on miscarriage. However, mixed exposure to these environmental factors still increases the risk of miscarriage. The potential mechanism may involve the influence of environmental factors on miscarriage through an immune‒inflammatory response.