Association between air pollutants exposure and in vitro fertilization outcomes: mediating role of remnant cholesterol and modifying effect of the ovarian sensitivity index

Ambient air pollution has been increasingly linked to in vitro fertilization (IVF) outcomes; however, the underlying biological mechanisms and susceptible subgroups remain poorly understood. We conducted a retrospective cohort study including 1012 women undergoing IVF treatment at the First Affiliated Hospital of Anhui Medical University to evaluate the associations between six ambient air pollutants (PM₂.₅, PM₁₀, NO₂, SO₂, CO, and O₃) and multiple IVF outcomes across long-term (1-year) and short-term (3-month) exposure windows using single-pollutant and two-pollutant models. In addition, exploratory mediation analyses were performed to statistically assess the potential mediating role of remnant cholesterol, and interaction and stratified analyses were conducted to evaluate effect modification by the ovarian sensitivity index (OSI). Long-term O₃ exposure was negatively associated with metaphase II (MII) rate (β = −0.29, 95% confidence interval (CI): −0.50 to − 0.08), normal fertilization rate (β = −0.35, 95% CI: −0.56 to − 0.13), and high-quality blastocyst rate (β = −0.40, 95% CI: −0.69 to − 0.10). Higher remnant cholesterol (RC) levels were negatively associated with normal fertilization rate (β = −0.10, 95% CI: −0.19 to − 0.02) but positively associated with blastocyst formation rate (β = 0.15, 95% CI: 0.05 to 0.25). In exploratory mediation analysis, RC statistically accounted for a small proportion of the association between O₃ exposure and the normal fertilization rate (proportion mediated = 8.20%). Moreover, significant effect modification by OSI was observed: a significant inverse association between O₃ exposure and high-quality blastocyst rate was present among women with high OSI (β = −0.58, 95% CI: −1.08 to − 0.08). Our results indicated that long-term ambient O 3 exposure was negatively associated with IVF outcomes. In exploratory mediation analysis, RC explained 8.20% proportion of the observed association between O 3 exposure and normal fertilization rate. In addition, OSI significantly modified the association between O 3 exposure and the high-quality blastocyst rate, with a significant inverse association observed only in women with high OSI. Together, these findings underscore the importance of considering air pollutant, potential metabolic correlates, and individual susceptibility in studies of air pollution and IVF outcomes.