Association of exposure to ozone and fine particulate matter with ovarian reserve among women with infertility

Evidence linking diminished ovarian reserve, a significant cause of female infertility, and exposure to particulate matter with aerodynamic diameters <= 2.5 mu m (PM2.5) or O3 exposure remains a critical knowledge gap in female fertility. This study investigated the association between ambient PM2.5, O3 pollution, and anti-Mullerian hormone (AMH), a sensitive marker of ovarian reserve, in reproductive-aged Chinese women. We enrolled 2212 women with spontaneous menstrual cycles who underwent AMH measurements at a reproductive medicine center between 2018 and 2021. The daily mean concentrations of outdoor PM2.5 and O3 were estimated using a validated spatiotemporal model, followed by matching the participants' residential addresses. Three exposure periods were designed according to AMH expression patterns during follicle development. A generalized linear model was used to investigate changes in AMH associated with air pollution. The results showed a mean AMH level of 3.47 +/- 2.61 ng/mL. During the six months from primary to early antral follicle stage (Period 1), each 10 mu g/m3 increase in PM2.5 and O3 exposure was associated with AMH changes of -0.21 (95% confidence interval [CI]: -0.48, 0.06) ng/mL and -0.31 (95% CI: -0.50, -0.12) ng/mL, respectively. Further analyses indicated that the reduced ovarian reserve measured by AMH level was only significantly associated with PM2.5 exposure during follicle development from the primary to preantral follicle stage (Period 2) but was significantly associated with O3 exposure during Periods 1, 2, and 3. These observations were robust in the dual-pollutant model considering co-exposure to PM2.5 and O3. The results indicated an inverse association between ovarian reserve and ambient O3 exposure and suggested distinct susceptibility windows for O3 and PM2.5 for reduced ovarian reserve. These findings highlight the need to control ambient air pollution to reduce invisible risks to women's fertility, especially at high O3 concentrations.