Preconception Multidimensional Heatwave Exposure and Infertility: A Prospective Cohort Study of Exposure Dynamics and Couple-Level Susceptibility

Background. Extreme heat is increasingly recognized as a threat to reproductive health, yet current evidence remains fragmented, focusing on biomarkers and short-term exposures. How different dimensions of heatwave exposure affect couple-level fecundability and infertility risk, particularly in the context of couple-level vulnerability and environmental context, remains poorly understood. Objectives. We aimed to investigate the associations between multidimensional heatwave exposure and infertility, evaluate the surrounding environment and couple-level vulnerability, and quantify the preventable reproductive burden. Methods. We analyzed data from a prospective cohort of 23,675 couples in Anhui, China, with up to 2 years of follow-up. Discrete-time Cox regression models were used to examine associations between heatwave exposure and time to pregnancy (TTP), and generalized linear models were applied to estimate infertility risk. Exposure-response relationships were further explored using restricted cubic splines. Effect modification was evaluated by built environment characteristics and blue-green space. To capture multidimensional reproductive vulnerability, we developed a couple-level heatwave susceptibility index (CHSI) by integrating machine learning feature importance and epidemiological effect estimates. Additionally, the potential impact fraction (PIF) was estimated to quantify the preventable reproductive burden. Results. A total of 2712 couples (11.5%) experienced infertility. Preconception heatwave exposure was associated with prolonged TTP and increased infertility risk, with the strongest associations observed during the 1-year window. Among all exposure metrics, heatwave event frequency showed the strongest association with TTP, suggesting that repeated heatwave occurrence may better capture reproductive risk than cumulative exposure alone. Reducing one heatwave event during the 1-year preconception window was associated with a PIF of 8.79%, corresponding to approximately 1001 additional expected conceptions. Substantial effect modification was observed. Community-level blue-green space exerted a buffering effect on heatwave-related reproductive risk, whereas higher couple-level CHSI was associated with increased heatwave-related reproductive vulnerability. Discussion. Heatwave-related reproductive risk appears to be jointly shaped by exposure patterns and couple-level vulnerability, highlighting climate adaptation needs in reproductive health.