Impact of cold excess on pregnancy outcomes in women undergoing assisted reproductive technology: A large retrospective cohort study in Anhui, China

Abstract

To investigate the association between cold exposure and implantation failure or pregnancy loss during different assisted reproductive technology (ART) exposure windows. This retrospective cohort study included 5905 embryo transfer cycles from the First Affiliated Hospital of the University of Science and Technology of China between 2018 and 2022. Individual cold exposure was quantified using a novel daily mean cold excess (DMCE) metric, calculated based on the 5th, 7.5th, and 10th percentile thresholds of historical temperature distributions. Associations between cold exposure across eight defined windows with implantation failure or pregnancy loss were assessed using logistic regression to estimate odds ratio (OR) and 95% confidence intervals (CI), adjusting for demographic, clinical, and environmental confounders. Subgroup analyses were performed to explore potential heterogeneity and sensitivity analyses were conducted to test the robustness of our findings. A total of 5905 participants (mean age 30.7 ± 4.6 years) were included, 2543 (43.1%) achieved a live birth. Significant increases in implantation failure or pregnancy loss risk were identified during the window from embryo transfer to the end of the first trimester, each 0.1-unit increase of DMCE was associated with elevated odds of implantation failure or early pregnancy loss, with ORs of 1.07 (95% CI: 1.03–1.11) for severe (DMCE_P5), 1.04 (95% CI: 1.02–1.07) for moderate (DMCE_P7.5), and 1.03 (95% CI: 1.01–1.05) for mild (DMCE_P10) cold definitions. Subgroup analyses revealed greater vulnerability among women with lower education levels and those undergoing fresh embryo transfer during the window from embryo transfer to the end of the first trimester. Results remained consistent across sensitivity analyses. High-intensity cold exposure during the first trimester represents a critical exposure period and independent risk factor for implantation failure or early pregnancy loss in ART pregnancies. These findings underscore the necessity of implementing thermal protection measures from embryo transfer to the first trimester, especially for vulnerable groups during winter months.