Association of Ambient Air Pollution and Pregnancy Outcomes Among Women with Assisted Reproductive Technology in Qingdao, China: A Retrospective Cohort Study

Shuyuan Chen,1,2,* Zewei Yu,2,* Yuquan Mao,1,3,* Yangying Xu,2 Fanhui Meng,4 Duan Li,2 Xueyu Wang,5 Yupeng Jia,6 Xiaowen Liu,1 Yujie Li,2 Cuifang Hao,2 Xin Du1,2 1Department of Integrated Traditional Chinese and Western Medicine, Qingdao Medical College, Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China; 2Reproductive Medicine Center, Women and Children’s Hospital Affiliated to Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China; 3The Department of Traditional Chinese Medicine of Qingdao University Affiliated Hospital, Qingdao, Shandong, 266000, People’s Republic of China; 4Qingdao Ecological and Agricultural Meteorological Center, Qingdao, Shandong, 266000, People’s Republic of China; 5The Oncology Department of Qingdao Fifth People’s Hospital, Qingdao, Shandong, People’s Republic of China; 6School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Cuifang Hao, Reproductive Medicine Center, Women and Children’s Hospital Affiliated to Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China, Tel +86 17605321871, Email cuifang-hao@163.com Xin Du, Reproductive Medicine Center, Women and Children’s Hospital Affiliated to Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China, Tel +86 19853279079, Email duxinsharontc@163.comBackground: Ambient air pollutants, a major global public health concern, have been widely documented in recent years as key risk factors for adverse reproductive system outcomes. Assisted reproductive technology (ART) has become an important therapeutic means for infertility, but its pregnancy outcomes are influenced by various environmental factors. Thus, we explored the effects of ambient air pollutants on populations undergoing ART.Methods: The retrospective cohort study included 3478 infertility patients with fresh embryo transplantation residing in Qingdao City who underwent in vitro fertilization and intracytoplasmic sperm injection in China from 2021 to 2023. We employed multivariable logistic regression to assess the effects of contaminants on oocyte quality, embryonic development, and pregnancy outcomes. Stratified analysis was conducted to identify potential vulnerable subpopulations.Results: Regression showed that NO2 exposure showed negative association with biochemical pregnancy rates (aOR=0.967, 95% CI=0.935– 0.999) and clinical pregnancy rates (aOR=1.044, 95% CI=1.001– 1.088). CO exposure was positively correlated with cleavage rate (aOR=1.293, 95% CI=1.048– 1.594) and day 3 high-quality embryo rate (aOR=1.462, 95% CI=1.054– 2.028). PM2.5 and NO2 exposure were negatively associated with the number of oocyte retrieval and MII oocytes. WQS index was negatively correlated with MII oocyte count (aOR=0.916, 95% CI=0.857– 0.978). BKMR analysis confirmed PM2.5 correlated negatively with MII oocyte count. Stratified analyses revealed women aged ≥ 35 were more sensitive to NO2, while those < 35 were to O3. Women with ≥ 7 oocytes were more sensitive to PM2.5 and NO2.Conclusion: Ambient air pollutants exert significant negative effects on ART-related reproductive outcomes. Women aged ≥ 35 were more sensitive to NO2, whereas those < 35 were O3. Women with ≥ 7 oocytes were more sensitive to PM2.5 and NO2. This study provides a scientific basis for the prevention of air pollution and clinical decision-making in ART population. It is necessary to develop personalized intervention strategies for sensitive populations and strengthen the environmental control of related pollutants. The timeline includes periods before oocyte retrieval, oocyte retrieval, β-HCG test day and confirmation of intrauterine gestation by ultrasound. Pollutants like PM subscript 2.5, PM subscript 10, CO, SO subscript 2, NO subscript 2 and O subscript 3 are examined. Graphs show adjusted odds ratios (aOR) for biochemical and clinical pregnancy, categorized by female age (greater than or equal to 35 years and less than 35 years) and number of oocytes obtained (greater than or equal to 7 and less than 7). The study finds decreases in the number of oocytes obtained, number of MII oocytes, fertilization rate, cleavage rate, day 3 high-quality embryo rate, biochemical pregnancy rate and clinical pregnancy rate due to pollution exposure.Infographic on pollution’s impact on pregnancy outcomes in fresh embryo transfer patients at Hospital QingDao.Keywords: ambient air pollution, assisted reproduction technology, laboratory outcomes, MII oocytes, clinical pregnancy, Bayesian kernel machine regression, BKMR