Chen Miaoxin ^1* Qiaoyu Chen ¹ Gengze Liao ^2* Chunyan Sun ^1* Cong Liu ³ Xia Meng ³ Wentao Li ^4* Andong Qiu ¹ ORHAN BUKULMEZ ⁵ Haidong Kan ³ Feng Wang ^6* Shelly Lap-ah TSE ⁶ Xiaoming Teng ^1*

• ¹ Centre for Assisted Reproduction, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital,, School of Medicine, Tongji University, Shanghai, Shanghai Municipality, China
• ² The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong Region, China
• ³ School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Lab of Health Technology Assessment,, Fudan University, Shanghai, Shanghai Municipality, China
• ⁴ Monash University, Melbourne, Victoria, Australia
• ⁵ University of Texas Southwestern Medical Center, Dallas, Texas, United States
• ⁶ The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Shatin, Hong Kong Region, China

Background: Excessive exposure to PM2.5 can be detrimental to reproductive health.The objective of this study was to investigate the potential associations between ambient PM2.5 exposure during different periods and negative pregnancy outcomes, such as miscarriage and preterm birth, in patients who underwent assisted reproductive technology (ART).Methods: This retrospective cohort study examined the outcomes of 2,839 infertile women aged ≤ 45 years who underwent their first fresh or frozen-thawed embryo transfer at the Shanghai First Maternity and Infant Hospital between April 2016 and December 2019. Satellite data were used to determine the daily average levels of PM2.5, and exposure was categorized as excessive if it exceeded the WHO's interim target 2 level of 50 µg/m 3 . The analysis was conducted separately for seven different periods. Our study used multinomial logistic regression models to explore the potential associations between PM2.5 exposure and adverse pregnancy outcomes. Sensitivity analysis was conducted by excluding women who underwent blastocyst transfer.Results: Daily PM2.5 exposure exceeding the threshold (50 µg/m 3 ) was associated with an increased risk of miscarriage during the period after confirmation of clinical pregnancy or biochemical pregnancy, with adjusted odds ratios (AORs) of 2.22 (95% CI 1.75-2.81) and 2.23 (95% CI 1.68-2.96), respectively. Moreover, for each increase of 10 µg/m 3 above the threshold for PM2.5, there was a 46% elevated risk of preterm birth (AOR = 1.46, 95% CI 1.09-1.94) during the period after the confirmation of clinical pregnancy and a 61% elevated risk of preterm birth (AOR = 1.61, 95% CI 1.16-2.23) during the period after the confirmation of biochemical pregnancy. Our stratified analyses revealed that women with an endometrial thickness <11 mm or who underwent frozen embryo transfer were more vulnerable to PM2.5 exposure, leading to higher rates of preterm birth.Conclusion: Excessive PM2.5 exposure after biochemical pregnancy or clinical pregnancy was associated with increased risks of preterm birth and miscarriage among women who underwent ART.