Association between ambient air pollution and pregnancy outcomes in patients undergoing in vitro fertilization in Shanghai, China: A retrospective cohort study

Background: The effects of ambient air pollutants on adverse pregnancy outcomes have been reported. However, studies about air pollutants exposure and pregnancy outcomes in patients undergoing IVF were limited and inconclusive. To date Shanghai has been the only city in China to implement a compulsory single embryo transfer policy for all patients undergoing their first embryo transfer procedure effective from January 2019. We aimed to investigate the associations between exposure to ambient air pollutants and biochemical pregnancy and live births, and to identify potential vulnerability characteristics of patients undergoing IVF in Shanghai, China. Methods: A retrospective cohort study was conducted on 2766 infertile patients aged ≤ 45 years who underwent first fresh or frozen-thawed cleavage stage embryo transfer in the Shanghai First Maternity and Infant Hospital during April 2016 and December 2019. Daily average ambient levels of six air pollutants (PM_2.5, PM₁₀, NO₂, SO₂, CO and O₃ max-8h) were obtained from fixed air monitors located in closest proximity to patients’ residences. The cumulative average level was calculated during three different exposure periods (period1: three months before oocyte retrieval to serum hCG test; period 2: from serum hCG test to live birth outcome; period 3: from three months before oocyte retrieval to live birth). Multiple logistic regression model was performed to investigate associations between exposure to ambient air pollutants and pregnancy outcomes. Stratified analyses were conducted to explore the potential effects modifier. Results: The biochemical pregnancy rate and live birth rate were 54.2% and 36.4%, respectively. The ambient NO₂ exposure was significantly associated with a 14% lower pregnancy rate during period 1 (aOR = 0.86, 95%CI: 0.75–0.99). The ambient PM₁₀ was related to significantly increased risk of lowering live birth rate among the patients during period 3 [aOR = 0.88(0.79–0.99)]. Stratified analysis showed that ambient PM₁₀ was also significantly associated with a reduced pregnancy rate (aOR = 0.82, 95% CI: 0.69–0.97) in patients who underwent single embryo transfer during period 1. Subjects who underwent single embryo transfer also had a decreased likelihood of a live birth when exposed to ambient SO₂ and O₃ during period 3 [aOR = 0.74(0.57–0.95), and 0.92 (0.83–0.98), respectively]. Moreover, O₃ exposure was associated with decreased live birth rates in patients living in non-urban areas. Sensitivity analyses indicated robust negative association between PM₁₀ exposure and live birth outcomes. Conclusions: Our study suggested that exposure to ambient air pollutants, in particular NO₂ and PM₁₀, was associated with an increased risk of lower rates of pregnancy and live birth respectively in patients undergoing IVF. Stratified analyses indicated that ambient SO₂ and O₃ levels were related to adverse pregnancy outcomes in some subgroups of IVF patients in this study. Notably, patients who underwent single embryo transfer were more susceptible to ambient air pollution exposure. Thus, prospective cohort studies are needed to investigate the underlying mechanisms and the susceptibility windows for women undergoing IVF treatment.