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The objective of this work is to compare the rate of spontaneous preterm birth and associated neonatal morbidity among low-risk pregnancies conceived spontaneously versus pregnancies conceived using infertility medications/intrauterine insemination (IFM/IUI). This population-based retrospective cohort study utilized the US Vital Statistics data set from 2015 to 2019. Low-risk pregnancies, resulting in a live birth, of individuals who conceived either spontaneously or with the assistance of IFM/IUI were examined. The primary measured outcome was the rate of spontaneous preterm delivery, defined as delivery before 37 weeks' gestation without induction of labor. Of the 19,382,574 deliveries during the study period, 7,876,515 (40.6%) met the inclusion criteria. While 7,843,328 (99.6%) conceived spontaneously, 33,187 (0.4%) conceived using IFM/IUI. The rate of spontaneous preterm delivery was significantly higher for patients who conceived using IFM/IUI (71.0 per 1,000 live births) compared to patients who conceived spontaneously (60.3 per 1,000 live births; adjusted relative risk, 1.40; 95% confidence interval, 1.35–1.46). While the rate of spontaneous preterm births and associated composite of neonatal adverse outcomes are significantly higher in pregnancies conceived using IFM/IUI than spontaneous conception, the mortality is similar. [ABSTRACT FROM AUTHOR]