Association of adverse birth outcomes with in vitro fertilization after controlling infertility factors based on a singleton live birth cohort

Infants conceived with in vitro fertilization (IVF) are exposed to underlying infertility and the IVF process. High risks of adverse birth outcomes (ABOs) were observed among these infants, including preterm birth, low birth weight, macrosomia, being large/small for gestational age (LGA/SGA). It is unclear whether the specific etiology of the rise of ABOs among IVF infants is IVF technology itself or underlying infertility. A total of 9,480 singletons conceived with IVF and 1,952,419 singletons from the general population were obtained in this study. Multivariable logistic regression model was used to assess variations in risk of ABOs according to causes of infertility. Poisson distributions were applied to calculate standardized risk ratios of IVF infants vs. general population after controlling the causes of infertility. Higher risk of preterm birth and low birth weight were observed among parents with polycystic ovary syndrome, endometriosis, uterine and semen abnormalities. Compared to the general population, after excluding the influence of infertility causes, singletons conceived with IVF were at higher risk of macrosomia (SRR = 1.28, 95% CI 1.14-1.44) and LGA (SRR = 1.25, 95% CI 1.15-1.35). The higher risk of ABOs in IVF was driven by both IVF treatments and infertility, which is important for improving IVF treatments and the managing pregnancies and child development.