Maternal and neonatal outcomes of assisted reproductive technology versus unassisted pregnancy: A propensity score-matched analysis

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Abstract
Background: Assisted reproductive technology (ART) is generally safe, but still associated with risks of various adverse maternal and neonatal outcomes.Methods: This retrospective cohort study included all deliveries (through either ART or unassisted pregnancy) during a period from January 5th, 2015 to September 30th, 2020 at the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. A propensity score-matched (PSM) analysis was conducted to compare adverse maternal and neonatal outcomes between ART and unassisted pregnancy. The PSM was performed at a 1:4 ratio using a caliper width that equals to 0.02 of the standard deviation of the propensity score logit. The results are presented as relative risk (RR) and 95% confidence interval (95%CI).Results: We screened a total of 78,022 deliveries: 4,310 (5.5%) through ART and the remaining 73,712 (94.5%) through unassisted pregnancy. The ART group had older age (33.2±3.9 vs 30.4±4.0 years), higher rate of cesarean section (70.2% vs 38.1%) and multiple pregnancies (23.6% vs 1.7%). In the PSM analysis (4,218 and 15,003 deliveries, respectively), the ART group had higher risks of preeclampsia (10.5% vs 5.7%, RR: 1.57, 95%CI: 1.44-1.71), gestational diabetes mellitus (19.5% vs 16.0%, RR: 1.27, 95%CI: 1.16-1.38) and placenta-related diseases, including placenta previa (2.7% vs 1.8%, RR: 1.52, 95% CI: 1.21-1.89), placenta accreta spectrum (6.8% vs 3.0%, RR: 1.95, 95%CI: 1.72-2.22) and abnormal placental morphology (8.4% vs 5.5%, RR: 1.22, 95%CI: 1.14-1.30). In singletons, the ART group had higher risks of large-for-gestational-age (LGA) (13.7% vs 10.2%, RR: 1.40, 95%CI: 1.25-1.57) and stillbirth (0.3% vs 0.1%, RR: 2.24, 95% CI: 1.25-4.03) but lower risk of small-for-gestational-age (SGA) (4.2% vs 5.4%, RR: 0.84, 95%CI: 0.73-0.97). In multiple births, the ART group had lower risks of SGA (13.4% vs 17.8%, RR:0.83, 95%CI: 0.74-0.93), preterm birth (44.8% vs 59.2%, RR: 0.56, 95%CI: 0.49-0.64) and stillbirth (0.1% vs 0.6%, RR: 0.42, 95%CI: 0.20-0.90). Analysis of the overall, pre-matching study population yielded largely similar findings.Conclusion: Pregnancy through ART was associated with higher risks of most maternal outcomes. Interestingly, the risks of neonatal outcomes differed between singleton and multiple birth groups.