In Vitro Fertilization and Adverse Pregnancy Outcomes in the Elective Single Embryo Transfer Era

Our objective was to estimate the association between in vitro fertilization (IVF) pregnancy and adverse pregnancy outcomes during delivery hospital admission in a contemporary, nation-wide cohort of births in the United States.

This retrospective, population-based cohort study used the National Inpatient Sample database to identify patients discharged from the hospital following delivery from 2014 to 2019. IVF pregnancies were identified using the International Classification of Disease-Revision 9/10 codes. Crude and adjusted odds ratios of preterm birth and other clinically significant adverse pregnancy outcomes were evaluated using multivariable logistic regression models. Trends in preterm birth and multiple pregnancy were estimated over the study period. The contribution of multiple pregnancy to preterm birth in IVF pregnancy was estimated in a mediation analysis.

Among 4,451,667 delivery-related discharges, IVF pregnancies were associated with 3.25 times the odds of preterm birth (95% confidence interval [CI]: 3.05-3.46, p < 0.001) compared with non-IVF pregnancy deliveries. Odds of preterm birth in IVF pregnancy delivery discharges decreased over the study period (p-value for linear trend = 0.009). The proportion of multiple pregnancies decreased in IVF pregnancy delivery discharges but remained stable in non-IVF pregnancy deliveries. The proportion of the adjusted effect of IVF pregnancy on preterm birth mediated through multiple pregnancy was 67.6% (95% CI: 62.6-72.7%).

While the odds of adverse pregnancy outcomes are increased compared with non-IVF pregnancies, the odds of preterm birth and multiple gestation have decreased among IVF pregnancies in the United States.

· Pregnancies conceived by in vitro fertilization (IVF) are at significantly higher risk of multiple gestation, preterm birth, and other pregnancy complications.. · Recent guidelines for artificial reproductive treatments recommend single-embryo transfer in IVF.. · Using population-wide data, we demonstrate a significant gradual decline in the rates of preterm birth and other pregnancy complications following IVF in the last decade, mostly mediated by a reduction in multiple pregnancies..