Iatrogenic and Demographic Determinants of the National Plural Birth Increase

OBJECTIVE:To study the contribution of ovulation induction and ovarian stimulation, in vitro fertilization (IVF) and unassisted conception to the increase in national plural births in the U.S., a significant contributor to adverse maternal and infant health outcomes. DESIGN:National and IVF-assisted plural birth data were derived from the Centers for Disease Control and Prevention's National Vital Statistics System (1967-2021, after introduction of Clomiphene Citrate in the U.S.) and the National Assisted Reproductive Technology Surveillance System (1997-2021), respectively. MAIN OUTCOME MEASURES:In addition to IVF-assisted plural births, the contributions of unassisted conception to plural births among women aged <35 and ≥35 years were estimated using plural birth rates from 1949-1966, and a Bayesian logistic model with race and age as independent variables. The contribution of ovulation induction and ovarian stimulation was estimated as the difference between national plural births and IVF-assisted and unassisted counterparts. RESULTS:From 1967-2021, the national twin birth rate increased 1.7-fold to a 2014 high (33.9/1000 live births), then declined to 31.2/1000 live births; the triplet and higher-order birth rate increased 6.7-fold to a 1998 high (1.9/1000 live births), then declined to 0.8/1000 live births. In 2021, the contribution of unassisted conception among women <35 to the national plural births was 56.1%, followed by ovulation induction and ovarian stimulation (19.5%), unassisted conception among women ≥35 (16.8%) and IVF (7.6%). During 2009-2021, the contribution of ovulation induction and ovarian stimulation has remained stable, the contribution of unassisted conception among women <35 and women ≥35 has increased, and the contribution of IVF has decreased. CONCLUSION:Ovulation induction and ovarian stimulation are leading iatrogenic contributors to plural births. They are, therefore, targets for intervention to reduce the adverse maternal and infant health outcomes associated with plural births. Maternal age ≥35 is a significant contributor to the national plural birth increase.