Estimation of the Contribution of Nonassisted Reproductive Technology Ovulation Stimulation Fertility Treatments to US Singleton and Multiple Births

Abstract

Infertility treatment with ovulation stimulation, either as part of assisted reproductive technologies (ARTs) or for non-ART infertility treatment, has been primarily responsible for the marked increase in multiple births in the United States in recent decades. The multiple-gestations resulting from both ART and non-ART treatments are associated with adverse sequelae, including markedly higher risks of pregnancy complications, premature delivery, infant death, and neurodevelopmental impairment in survivors. A number of studies have reported that ART-conceived singletons are also at higher risk of these outcomes than naturally conceived singletons. Although there is an ongoing, population-based surveillance system in the United States for ART-induced births, there is no comparable system to monitor non-ART infertility treatments, thus the contribution of each to multiple births in the United States is not known. The investigators present data from a multistep modeling process that was developed to estimate the proportions of multiple and singleton livebirths conceived in 2005 by use of non-ART ovulation stimulation. Published surveillance data provided an estimate of the proportion of US multiple births conceived naturally and by ART; it was assumed that the remainder was conceived with non-ART treatments. A meta-analysis of peer-reviewed literature published from 1997 to 2007 was used to estimate the contribution of non-ART ovulation treatment to the risk of multiple-gestation in the annual US birth cohort. A non-ART fetal survival factor was applied to obtain multiple-birth risk estimates. This estimate and the investigator's previous estimate of the proportion of US multiple births attributable to non-ART ovulation stimulation provided an estimate of the total and singleton (derived through subtraction of multiple births) proportion of infants conceived using non-ART induction. Based on the model data, the investigators estimated that the mean percentage of all US births in 2005 conceived with non-ART ovulation stimulation was 4.62% (95% uncertainty range, 2.8%-7.8%), which is 4 times more that the number contributed by ART treatment and equates to more than 190,000 livebirths. Of all singleton pregnancies, 3.98% were conceived with non-ART ovulation stimulation, and 22.8% of all multifetal pregnancies resulted from non-ART ovulation stimulation. These findings demonstrate that non-ART ovulation induction treatment in the United States is associated with a higher multiple-birth-attributable risk than ART. The estimated percentage contribution to US births is 2 to 6 times higher than the contribution of ART.