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.
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