Evidence acquired during and after World War II suggested that twinning correlated more with nutrition than with body size. Widespread undernourishment in Europe during those years was associated with a marked fall in the dizygotic twinning rate (Bulmer, 1959). Several investigators have reported a greater prevalence of twinning among women who have taken supplementary folic acid (Ericson, 2001; Haggarty, 2006). Conversely, in a systematic review, Muggli and Halliday (2007) were unable to demonstrate a significant association. Analysis of twinning rate in Texas after folic acid fortiication of cerealgrain products also failed to demonstrate an independent increase in twinning rates (Waller, 2003).
he common factor linking race, age, weight, and fertility to multifetal gestation may be FSH levels (Benirschke, 1973). This theory is supported by the fact that greater fecundity and a higher rate of dizygotic twinning have been reported in women who conceive within 1 month after stopping oral contraceptives, but not during subsequent months (Rothman, 1977). This may be due to the sudden release of pituitary gonadotropin in amounts greater than usual during the irst spontaneous cycle after stopping hormonal contraception. Indeed, the paradox of declining fertility but increasing twinning with advancing maternal age can be explained by an exaggerated pituitary release of FSH in response to decreased negative feedback from impending ovarian failure (Beemsterboer, 2006).
Ovulation induction with FSH plus human chorionic gonadotropin (hCG) or clomiphene citrate remarkably enhances the likelihood of multiple concurrent ovulations. In their review of this practice, McClamrock and coworkers (2012) reported rates of twins and higher-order multifetal pregnancies as high as 28.6 percent and 9.3 percent, respectively. Rates this high remain a major concern. Two ongoing multicenter trialsAssessment of Multiple Gestations from Ovarian Stimulation (AMIGOS) and Pregnancy in Polycystic Ovary Syndrome II (PPCOSII)-are designed to provide guidance on achieving maximum pregnancy rates while minimizing multifetal gestation rates (Diamond, 2015; Legro, 2014).
In general with in vitro fertilization (IVF), the greater the number of embryos that are transferred, the greater the risk of twins and other multifetal gestations. In 2014, ART contributed to 1.6 percent of all newborns in the United States and to 18.3 percent of all neonates in multifetal gestations (Sunderam, 2017). The American Society for Reproductive Medicine (2017) recently revised their age-related guidelines regarding the number of cleavage-stage embryos or blastocysts to transfer during IVF. This efort aims to reduce the incidence of higher-order multifetal pregnancies. Based on these new recommendations, women younger than 35 years are encouraged to receive a single-embryo transfer, regardless of embryo stage.
hese practices have efectively lowered multifetal rates, and the rate of triplet or higher-order multifetal pregnancy has declined every year since 2009 (Kulkarni, 2013; Martin, 2017).