With Louise Brown’s 40th birthday looming, in vitro fertilization (IVF) has come of age. Over 3 million IVF babies have been born worldwide and 1.7% of US births are now annually attributable to assisted reproductive technology (ART).1 Since 1980, there have been progressive refinements in the laboratory and clinical aspects producing consistent, incremental improvements in success rates that have only leveled off in the past 10 years.2 Currently, at least 50% of women younger than age 38 can expect to have a successful outcome following a single first treatment cycle including either immediate transfer with fresh embryos or subsequent, delayed transfer with frozen embryos.3 While questions of efficacy have long been resolved, reassurance regarding safety has taken longer. Earlier studies raised concerns regarding a possible increased risk of birth defects in offspring born through use of assisted reproductive technology (ART) or after malignancy in women undergoing ovulation induction, but these risks, if they do exist, are of a very small magnitude. However, there is no debate about ART’s contribution to risk of multiple pregnancy.
In the United States, 20% of IVF pregnancies result in delivery of a multiple pregnancy, accounting for 17% of all twin births and 32% of the total number of higher-order multiples (greater than twins, HOMs).4 Since 1998, there has been significant progress in and focus on reducing incidence of HOMs with adoption of guidelines limiting the number of embryos recommended for transfer but there has been little corresponding progress in reducing incidence of twin pregnancy.5,6 In 2015, only 40% of women younger than age 35 had a single-embryo transfer (SET)3 Recent data from SART show that almost 20% of IVF live births are multiples, with 19% twins and 0.5% HOMs.3 The overall risk of twin pregnancy in the United States is 3%.7ART-derived dizygotic twin pregnancies are associated with increased risk of placenta previa, cesarean delivery, preterm birth, very preterm birth (VPTB), low birth weight (LBW), and a higher risk of congenital malformations, all leading to even greater subsequent morbidity.8 Compared with infants derived from 2 IVF singleton pregnancies, IVF-derived twins have higher rates of respiratory complications, sepsis and jaundice.9 In contrast, risks of adverse perinatal outcome are comparable for SET- and non-ART-derived singletons and lower than for twin pregnancies resulting from embryo transfer of 2 or more embryos.10
Many countries have long recognized the increased risks of multiple gestation and mandated SET for women younger than a specified age, usually 38 or 40. Most countries with legislation proscribing multiple embryo transfer offer substantial financial coverage for ART services and have a vested interest in preventing neonatal complications and reducing costs incurred with prematurity. There has been a longstanding, pervasive international trend towards acceptance of SET as a standard of care but the United States has been slower to adopt.