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On Dec. 23, 2015, the Division of Vital Statistics of the National Centers for Health Statistics reported that the 2014 national twin birth rate reached an all-time high of 33.9 per 1000 live births. The report went on to state that this latest record “was not significantly higher than the rate for 2013” but that it represented “a new high for the nation.” The corresponding figure for non-Hispanic black mothers stood at 40 per 1000 live births. The adverse consequences of a rising national twin birth rate cannot be overstated. Notably, 11% and 59% of the twins comprising the 2014 cohort were born “very preterm” (<32 completed weeks of gestation) and “preterm”(<37 completed weeks of gestation), respectively. What is more, 10% and 55% of the twins in question were characterized as “very low birthweight” (<1500 g) and “low birthweight” (<2500 g), respectively. In a word, >1 of every 2 twins born in 2014 was either preterm or low birthweight. A total of 18 states registered twin birth rates in excess of the overall national figure. New Jersey, Massachusetts, and Connecticut, all home to state-mandated underwriting of infertility care, led the way with rates of 43.1, 42.8, and 40.5 per 1000 live births, respectively. The lowest twin birth rates were noted in Arizona, Arkansas, Oklahoma, and South Dakota (28.5, 28.8, 29.7, and 29.7 per 1000 live births, respectively). It is the purpose of this commentary to describe the ontogeny of the twin births “epidemic,” define the forces that have shaped it, and highlight potential remedies.
Ontogeny of the twin births epidemic
The basal (naturally occurring) national twin birth rate of the United States, long concealed by half a century of fertility promotion, is 20.1 per 1000 live births as determined over the 1949 through 1966 interval. This basal rate predates the 1967 introduction of the first fertility-promoting principal (clomiphene citrate) and thereby the looming indeed inevitable twin birth epidemic. This low a national twin birth rate is unlikely to be seen again anytime soon and probably never, given the irreversible nature of the forces that have seen to its rise.
It was not until 1986 that the national twin birth rate began its progressive ascent ( Figure ). By then, clomiphene citrate was widely used and the growing if nascent in vitro fertilization (IVF) enterprise was underway. By 1996, aided and abetted by the growing utilization of IVF and the emergence of superovulation followed by intrauterine insemination (IUI), the national twin birth rate reached the 25 per 1000 live births mark ( Figure ). By 2001, the national twin birth rate broke the 30 per 1000 live births barrier ( Figure ). All told, these progressive increments have resulted in an overall 1.7-fold increase in the national twin birth rate relative to its basal counterpart. More importantly, the rising national twin birth rate has yet to reverse its course ( Figure ). In this regard, the national twin birth rate parts way with the national higher-order birth rate for which a decrement of 41% has been noted since its 1998 high.
Drivers of the twin births epidemic
The twin births epidemic is an iatrogenic construct linked to the growing utilization of fertility-promoting technology over the last half century. Stated differently, the twin birth epidemic constitutes an unintended consequence of the fertility-promoting revolution and its quest to vanquish barrenness. Earlier collaborative efforts of this group have clearly established that IVF does not fully account for the twin births epidemic. In fact, since 1997, IVF has not been the leading contributor to the national twin birth rate. That distinction has been assumed by non-IVF treatment modalities. As recently as 2013, the last year for which reliable data are available, the declining contribution of IVF accounted for no more than 16% of the national twin birth rate. In contrast, non-IVF treatment modalities have contributed as much as 20% to the national twin birth rate. In 2013 alone, no less than 36% of all twin infants born (47,637 of a total of 132,324) were deemed iatrogenic in origin.
Non-IVF treatment modalities are composed of 2 main varieties. Ovulation induction, for its part, is designed to bring about, indeed reestablish, ovulation in women who are otherwise anovulatory. Superovulation followed by IUI, in turn, aims to enhance the conception rates of ovulatory women with unexplained subfertility. Both treatment modalities are not as predictable as IVF wherein the number of embryos transferred (ET) can be carefully controlled. As a result, both treatment modalities are associated with significant birth plurality rates. Further, both treatment modalities are frequently administered over multiple cycles by a broad swath of practitioners be they reproductive endocrinology and infertility specialists or general obstetricians and gynecologists. Taken together, these realities are commensurate with the observation that non-IVF treatment modalities shoulder a significant share of the responsibility for the genesis and maintenance of the twin births epidemic.
The continued if diminishing contribution of IVF to the twin births epidemic represents a “casualty” of transitioning ET patterns from ≥3 ETs, to double ETs (DETS), to single ETs (SETs). Stated differently, until such time that most ETs are of the SET variety, DETs will, by necessity, remain the most prevalent transfer variant. This reality is borne out by data from the National Assisted Reproductive Technology Surveillance program of the Centers for Disease Control and Prevention. As recently as 2013, DETs accounted for 55% of all ETs. Additionally, twins comprised a substantial if declining proportion (39%) of all IVF births. Still, there is every reason to believe that the percent of DETs will decline as SETs (30% in 2013) continue their rise. A commensurate decrease in the IVF-attributable twin birth rate should follow suit. A new status quo aspiring to that achieved by nations such as Australia and New Zealand is not beyond the realm of possibility. As recently as 2013, data reported by the relevant registry reveal that SETs and DETs constituted 80% and 20% of all ETs, respectively.
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