There is good news and bad news in the Centers for Disease Control and Prevention's 2002 National Vital Statistics Report on births in the United States.1 The good news: teenage births and tobacco use during pregnancy are down (30% and 42%, respectively) and more women (nearly 84%) are receiving early prenatal care. The bad news: Our preterm delivery rate has now reached 12.1%, up 29% from 1981. According to the CDC, the chief culprit in this escalation is multifetal births due to assisted reproductive technology (ART).1 A look at the statistics on twins, triplets, and higher-order multiples and the role that ART plays in their occurrence suggests that it's time to implement a rational approach to reimbursement for high-tech baby making.
As of 2002, 16% of all preterm deliveries in the US (79,684 of more than 4 million) were due to multifetal gestations. The twin birth rate rose 3% in 2002, to an extraordinary 3.1% of all live births. This represents a 65% increase over the past two decades and a 38% increase since 1990. The incidence of triplets and higher-order multiples is now 1.84 per 1,000 live births. Among non-Hispanic whites, the probability of giving birth to twins has increased 50% since 1990 and the rate of triplet and higher-order multiples is now 2.5 per 1,000 live births.
The CDC rightly ascribes this acceleration in multifetal births to increased access to technologies such as in vitro fertilization and non-ART therapies and procedures such as ovulation induction (OI) and intrauterine insemination (IUI). In 2000 only 18% of triplets were naturally conceived, with 40% a result of ART and 40% likely due to OI/IUI. That year, the 99,629 ART procedures performed in the US resulted in the birth of 35,025 infants, 44% of whom were twins and 9% of whom were triplets and higher-order multiples, for a combined multifetal pregnancy rate of 53%!2 While it's impossible to know how many non-ART fertility treatments are administered each year, since they are not monitored by the CDC, the number likely is comparable to the ART cases, and no doubt associated with even more triplet and higher-order multiple gestations.
Nearly 7% of twins and 19% of triplets and higher-order multiples die before reaching 1 year of age, which is not surprising, given that 12% of twins, 36% of triplets, and 60% of quadruplets are born prior to 32 completed weeks' gestation, a period of high perinatal mortality and morbidity.1,3 Moreover, 9.2% of surviving twins have moderate handicaps and 3.4% have severe handicaps, compared with 12.1% and 5.7%, respectively, for triplets and higher-order multiples. An analysis of the Western Australian cerebral palsy (CP) register shows a 2.8% prevalence of the problem among triplets who survive beyond their first year, and 0.7% among twins surviving to their first birthday.4 The risk of CP increases more than fourfold with twins and more than 17-fold with triplets.
Besides the very significant quality-of-life ramifications, indiscriminate use of ART also has economic consequences for society. Callahan and colleagues found that at Brigham and Womens Hospital in Boston, between 1986 and 1991, ART was associated with 2% of singleton births, 35% of twin births, and 77% of other higher-order multiple gestations, at average costs of $9,845, $37,947, and $109,765, respectively.5 Had all of those gestations been singletons, they estimated that the local health-care delivery system would have saved more than $3 million per year. Extrapolating these figures, it's clear that multifetal gestations arising from ART and OI/IUI cost our country billions of dollars annually for neonatal intensive care. Billions more must be added to factor in costs associated with CP and major handicaps, not to mention the emotional devastation to the families.
We have clear evidence that the number of embryos transferred is directly linked to the risk of multiples with ART, but less compelling data in the area of success rates.2,6 For example, among women younger than age 35, the live birth rate per transfer was actually higher when two embryos were transferred than when three, four, or five or more embryos were used (42% vs. 39.7%, 35.4%, and 33.6%, respectively).2 In contrast, the multiple rate climbed, from 33.9% with transfer of two embryos to 41.4%, 43.2%, and 46.5% with transfer of three, four, or five or more embryos, respectively. More importantly, the rate of triplets climbed precipitously from 0.8% with transfer of two embryos to 7.4%, 8.4% and 10.7% with transfer of three, four, or five or more embryos.2
Overall, live birth rates after ART decline with increasing maternal age, so more embryos are being transferred into women between 35 and 42 years. But in the US, this approach has significantly increased their risk of multiples while only modestly increasing their chance of a live birth. A similar observation has been made in the United Kingdom by Templeton and Morris.6 Among women undergoing ART, they found that the likelihood of live birth increased with the number of eggs fertilized, presumably due to greater selection of available embryos. However, transferring only two embryos rather than four did not diminish likelihood of a live birth, whereas risk of multiple birth progressively increased with transfer of every embryo beyond two.
What drives ART centers to transfer more than two embryos? One factor is intense competition generated by publication of statistics from the Society for Assisted Reproductive Technology (SART). Clearly patients are aware of these numbers and gravitate toward centers with higher live birth rates. I suspect, however, that a 37-year-old woman would accept a two- rather than four-embryo transfer and a 2.5% reduction in the live birth rate if she knew it would lower her likelihood of triplets more than tenfold. Perhaps patients should focus more on an ART center's multiple rate than on the overall success rate. Given a choice between a second IVF cycle and three fetuses affected with CP, most couples would choose the former.
Confronted by the public health implications of ART, many European nations with government-based medical systems have opted to prohibit transfer of more than two embryos, and there is growing discussion about lowering the number to one. In 2001, the International Federation of Fertility Societies reported that 37 of 39 member-countries had passed regulations or guidelines addressing the number of embryos permitted to be transferred.7 The Belgian government, for one, is convinced that by covering the costs of ART but limiting transfers to one or two embryos, they can reduce health-care costs! Since July 1, 2003, six ART cycles have been reimbursable by that government, provided that single-embryo transfers are done on the first attempt in women under 35 years and either single or double transfers are conducted in women over 35 years. Two transfers are allowed for subsequent cycles. The Belgium government has calculated that they will actually save money covering ART cycles by avoiding multifetal pregnancies.
I believe it is time for US insurers to adopt a similar strategy. By covering the costs of six ART cycles and limiting the number of embryos transferred to one or two, billions of dollars potentially will be saved by the reduction in neonatal intensive care and long-term rehabilitation costs. If insurers are not astute enough to reach this conclusion on their own, it is incumbent upon state governments to help them protect their own economic self-interest by mandating such coverage.
1. Births: Final Data for 2002. National Vital Statistics Reports. Vol. 52, No. 10, December 17, 2003.
2. Assisted Reproductive Technology Surveillance United States, 2000 CDC MMWR 2003;52:1-16.
3. Luke B, Keith LG. The contribution of singletons, twins and triplets to low birth weight, infant mortality and handicap in the United States. J Reprod Med. 1992;37:661-666.
4. Petterson B, Nelson KB, Watson L, et al. Twins, triplets, and cerebral palsy in births in Western Australia in the 1980s. BMJ. 1993;307:1239-1243.
5. Callahan TL, Hall JE, Ettner SL, et al. The economic impact of multiple-gestation pregnancies and the contribution of assisted-reproduction techniques to their incidence. N Engl J Med. 1994;331:244-249.
6. Templeton A, Morris JK. Reducing the risk of multiple births by transfer of two embryos after in vitro fertilization. N Engl J Med. 1998;339:573-577.
7. Katz P, Nachtigall R, Showstack J. The economic impact of the assisted reproductive technologies. Nat Cell Biol. 2002;4 suppl:S29-32.
Charles J. Lockwood, MD
Charles Lockwood. Editorial: It's time for a rational approach to ART. Contemporary Ob/Gyn Feb. 1, 2004;49:9, 10.