Fertility treatments are known to have a profound impact on the lives of the individuals who use them, but what about their impact on the nation's vital statistics? In search of that answer, Brown University researchers recently calculated that more than a third of twin births and more than three-quarters of triplets or higher-order births during 2011 were the result of fertility treatments. Their results are published in the New England Journal of Medicine. "We do have a real problem with way too many multiple births in the U.S. with consequences to both mothers and babies," Eli Y. Adashi, MD, professor of obstetrics and gynecology at Brown University, stated in a press release. "It's an unintended consequence of otherwise well intentioned and remarkable technology."

Mining the Data

In vitro fertilization (IVF) is the process by which an egg is fertilized by sperm outside the body and then implanted in a woman’s womb. The first successful IVF procedure dates back to 1978 and the child born of that procedure, Louise Brown, has gone on to have children of her own. Today, a whole range of other fertility treatments exist, including fertility drugs, which stimulate the production of eggs; artificial insemination, in which sperm is medically as opposed to naturally introduced into the female vagina; and assisted reproductive technology (ART), which encompasses all methods of achieving birth through artificial or partially artificial means, such as surrogacy as well as IVF.

Although information on ground-breaking IVF procedures has been generally available since 1997, very little data has ever been compiled on non-IVF procedures and their possible contribution to rates of multiple births. The reason this information is crucial is because multiple gestations may come with higher health risks for babies and mothers alike. Twins, triplets, and other multiples are more likely to have problems with their brain development and nerves if they are born early. At the same time, while pregnant, a mother is more likely to develop high blood pressure or diabetes.

In order to investigate statistical outcomes arising from these treatments, the Brown research team worked with Aniket Kulkarni of the U.S. Centers for Disease Control and Prevention to arrive at their estimates. First, the team gathered data on multiple births between the years 1962 and 1966 (before the availability of medical fertility treatments); this data from the 1960s provided a statistical baseline for natural multiple birth rates without medical intervention. Next, the team collected similar data for the years between 1971 and 2011. After completing their dataset, the team then estimated the role of non-IVF technologies by subtracting the multiple births which arose from IVF from the overall number of multiple births, taking into account the impact of maternal age on birth plurality. What did they find?

The contribution of fertility treatments over the last four decades was simply remarkable: Between 1971 and 2011, the percent of U.S. births that were multiples doubled to 3.5 percent from 1.8 percent. Meanwhile, IVF improved during that same time span so that single embryo transfers often succeeded in producing healthy pregnancies. Since 1998, when new IVF guidelines discouraged implantation of three or more embryos, the proportion of triplets or higher multiple births resulting from medical assistance actually dropped from a peak of 84 percent. Yet, non-IVF fertility treatments — such as ovarian stimulation and ovulation induction using the frequently prescribed drug Clomid (clomiphene citrate) — increased during that period to become the predominant source of medically assisted multiple births.

"IVF is moving, in a sense, in the right direction and cleaning up its act, whereas the non-IVF technologies are at a minimum holding their own and possibly getting worse," Adashi stated in a press release. "From a policy point of view what that means is that [we] need to focus on the non-IVF technologies, which really hasn't been done in a concerted way because they weren't considered all that relevant to this mix."

Source: Adashi EY, Kulkarni A, Jamieson D, et al. Fertility treatments and multiple births in the United States. New England Journal of Medicine. 2013.