Fertility Treatment–Related Multiple Births Start to Decline

Larry Hand

December 04, 2013

Although fertility treatments have contributed to a substantial increase in the number of multiple births in the United States during the last 4 decades, the rate of triplet or higher-order births during the last few years has decreased, according to an article published in the December 5 issue of the New England Journal of Medicine. The decrease is likely a result of fewer transfers of 3 or more embryos during in vitro fertilization (IVF).

Aniket D. Kulkarni, MB BS, MPH, from the Women's Health and Fertility Branch of the Centers for Disease Control and Prevention, Atlanta, Georgia, and colleagues conducted an analysis of natural conception birth data for the years 1962 through 1966, before fertility treatments, and compared that with data on births from 1971 through 2011.

The researchers then calculated estimates for the annual proportion of births attributable to either IVF or non-IVF treatments compared with natural conception births., The researchers factored maternal age into their estimates to compensate for the trend of women having multiple births at older ages.

Although twin births increased by a factor of 1.9 from 1971 to 2009, the year of the highest rate of twin births, the rate of triplet and higher-order births increased by a factor 6.7, with 1998 being the year of the highest rate of triplet or higher births. After that, the rate of triplet or higher births actually declined 29%, going from 1.94 to 1.37 per 1000 live births between 1998 and 2011 (P < .001).

Proportionally, total multiple births increased from 1.8% of total births in 1971 to 3.5% in 2011. Multiple births declined among women younger than 30 years (39% twins, 60% triplet or higher), whereas twin and triplet or higher births increased from 24% to 54%, for an increase of 125%, among women older than 30 years.

Twin births resulting from medically assisted conceptions increased from 27% of births in 1998 to 36% in 2011 (P < .001), whereas the proportion of medically assisted triplet and higher births declined from 84% in 1998 to 77% in 2011 (P < .001).

The proportion of twin births attributable to IVF increased during the period from 1998 to 2011 (70%; P < 0.001), whereas the proportion of triplet or higher births attributable to IVF declined (33%; P < .001. The proportion of twin births attributed to non-IVF treatments increased from 16% in 1998 to 19% in 2011 (P = .008), whereas the proportion of triplet or higher births attributed to non-IVF treatments increased from 36% to 45% (P < .001).

"Concrete Sense"

"From a clinic perspective, this gives us a concrete sense of all the multiples that are born in the United States, how IVF procedures are contributing to that trend, and also non-IVF procedures," Jennifer F. Kawwass, MD, from the Department of Gynecology and Obstetrics at the Emory University School of Medicine in Atlanta, told Medscape Medical News.

"It is reassuring that they noticed that the rate of triplets has decreased from 1998 to 2011, which is likely a reflection of the guidelines from the American Society of Reproductive Medicine in 1998, and that it was coupled with a decrease in the number of triple-embryo transfers and an increase in single-embryo transfers over that same time period," she continued.

However, she added, "There's still room for improvement."

Multiple births increase risks of adverse events for mothers and fetuses, such as preterm delivery leading to morbidity for the baby and risks of hypertension, preeclampsia, and gestational diabetes for mothers, she said.

"The contribution of non-IVF medical conceptions to multiples is still increased over that period of time, so that suggests that there is room to improve the number of multiples that are resulting from procedures other than IVF," Dr. Kawwass explained.

A strength of the study is the age factoring, she said. "As women get older, they're more likely to have a multiple birth by natural conception alone, so [the researchers] factored in increasing maternal age into their calculation, which is something that has not been done in previous studies. By incorporating maternal age into their model, they were less likely to be overestimating the risks."

This research was supported by the Centers for Disease Control and Prevention. One coauthor has reported receiving fees for board membership and holding stock in Alere. The other authors and Dr. Kawwass have disclosed no relevant financial relationships.

N Engl J Med. 2013;369:2218-2225. Abstract

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