Progesterone Treatment Does Not Prevent Preterm Birth in Twin Pregnancy

Progesterone therapy does not reduce the chances of preterm birth in women pregnant with twins, reported researchers in a network sponsored by the National Institutes of Health.

An earlier study showed progesterone therapy reduced the risk for preterm birth in another category of high risk pregnant women—those carrying a single baby who had delivered a single baby prematurely in the past.

“This study shows that progesterone therapy is not beneficial for all women at risk for giving birth prematurely,” said Duane Alexander, M.D., Director of the NICHD, the NIH institute that supported the research network. “So far, the evidence supports progesterone therapy as a means to reduce preterm birth only in women pregnant with a single baby who are at risk for premature delivery because of a prior preterm birth.”

After the initial study showed progesterone therapy could reduce the likelihood of preterm birth in women carrying a single baby and who had previously given birth prematurely, many physicians began prescribing the therapy for women pregnant with twins and for other categories of women at risk for preterm birth as well. In addition to women carrying two or more babies, and those who have delivered prematurely before, also at risk for preterm delivery are pregnant women having a shortened cervix (the lower part of the uterus) and certain infections of the reproductive tract.

The study appears in the August 2, 2007 issue of The New England Journal of Medicine.

A large team of researchers from the NICHD Maternal-Fetal Medicine Units Network, led by Dwight J. Rouse, M.D., Professor of Obstetrics and Gynecology at the University of Alabama at Birmingham School of Medicine, conducted the study.

In the study, 655 women pregnant with twins were randomly assigned to receive weekly injections of a placebo or the form of progesterone known as 17-alpha hydroxyprogesterone caproate (17-OHPC), explained Catherine Y. Spong, M.D., Branch Chief of NICHD’s Pregnancy and Perinatology Branch, and the NICHD author of the study.

Progesterone is a female hormone that is produced in large quantities during pregnancy. Researchers with the Maternal Fetal Medicine Units Network reported in 2003 that weekly injections of progesterone reduced the risk of preterm birth by 34 percent among pregnant women who had given birth prematurely in an earlier pregnancy.

Women in the current study were randomly assigned to groups receiving weekly injections of either 250 mg of progesterone or a placebo. The injections started when the women were 16-20 weeks pregnant and continued until the 35th week of pregnancy or until the woman gave birth. Women in both groups had similar characteristics such as age, race, and marital status.

The researchers found that the use of progesterone did not reduce premature birth in twin pregnancies when compared with the placebo group: 41.5 percent of women on progesterone treatments delivered prematurely (before 35 weeks) or experienced fetal loss vs. 37.3 percent of women receiving placebo injections. Fetal loss describes the loss of the baby because of such factors as stillbirth or miscarriage, said Dr. Spong.

There was no difference between the two groups in the amount of time the baby spent in the womb before it was delivered. Progesterone treatment did not affect the proportion of deliveries before 37 weeks or before 32 or 28 weeks, when compared to the placebo group.

Whether the child was conceived using assisted reproductive methods or conceived spontaneously did not affect these results, nor did the type of placentation (whether the babies shared a placenta or had two separate placentas). The study could not determine whether progesterone therapy could reduce the chances of preterm birth in women pregnant with twins who had delivered prematurely in a previous pregnancy. Fewer than 10 percent of women participating in the current study had experienced a prior preterm delivery—a number too small to allow a reliable estimate of the effect of treatment in this group of women.

Premature infants are often very small and at greater risk for life-threatening infections, blindness, breathing problems, learning and developmental disabilities, and cerebral palsy. Premature babies are also more likely to die from SIDS (sudden infant death syndrome) than full-term infants. Premature birth is one of the leading causes of infant death.

Women pregnant with twins are at higher risk for preterm birth than are other pregnant women, with more than half delivering prematurely, said Dr. Spong. Over one quarter of all very low birth weight infants (less than 1500 grams or 3.3 pounds) are the result of a multiple pregnancy. Multiple pregnancy accounts for one in seven infant deaths, she said.

Overall, the number of twin births has increased in recent years. Between 1980 and 2004, the rate of twin birth rose from 18.9 to 32.2 per 1000 live births, the study authors wrote, citing data from the National Center for Health Statistics.

Dr. Spong added that NIH-funded researchers are testing progesterone in other groups of women who are at risk for preterm birth, such as women with shortened cervixes and women pregnant with triplets.


The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Web site at

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit

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