One modality that showed promise for prevention of preterm labor in small trials was treatment with progestational agents. Two separate meta-analyses assessing the effects of progesterone on preterm labor arrived at contradictory conclusions. Goldstein found no evidence of effectiveness of progestational compounds in the prevention of preterm delivery. Daya, on the other hand, showed a beneficial effect. A third meta-analysis, restricted to trials of 17-alpha Hydroxyprogesterone Caproate showed, in composite, a significant reduction in the rate of preterm delivery. A recently reported trial comparing 17-alpha Hydroxyprogesterone Caproate therapy with placebo to prevent preterm birth in a select, high-risk group of women (documented history of a previous spontaneous preterm birth <37 weeks of gestation) was terminated prematurely when results showed a significant protection against recurrent preterm birth for women who received 17-alpha Hydroxyprogesterone Caproate. Other studies, using the same form of progesterone, did not demonstrate such a beneficial effect. A study in 1980 has failed to show any benefit of 17-alpha Hydroxyprogesterone Caproate in women with twin gestations. In that study, 77 women with twin gestations were treated during the last trimester with weekly injections of either 17-alpha Hydroxyprogesterone Caproate or a placebo. The study was limited by the small sample size. In addition, the progesterone therapy was started late in the third trimester of gestation which could partly explain the inability to detect a beneficial effect of progesterone in this group of patients using that particular regimen. Most reported trials on other progesterone compounds have failed to demonstrate a substantial effect in reducing the risk of preterm delivery. However, a recent small randomized placebo-controlled trial of supplemental vaginal progesterone in women at high risk for preterm birth revealed that the preterm birth rate at less than 34 weeks of gestation was significantly lower among women receiving progesterone than among those receiving placebo.8 The results of this study and that of the National Institute of Child Health and Human Development7 support the hypothesis that progesterone supplementation reduces preterm birth in a select very high-risk group of women. In fact, the American College of Obstetricians and Gynecologists Committee on Obstetric Practice believes that further studies are needed to evaluate the use of progesterone in patients with other high-risk obstetric factors, such as multiple gestations, short cervical length, or positive test results for cervicovaginal fetal fibronectin.