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Examining the Evidence

Does vaginal progesterone reduce the risk of preterm birth in a high-risk woman?

September 2008 · Vol. 20, No. 09

No Prophylactic treatment with vaginal progesterone did not reduce the incidence of preterm birth (i.e., birth at 32 weeks’ gestation or earlier) in women who had a history of spontaneous preterm birth, according to the results of a randomized, double-blind, placebo-controlled multinational trial.


Two studies published in 2003 rekindled interest in the use of progestational agents for the prevention of recurrent preterm birth. Da Fonseca and colleagues randomized patients who had risk factors for premature birth to daily vaginal administration of a natural progesterone suppository or placebo and demonstrated a significant reduction in birth before 34 weeks. 1 In a larger, multicenter trial in the United States, Meis and associates randomized patients who had a prior preterm birth to weekly administration of intramuscular 17α-progesterone caproate or placebo. 2 Compared with the control group, the treatment group had a one-third reduction in births before 37 weeks, and a near 50% reduction in deliveries before 32 weeks’ gestation.

Since these studies were published, there has been much enthusiasm about the use of progesterone to reduce the incidence of preterm birth, but obstacles remain to widespread implementation of recommendations. First, 17α-progesterone caproate is not approved by the Food and Drug Administration for any indication in this country, and is not available from any major drug manufacturer. Physicians who have adopted its use for patients who have a history of preterm birth have to obtain it from a compounding pharmacy.

Use of a vaginally administered preparation would likely overcome these obstacles and meet with greater patient acceptance, but widespread use awaits further research confirming its efficacy.

In outcomes, few differences between treatment and placebo groups

O’Brien and colleagues recruited women between 18 and 23 weeks’ gestation who had previously delivered prematurely and assigned them to daily vaginal administration of 90 mg of progesterone (in gel) or placebo. Treatment was administered until 37 weeks’ gestation, delivery, or premature rupture of membranes. Outcomes were similar in the two groups, with no statistical differences in delivery before 32 or 37 weeks’ gestation, or in mean birth weight.

Nor did the groups differ in the incidence of admission for preterm labor, use of tocolytic therapy, neonatal morbidity, or NICU admission.

The authors concluded that vaginally administered progesterone does not reduce the frequency of recurrent preterm birth in women who have a history of spontaneous preterm birth.


The negative results of this well-designed study should persuade you not to adopt the vaginal route of progesterone administration as a means of preventing recurrent preterm birth. Although data have been published that vaginal progesterone reduces the rate of preterm birth in patients with a very short cervical length (≤15 mm), this is a small fraction of the patients at risk.

The final word isn’t in yet, but studies under way may shed light on the optimal dosing and route of administration for different subpopulations of patients—so that further benefit can be achieved.—ALAN M. PEACEMAN, MD


1. Da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk. Am J Obstet Gynecol. 2003;188:419-424.

2. Meis PJ, Klebanoff M, Thom E, et al. For the National Institute of Child Health and Human Development Maternal–Fetal Medicine Units Network. Prevention of recurrent preterm delivery by 17-alpha-hydroxyprogesterone caproate. N Engl J Med. 2003;348:2379-2385.