Vaginal Progesterone Reduces the Rate of Preterm Birth in Women With a Sonographic Short Cervix: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

Boston University, Boston, Massachusetts, United States
Ultrasound in Obstetrics and Gynecology (Impact Factor: 3.85). 07/2011; 38(1):18-31. DOI: 10.1002/uog.9017
Source: PubMed


Women with a sonographic short cervix in the mid-trimester are at increased risk for preterm delivery. This study was undertaken to determine the efficacy and safety of using micronized vaginal progesterone gel to reduce the risk of preterm birth and associated neonatal complications in women with a sonographic short cervix.
This was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled asymptomatic women with a singleton pregnancy and a sonographic short cervix (10-20 mm) at 19 + 0 to 23 + 6 weeks of gestation. Women were allocated randomly to receive vaginal progesterone gel or placebo daily starting from 20 to 23 + 6 weeks until 36 + 6 weeks, rupture of membranes or delivery, whichever occurred first. Randomization sequence was stratified by center and history of a previous preterm birth. The primary endpoint was preterm birth before 33 weeks of gestation. Analysis was by intention to treat.
Of 465 women randomized, seven were lost to follow-up and 458 (vaginal progesterone gel, n=235; placebo, n=223) were included in the analysis. Women allocated to receive vaginal progesterone had a lower rate of preterm birth before 33 weeks than did those allocated to placebo (8.9% (n=21) vs 16.1% (n=36); relative risk (RR), 0.55; 95% CI, 0.33-0.92; P=0.02). The effect remained significant after adjustment for covariables (adjusted RR, 0.52; 95% CI, 0.31-0.91; P=0.02). Vaginal progesterone was also associated with a significant reduction in the rate of preterm birth before 28 weeks (5.1% vs 10.3%; RR, 0.50; 95% CI, 0.25-0.97; P=0.04) and 35 weeks (14.5% vs 23.3%; RR, 0.62; 95% CI, 0.42-0.92; P=0.02), respiratory distress syndrome (3.0% vs 7.6%; RR, 0.39; 95% CI, 0.17-0.92; P=0.03), any neonatal morbidity or mortality event (7.7% vs 13.5%; RR, 0.57; 95% CI, 0.33-0.99; P=0.04) and birth weight < 1500 g (6.4% (15/234) vs 13.6% (30/220); RR, 0.47; 95% CI, 0.26-0.85; P=0.01). There were no differences in the incidence of treatment-related adverse events between the groups.
The administration of vaginal progesterone gel to women with a sonographic short cervix in the mid-trimester is associated with a 45% reduction in the rate of preterm birth before 33 weeks of gestation and with improved neonatal outcome.

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Available from: Harish M Sehdev
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    • "Similarly, current strategies to prevent early spontaneous delivery are limited in scope and effect [39]. Apart from modification of lifestyle factors, therapies with the most evidence include vaginal progesterone supplementation [48] and cervical cerclage [49]. These interventions have mostly been studied in women with a history of preterm birth and/or with a short cervix in the midtrimester. "
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    • "Modern obstetrics are still not able to predict, prevent or treat PTD [16]. Progesterone substitution, the only promising intervention identified to date, has been shown to reduce the chance of spontaneous PTD in high-risk pregnancies, but such cases account for only a small proportion of all pregnancies [17-19]. "
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    • "Using clinical and sonographic variables, it is possible to identify a cohort of patients who are candidates for therapy [43]. Indeed, vaginal application of progesterone is currently used to prevent preterm birth in the setting of a short cervix [17], [44]. In non-pregnant women, cervical mucus viscosity and elasticity have been correlated with improved host defense against upper genital tract infections [43], [44]. "
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