We sought to evaluate the efficacy of maintenance tocolysis with vaginal progesterone compared to control (placebo or no treatment) in singleton gestations with arrested preterm labor (PTL) in a metaanalysis of randomized controlled trials.

Searches were performed in MEDLINE, OVID, Scopus, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials with the use of a combination of key words and text words related to “progesterone,” “tocolysis,” and “preterm labor” from 1966 through November 2014. We included all randomized trials of singleton gestations that had arrested PTL and then were randomized to maintenance tocolysis treatment with either vaginal progesterone or control (either placebo or no treatment). All published randomized studies on progesterone tocolysis were carefully reviewed. Exclusion criteria included maintenance tocolysis in women with preterm premature rupture of membrane, maintenance tocolysis with 17-alpha-hydroxyprogesterone caproate, and maintenance tocolysis with oral progesterone. The summary measures were reported as relative risks (RRs) with 95% confidence interval (CI). The primary outcome was preterm birth (PTB) <37 weeks.

Five randomized trials, including 441 singleton gestations, were analyzed. Women who received vaginal progesterone maintenance tocolysis for arrested PTL had a significantly lower rate of PTB <37 weeks (42% vs 58%; RR, 0.71; 95% CI, 0.57–0.90; 3 trials, 298 women). Women who received vaginal progesterone had significantly longer latency (mean difference 13.80 days; 95% CI, 3.97–23.63; 4 trials, 368 women), later gestational age at delivery (mean difference 1.29 weeks; 95% CI, 0.43–2.15; 4 trials, 368 women), lower rate of recurrent PTL (24% vs 46%; RR, 0.51; 95% CI, 0.31–0.84; 2 trials, 122 women), and lower rate of neonatal sepsis (2% vs 7%; RR, 0.34; 95% CI, 0.12–0.98; 4 trials, 368 women).

Maintenance tocolysis with vaginal progesterone is associated with prevention of PTB, significant prolongation of pregnancy, and lower neonatal sepsis. However, given the frequent lack of blinding and the generally poor quality of the trials, we do not currently suggest a change in clinical care of women with arrested PTL. We suggest instead well-designed placebo-controlled randomized trials to confirm the findings of our metaanalysis.