Vaginal progesterone for preterm birth prevention in women with arrested preterm labor

Abstract

Objective

We tested the hypothesis that administration of vaginal progesterone in women with arrested preterm labor would result in lower rates of preterm birth <37 weeks compared to placebo.

Study design

We performed a randomized, placebo-controlled trial comparing vaginal progesterone to placebo in women with arrested preterm labor. Our trial included women with a singleton or twin gestation at 24^0/7–33^6/7 weeks’ gestation who presented with preterm labor with cervical dilation ≥1 centimeter but remained undelivered. Participants were randomized to receive vaginal progesterone 200 mg daily or an identical placebo. The primary outcome was preterm birth <37 weeks. We performed an updated systematic review and meta-analysis of clinical trials, including our results. We searched MEDLINE, EMBASE, CINHAL, Scopus, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov using the key terms to identify relevant trials. The risk of bias was appraised using the Cochrane risk-of-bias tool. Data were synthesized using random-effects models. Heterogeneity was assessed using Higgins I².

Results

The randomized trial was prematurely terminated due to slow recruitment. There were 18 women randomized to receive vaginal progesterone who had complete follow-up data and 18 women in the placebo group. The risk of preterm birth <37 weeks was not significantly different in the groups (RR 1.10, 95% CI 0.63–1.19). Secondary outcomes were also similar. Thirteen trials with 1658 women (835 in the vaginal progesterone and 823 in the control groups) were included in the meta-analysis. Risk of preterm birth <37 weeks was similar in women who received progesterone and those in the control group (pooled RR 1.06, 95% CI 0.83–1.35). Latency was significantly longer among women with arrested preterm labor who received vaginal progesterone (weighted mean difference: 9.2 d, 95% CI 3.2–15.1), but further analysis showed that prolonged latency was only observed in the subgroup of studies that were not placebo-controlled.

Conclusions

This randomized controlled trial and meta-analysis do not support the use of vaginal progesterone for the prevention of preterm birth in women who present in preterm labor.

Keywords:

• Progesterone
• vaginal administration of progesterone
• arrested labor
• preterm labor
• tocolysis

Acknowledgments

The authors would like to thank Stephanie Schulte, medical librarian and assistant director of research and education services at the Health Sciences Library at the Ohio State University for her assistance in developing the search strategy for the systematic review and meta-analysis.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Study registration

The randomized controlled trial was registered with clinicaltrials.gov on 25 April 2013. Participant enrollment began in May 2013. Clinical trial identification number: NCT01840228. https://clinicaltrials.gov/ct2/show/NCT01840228?term=progesterone&cond=Preterm+Labor&draw=3&rank=17. The systematic review and meta-analysis was registered with the PROSPERO registry for systematic reviews on May 5, 2020. Review identification number: PROSPERO 2020 CRD42020184215.

Additional information

Funding

The study was funded by the Thrasher Research Fund through the Early Career Award. The sponsor had no role in the study design; collection, analysis, or interpretation of data; writing of the report; or decision to submit the manuscript for publication.