Combined vaginal progesterone and cervical cerclage in the prevention of preterm birth: A systematic review and meta-analysis

BACKGROUND: Vaginal progesterone and cervical cerclage are both effective interventions for reducing preterm birth (PTB). It is currently unclear whether combined therapy offers superior effectiveness compared to single therapy. OBJECTIVE: To determine the efficacy of combining cervical cerclage and vaginal progesterone in the prevention of PTB. DATA SOURCES: We searched Medline (Ovid), EMBASE (Ovid), PsycINFO (Ovid), CINAHL (EBSCOhost), Cochrane Library (Wiley) and Scopus (from their inception to 2020). STUDY ELIGIBILITY CRITERIA: The review accepted randomized and pseudo-randomized control trials, non-randomized experimental control trials, and cohort studies. High risk patients (shortened cervical length <25mm or prior PTB) who were assigned cervical cerclage, vaginal progesterone, or both for the prevention of PTB were included. Only singleton pregnancies were assessed. STUDY APPRAISAL AND SYNTHESIS METHODS: The primary outcome was birth <37 weeks. Secondary outcomes included birth <28, <32 and <34 weeks, gestational age (GA) at delivery, days between intervention and delivery, preterm premature rupture of membranes, neonatal mortality, neonatal intensive care unit admission, intubation and birthweight. Following title and full-text screening, eight papers were included in the final analysis. Risk of bias was assessed using the Cochrane Collaboration tool for assessing the risk of bias (ROBINS-I and RoB-2). Quality of evidence was assessed using the GRADE tool. RESULTS: Combined therapy was associated with lower risk of PTB <37 weeks compared to progesterone alone (RR 0.75, 95% CI 0.58, 0.96). Compared to cerclage only, combined therapy was associated with less PTB <32 weeks, decreased neonatal mortality, increased GA and a longer interval between intervention and delivery. Compared to progesterone alone, combined therapy was associated with less PTB <32 weeks, less PTB<28 weeks, increased GA, decreased neonatal mortality and decreased neonatal intensive care unit admissions. CONCLUSIONS: Combined treatment of cervical cerclage and vaginal progesterone could potentially result in a greater reduction in PTB compared to single therapy. Further well-conducted and adequately powered randomized controlled trials are needed to assess these promising findings.