Prevention of Preterm Birth by Cervical Pessary Combined with Vaginal Progesterone: a Systematic Review and Meta-analysis with Trial Sequential Analysis

Abstract

This study was to assess the effectiveness of cervical pessary combined with vaginal progesterone for the prevention of preterm birth (PTB). Ten studies about singleton [five randomized controlled trials (RCTs), vs vaginal progesterone; four cohorts, vs vaginal progesterone; two cohorts, vs cervical cerclage + vaginal progesterone] and two cohort studies about multiple pregnancies (vs vaginal progesterone) were included after searching electronic databases. For singleton pregnancies, the meta-analysis of three non-RCTs [relative risk (RR) = 0.41, p = 0.001] or total trials in non-Asian country (RR = 0.56, p = 0.03) revealed that compared with vaginal progesterone alone, cervical pessary + vaginal progesterone treatment had significant effectiveness on preventing PTB < 34 weeks, but not for five RCTs; meta-analysis of two trials showed that cervical pessary + vaginal progesterone had no significant prevention effects of PTB compared with cervical cerclage + vaginal progesterone. For multiple pregnancies, meta-analysis of two trials showed that compared with vaginal progesterone, cervical pessary + vaginal progesterone treatment increased neonatal birth weight (standardized mean difference = 0.50, p = 0.01). Trial sequential analysis implied additional studies were required. Four studies vs other controls (pessary, three-combined, tocolysis, conservative or no treatment; one study, each) were selected for systematic review. In conclusion, cervical pessary combined with vaginal progesterone may be safe and effective to prevent PTB in singleton pregnancies and increase neonatal birth weight in the multiple pregnancies compared with vaginal progesterone alone.

Keywords: Cervical pessary; Delivery; Perinatal outcome; Preterm birth; Vaginal progesterone.

Fig. 1

PRISMA flow diagram showing literature search process

Fig. 2

Forest plot to assess the efficacy of cervical pessary plus vaginal progesterone compared to the vaginal progesterone alone treatment group. A–C Meta-analysis of RCTs (A, a random-effects model), non-RCT (B, a fixed-effects model), and total trials (C, a random-effects model) to observe the effects on preventing preterm birth before 34 weeks of gestation in singleton pregnancies. RCTs, randomized controlled trials; CI, confidence interval

Fig. 3

Sensitivity analysis for RCTs (A), non-RCT (B), and total trials (C) to observe the effects on preventing preterm birth < 34 weeks of gestation in singleton pregnancies. RCTs, randomized controlled trials; CI, confidence interval

Fig. 4

Trial sequential analysis for the effects of cervical pessary plus vaginal progesterone on preterm birth < 34 weeks of gestation in singleton pregnancies using five RCTs. RCTs, randomized controlled trials; RIS, required information size

Fig. 5

Trial sequential analysis for the effects of cervical pessary plus vaginal progesterone on preterm birth < 34 weeks of gestation in singleton pregnancies using three non-RCTs. RCTs, randomized controlled trials; RIS, required information size

Fig. 6

Trial sequential analysis for the effects of cervical pessary plus vaginal progesterone on preterm birth < 34 weeks of gestation in singleton pregnancies using five RCTs and three non-RCTs. RCTs, randomized controlled trials; RIS, required information size