Research Letter

A stepwise approach for the management of short cervix: time to evolve beyond progesterone treatment in the presence of progressive cervical shortening

Vaginal progesterone and cervical cerclage are both effective interventions for reducing preterm birth. It is currently unclear whether combined therapy offers superior effectiveness than single therapy. This study aimed to determine the efficacy of combining cervical cerclage and vaginal progesterone in the prevention of preterm birth.

We searched Medline (Ovid), EMBASE (Ovid), PsycINFO (Ovid), CINAHL (EBSCOhost), Cochrane Library (Wiley), and Scopus (from their inception to 2020).

The review accepted randomized and pseudorandomized control trials, nonrandomized experimental control trials, and cohort studies. High risk patients (shortened cervical length <25mm or previous preterm birth) who were assigned cervical cerclage, vaginal progesterone, or both for the prevention of preterm birth were included. Only singleton pregnancies were assessed.

The primary outcome was birth <37 weeks. Secondary outcomes included birth <28 weeks, <32 weeks and <34 weeks, gestational age at delivery, days between intervention and delivery, preterm premature rupture of membranes, cesarean delivery, neonatal mortality, neonatal intensive care unit admission, intubation, and birthweight. Following title and full-text screening, 11 studies 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 (Grading of Recommendations, Assessment, Development, and Evaluations) tool.

Combined therapy was associated with lower risk of preterm birth at <37 weeks than cerclage alone (risk ratio, 0.51; 95% confidence interval, 0.37−0.79) or progesterone alone (risk ratio, 0.75; 95% confidence interval, 0.58−0.96). Compared with cerclage only, combined therapy was associated with preterm birth at <34 weeks, <32 weeks, or <28 weeks, decreased neonatal mortality, increased birthweight, increased gestational age, and a longer interval between intervention and delivery. Compared with progesterone alone, combined therapy was associated with preterm birth at <32 weeks, <28 weeks, decreased neonatal mortality, increased birthweight, and increased gestational age. There were no differences in any other secondary outcomes.

Combined treatment of cervical cerclage and vaginal progesterone could potentially result in a greater reduction in preterm birth than in single therapy. Further, well-conducted and adequately powered randomized controlled trials are needed to assess these promising findings.

Several articles have implied that progestogen supplementation during pregnancy to reduce the risk of preterm birth may increase the risk for developing gestational diabetes mellitus.

The purpose of the present meta-analysis was to accumulate existing evidence concerning this correlation.

We searched Medline (1966–2019), Scopus (2004–2019), Clinicaltrials.gov (2008–2019), EMBASE (1980–2019), Cochrane Central Register of Controlled Trials CENTRAL (1999–2019), and Google Scholar (2004–2019) databases.

Randomized trials and observational studies were considered eligible for inclusion in the present meta-analysis. To minimize the possibility of article losses, we avoided language, country, and date restrictions.

The methodological quality of included studies was evaluated with the Cochrane risk of bias and the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool. Meta-analysis was performed with the RevMan 5.3 and secondary analysis with the Open Meta-Analyst software. Trial sequential analysis was conducted with the trial sequential analysis program.

Overall, 11 studies were included in the present meta-analysis that recruited 8085 women. The meta-analysis revealed that women who received 17-alpha hydroxyprogesterone caproate had increased the risk of developing gestational diabetes mellitus (risk ratio, 1.73, 95% confidence interval, 1.32–2.28), whereas women who received vaginal progesterone had a decreased risk, although the effect did not reach statistical significance because of the unstable estimate of confidence intervals (risk ratio, 0.82, 95% confidence interval, 0.50–1.12). Meta-regression analysis indicated that neither the methodological rationale for investigating the prevalence of gestational diabetes mellitus (incidence investigated as primary or secondary outcome) (coefficient of covariance, –0.36, 95% confidence interval, –0.85 to 0.13, P = .154) nor the type of investigated study (randomized controlled trial/observational) (coefficient of covariance –0.361, 95% confidence interval, –1.049 to 0.327, P = .304) significantly altered the results of the primary analysis. Trial sequential analysis suggested that the meta-analysis concerning the correlation of 17-alpha hydroxyprogesterone caproate was of adequate power to reach firm conclusions, whereas this was not confirmed in the case of vaginal progesterone.

The results of the present meta-analysis clearly indicate that women who receive supplemental 17-alpha hydroxyprogesterone caproate for the prevention of preterm birth have an increased risk of developing gestational diabetes mellitus. On the other hand, evidence concerning women treated with vaginal progesterone remains inconclusive.