Cervical pessary is not superior to vaginal progesterone in individuals with a singleton pregnancy and a short cervix: a randomized controlled trial

Background: For asymptomatic individuals with a singleton pregnancy and a short cervix, vaginal progesterone significantly decreases the risk of PTB and improves perinatal outcomes. Cervical pessary is another option that has been evaluated with inconclusive results. There is, however, a lack of head-to-head comparisons between pessary and vaginal progesterone in this high risk population.

Objective: This randomized controlled trial (RCT) aims to compare the effectiveness of pessary and vaginal progesterone for the prevention of PTB in individuals with a singleton pregnancy and a CL ≤25 mm.

Study design: We conducted an open-label, multi-center, RCT (NCT04300322) at 3 hospitals in Vietnam. Asymptomatic individuals with a singleton pregnancy and a CL ≤25 mm (at 16-22 weeks) were randomized (1:1 ratio) to receive either an Arabin cervical pessary or 200-mg vaginal progesterone daily. Primary outcome was PTB <37 weeks of any cause. Secondary outcomes were maternal and neonatal complications. We planned to recruit 804 women to assess a 10% absolute risk reduction in PTB <37 weeks (alpha-error 0.05, power 80%, 5% lost to follow-up). In view of the potential harm of pessary on perinatal mortality and PTB <28 weeks reported recently in 2 recent trials, our study was halted on June 2023. Analysis was by intention-to-treat.

Results: Between May 2020 and May 2023, we randomized 301 participants to pessary (N=150) or vaginal progesterone (N=151). Seven participants withdrew consent and 13 were lost to follow-up, resulting in 281 participants available for analysis (pessary group N=139; vaginal progesterone group N=142). The primary outcome, any PTB <37 weeks rate, occurred in 15.1% in the pessary group vs 14.1% in the vaginal progesterone group (RR 1.07; 95% CI, 0.61-1.9). PTB <28 weeks and perinatal death rates were higher in the pessary group, although these differences did not reach statistical significance (7.9% vs 4.2%, RR 1.87; 95% CI, 0.71%-4.9% and 4.3% vs 2.8%, RR 1.5; 95% CI, 0.34-9.2; respectively). Vaginal discharge was significantly more frequent in the pessary group.

Conclusion: In this prematurely halted RCT involving individuals with a singleton pregnancy and a CL ≤25 mm, the use of cervical pessary was not found to be superior to vaginal progesterone in preventing preterm birth before 37 weeks. However, vaginal progesterone was associated with nonsignificantly lower rates of PTB <34, <28 weeks, and perinatal death. Our findings, along with other curent evidence, suggest that vaginal progesterone should be preferred over pessary for PTB prevention in individuals with a singleton pregnancy and a short cervix.