Vaginal progesterone ineffective in preventing preterm birth

A recent multicenter randomised clinical trial has cast doubt on the efficacy of vaginal micronised progesterone (VMP) in preventing preterm birth in women with arrested preterm labour (APTL)

Conducted across three university-affiliated medical centres in Israel, the study aimed to evaluate the effectiveness of daily 400 mg VMP in prolonging pregnancy after APTL.

The trial, spanning from December 2018 to February 2023, enrolled 129 participants with singleton and twin pregnancies who had undergone tocolysis between 24 to 34 weeks of gestation. Participants were randomly assigned to receive either VMP (200 mg twice daily) or no treatment until 36 weeks 6 days’ gestation or delivery, whichever came first.

Study’s findings

The study found no significant difference between the VMP group and the untreated group in terms of pregnancy prolongation or the rate of spontaneous preterm delivery (SPTD) before 37 weeks’ gestation. Both groups showed similar mean durations from enrollment to delivery (VMP: 40.0 days vs No treatment: 37.4 days) and rates of SPTD (25% vs 30%, respectively).

A subgroup analysis of twin pregnancies revealed that VMP did lead to significant benefits. Twins receiving VMP experienced longer pregnancy durations (43.7 days vs 26.1 days), delayed delivery weeks (36.5 weeks vs 34.7 weeks), shorter neonatal intensive care unit (NICU) stays (4.9 days vs 13.2 days), shorter overall hospital stays (8.3 days vs 15.1 days), and higher birth weights (2444 g vs 2018 g) compared to those without treatment.

Despite these positive outcomes in twins, the overall findings suggest that VMP at the studied dosage and regimen does not effectively prevent preterm birth in pregnancies following APTL.

How safe is preventing preterm birth?

The study’s lead author emphasised the need for further research to better understand the differential response observed in twin pregnancies versus singleton pregnancies. Factors such as uterine dynamics in multifetal pregnancies and differing hormonal responses may contribute to these divergent outcomes.

These findings contribute to ongoing debates in obstetric care regarding the use of progesterone supplementation to prevent preterm birth. Given the high stakes involved, preterm birth being a leading cause of neonatal mortality and morbidity, clinicians and researchers continue to seek effective strategies to mitigate this risk in high-risk pregnancies.

While VMP showed promise in twin pregnancies, its overall ineffectiveness in singleton pregnancies following APTL shows the complexity of managing preterm birth risk and the ongoing challenges in finding universally effective treatments.