# Pregnancy outcomes in women at high risk of preterm birth receiving a vaginal cervical cerclage with, or without, progesterone: A retrospective, secondary analysis of the C-STICH randomised controlled trial data

## TL;DR

This study found that combining vaginal cervical cerclage with progesterone may reduce pregnancy loss in high-risk women.

## Contribution

The study provides new evidence on the combined use of cerclage and progesterone for reducing pregnancy loss.

## Key findings

- Progesterone use with cerclage was linked to a 5.9% pregnancy loss rate versus 8.3% without.
- Adjusted analysis showed a statistically significant reduction in pregnancy loss risk.
- The study highlights the potential of combination therapy in high-risk pregnancies.

## Abstract

Vaginal cervical cerclage and progesterone are established treatments for prevention of pregnancy loss and prematurity. There is limited data to assess the effect of these treatments in combination. The objective of this study was to investigate the association between progesterone and no progesterone treatment on pregnancy outcomes in women at high risk of preterm birth who had received a vaginal cervical cerclage.

This is a secondary post-hoc analysis of women recruited to the C-STICH randomised controlled trial, which recruited in 75 obstetric units in the UK between 2015 and 2021. In the C-STICH trial, women with a singleton pregnancy, receiving a vaginal cervical cerclage due to a history of pregnancy loss or premature birth, or if indicated by ultrasound, were randomised to cerclage with braided or monofilament suture, with a primary outcome of pregnancy loss, defined as miscarriage, stillbirth, or neonatal death in the first week of life. In this secondary analysis, the primary outcome was pregnancy loss, defined as miscarriage and perinatal mortality, including any stillbirth or neonatal death in the first week of life. Secondary maternal outcomes included miscarriage and previable neonatal death; stillbirth; gestational age at delivery; preterm pre labour rupture of membranes, and sepsis. Secondary neonatal outcomes included early/late neonatal death and sepsis. For each outcome, regression models were fitted adjusting for prespecified prognostic variables.

From the 2,048 women recruited to C-STICH, 1943 (95%) women had a vaginal cerclage placed and available progesterone data. Of these, 834 (43%) women received progesterone and 1,109 (57%) did not receive progesterone. In women with primary outcome data available, in our predefined analysis pregnancy loss occurred in 49 (5.9%) of 832 women who received progesterone and 91 (8.3%) of 1,103 women who did not receive progesterone (adjusted* risk ratio 0.70 (95% confidence interval (CI) [0.50, 0.99]); adjusted risk difference −0.02 (95% CI [−0.04, −0.001], *adjusted for indication, obstetric history, surgical technique, and maternal age). Further exploratory analysis excluding women who had termination of pregnancy for foetal anomaly demonstrated a nonsignificant reduction in the risk of pregnancy loss. Key limitations of this study include a nonrandomised trial design and unknown confounding relating to variation in progesterone use.

In women with a vaginal cervical cerclage and concomitant progesterone there appears to be an association with a reduced risk of pregnancy loss. This combination therapy may be an important opportunity to further reduce the risk of pregnancy loss in this high-risk cohort.

We aimed to evaluate whether the risk of pregnancy loss in women at high risk of premature birth with a vaginal cervical suture in place is different with and without progesterone treatment.

The researchers completed a secondary analysis of the data from C-STICH, a randomised controlled trial of different suture types for vaginal cervical cerclage, to compare outcomes pregnancy outcomes with and without additional progesterone therapy.

Use of progesterone and vaginal cerclage was associated with a statistically significant reduction in the risk of pregnancy loss in an adjusted analysis (5.9% versus 8.3%).

In women at high risk of preterm birth, combination therapy with vaginal cervical cerclage, and progesterone is associated with a statistically significant reduction in the risk of pregnancy loss.

This analysis benefits from the large population recruited to the C-STICH trial but interpretation is limited by the available details regarding timing and indications for progesterone use.

A future randomised trial is not realistic, however, progesterone is a widely accepted therapy for prevention of preterm birth, and this research provides new evidence to guide the clinical management of women at high risk of preterm birth.

In a secondary analysis of the CSTICH trial, Victoria Hodgetts Morton and colleagues investigate the association between progesterone treatment versus no treatment on pregnancy outcomes in women at high risk of preterm birth who had received a vaginal cervical cerclage.