Women with twin pregnancy are at high risk for spontaneous preterm delivery. Progesterone
seems to be effective in reducing preterm birth in selected high-risk singleton pregnancies,
albeit with no significant reduction in perinatal mortality and little evidence of
neonatal benefit. We investigated the use of progesterone for prevention of preterm
birth in twin pregnancy.
In this double-blind, placebo-controlled trial, 500 women with twin pregnancy were
recruited from nine UK National Health Service clinics specialising in the management
of twin pregnancy. Women were randomised, by permuted blocks of randomly mixed sizes,
either to daily vaginal progesterone gel 90 mg (n=250) or to placebo gel (n=250) for
10 weeks from 24 weeks' gestation. All study personnel and participants were masked
to treatment assignment for the duration of the study. The primary outcome was delivery
or intrauterine death before 34 weeks' gestation. Analysis was by intention to treat.
Additionally we undertook a meta-analysis of published and unpublished data to establish
the efficacy of progesterone in prevention of early (<34 weeks' gestation) preterm
birth or intrauterine death in women with twin pregnancy. This study is registered,
number ISRCTN35782581.
Three participants in each group were lost to follow-up, leaving 247 analysed per
group. The combined proportion of intrauterine death or delivery before 34 weeks of
pregnancy was 24.7% (61/247) in the progesterone group and 19.4% (48/247) in the placebo
group (odds ratio [OR] 1.36, 95% CI 0.89-2.09; p=0.16). The rate of adverse events
did not differ between the two groups. The meta-analysis confirmed that progesterone
does not prevent early preterm birth in women with twin pregnancy (pooled OR 1.16,
95% CI 0.89-1.51).
Progesterone, administered vaginally, does not prevent preterm birth in women with
twin pregnancy.
Chief Scientist Office of the Scottish Government Health Directorate.