Vaginal progesterone for the prevention of spontaneous preterm birth in high-risk pregnant women: a narrative review

Preterm birth (PTB) remains one of the most important problems in modern obstetrics and neonatology and is a leading cause of perinatal morbidity and mortality. The most consistent evidence for vaginal progesterone efficacy has been obtained primarily in women with a singleton pregnancy and sonographic short cervical length, rather than in all high-risk pregnant women. This narrative review summarizes current data on the role of vaginal progesterone in PTB prevention, including pharmacological aspects, indications for use, clinical efficacy, contradictory evidence, practical recommendations, and cost-effectiveness. The review is based on 71 sources, including publications from 2019–2026 and key earlier randomized trials, meta-analyses, and clinical guidelines that are methodologically or clinically relevant to evaluating vaginal progesterone for PTB prevention. The most consistent evidence for vaginal progesterone use was obtained in women with singleton pregnancy and short cervical length (≤ 25 mm). In multiple pregnancy, efficacy appears to be limited to the subgroup of women with short cervical length. Evidence regarding vaginal progesterone efficacy in women with former PTB without cervical shortening remains contradictory. International guidelines generally support the use of vaginal progesterone in women with short cervix in singleton pregnancy. In case of shortening, cervical length screening followed by vaginal progesterone administration may be a cost-effective strategy when adapted to local healthcare conditions.

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