Stewart LA, Simmonds M, Duley L, et al. - Preterm birth, which is a global health priority, and adverse neonatal outcomes could be reduced by using a progestogen during high-risk pregnancy. Herein, a systematic review was performed of randomized trials comparing vaginal progesterone, intramuscular 17-hydroxyprogesterone caproate (17-OHPC), or oral progesterone with control, or with each other, in asymptomatic women at risk of preterm birth. A total of 47 eligible trials were identified in initial searches. Thirty of these trials had available individual participant data. Later on, an additional trial was included in a targeted update. Hence, there was availability of data from a total of 31 trials (11,644 women and 16,185 offspring). Findings suggest that in high-risk singleton pregnancies, reduction in birth before 34 weeks' gestation occurs in correlation with vaginal progesterone and 17-OHPC. Given increased underlying risk, women with a short cervix exhibit greater absolute risk reduction, hence these women might benefit the most from the treatment. Evidence supporting the use of oral progesterone is insufficient. Based on findings, they emphasize discussing an individual's risk, potential benefits, harms and practicalities of intervention in shared decision making with women with high-risk singleton pregnancies. Evidence does not yield support for treatment of unselected multifetal pregnancies with a progestogen.