Background: Progesterone has established roles in preventing preterm labor in women with history of spontaneous preterm labor and short cervix, but there is little evidence to support its use to prevent preterm delivery in women with threatened preterm labor.

Objective: To evaluate clinical efficacy of oral and vaginal progesterone on prevention of preterm delivery before 34 and 37 weeks in threatened preterm labor.

Materials and Methods: The present study was a 3-arm randomized control trial, 231 singleton pregnancies of 28- to 33-weeks-6-days who had threatened preterm labor were recruited and randomized to three groups,1) 200 mg/day vaginal micronized progesterone, 2) 30 mg/day oral dydrogesterone and 3) control group with no progesterone. All groups received identical standard treatment for threatened preterm labor. Comparison of primary outcomes, which is the preterm delivery before 34 and 37 weeks, across groups were performed using chi-square test. Secondary outcomes, which are latency period, cervical change, maternal morbidity, neonatal morbidity, and mortality, were also compared.

Results: Proportion of preterm delivery before 34 weeks was not significantly different across the three treatment groups at 16.0%, 12.0%, and 5.2% in control, oral progesterone, and vaginal progesterone groups, respectively (p=0.098). Concerning pairwise comparison, vaginal progesterone was more efficacious in preventing preterm delivery before 34 weeks than the control group (p=0.030), while oral progesterone was similarly effective to the control group (p=0.638). Proportion of preterm delivery before 37 weeks was not significantly different across the three treatment groups at 41.3%, 45.3%, and 31.2% in control, oral, and vaginal progesterone groups, respectively (p=0.182). Latency period differed across three treatment groups with a median latency of 36.5, 42.0, and 43.0 days in control, oral, and vaginal progesterone groups, respectively (p=0.041). Changes in cervical length and Bishop scores were not different across treatment groups.

Conclusion: Vaginal progesterone could prevent preterm delivery before 34 weeks and prolong latency period in women with threatened preterm labor.