**7. Vaginal administration of progesterone**

Vaginal progesterone appears to reduce the risk of preterm delivery. In a statistical meta-analysis of randomized trials that administered vaginal progesterone to asymptomatic pregnant women with shortened cervical length, vaginal progesterone was found to reduce delivery before 28 weeks of gestation (RR 0.51; 95% CI 0.31, 0.85), before 33 weeks of gestation (RR 0.56; 95% CI 0.31, 0.85) and before 35 weeks of gestation (RR 0.67; 95% CI 0.51, 0.89) [36–42].

Also, the use of vaginal progesterone was associated with a reduction in neonatal mortality and morbidity (RR 0.59; 95% CI 0.38, 0.91). Despite the fact that this tendency was not statistically significant, preterm birth at 33 weeks of gestation was found to be less likely in asymptomatic women with a cervical length of less than 25 mm in the second trimester of pregnancy. Also, the use of vaginal progesterone is associated with a 48% reduction in neonatal mortality as well as in the incidence of neonatal complications (RR 0.52; 95% CI 0.29, 0.93). In twin pregnancies, however, vaginal progesterone has been found not to reduce neonatal mortality and mortality (RR 0.97; 95% CI 0.77, 1.2). It is important to note, however, that in selected cases and with a cervical length below 25 mm before 24 weeks of gestation, vaginal progesterone can significantly reduce neonatal mortality and the incidence of neonatal complications (RR 0.56; 95% CI 0.42, 0.75) [42–46].

The daily recommended dose of progesterone is 90 mg in gel form and 200 mg in vaginal tablets (100 mg twice daily). The efficacy of higher doses of progesterone (400 mg) in reducing preterm birth and neonatal mortality and morbidity has not been proven. There appears to be a trend, but not statistically significant, of an increased incidence of cholestasis of pregnancy in a subgroup of women who received higher doses of progesterone.
