Preterm birth

Progesterone supplementation is one of the treatment options for prevention of preterm birth. Meta-analyses have confirmed that progesterone is effective at reducing the risk of preterm birth before 34 weeks and before 37 weeks in women with singleton pregnancies and a history of a previous preterm birth, and at reducing the risk of preterm birth before 34 weeks in women with a short cervix.28.29 No significant differences were found between natural progesterone (oral/vaginal) and IM 17OHP-C28 or between routes of administration (oral, vaginal and IM).29
Studies evaluating oral NMP for prevention of preterm birth are summarised in Table 3 . Three RCTs compared oral NMP with placebo for prevention of preterm delivery (PTD) in women with a history of previous spontaneous PTD. Two of these studies (n = 150, and n = 212) found that oral NMP significantly reduced the rate of PTD and increased the mean gestational age at delivery compared with placebo.30,31 The third study (n = 33) found numerical improvements in these parameters with oral NMP compared with placebo, but the differences did not achieve statistical significance, probably because the study was underpowered.32 A meta-analysis of these same three studies demonstrated a significantly decreased risk of preterm birth at <37 weeks gestation (relative risk [RR] 0.68; 95% CI 0.55−0.84) and at <34 weeks gestation (RR 0.55; 95% CI 0.43−0.71), and increased gestational age of delivery (mean difference 1.71 weeks; 95% CI 1.11−2.30) with oral NMP compared with placebo.33 A noncomparative observational study (n = 345) also suggested that oral NMP may be effective at preventing PTD.34 A small retrospective analysis comparing different routes of administration of progesterone in women at high-risk for preterm labour (n = 30) found a numerically lower rate of PTD with vaginal progesterone than with oral NMP, but no statistical comparison was performed.35
Studies investigating oral NMP as maintenance tocolysis are few (Table 3 ). A small RCT from France reported no differences between oral NMP and placebo in terms of pregnancy prolongation; however, adjuvant oral NMP significantly reduced the requirement for intravenous β-mimetic (ritrodrine) and shortened the mean hospital stay by 4.2 days.36 A RCT from India in 90 women with arrested preterm labour found that maintenance tocolysis with oral NMP significantly prolonged the latency period (days gained until delivery) and significantly reduced the number of preterm births compared with placebo.37