Does the route of administration matter? Systematic review and meta-analysis of randomized clinical trials between vaginal versus intramuscular progesterone administration in the prevention of preterm birth

ABSTRACT
Objective. To determine the effectiveness of intramuscular progesterone compared to vaginal application in the prevention of asymptomatic preterm birth (PTB) in randomized clinical trials.
Materials and Methods. A systematic search of electronic databases (Embase, PubMed and Scopus) was performed. Randomized clinical trials comparing vaginal and Intramuscular progesterone (17-OHPC) in pregnant women at high risk of PTB. Additionally, bias and certainty assessment were performed.
Results. Six clinical trials with a total of 1,408 randomized patients were included. The reported incidence of PTB < 37 weeks ranged from 10.9% to 43.9% for vaginal progesterone, and 14.0% to 38% for 17-OHPC. At the time of meta-analysis, patients receiving 17-OHPC was associated with a lower in- cidence of PTB < 28 weeks than vaginal use (Risk Difference 0.14; CI 0.01-0.29; I²= 83.9%; T² = 0.02) with no significant difference in differences in PTB < 37 and < 34 weeks. Additionally, on neonatal outcomes, the most common was admission to the neonatal ICU independent of the method of administration (6.1% and 7.7%), followed by APGAR < 7 (4.1% and 5.2%), with no significant differences in neonatal outcomes.
Conclusions. Both the use of vaginal progesterone and 17-OHPC in the prevention of PTB in singleton high-risk gestations are reasonable options, with similar incidence of PTB and no additional impact on short-term neo- natal complications. Thus, costs, resource availability and patiences should be considered when choosing a route of administration.