A Randomized Controlled Trial of Intramuscular Versus Vaginal Progesterone for the Prevention of Recurrent Preterm Birth

Preterm birth (PTB) is responsible for most of the neonatal deaths that occur in the absence of congenital anomalies. It is also a major cause of long-term disabilities, including cerebral palsy, blindness, and deafness in childhood. Research has shown that PTB occurs in 10% to 12% of all pregnancies in the United States. One of the methods demonstrated to reduce this risk is the administration of progesterone, either intramuscularly or intravaginally. However, the route of administration and the effective dose for reducing recurrent PTB remain undetermined. The objective of this study was to compare differences in maternal and perinatal outcomes associated with use of 17 alpha-hydroxyprogesterone caproate (17-OHPC) versus vaginal progesterone among pregnant women with a history of PTB. Between June 1, 2007, and April 30, 2010, a prospective randomized controlled trial (RCT) was conducted among women who presented to the University of Oklahoma Medical Center, Oklahoma City, for prenatal care. Eligible participants included women with singleton pregnancies of between 16 weeks plus 0 days and 20 weeks plus 6 days; these women were randomly allocated using a computer-generated randomization sequence to receive either a weekly intramuscular injection of 17-OHPC (250 mg) or a daily vaginal progesterone suppository (100 mg). While the primary outcome measure was delivery before 37 weeks, the secondary outcomes included delivery before 34 and 28 weeks, maternal variables, and perinatal variables. Of the 174 women who underwent randomization, 66 in the intramuscular progesterone group and 79 in the vaginal progesterone group were included in the efficacy analysis. Delivery before 37 weeks occurred in 29 women (43.9%) in the intramuscular progesterone group and 30 women (37.9%) in the vaginal progesterone group (P = 0.50). Results of the study indicated that different progesterone preparations displayed similar efficacy in reducing the rate of recurrent PTB among a cohort of women with singleton pregnancy and a history of spontaneous PTB (SPTB). The authors concluded that there is comparable efficacy of progesterone in reducing the rate of recurrent PTB irrespective of the formulation.