Progesterone/Progestagens to Prevent Preterm Birth: When and How

Prematurity is a leading cause of neonatal morbidity and mortality, accounting for most part of the deaths of infants without congenital anomalies. Also, the cost of neonatal intensive care and long-term care for infants born preterm is enormous. The medical, psychological, and economic burdens of preterm births are very important. In spite of advances in obstetrical care, the rate of preterm delivery in industrialized countries (approximately 10%) has not decreased over the past 40 years. In fact, it has increased slightly, partly due to the use of assisted reproductive technologies and to the rise of indicated preterm deliveries for maternal or fetal reasons. Progesterone (P) is the primary factor of uterine quiescence that permits the physical distension of the uterine muscle throughout pregnancy. In all species, except humans, a drop in P levels precedes labor, whereas P levels remain constant in humans until delivery. Yet the labor inducing properties of anti P products such as RU-486 have led to hypothesize a "functional P withdrawal" prior to labor in humans. In spite of early trials suggesting a benefit with progesterone/progestagens in preventing premature labor, the doubts in its efficacy, particularly linked to the very weak concentrations of exogenous administration compared to the high levels of endogenous P, have dissuaded its use in obstetrics for some years. Two recent studies, however, give a new momentum towards the use of progestagens for the prevention of premature delivery in a particular high-risk population: women with a prior preterm birth. Nevertheless, the use of progestagens in other populations at risk for preterm delivery should not be encouraged outside of clinical trials. In this review article we will discuss the indications for progesterone for prevention of preterm delivery, as well as the formulations to use.