Rationale for current and future progestin-based therapies to prevent preterm birth

Abstract

Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality worldwide. The only medicinal therapy currently recommended to prevent PTB is prophylactic progestin therapy in the form of micronized progesterone (P4) administered daily via vaginal suppository from the 24th to the 34th week of gestation or 17α-hydroxyprogesterone caproate in oil administered weekly from the 16th to the 36th week of gestation via an intramuscular injection. These therapies decrease the risk of PTB in women with an elevated risk of PTB indicated by a history of PTB or by a short cervix measured by sonography at mid-gestation. The mechanism by which progestin therapy prevents PTB in some women is not clear but may involve non-progestin mechanism and/or supplementation of localized progestin deficiency. Advances in understanding the molecular biology and physiology of P4 signaling via the P4 receptor isoforms in uterine cells reveal novel therapeutic targets; this may improve the effectiveness of progestin therapy to prevent PTB in the majority of pregnancies by targeting key steps in the pathway leading to inflammation-induced parturition.

Keywords: Mechanism; Preterm birth; Prevention; Progestin therapy.