[The use of progestatives for the prevention of spontaneous preterm birth]

To identify clinical situations in which progestatives used to reduce the risk of spontaneous preterm delivery and/or reduced adverse neonatal outcomes have been evaluated and identify situations in which 17OHPC or vaginal progesterone might be recommended.

Bibliographic searches were performed in the Medline and Cochrane databases with the use of a combination of keywords and text words related to "progesterone", "tocolysis", and "preterm labor" from 1956 through July 2016.

17OHPC administrated after 16 weeks gestational age is not associated with an increased risk of birth defect (LE3). Because of discrepancies on the risk associated with first trimester utilization, it is recommended not to use it before 16 weeks (grade C). Utilization of 17OHPC and vaginal progesterone during both second and third trimester is not associated with an increased risk of congenital abnormalities and developmental adverse outcomes (LE3). Utilization of progestatives is not associated with an increased risk of intrahepatic cholestasis of pregnancy (LE3) and gestational diabetes (LE3). 17OHPC is not recommended as a primary prevention of preterm delivery in a population of women with monofetal pregnancy without history of preterm delivery (grade C). Although systematic screening of short cervix is not recommended (Professional consensus), the discovery of a short cervix (<20mm) between 16 and 24 weeks in an asymptomatic woman with monofetal pregnancy without history of preterm delivery indicates the daily administration of vaginal progesterone until 36 weeks gestational age (grade B). In a randomized controlled trial, 17OHPC is associated with a decreased risk of preterm delivery before 34 weeks gestationnal age (LE2) and with a reduction of neonatal morbidity (LE3) in women with at least one previous preterm delivery before 34 weeks gestationnal age. It is not possible to recommend the systematic use of 17OHPC on the basis of this sole trial with limited external validity (Professional consensus). Vaginal progesterone do not seem to be associated with a decreased risk of preterm delivery before 34 weeks (LE3), a better neonatal outcome (LE3) or a better cognitive development at the age of two (LE3) among asymptomatic patients with an history of preterm delivery (Professional consensus). Utilization of 17OHPC (LE2) in patients with monofetal pregnancy, a short cervix (<25mm) and a history of preterm delivery is not associated with reduced risk of preterm delivery. The utilization of 17OHPC is not recommended in this clinical context (grade B). In this context, vaginal progesterone may be associated with a decreased risk of preterm delivery (NP3) but further studies are needed to recommend its utilization (Professional consensus). Although some studies suggest a tocolytic effect of progestatives in case of preterm labor, qualitative scientific data are lacking to recommend this treatment in this situation (Professional consensus). Utilization of 17OHPC or vaginal progesterone after arrested preterm labor is not associated with a reduction of the risk of preterm delivery (LE1). Utilization of progestatives is not recommended after arrested preterm labor (grade A). In asymptomatic patients with twin pregnancies and normal or unknown cervix length, 17OHPC and vaginal progesterone are not associated with a reduction of the risk of preterm delivery (LE2). The utilization of progestatives is not recommended in this context (grade B). In patients with twin pregnancies with a short cervix (<25mm), the utilization of 17OHPC (LE1) and vaginal progesterone (LE3) is not associated with a reduction of the risk of preterm delivery and better perinatal outcome. The utilization of 17OHPC (grade A) or vaginal progesterone (grade C) is not recommended in this context. Utilization of 17OHPC progesterone is not associated with beneficial effect in patients with triple pregnancy (LE2). The utilization of 17OHPC is not recommended in this context (grade B).

Asymptomatic women with monofetal pregnancy without history of preterm delivery and a short cervix between 16 and 24 weeks is the only population in which vaginal progesterone is recommended.