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Progesterone supplementation to reduce the risk of spontaneous preterm birth

Errol R Norwitz, MD, PhD
Section Editor
Charles J Lockwood, MD, MHCM
Deputy Editor
Vanessa A Barss, MD, FACOG


Preterm birth (delivery prior to 37 weeks or 259 days of gestation) complicates 1 in 8 deliveries in the United States, but accounts for over 85 percent of all perinatal morbidity and mortality. Efforts to delay delivery in women presenting with acute preterm labor have been largely unsuccessful. For this reason, much attention has focused on preventative strategies.


Progesterone is a steroid hormone initially produced by the corpus luteum. In early pregnancy, progesterone is critical for pregnancy maintenance until the placenta takes over this function at 7 to 9 weeks of gestation, and its name is derived from this function: pro-gestational steroidal ketone. Indeed, removal of the source of progesterone (the corpus luteum) [1] or administration of a progesterone receptor antagonist [2] readily induces abortion before 7 weeks (49 days) of gestation.

Progesterone appears to be important in maintaining uterine quiescence in the latter half of pregnancy; however, the mechanism is unclear [3-5]. Functional withdrawal of progesterone activity at the level of the uterus appears to occur proximate to the onset of labor both at term and preterm, without a significant change in serum progesterone levels in the weeks preceding labor [3-10]. In addition, progesterone prevents apoptosis in fetal membrane explants, under both basal and pro-inflammatory conditions [11]. This may help prevent preterm premature rupture of membranes, which is a common cause of preterm birth.


The efficacy of progesterone supplementation for prevention of preterm birth depends primarily on appropriate patient selection (table 1). In addition, in vitro and animal research suggest that the type of progestin, formulation, dose, and route of delivery have a significant impact on efficacy [12,13]. These factors likely played a role in the discordant findings reported in the trials discussed below.

Pregnancies likely to benefit from progesterone supplementation — Randomized trials have provided convincing evidence that progesterone supplementation reduces the rate of spontaneous singleton preterm birth in women who have had a previous spontaneous preterm singleton birth and in women with a short cervix on ultrasound examination in the current pregnancy [14]. Neonatal morbidity and neonatal mortality are also reduced. This evidence is reviewed below.


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Literature review current through: Jul 2015. | This topic last updated: Jul 1, 2015.
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