Progesterone supplementation to reduce the risk of spontaneous preterm birth
- Errol R Norwitz, MD, PhD
Errol R Norwitz, MD, PhD
- Professor and Chair
- Department of Obstetrics and Gynecology
- Tufts Medical Center and Tufts University School of Medicine
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.
ROLE OF PROGESTERONE IN PREGNANCY MAINTENANCE
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)  or administration of a progesterone receptor antagonist  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 . This may help prevent preterm premature rupture of membranes, which is a common cause of preterm birth.
EFFICACY OF PROGESTERONE FOR PREVENTION 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 . Neonatal morbidity and neonatal mortality are also reduced. This evidence is reviewed below.
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- Grobman WA, Thom EA, Spong CY, et al. 17 alpha-hydroxyprogesterone caproate to prevent prematurity in nulliparas with cervical length less than 30 mm. Am J Obstet Gynecol 2012; 207:390.e1.
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- ROLE OF PROGESTERONE IN PREGNANCY MAINTENANCE
- EFFICACY OF PROGESTERONE FOR PREVENTION OF PRETERM BIRTH
- Pregnancies likely to benefit from progesterone supplementation
- - Spontaneous singleton preterm birth in prior pregnancy
- Seminal trials
- - Short cervix in current pregnancy
- Pregnancies where the benefit of progesterone supplementation is unclear
- - Positive fetal fibronectin test
- - Cerclage
- - Preterm premature rupture of membranes
- - Threatened preterm labor
- - After threatened preterm labor
- - Spontaneous twin preterm birth in prior pregnancy
- - Multiple gestations
- Twin pregnancy
- Triplet pregnancy
- Uterine anomaly or ART
- SIDE EFFECTS AND ADVERSE EFFECTS
- PROGESTERONE PREPARATIONS, ROUTES, AND DOSES
- Hydroxyprogesterone caproate
- Vaginal progesterone preparations
- Oral progesterone
- SUMMARY AND RECOMMENDATIONS