Vaginal Progesterone to Prevent Preterm Delivery in Women With Preterm Labor (4P)

The administration of vaginal progesterone, in addition to standard tocolysis, will decrease the risk of delivering prematurely and of recurrent preterm labor. We also hypothesize that the reduction in preterm delivery will be associated with a decrease in infant mortality and morbidity.

The principal aim is to demonstrate that progesterone reduces preterm birth before 37 weeks of gestation. Secondary aims are to show that progesterone 1) reduces preterm birth before 32 and before 34 weeks of gestation 2) reduces the number and duration of recurring episodes of preterm labor and 3) reduces infant mortality and morbidity.

• Preterm Delivery
• Morbidity
• Perinatal Mortality

• Drug: progesterone
  vaginal capsules containing 200 mg of natural progesterone, once a day, until 36 6/7 weeks of gestation or until preterm delivery (whichever occurs first).
  Other Name: Utrogestan
• Drug: placebo
  vaginal capsules containing placebo, once a day, until 36 6/7 weeks of gestation or until preterm delivery (whichever occurs first).

• Experimental: 1
  Intervention: Drug: progesterone
• Placebo Comparator: 2
  Intervention: Drug: placebo

Inclusion Criteria:

• Gestational age between 240/7 et 336/7 weeks of gestation (based on a reliable estimate by ultrasound performed before 22 weeks)
• Singleton pregnancy
• Intact membranes

• Preterm labor defined as:

  • 2 or more regular and painful uterine contractions in 10 minutes plus one or plus of the following criteria:
  • short cervix detected by vaginal ultrasound scanning (cervical length less than 30 mm until 31 weeks and less than 25 mm from 32 weeks)
  • cervical changes detected clinically (cervical length less or equal 10 mm or Bishop score less than 6
  • cervical changes during hospitalization (more or equal 5 mm between two clinical or US exams)
  • positive fetal fibronectin
• Age ≥ 18 years old
• Signed informed consent
• Possible and accepted follow-up

Exclusion Criteria:

• Multiple gestation
• Cervical cerclage
• Hydramnios (AFI >95th percentile for gestational age or greatest pocket >8 cm)
• Premature rupture of membranes
• Chorioamnionitis (criteria for clinical diagnosis are: elevated WBC, elevated CRP, maternal tachycardia, fetal tachycardia, uterine tenderness and/or amniotic fluid foul odor)
• Cervical dilatation > 3 cm
• Placenta praevia or abruptio placentae
• Intra-uterine growth restriction or non-reassuring fetal status
• Pre-eclampsia or severe hypertension
• Any other maternal or fetal pathology which should indicate medically preterm delivery

• Centre Hospitalier Universitaire Vaudois
• University Hospital Inselspital, Berne
• Basel Women’s University Hospital
• University of Zurich
• Kantonsspital Chur
• Cantonal Hospital of St. Gallen
• Luzerner Kantonsspital
• Kantonsspital Winterthur KSW
• Besins Laboratory, Belgium
• Hospital Bernardino Rivadavia Buenos Aires
• Hospital Carlos G. Durand Buenos Aires
• CEMIC Buenos Aires
• Hospital Donación Francisco Santojanni Buenos Aires
• Hospital Dr. Cosme Argerich Buenos Aires
• Hospital Dr. T. Alvarez Buenos Aires
• Hospital Italiano de Buenos Aires
• Hospital J. M. Penna Buenos Aires
• Hospital Materno Infantil Ramón Sardá Buenos Aires
• Hospital Interzonal Alberto Antranik Eurnekian, provincia Buenos Aires
• Hospital Municipal Materno Infantil Comodoro Hugo Cesar Meisner, provincia Buenos Aires
• Hospital Comunal de Tigre, provincia Buenos Aires
• Hospital Dr. Arturo Oñativia, provincia Buenos Aires
• Hospital Dr. Carlos Bocalandro, provincia Buenos Aires
• Hospital Héroes de Malvinas, provincia Buenos Aires
• Hospital Magdalena V. de Martínez, provincia Buenos Aires
• Hospital Mariano y Luciano de la Vega, provincia Buenos Aires
• Hospital Municipal Ostaciana B. de Lavignolle, provincia Buenos Aires
• Hospital Materno Infantil de San Isidro, provincia Buenos Aires
• Hospital Virgen del Carmen, provincia Buenos Aires
• Hospital J. B. Iturraspe, Santa Fe
• Hospital Maternidad Nuestra Señora De Las Mercedes, Tucumán
• Hospital Materno Infantil San Roque, Entre Ríos
• Hospital Villa Dolores, Córdoba