title: Increased doses of vaginal progesterone for the prevention of preterm birth in twin pregnancies: a randomised controlled double-blind multicentre trial.
abstract: OBJECTIVE
  Previous trials have shown little benefit for preventing preterm birth in twin pregnancies using 90-200 mg of daily vaginal natural progesterone. Higher doses have not been tested. Our aim was to determine the efficacy and safety of two different daily doses of vaginal natural progesterone (200 and 400 mg), compared with placebo, for preventing preterm birth in unselected twin pregnancies.
  
  
  METHODS
  Randomised controlled double-blind multicentre trial (1:1:1).
  
  
  METHODS
  The study was carried out in five university centres from Valencia, Murcia and Alicante (Spain).
  
  
  METHODS
  Women with dichorionic diamniotic twin pregnancies.
  
  
  METHODS
  The women self-inserted two vaginal pessaries daily, containing placebo (n = 96), 200 mg of natural progesterone (n = 97) or 400 mg of natural progesterone (n = 97), from 20 to 34 weeks of gestation or delivery. Randomisation was performed by an external centre. Data were analysed on an intention-to-treat basis.
  
  
  METHODS
  Preterm birth rate.
  
  
  RESULTS
  The baseline characteristics for placebo and progesterone groups were similar. Comparison of the three groups and analysis of progesterone-treated versus untreated women showed similar pregnancy and neonatal outcomes. The proportion of preterm and very preterm births, low birthweight, perinatal mortality and neonatal morbidity showed no differences between the three groups. Similar results were also obtained when comparing the 200- versus 400-mg progesterone groups. No serious adverse effects were encountered.
  
  
  CONCLUSIONS
  Vaginal progesterone therapy was generally well tolerated, but failed to prevent preterm births in unselected dichorionic diamniotic twin pregnancies. The 400-mg progesterone dose offered no advantages over the 200-mg regimen.
authors.affiliation: Instituto Valenciano de Infertilidad, Universidad de Valencia, Valencia, Spain. vicente.serra-serra@uv.es
authors.forename: V
authors.initials: V
authors.lastname: Serra
authors.forename: A
authors.initials: A
authors.lastname: Perales
authors.forename: J
authors.initials: J
authors.lastname: Meseguer
authors.forename: J J
authors.initials: JJ
authors.lastname: Parrilla
authors.forename: C
authors.initials: C
authors.lastname: Lara
authors.forename: J
authors.initials: J
authors.lastname: Bellver
authors.forename: R
authors.initials: R
authors.lastname: Grifol
authors.forename: I
authors.initials: I
authors.lastname: Alcover
authors.forename: M
authors.initials: M
authors.lastname: Sala
authors.forename: J C
authors.initials: JC
authors.lastname: Martínez-Escoriza
authors.forename: A
authors.initials: A
authors.lastname: Pellicer
mesh_terms: D000282:Administration, Intravaginal; D000328:Adult; D001724:Birth Weight; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D055118:Medication Adherence; D010570:Pessaries; D011247:Pregnancy; D011256:Pregnancy Outcome; D059285:Pregnancy, Twin; D047928:Premature Birth / Q000517:prevention & control*; D011374:Progesterone / Q000008:administration & dosage*; D011372:Progestins / Q000008:administration & dosage*; D012648:Self Care
chemical_list: D011372:Progestins; D011374:Progesterone