title: Misoprostol dose and route after mifepristone for early medical abortion: a randomised controlled noninferiority trial.
abstract: OBJECTIVE
  To compare 400 and 800 microg sublingual or vaginal misoprostol 24 hours after 200 mg mifepristone for noninferiority regarding efficacy in achieving complete abortion for pregnancy termination up to 63 days of gestation.
  
  
  METHODS
  Placebo-controlled, randomised, noninferiority factorial trial, stratified by centre and length of gestation. Misoprostol 400 or 800 microg, administered either sublingually or vaginally, with follow up after 2 and 6 weeks.
  
  
  METHODS
  Fifteen obstetrics/gynaecology departments in ten countries.
  
  
  METHODS
  Pregnant women (n = 3005) up to 63 days of gestation requesting medical abortion.
  
  
  METHODS
  Two-sided 95% CI for differences in failure of complete abortion and continuing pregnancy, with a 3% noninferiority margin, were calculated. Proportions of women with adverse effects were recorded.
  
  
  METHODS
  Complete abortion without surgical intervention (main); continuing live pregnancies, induction-to-abortion interval, adverse effects, women's perceptions (secondary).
  
  
  RESULTS
  Efficacy outcomes analysed for 2962 women (98.6%): 90.5% had complete abortion after 400 microg misoprostol, 94.2% after 800 microg. Noninferiority of 400 microg misoprostol was not demonstrated for failure of complete abortion (difference: 3.7%; 95% CI 1.8-5.6%). The 400-microg dose showed higher risk of incomplete abortion (P < 0.01) and continuing pregnancy (P < 0.01) than 800 microg. Vaginal and sublingual routes had similar risks of failure to achieve complete abortion (P = 0.47, difference in sublingual minus vaginal -0.7%, 95% CI -2.6-1.2%). A similar pattern was observed for continuing pregnancies (P = 0.21). Fewer women reported adverse effects with vaginal than sublingual administration and with the 400-microg dose than the 800-microg dose. Of the women, 94% were satisfied or highly satisfied with the regimens, 53% preferred the sublingual route and 47% preferred the vaginal route.
  
  
  CONCLUSIONS
  A 400-microg dose of misoprostol should not replace the 800-microg dose when administered 24 hours after 200 mg mifepristone for inducing abortion in pregnancies up to 63 days. Sublingual and vaginal misoprostol have similar efficacy, but vaginal administration is associated with a lower frequency of adverse effects.
authors.affiliation: Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland. helena.vonhertzen@gmail.com
authors.forename: H
authors.initials: H
authors.lastname: von Hertzen
authors.forename: N T M
authors.initials: NT
authors.lastname: Huong
authors.forename: G
authors.initials: G
authors.lastname: Piaggio
authors.forename: M
authors.initials: M
authors.lastname: Bayalag
authors.forename: E
authors.initials: E
authors.lastname: Cabezas
authors.forename: A H
authors.initials: AH
authors.lastname: Fang
authors.forename: K
authors.initials: K
authors.lastname: Gemzell-Danielsson
authors.forename: N D
authors.initials: ND
authors.lastname: Hinh
authors.forename: S
authors.initials: S
authors.lastname: Mittal
authors.forename: E H Y
authors.initials: EH
authors.lastname: Ng
authors.forename: K
authors.initials: K
authors.lastname: Chaturachinda
authors.forename: B
authors.initials: B
authors.lastname: Pinter
authors.forename: L
authors.initials: L
authors.lastname: Puscasiu
authors.forename: L
authors.initials: L
authors.lastname: Savardekar
authors.forename: S
authors.initials: S
authors.lastname: Shenoy
authors.forename: A
authors.initials: A
authors.lastname: Khomassuridge
authors.forename: H T D
authors.initials: HT
authors.lastname: Tuyet
authors.forename: A
authors.initials: A
authors.lastname: Velasco
authors.forename: A
authors.initials: A
authors.lastname: Peregoudov
mesh_terms: D000020:Abortifacient Agents, Nonsteroidal / Q000008:administration & dosage*; D000021:Abortifacient Agents, Steroidal / Q000008:administration & dosage*; D000028:Abortion, Induced / Q000379:methods*; D000282:Administration, Intravaginal; D000286:Administration, Sublingual; D000328:Adult; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D015735:Mifepristone / Q000008:administration & dosage*; D016595:Misoprostol / Q000008:administration & dosage*; D017060:Patient Satisfaction; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D016896:Treatment Outcome
chemical_list: D000020:Abortifacient Agents, Nonsteroidal; D000021:Abortifacient Agents, Steroidal; D016595:Misoprostol; D015735:Mifepristone