title: [Misoprostol: off-label use in the first trimester of pregnancy (spontaneous abortion, and voluntary medical termination of pregnancy)].
abstract: OBJECTIVE
  State of knowledge about misoprostol's use out of its marketing authorization during the first trimester of pregnancy, in early miscarriage or to induce abortion or medical termination of pregnancy.
  
  
  METHODS
  French and English publications were searched using PubMed, Cochrane Library and international learned societies recommendations.
  
  
  RESULTS
  Cervical ripening prior to surgical uterine evacuation during the first trimester of pregnancy facilitates cervical dilatation and reduces operative time and uterine retention risk. Misoprostol, mifepristone and osmotic cervical dilators are equally efficient. Concerning first trimester miscarriage, surgical uterine evacuation remains the most effective and the quickest method of treatment (EL 1). Depending on the clinical situation, medical treatment using misoprostol (missed miscarriage) or expectative attitude (incomplete miscarriage) does not increase the risk of complications, neither haemorrhagic nor infectious (EL 1). However, these alternatives generally require longer outpatient follow-up, which leads to more consultations, prolonged bleeding and not planned surgical procedures (EL 1). Concerning missed miscarriage, a vaginal dose of 800 μg of misoprostol, possibly repeated 24 to 48 hours later, seems to offer the best efficiency/tolerance ratio (EL 2). Concerning early abortion, medical method is a safe and efficient alternative to surgery (EL 2). Success rates are inversely proportional to gestational age (EL 2). According to the modalities of its marketing authorization, 400 μg of misoprostol can only be given by oral route, for less than 7 weeks of amenorrhea (WA) pregnancies and after 36 to 48 hours following 600 mg of mifepristone (EL 1). However, 200mg of mifepristone is as efficient as 600 mg (EL 1). Beyond 7WA, misoprostol buccal dissolution (sublingual or prejugal) or vaginal administration are more efficient and better tolerated than oral ingestion (EL 1). Between 7 and 9WA, the best protocol in terms of efficiency and tolerance is the association of 200mg of mifepristone followed 24 to 48 hours later by 800 μg of vaginal, sublingual or buccal misoprostol (EL 1). An additional dose of 400 μg can be given 3 hours later if necessary (EL 3). In case of buccal administration, the dose of 400 μg seems to offer the same efficiency with a better tolerance but further evaluation is needed (EL 2). Between 9 and 12WA, medical treatment is less efficient than surgery and its tolerance is lower (EL 2). However, a protocol of 200mg of mifepristone followed 36 to 48 hours later by 800 μg of vaginal or sublingual misoprostol, plus an additional 400 μg dose every 3-4 hours (until 4-5 doses maximum) seems safe and efficient (EL 5).
  
  
  CONCLUSIONS
  Misoprostol use during the first trimester of pregnancy is a safe and efficient alternative to surgery as long as detailed protocols adjusted to each clinical situation are respected.
authors.affiliation: Service de gynécologie obstétrique et médecine de la reproduction, CHU de Caen, avenue de la Côte-de-Nacre, 14033 Caen cedex 9, France. Electronic address: beucher-g@chu-caen.fr.
authors.forename: G
authors.initials: G
authors.lastname: Beucher
authors.affiliation: Service de gynécologie obstétrique et médecine de la reproduction, CHU de Caen, avenue de la Côte-de-Nacre, 14033 Caen cedex 9, France; UFR de médecine, université de Caen/Basse-Normandie, avenue de la Côte-de-Nacre, 14033 Caen cedex 9, France.
authors.forename: P
authors.initials: P
authors.lastname: Dolley
authors.affiliation: Service de gynécologie obstétrique, centre hospitalier de l'Ouest Guyanais, 16, avenue du Général-de-Gaulle, BP 245, 97393 Saint-Laurent-du-Maroni cedex, Guyane française.
authors.forename: G
authors.initials: G
authors.lastname: Carles
authors.affiliation: Service de gynécologie obstétrique et médecine de la reproduction, CHU de Caen, avenue de la Côte-de-Nacre, 14033 Caen cedex 9, France.
authors.forename: F
authors.initials: F
authors.lastname: Salaun
authors.affiliation: Service de gynécologie obstétrique et médecine de la reproduction, CHU de Caen, avenue de la Côte-de-Nacre, 14033 Caen cedex 9, France.
authors.forename: I
authors.initials: I
authors.lastname: Asselin
authors.affiliation: Service de gynécologie obstétrique et médecine de la reproduction, CHU de Caen, avenue de la Côte-de-Nacre, 14033 Caen cedex 9, France; UFR de médecine, université de Caen/Basse-Normandie, avenue de la Côte-de-Nacre, 14033 Caen cedex 9, France.
authors.forename: M
authors.initials: M
authors.lastname: Dreyfus
mesh_terms: D000020:Abortifacient Agents, Nonsteroidal; D000028:Abortion, Induced / Q000379:methods*; D000278:Administration, Buccal; D000282:Administration, Intravaginal; D000286:Administration, Sublingual; D020070:Cervical Ripening; D005260:Female; D005602:France; D006801:Humans; D016595:Misoprostol / Q000008:administration & dosage* / Q000009:adverse effects; D056687:Off-Label Use; D011247:Pregnancy; D011261:Pregnancy Trimester, First
chemical_list: D000020:Abortifacient Agents, Nonsteroidal; D016595:Misoprostol
keywords: Aspiration utérine; Cervical ripening; Chirurgical uterine evacuation; Early miscarriage; Early pregnancy failure; Fausse couche spontanée précoce; Interruption médicale de grossesse; Medical abortion; Misoprostol; Préparation cervicale; Termination of pregnancy; Échec précoce de grossesse