Misoprostol : utilisation hors AMM au premier trimestre de la grossesse (fausses couches spontanées, interruptions médicales et volontaires de grossesse)

Abstract

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.French and English publications were searched using PubMed, Cochrane Library and international learned societies recommendations.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).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.