title: Overview and guidelines of off-label use of methotrexate in ectopic pregnancy: report by CNGOF.
abstract: Our objective is to describe off-label use of methotrexate in ectopic pregnancy treatment using evidence based medicine. The patient group includes all women with a pregnancy outside the usual endometrium, or of unknown location. Method used was a Medline search on ectopic pregnancy managed using methotrexate treatment; evidence synthesis was done based on this current literature analysis. Level of evidence (LE) were given according to the centre for evidence base medicine rules. Grade was proposed for guidelines but no recommendation was possible as misoprostol is off label use for all the indications studied. In the absence of any contraindication, the protocol recommended for medical treatment of ectopic pregnancy is a single intramuscular injection of methotrexate (MTX) at a dosage of 1mg/kg or 50mg/m(2) (Grade A). It can be repeated once at the same dose should the hCG concentration not fall sufficiently. Pretreatment laboratory results must include a complete blood count and kidney and liver function tests (in accordance with its marketing authorization). MTX is an alternative to conservative treatment such as laparoscopic salpingotomy for uncomplicated tubal pregnancy (Grade A) with pretreatment hCG levels≤5000IU/l (Grade B). Expectant management is preferred for hCG levels<1000IU/l or in the process of spontaneous decreasing (Grade B). Intramuscular MTX is also recommended after the failure of surgical salpingotomy (Grade C) or immediately after surgery, if monitoring is not possible. Except in special circumstances, a local insitu ultrasound-guided MTX injection is not recommended for unruptured tubal pregnancies (Grade B). In situ MTX is an option for treating cervical, interstitial, or cesarean-scar pregnancies (Grade C). In pregnancies of unknown location persisting more than 10days in an asymptomatic woman who has an hCG level>2000IU/l, routine MTX treatment is an option. MTX is not indicated for combination with treatments such as mifepristone or potassium.
authors: Centre Hospitalo-Universitaire de Tours, Hôpital Bretonneau Faculté de Médecine de Tours, François Rabelais, Boulevard Tonnellé, 37044 Tours Cedex 1, France; UMR Inserm U 930, université François-Rabelais, 2, Boulevard Tonnellé, 37044 Tours Cedex 9, France; CNGOF, 91 Boulevarde de Sébastopol, 75002 Paris, France. Electronic address: marret@med.univ-tours.fr.
authors: Henri
authors: H
authors: Marret
authors: Université Versailles St-Quentin, unité de recherche EA 7285, 2 avenue de la source de la Bièvre, 78180 Montigny-le-Bretonneux, France; Service de gynécologie et obstétrique, Centre Hospitalier Intercommunal de Poissy-Saint-Germain-en-Laye, 10 rue du Champ Gaillard, BP 3082, 78303 Poissy Cedex, France; CNGOF, 91 Boulevarde de Sébastopol, 75002 Paris, France.
authors: Arnaud
authors: A
authors: Fauconnier
authors: Service de gynécologie-obstétrique, Hôpital de la Croix-Rousse - Hospices civils de Lyon, Université Claude Bernard Lyon 1, 103 Grande Rue de la Croix-Rousse, 69004 Lyon, France; CNGOF, 91 Boulevarde de Sébastopol, 75002 Paris, France.
authors: Gil
authors: G
authors: Dubernard
authors: Service de gynécologie-obstétrique, Hôpital de la Croix-Rousse - Hospices civils de Lyon, Université Claude Bernard Lyon 1, 103 Grande Rue de la Croix-Rousse, 69004 Lyon, France; CNGOF, 91 Boulevarde de Sébastopol, 75002 Paris, France.
authors: Hélène
authors: H
authors: Misme
authors: Centre régional de pharmacovigilance, CHU Angers, 4 rue Larrey, 49933 Angers Cedex 9, France; CNGOF, 91 Boulevarde de Sébastopol, 75002 Paris, France.
authors: Laurence
authors: L
authors: Lagarce
authors: Service de gynécologie - obstétrique, CHU du Kremlin-Bicêtre, 78 avenue du général Leclerc, 94276 Le Kremlin-Bicêtre, France; CNGOF, 91 Boulevarde de Sébastopol, 75002 Paris, France.
authors: Magali
authors: M
authors: Lesavre
authors: Service de gynécologie - obstétrique, CHU du Kremlin-Bicêtre, 78 avenue du général Leclerc, 94276 Le Kremlin-Bicêtre, France; CNGOF, 91 Boulevarde de Sébastopol, 75002 Paris, France.
authors: Hervé
authors: H
authors: Fernandez
authors: Université Versailles St-Quentin, unité de recherche EA 7285, 2 avenue de la source de la Bièvre, 78180 Montigny-le-Bretonneux, France; Service de gynécologie et obstétrique, Centre Hospitalier Intercommunal de Poissy-Saint-Germain-en-Laye, 10 rue du Champ Gaillard, BP 3082, 78303 Poissy Cedex, France; CNGOF, 91 Boulevarde de Sébastopol, 75002 Paris, France.
authors: Camille
authors: C
authors: Mimoun
authors: Centre Hospitalo-Universitaire de Marseille, Hôpital de la Conception Pôle de Gynécologie Obstétrique, 147 Boulevard Baille, 13005 Marseille, France; CNGOF, 91 Boulevarde de Sébastopol, 75002 Paris, France.
authors: Claire
authors: C
authors: Tourette
authors: Service Gynécologie Obstétrique et Médecine de le Reproduction, CHU Estaing, 1 Place Lucie Aubrac, 63003 Clermont-Ferrand Cedex, France; CNGOF, 91 Boulevarde de Sébastopol, 75002 Paris, France.
authors: Sandra
authors: S
authors: Curinier
authors: Service Gynécologie Obstétrique et Médecine de le Reproduction, CHU Estaing, 1 Place Lucie Aubrac, 63003 Clermont-Ferrand Cedex, France; CNGOF, 91 Boulevarde de Sébastopol, 75002 Paris, France.
authors: Benoit
authors: B
authors: Rabishong
authors: Centre Hospitalo-Universitaire de Marseille, Hôpital de la Conception Pôle de Gynécologie Obstétrique, 147 Boulevard Baille, 13005 Marseille, France; CNGOF, 91 Boulevarde de Sébastopol, 75002 Paris, France.
authors: Aubert
authors: A
authors: Agostini
mesh_terms: D000020:Abortifacient Agents, Nonsteroidal / Q000627:therapeutic use*; D000328:Adult; D005260:Female; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use*; D056687:Off-Label Use; D011247:Pregnancy; D011271:Pregnancy, Ectopic / Q000188:drug therapy*
chemical_list: D000020:Abortifacient Agents, Nonsteroidal; D008727:Methotrexate
keywords: Cervical pregnancy; Ectopic pregnancy; Guideline; Interstitial pregnancy; Methotrexate; hCG