title: Unexplained Recurrent Miscarriage and Recurrent Implantation Failure: Is There a Place for Immunomodulation?
abstract: To describe and analyze the benefit of immunomodulatory drugs for recurrent miscarriages and implantation failures. The literature research was conducted in Medline, Embase and Cochrane Library concerning recurrent miscarriages and implantation failures and steroids, progesterone, intralipids, TNF-α antagonists, G-CSF, hydroxychloroquine, intravenous immunoglobulins, endometrial scratching. Using meta-analysis, modest benefit was found for progesterone to obtain a live birth, with odds ratio at 1.38 (95% CI: 1.07-1.77) and significant heterogeneity (P = 0.01, I(2) = 78%). In early ≥3 miscarriages, patients treated by TNF-α antagonists (adalimumab or etanercept; n = 17) combined with low-dose aspirin, heparin and intravenous immunoglobulins have a live births of 71% (12/17), vs 19% with aspirin+heparin (4/21) (P = 0.0026). Sixty-eight patients with unexplained recurrent miscarriage were randomized to receive either G-CSF (filgastrim, Neupogen, 1 μ/kg/day SC, n = 35) after the ovulation until the 9th weeks of gestation or placebo (n = 33). Among patients treated with G-CSF, 29/35 (82.8%) have live birth and 16/33 (48.5%) of controls (P = 0.006). Among 200 women with recurrent miscarriages and implantation failure treated with intralipids, the pregnancy rate was 52%, with pregnancy ongoing/live birth rate at 91%. The physiopathological rational for immunotolerance failure in this topic raise the need to demonstrate the efficacy of immunomodulatory drugs, define the patients subsets and develop treatment strategies.
authors: AP-HP, Hôpital Saint-Antoine, Service de Médecine Interne and Inflammation-(DHU i2B), Paris, France.
authors: Arsène
authors: A
authors: Mekinian
authors: AP-HP, Hôpital Tenon, Service d'Obstétrique et de Procréation Médicalement Assistée, Paris, France.
authors: Jonathan
authors: J
authors: Cohen
authors: Systemic Autoimmune Disease Unit, Department of Internal Medicine I, Vall d'Hebrón University Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors: Jaume
authors: J
authors: Alijotas-Reig
authors: AP-HP, Hôpital Jean Verdier, Service d'Obstétrique, Bondy, France.
authors: Lionel
authors: L
authors: Carbillon
authors: AP-HP, Hôpital Bichat, Auto-immunité et Hypersensibilité, Paris, France.
authors: Pascale
authors: P
authors: Nicaise-Roland
authors: AP-HP, Hôpital Trousseau, Service d'Obstétrique, Paris, France.
authors: Gilles
authors: G
authors: Kayem
authors: AP-HP, Hôpital Tenon, Service d'Obstétrique et de Procréation Médicalement Assistée, Paris, France.
authors: Emile
authors: E
authors: Daraï
authors: AP-HP, Hôpital Saint-Antoine, Service de Médecine Interne and Inflammation-(DHU i2B), Paris, France.
authors: Olivier
authors: O
authors: Fain
authors: AP-HP, Hôpital Tenon, Service d'Obstétrique et de Procréation Médicalement Assistée, Paris, France.
authors: Marie
authors: M
authors: Bornes
mesh_terms: D000026:Abortion, Habitual / Q000188:drug therapy / Q000276:immunology; D000068879:Adalimumab / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D010064:Embryo Implantation / Q000187:drug effects / Q000276:immunology; D000068800:Etanercept / Q000627:therapeutic use; D005260:Female; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use*; D056747:Immunomodulation; D011247:Pregnancy
chemical_list: D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D006493:Heparin; D000068879:Adalimumab; D000068800:Etanercept; D001241:Aspirin
keywords: Immunomodulation; implantation failure; pregnancy; unexplained miscarriages