Unexplained Recurrent Miscarriage and Recurrent Implantation Failure: Is There a Place for Immunomodulation?

Arsène Mekinian, Jonathan Cohen, Jaume Alijotas-Reig, Lionel Carbillon, Pascale Nicaise-Roland, Gilles Kayem, Emile Daraï, Olivier Fain, Marie Bornes

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61 Citations (Scopus)


© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 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, I2 = 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.
Original languageEnglish
Pages (from-to)8-28
JournalAmerican Journal of Reproductive Immunology
Issue number1
Publication statusPublished - 1 Jul 2016


  • Immunomodulation
  • implantation failure
  • pregnancy
  • unexplained miscarriages


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