Mekinian Arsène, Cohen Jonathan, Alijotas-Reig Jaume, Carbillon Lionel, Nicaise-Roland Pascale, Kayem Gilles, Daraï Emile, Fain Olivier, Bornes Marie
AP-HP, Hôpital Saint-Antoine, Service de Médecine Interne and Inflammation-(DHU i2B), Paris, France.
AP-HP, Hôpital Tenon, Service d'Obstétrique et de Procréation Médicalement Assistée, Paris, France.
Am J Reprod Immunol. 2016 Jul;76(1):8-28. doi: 10.1111/aji.12493. Epub 2016 Feb 5.
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.
描述并分析免疫调节药物对复发性流产和植入失败的益处。在医学数据库（Medline）、荷兰医学文摘数据库（Embase）和考科蓝图书馆中进行了关于复发性流产、植入失败以及类固醇、孕酮、脂肪乳剂、肿瘤坏死因子-α拮抗剂、粒细胞集落刺激因子、羟氯喹、静脉注射免疫球蛋白、子宫内膜搔刮术的文献研究。采用荟萃分析发现，孕酮对实现活产有一定益处，优势比为1.38（95%置信区间：1.07 - 1.77），且存在显著异质性（P = 0.01，I² = 78%）。在早期≥3次流产的患者中，接受肿瘤坏死因子-α拮抗剂（阿达木单抗或依那西普；n = 17）联合低剂量阿司匹林、肝素和静脉注射免疫球蛋白治疗的患者活产率为71%（12/17），而接受阿司匹林 + 肝素治疗的患者活产率为19%（4/21）（P = 0.0026）。68例不明原因复发性流产患者被随机分为两组，一组在排卵后至妊娠第9周接受粒细胞集落刺激因子（非格司亭，优保津，1μg/kg/天皮下注射，n = 35），另一组接受安慰剂（n = 33）。接受粒细胞集落刺激因子治疗的患者中，29/35（82.8%）实现活产，对照组为16/33（48.5%）（P = 0.006）。在200例接受脂肪乳剂治疗的复发性流产和植入失败的女性中，妊娠率为52%，持续妊娠/活产率为91%。该主题中免疫耐受失败的生理病理机制表明，有必要证实免疫调节药物的疗效，明确患者亚组并制定治疗策略。
