There is a trend towards offering immunotherapy to women with unexplained reproductive failure based on abnormal Natural Killer (NK) cell levels. Previous systematic reviews evaluating immunotherapy usage have not focused on women with abnormal level of NK cells. To address the gap in literature, this systematic review aims to evaluate the efficacy of immunotherapy to improve pregnancy outcome in women with recurrent miscarriage (RM) or implantation failure (RIF) specifically selected based on abnormal levels and/or activity of NK cells. Six databases were searched for peer-reviewed studies following PRISMA guidelines. Risk of bias assessment was conducted using RoB2 for randomized controlled trials (RCT) and ROBINS-I for non-RCT. Of 1025 studies identified, seven studies on intravenous immunoglobulin (IVIG) (four), prednisolone (one), etanercept (one) and intralipid (one) were included. Meta-analysis of the non-RCT IVIG studies (557 participants; 312 intervention, 245 controls) showed livebirth in favour of intervention (RR 2.57; 95 % CI = 1.79–3.69; p < 0.05), however there were significant heterogeneity (I² = 62 %) and moderate to severe risk of bias in these studies. Individual RCTs reported improved livebirth outcome in etanercept, intralipid and prednisolone and this was significant in the former two (p < 0.05). In conclusion, there may be some benefit of immunotherapy, but paucity of high quality evidence means that it is not possible to support the use of immunotherapy even when selected based on abnormal NK cell level/activity. Further research with application of scientifically validated immunological biomarkers in well-planned large scale RCTs will determine whether immunotherapy is beneficial in this subpopulation of women.

有一种趋势是为基于异常自然杀伤 (NK) 细胞水平的无法解释的生殖失败的女性提供免疫治疗。先前评估免疫疗法使用的系统评价并未关注 NK 细胞水平异常的女性。为了解决文献中的空白，本系统评价旨在评估免疫疗法在改善复发性流产 (RM) 或植入失败 (RIF) 妇女的妊娠结局方面的功效，这些妇女根据 NK 细胞的异常水平和/或活性特别选择。根据 PRISMA 指南，在六个数据库中搜索了同行评审的研究。偏倚风险评估使用 RoB2 进行随机对照试验 (RCT) 和 ROBINS-I 进行非 RCT。在确定的 1025 项研究中，7 项关于静脉注射免疫球蛋白 (IVIG)（四项）、泼尼松龙（一项）、包括依那西普（一种）和内脂（一种）。非 RCT IVIG 研究（557 名参与者；312 名干预，245 名对照）的荟萃分析显示活产有利于干预（RR 2.57；95 % CI = 1.79–3.69；p < 0.05），但是存在显着的异质性（I²  = 62 %) 和这些研究中的中度至重度偏倚风险。个别 RCT 报告了依那西普、tralipid 和泼尼松龙的活产结果改善，这在前两者中显着（p < 0.05）。总之，免疫疗法可能有一些好处，但缺乏高质量证据意味着即使根据异常 NK 细胞水平/活性进行选择，也不可能支持使用免疫疗法。在精心策划的大规模 RCT 中应用经过科学验证的免疫生物标志物的进一步研究将确定免疫疗法是否对这一女性亚群有益。