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目的 采用Meta方法来分析静脉注射免疫球蛋白(IVIG)在治疗复发性流产(RSA)对外周血自然杀伤(NK)细胞及妊娠结局的影响。方法 计算机检索PubMed、Web of Science、Embase、Cochrane Library和中国知网(CNKI)数据库，以复发性流产、反复流产、习惯性流产、静脉注射免疫球蛋白、自然杀伤细胞等为关键词进行文献检索，检索时间自建库至2022年4月。由2名评价员分别按照Cochrane手册、纽卡斯尔-渥太华量表(NOS)、Minors量表评价随机对照试验(RCT)、队列研究、无对照组的单臂试验研究的文献质量和偏倚风险；采用Rev Man5.4.1软件进行Meta分析。结果 本Meta分析共纳入14篇文献，包含1 393例患者。纳入的14篇文献中8篇为中质量文献，6篇为高质量文献。Meta分析结果显示，在改善外周血NK细胞数量方面，当一次性给药(1～5 d)时，IVIG治疗后NK细胞数量显著低于治疗前[I2=22%,95%CI(1.99,3.82),P<0.05];当连续给药时，无论是治疗至孕12周左右[I2=56%,95%CI(6.46,8.27),P<0.05],还是治疗至孕中晚期(26～34周)[I2=64%,95%CI(1.15,6.51),P<0.05],治疗后外周血NK数量显著低于治疗前；在改善NK细胞活性方面，IVIG治疗后NK细胞活性显著低于治疗前[I2=64%,95%CI(4.30,12.07),P<0.05];在改善活产率和流产率方面，与不干预组或安慰剂组相比较，IVIG组活产率显著升高[I2=0%,95%CI(3.70,8.56),P<0.05],而流产率显著降低[I2=0%,95%CI(0.12,0.27),P<0.05]。结论 IVIG治疗可显著降低RSA患者外周血NK细胞数量及活性，显著改善妊娠结局；但本结论还需要进行大规模、多中心的高质量RCT进行验证。
Abstract：Objective:To evaluate the effect of intravenous immunoglobulin(IVIG) therapy on peripheral blood natural killer(NK) cells and pregnancy outcomes in patients with recurrent spontaneous abortion(RSA) through Meta-analysis.Methods:The databases of PubMed, Web of Science, Embase, Cochrane Library and CNKI were searched by computer, and the literature was searched with the keywords of recurrent spontaneous abortion, recurrent abortion, habitual abortion, intravenous immunoglobulin, natural killer cells, etc. The retrieval time is from the establishment of the database to April 2022. Two reviewers screened the literature independently and assessed the quality and bias risk of the randomized controlled trials(RCTs),cohort studies and single-arm trials without controls according to the Cochrane Manual, Newcastle-Ottawa Scale(NOS),and Minors scale, respectively. The RevMan5.4.1 was used to perform Meta-analysis.Results:Fourteen studies containing 1 393 patients were included in the meta-analysis. Among 14 papers included, 8 were of medium quality and 6 were of high quality. Meta-analysis results show that the number of peripheral blood NK cells was significantly reduced when the course of IVIG therapy was 1 to 5 days [I2=22%,95%CI(1.99,3.82),P<0.05]. When continuously administered, the number of NK cells in peripheral blood after treatment was significantly reduced than that before treatment, no matter from treatment to about 12 weeks of gestation [I2=56%,95%CI(6.46,8.27),P<0.05] or to the middle and late pregnancy(26-34 weeks) [I2=64%,95%CI(1.15,6.51),P<0.05]. The NK cell activity after IVIG treatment was significantly lower than that before treatment [I2=64%,95%CI(4.30,12.07),P<0.05]. Compared with the placebo group, IVIG therapy improved the live birth rate [I2=0%,95%CI(3.70,8.56),P<0.05] and reduced the abortion rate [I2=0%,95%CI(0.12,0.27),P<0.05].Conclusions:IVIG therapy significantly reduces the quantity and activity of peripheral blood NK cells, improves the pregnancy outcomes. However, multi-center randomized controlled trials with larger sample and high quality are needed to verify the conclusion.
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基本信息:
中图分类号:R714.21
引用信息:
[1]陈远莹,黄伟育,杨一华.静脉注射免疫球蛋白治疗对复发性流产患者的外周血自然杀伤细胞及妊娠结局影响的Meta分析[J].生殖医学杂志,2023,32(01):79-88.
基金信息:
广西自然科学基金(2018GXNSFDA050017,2019GXNSFFA245013)
2023-01-15
2023-01-15