宫腔内灌注G-CSF对改善薄型子宫内膜临床疗效的系统评价与Meta分析

Effectiveness of intrauterine infusion of granulocyte colony-stimulating factor for thin endometrium:a systematic review and meta-analysis

目的系统评价宫腔内灌注粒细胞集落刺激因子(G-CSF)对改善薄型子宫内膜的有效性,为临床应用G-CSF治疗薄型子宫内膜提供参考依据。方法计算机检索Pubmed、Embase、CNKI等中、英文数据库,系统搜集宫腔内灌注G-CSF治疗薄型子宫内膜的实验性和观察性研究,检索时限为从建库至2016年7月。由2位研究者独立地筛选文献、提取资料和评价纳入研究的偏倚风险后,采用Revman 5.3软件进行Meta分析。结果最终纳入14篇文献,其中2个随机对照试验、5个非随机对照实验以及7个队列研究,共944例患者。Meta分析结果显示:与对照组比较,宫腔内灌注G-CSF可显著改善子宫内膜厚度[MD=1.43,95%CI(0.67,2.19),P=0.000 2]、提高临床妊娠率[RR=2.48,95%CI(1.37,4.51),P=0.003]和降低周期取消率[RR=0.44,95%CI(0.29,0.66),P<0.000 1]。而在胚胎种植率方面,两组差异无统计学意义[RR=1.90,95%CI(0.99,3.67),P=0.05]。漏斗图显示发表偏倚存在的可能性较小。结论现有证据表明,经阴道宫腔内灌注G-CSF具有改善子宫内膜厚度、提高临床妊娠率和降低人工周期取消率等优势。但鉴于纳入研究数量和质量有限,上述结论仍应被谨慎对待,并有待更多高质量研究予以验证。

Objective. To systematically review the effectiveness of transvaginal intrauterine perfusion of granulocyte colony-stimulating factor （G-CSF） for the patients with thin endometrium and providing evidence for clinical treatment. Methods： Several different electronic databases including PubMed,Embase,CNKI and so forth were searched from inception to July 1^st 2016. Study selection, data extraction, bias evaluation and quality assessment were performed by two reviewers independently. Then, meta-analysis was performed using Revman 5.3 software. Results. Fourteen eligible studies involving 944 patients varied from 2 randomized controlled trials （RCTs）,5 non-randomized experimental studies and 7 cohort studies were included. The results of meta- analysis demonstrated that intrauterine G-CSF infusion did improve endometrial thickness （MD = 1.43,95 %CI： O. 67 to 2.19, P = 0. 000 2）, and increase clinical pregnancy rate （RR = 2.48,95 % CI： 1.37 to 4.51,P=0. 003）,and decrease the cycle cancellation rate （RR=0. 44,95%CI： 0.29 to 0.66,P〈0. 0001） compared with placebo or non-interfering control group. However,there was no statistically difference in embryo implantation rate （RR=1.90,95%CI. 0.99 to 3.67,P-0.05）. Funnel plots showed a relatively low publication bias. Conclusions. The current data indicates that transvaginal intrauterine perfusion of G-CSF can improve endometrial thickness,clinical pregnancy rate and decrease the cycle cancellation rate. However, a larger number of well-designed studies are required to be verified.