Tong Ling, Wei Xianjiang
Department of Gynaecology and Obstetrics, XiXi Hospital of Hangzhou, Hangzhou, 310023, China.
Department of Gynaecology and Obstetrics, Hangzhou Red Cross Hospital, Hangzhou 310000, China.
Chin Med Sci J. 2016 Nov 20;31(4):239-246. doi: 10.1016/s1001-9294(17)30007-x.
Objective This study was designed to evaluate the efficacy and safety of aspirin-heparin treatment for un-explained recurrent spontaneous abortion (URSA). Methods Literatures reporting the studies on the aspirin-heparin treatment of un-explained recurrent miscarriage with randomized controlled trials (RCTs) were collected from the major publication databases. The live birth rate was used as primary indicator, preterm delivery, preeclampsia, intrauterine growth restriction, and adverse reactions (thrombocytopenia ) were used as the secondary indicators. The quality of the included studies was evaluated using RCT bias risk assessment tool in the Cochrane Handbook (v5.1.0). Meta-analysis was conducted using RevMan (v5.3) software. Subgroup analyses were conducted with an appropriately combined model according to the type of the treatments if heterogeneity among the selected studies was detected. Results Six publications of RCTs were included in this study. There were a total of 907 pregnant women with diagnosis of URSA, 367 of them were pooled in the study group with aspirin-heparin therapy and 540 women in the control group with placebo, aspirin or progesterone therapy. Meta-analysis showed that the live birth rate in the study group was significantly different from that in the control group [RR = 1.18, 95% CI (1.00-1.39), P=0.04]. Considering the clinical heterogeneity among the six studies, subgroup analysis were performed. Live birth rates in the aspirin-heparin treated groups and placebo groups were compared and no significant difference was found. There were no significant differences found between the two groups in the incidence of preterm delivery [RR=1.22, 95% CI (0.54-2.76), P=0.64], preeclampsia [RR=0.52, 95% CI (0.25-1.07), P=0.08], intrauterine growth restriction [RR=1.19, 95% CI (0.56-2.52), P=0.45] and thrombocytopenia [RR=1.17, 95% CI (0.09-14.42), P=0.90]. Conclusion This meta-analysis did not provide evidence that aspirin-heparin therapy had beneficial effect on un-explained recurrent miscarriage in terms of live birth rate, but it was relatively safe for it did not increase incidence of adverse pregnancy and adverse events. More well-designed and stratified double-blind RCT, individual-based meta-analysis regarding aspirin-heparin therapy are needed in future.
目的 本研究旨在评估阿司匹林 - 肝素治疗不明原因复发性自然流产（URSA）的疗效和安全性。方法 从主要出版物数据库中收集报告阿司匹林 - 肝素治疗不明原因复发性流产的随机对照试验（RCT）研究的文献。活产率作为主要指标，早产、子痫前期、胎儿生长受限和不良反应（血小板减少症）作为次要指标。使用Cochrane手册（第5.1.0版）中的RCT偏倚风险评估工具评估纳入研究的质量。使用RevMan（第5.3版）软件进行荟萃分析。如果在所选研究中检测到异质性，则根据治疗类型使用适当的合并模型进行亚组分析。结果 本研究纳入了6篇RCT出版物。共有907例诊断为URSA的孕妇，其中367例纳入研究组接受阿司匹林 - 肝素治疗，540例妇女在对照组接受安慰剂、阿司匹林或孕酮治疗。荟萃分析表明，研究组的活产率与对照组有显著差异[RR = 1.18，95%CI（1.00 - 1.39），P = 0.04]。考虑到六项研究之间的临床异质性，进行了亚组分析。比较了阿司匹林 - 肝素治疗组和安慰剂组的活产率，未发现显著差异。两组在早产发生率[RR = 1.22，95%CI（0.54 - 2.76），P = 0.64]、子痫前期[RR = 0.52，95%CI（0.25 - 1.07），P = 0.08]、胎儿生长受限[RR = 1.19，95%CI（0.56 - 2.52），P = 0.45]和血小板减少症[RR = 1.17，95%CI（0.09 - 14.42），P = 0.90]方面均无显著差异。结论 本荟萃分析未提供证据表明阿司匹林 - 肝素治疗在活产率方面对不明原因复发性流产有有益作用，但相对安全，因为它不会增加不良妊娠和不良事件的发生率。未来需要更多设计良好的分层双盲RCT以及关于阿司匹林 - 肝素治疗的基于个体的荟萃分析。
