米非司酮配伍米索前列醇行早期妊娠药物流产的有效性评价

Evaluation of the Effectiveness of Mifepristone Concomitant with Misoprostol for Medical Abortion

目的系统评价米非司酮配伍米索前列醇行药物流产的有效性。方法计算机检索中国生物医学文献数据库(CBM)等9种数据库,手工检索《生殖医学杂志》等10种杂志,追查已纳入文献的参考文献,纳入所有前瞻性临床对照研究。两位系统评价员独立进行文献筛查、质量评价和资料提取,并交叉核对,如遇分歧与第三者讨论解决。Meta分析采用RevMan4.2软件,文献间经异质性检验(α=0.05),无异质性采用固定效应模型合并分析;有异质性则分析异质性原因,并用敏感性分析、亚组分析或随机效应模型处理。二分类变量用比值比(OR)表示;连续性变量用加权均数差(WMD)表示,二者均计算95%CI。结果共纳入药物流产与手术流产比较的原始研究8篇(3348例),同种药物不同孕龄比较的文献9篇(6116例);米非司酮分服与顿服比较的文献5篇(1934 例);米非司酮与米索前列醇不同间隔时间比较的文献2篇(2381例)。国外原始研究的质量高于国内文献。药物流产完全流产率低于手术流产[OR合并0.18,95%CI(0.11,0.27)];药物流产不完全流产率和流产失败率均高于手术流产,其OR合并值及95%CI分别为3.32(1.79,6.17)和7.36(4.17,12.98);孕龄>49天组完全流产率低于孕龄≤49天组,其OR合并(95%CI)为0.51(0.43,0.61);孕龄>49天组的不完全流产率和流产失败率高于孕龄≤49天组,其OR合并(95%CI)分别为1.66(1.32,2.09)和3.37(2.30,4.94)。米非司酮分服与顿服的完全流产率、不完全流产率、流产失败率、孕囊排除时间、第一次月经恢复时间和流产后平均出血时间的差别无统计学意义。米非司酮与米索前列醇不同间隔时间比较,间隔<48h组完全流产率较高,有统计学意义,不完全流产率、流产失败率的差异均无统计学意义。结论提高国内原始研究的质量非常重要。虽然手术流产的完全流产率更高,但药物流产的完全流产率也能达到91.6%(1648/1800),临床可以接受。孕龄>49天比≤49天的完全流产率更低,有统计学意义,但孕龄>49天组的完全流产率也能达到87%(2590/3013),故适当放宽法定药物流产适用孕龄值得考虑,尤其是对有禁忌症和恐惧手术的孕妇。米非司酮分服与顿服的效果相似,顿服在给药程序上更简单,可推广应用。缩短用药间隔的方案因病人更易接受而应予以考虑,但确定最佳间隔时间尚需更多证据。

Objective To evaluate the effectiveness of mifepristone concomitant with misoprostol for medical abortion. Methods We searched the related original studies worldwide, and controlled prospective studies and systematic reviews based on randomized controlled trials （ RCTs）. Nine electronic databases were searched. Ten journals and reference lists of eligible studies were handsearched. Two reviewers independently screened the studies for eligibility, evaluated the quality, and extracted the data from eligible studies, with confirmation by cross checking. Any disputes were decided by a third person. Meta-analysis was conducted using statistical software RevMan 4.2. After heterogeneity test was done （α=0.05 ） , data without heterogeneity were pooled using a fixed effect model, and those with heterogeneity could be solved by sensitivity＂ analysis, subgroup analysis or random effect model. Results We found eight original trials （ n = 3 348 ） that compared medical abortion with surgical abortion, nine trials （n =6 116） that investigating the effect of gestational ages on medical abortion, five trials （n = 1 934） on the use of mifepristone and two trials （n =2381 ） on intervals of administration of mifepristone and misoprostol were located. Quality of foreign studies was better than that of Chinese studies. Therate of complete abortion was higher in surgical abortion group than that in medical abortion group with odds ratio （OR） 0. 18 and 95% confidence interval （CI） 0. 11 to 0.27. The rate of incomplete abortion and abortion failure was higher in medical abortion group with OR 3.32, and 95% CI 1.79 to 6.17, OR 7.36, 95% CI 4. 17 to 12.98, respectively. The rate of complete abortion in the group with gestational age over 49 days was lower than that with gestational age under 49 days with OR 0.51 and 95% CI 0.43 to 0.61. The rate of incomplete abortion and abortion failure was higher in the group with gestational age over 49 days with OR 1.66, 95% CI 1.32 to 2.09 and OR 3.37, 95% CI 2.30 to 4. 94.There were no significant differences observed in the rates of complete abortion, incomplete abortion, abortion failed, time of expelling pregnant sac and time of menses recovery between the single and multi-dosage of mifepristone. Except for the rate of complete abortion, which was higher in 〈48h group, there was a comparable effectiveness for different intervals of mifepristone and ntisoprostol. Conclusions This review showes that it is important to improve the quality of Chinese original studies. Although the effectiveness is better in the surgical abortion group, the rate of complete abortion of medical abortion achieved is 91.6% （ 1 648/1 800）. This is acceptable for clinicians and women who do not want to be pregnance. The rate of complete abortion is lower in the gestation over 49 days, which had a statistically difference, but little clinical significance. It is necessary to consider increasing the gestational age of medical abortion, especially for those women who have contradictions of surgical abortion or are afraid of operation. Effectiveness of single dosage of mifeprostone is similar to that ofmulti-dosage, but single dosage might be more convenient. This review suggests that shortening the interval ofmifepristone and misoprostol administration should be considered and the best and shortest interval time need to be identified with better evidence.