Division of Family Planning, Department of Obstetrics and Gynecology, Hospital of the University of Pennsylvania, Philadelphia, PA.
Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, Philadelphia, PA.
Am J Obstet Gynecol. 2020 Oct;223(4):551.e1-551.e7. doi: 10.1016/j.ajog.2020.04.006. Epub 2020 Apr 17.
Early pregnancy loss is a common event in the first trimester, occurring in 15%-20% of confirmed pregnancies. A common evidence-based medical regimen for early pregnancy loss uses misoprostol, a prostaglandin E1 analog, with a dosage of 800 μg, self-administered vaginally. The clinical utility of this regimen is limited by suboptimal effectiveness in patients with a closed cervical os, with 29% of patients experiencing early pregnancy loss requiring a second dose after 3 days and 16% of patients eventually requiring a uterine aspiration procedure.
This study aimed to evaluate clinical predictors associated with treatment success in patients receiving medical management with mifepristone-misoprostol or misoprostol alone for early pregnancy loss.
We performed a planned secondary analysis of a randomized trial comparing mifepristone-misoprostol with misoprostol alone for management of early pregnancy loss. The published prediction model for treatment success of single-dose misoprostol administered vaginally included the following variables: active bleeding, type of early pregnancy loss (anembryonic pregnancy or embryonic and/or fetal demise), parity, gestational age, and treatment site; previous significant predictors were vaginal bleeding within the past 24 hours and parity of 0 or 1 vs >1. To determine if these characteristics predicted differential proportions of patients with treatment success or failure, we performed bivariate analyses; given the small proportion of treatment failures in the combined treatment arm, both arms were combined for analysis. Thereafter, we performed a logistic regression analysis to assess the effect of these predictors collectively in each of the 2 treatment groups separately as well as in the full cohort as a proxy for the combined treatment arm. Finally, by using receiver operating characteristic curves, we tested the ability of these predictors in association with misoprostol treatment success to discriminate between treatment success and treatment failure. To quantify the ability of the score to discriminate between treatment success and treatment failure in each treatment arm as well as in the entire cohort, we calculated the area under the curve. Using multivariable logistic regression, we then assessed our study population for other predictors of treatment success in both treatment groups, with and without mifepristone pretreatment.
Overall, 297 evaluable participants were included in the primary study, with 148 in the mifepristone-misoprostol combined treatment group and 149 in the misoprostol-alone treatment group. Among patients who had vaginal bleeding at the time of treatment, 15 of 17 (88%) in the mifepristone-misoprostol combined treatment group and 12 of 17 (71%) in the misoprostol-alone treatment group experienced expulsion of pregnancy tissue. Among patients with a parity of 0 or 1, 94 of 108 (87%) in the mifepristone-misoprostol treatment group and 66 of 95 (69%) in the misoprostol-alone treatment group experienced expulsion of pregnancy tissue. These clinical characteristics did not predict treatment success in the combined cohort alone (area under the curve=0.56; 95% confidence interval, 0.48-0.64). No other baseline clinical factors predicted treatment success in the misoprostol-alone treatment arm or mifepristone pretreatment arm. In the full cohort, the significant predictors of treatment success were pretreatment with mifepristone (adjusted odds ratio=2.51; 95% confidence interval, 1.43-4.43) and smoking (adjusted odds ratio=2.15; 95% confidence interval, 1.03-4.49).
No baseline clinical factors predicted treatment success in women receiving medical management with misoprostol for early pregnancy loss. Adding mifepristone to the medical management regimen of early pregnancy loss improved treatment success; thus, mifepristone treatment should be considered for management of early pregnancy loss regardless of baseline clinical factors.
早期妊娠丢失是孕早期常见的现象，约 15%-20%的已确认妊娠会发生这种情况。一种常见的循证医学治疗方案是使用米非司酮和米索前列醇联合治疗早期妊娠丢失，剂量为 800μg，经阴道自行给药。该方案的临床效果受到限制，对于宫颈口闭合的患者效果不佳，有 29%的患者在 3 天后需要第二次给药，16%的患者最终需要进行子宫抽吸术。
本研究旨在评估接受米非司酮-米索前列醇或米索前列醇单独治疗的早期妊娠丢失患者的治疗成功相关的临床预测因素。
我们对一项比较米非司酮-米索前列醇与米索前列醇单独治疗早期妊娠丢失的随机试验进行了计划的二次分析。单一剂量米索前列醇经阴道给药的治疗成功预测模型包括以下变量：活动性出血、早期妊娠丢失类型（空孕囊或胚胎和/或胎儿死亡）、产次、孕周和治疗部位；之前的重要预测因素是过去 24 小时内阴道出血和产次为 0 或 1 与>1。为了确定这些特征是否预测治疗成功或失败的患者比例，我们进行了双变量分析；由于联合治疗组治疗失败的比例较小，因此将两个治疗组合并进行分析。此后，我们进行了逻辑回归分析，以评估这些预测因素在每个治疗组中的作用，以及作为联合治疗组的替代指标。最后，我们通过接受者操作特征曲线，测试了这些预测因素与米索前列醇治疗成功的关联，以区分治疗成功和治疗失败。为了量化每个治疗组以及整个队列中，该评分在预测治疗成功和治疗失败方面的能力，我们计算了曲线下面积。然后，我们使用多变量逻辑回归评估了我们的研究人群中其他与治疗成功相关的预测因素，包括米非司酮预处理和无米非司酮预处理。
总的来说，297 名符合条件的参与者被纳入了主要研究，其中 148 名在米非司酮-米索前列醇联合治疗组，149 名在米索前列醇单独治疗组。在治疗时阴道出血的患者中，米非司酮-米索前列醇联合治疗组中有 17 名（88%）患者和米索前列醇单独治疗组中有 17 名（71%）患者发生妊娠组织排出。在产次为 0 或 1 的患者中，米非司酮-米索前列醇治疗组中有 108 名（87%）患者和米索前列醇单独治疗组中有 95 名（69%）患者发生妊娠组织排出。这些临床特征在联合队列中不能预测治疗成功（曲线下面积=0.56；95%置信区间，0.48-0.64）。其他基线临床因素不能预测米索前列醇单独治疗组或米非司酮预处理组的治疗成功。在整个队列中，治疗成功的显著预测因素是米非司酮预处理（调整后的优势比=2.51；95%置信区间，1.43-4.43）和吸烟（调整后的优势比=2.15；95%置信区间，1.03-4.49）。
在接受米索前列醇治疗的早期妊娠丢失患者中，没有基线临床因素可以预测治疗成功。在早期妊娠丢失的药物治疗方案中添加米非司酮可以提高治疗成功的机会；因此，无论基线临床因素如何，都应考虑使用米非司酮治疗早期妊娠丢失。
