英国伯明翰大学Adam J Devall比较了米非司酮+米索前列醇与单独米索前列醇治疗稽留流产的效果。2020年8月24日，该研究发表在《柳叶刀》杂志上。

抗孕激素药米非司酮和前列腺素米索前列醇可用于治疗稽留流产。然而，尚不清楚米非司酮和米索前列醇的组合是否比单独使用米索前列醇更有效。研究组分析了与单独使用米索前列醇相比，米非司酮+米索前列醇是否会更有效地治疗稽留流产。

研究组在英国的28家医院进行了一项多中心、双盲、安慰剂对照、随机试验，2017年10月3日至2019年7月22日，招募了711名年龄为16岁及以上、孕14周前经盆腔超声扫描诊断为稽留流产、选择接受流产的医疗处理、且知情同意的女性。将其按1：1随机分配，其中357名接受米非司酮和米索前列醇治疗，354名接受安慰剂和米索前列醇治疗。主要结局为随机分配后7天内未能自发排出孕囊。

711名女性中有696名（98%）完成试验。米非司酮+米索前列醇组348名女性中有59名（17%）在7天之内没有自然排出孕囊，而安慰剂+米索前列醇组348名女性中有82名（24%），风险比为0.73，组间差异显著。米非司酮+米索前列醇组355名女性中有62名（17％）需要手术干预以完成流产，而安慰剂+米索前列醇组353名女性中有87名（25％），风险比为0.71，差异具有统计学意义。两组间不良事件的发生率没有差异。

研究结果表明，米非司酮+米索前列醇治疗稽留流产，成功流产率显著高于单独米索前列醇，值得临床推广，以减少手术流产的几率。

附：英文原文

Title: Mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage (MifeMiso): a randomised, double-blind, placebo-controlled trial

Author: Justin J Chu, Adam J Devall, Leanne E Beeson, Pollyanna Hardy, Versha Cheed, Yongzhong Sun, Tracy E Roberts, C Okeke Ogwulu, Eleanor Williams, Laura L Jones, Jenny H La Fontaine Papadopoulos, Ruth Bender-Atik, Jane Brewin, Kim Hinshaw, Meenakshi Choudhary, Amna Ahmed, Joel Naftalin, Natalie Nunes, Abigail Oliver, Feras Izzat, Kalsang Bhatia, Ismail Hassan, Yadava Jeve, Judith Hamilton, Shilpa Deb, Cecilia Bottomley, Jackie Ross, Linda Watkins, Martyn Underwood, Ying Cheong, Chitra S Kumar, Pratima Gupta, Rachel Small, Stewart Pringle, Frances Hodge, Anupama Shahid, Ioannis D Gallos, Andrew W Horne, Siobhan Quenby, Arri Coomarasamy

Issue&Volume: 2020-08-24

Abstract: Background

The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. However, it is unclear whether a combination of mifepristone and misoprostol is more effective than administering misoprostol alone. We investigated whether treatment with mifepristone plus misoprostol would result in a higher rate of completion of missed miscarriage compared with misoprostol alone.

Methods

MifeMiso was a multicentre, double-blind, placebo-controlled, randomised trial in 28 UK hospitals. Women were eligible for enrolment if they were aged 16 years and older, diagnosed with a missed miscarriage by pelvic ultrasound scan in the first 14 weeks of pregnancy, chose to have medical management of miscarriage, and were willing and able to give informed consent. Participants were randomly assigned (1:1) to a single dose of oral mifepristone 200 mg or an oral placebo tablet, both followed by a single dose of vaginal, oral, or sublingual misoprostol 800 μg 2 days later. Randomisation was managed via a secure web-based randomisation program, with minimisation to balance study group assignments according to maternal age (<30 years vs ≥30 years), body-mass index (<35 kg/m2 vs ≥35 kg/m2), previous parity (nulliparous women vs parous women), gestational age (<70 days vs ≥70 days), amount of bleeding (Pictorial Blood Assessment Chart score; ≤2 vs ≥3), and randomising centre. Participants, clinicians, pharmacists, trial nurses, and midwives were masked to study group assignment throughout the trial. The primary outcome was failure to spontaneously pass the gestational sac within 7 days after random assignment. Primary analyses were done according to intention-to-treat principles. The trial is registered with the ISRCTN registry, ISRCTN17405024.

Findings

Between Oct 3, 2017, and July 22, 2019, 2595 women were identified as being eligible for the MifeMiso trial. 711 women were randomly assigned to receive either mifepristone and misoprostol (357 women) or placebo and misoprostol (354 women). 696 (98%) of 711 women had available data for the primary outcome. 59 (17%) of 348 women in the mifepristone plus misoprostol group did not pass the gestational sac spontaneously within 7 days versus 82 (24%) of 348 women in the placebo plus misoprostol group (risk ratio [RR] 0·73, 95% CI 0·54–0·99; p=0·043). 62 (17%) of 355 women in the mifepristone plus misoprostol group required surgical intervention to complete the miscarriage versus 87 (25%) of 353 women in the placebo plus misoprostol group (0·71, 0·53–0·95; p=0·021). We found no difference in incidence of adverse events between the study groups.

Interpretation

Treatment with mifepristone plus misoprostol was more effective than misoprostol alone in the management of missed miscarriage. Women with missed miscarriage should be offered mifepristone pretreatment before misoprostol to increase the chance of successful miscarriage management, while reducing the need for miscarriage surgery.

DOI: 10.1016/S0140-6736(20)31788-8

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31788-8/fulltext