Mizrachi Yossi, Dekalo Ann, Gluck Ohad, Miremberg Hadas, Dafna Lotem, Feldstein Ohad, Weiner Eran, Bar Jacob, Sagiv Ron
Department of Obstetrics & Gynecology, Edith Wolfson Medical Center, 62 Halochamim St. POB 58100, Holon, Israel, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Israel.
Hum Reprod. 2017 Jun 1;32(6):1202-1207. doi: 10.1093/humrep/dex074.
Does repeat administration of misoprostol for early pregnancy loss increase the treatment success rate?
Repeat administration of misoprostol does not increase the treatment success rate, and is associated with more analgesics use.
Misoprostol reduces the need for surgical evacuation and shortens the time to complete expulsion in patients with early pregnancy loss. However, the impact of repeat doses of misoprostol is not clear.
STUDY DESIGN, SIZE, DURATION: A randomized clinical trial was conducted in a single tertiary hospital, recruiting women with early pregnancy loss (<12 weeks), seeking medical treatment, between August 2015 and June 2016. A sample size of 160 patients was sufficient to detect a 30% decrease in treatment success.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants received 800 μg of misoprostol vaginally on Day 1, and were then randomly assigned into two groups: Patients in the single-dose group were evaluated on Day 8. Patients in the repeat-dose group were evaluated on Day 4, when they were given a repeat dose if required, and scheduled for re-evaluation on Day 8. If complete expulsion was not achieved on Day 8 (endometrial thickness >15 mm or the presence of gestational sac on transvaginal sonography), participants underwent surgical evacuation. The primary outcome was treatment success, defined as no need for surgical intervention up to Day 8.
Final analysis included 87 participants in the single-dose group and 84 participants in the repeat-dose group, out of whom 41 (48.8%) received a second dose. Treatment succeeded in 67 (77%) patients in the single-dose group and 64 (76%) patients in the repeat-dose group (RR 0.98; 95% CI 0.83-1.16; P = 0.89). Patients in the repeat-dose group reported more use of over the counter analgesics (82.1% versus 69.0%, P = 0.04).
LIMITATIONS, REASONS FOR CAUTION: The study was not blinded and our definition of complete expulsion may be debated. Follow-up time was not equal in all participants, since some had a complete expulsion on Day 4 and some underwent emergent D&C before Day 8. This, however, should not affect the primary outcome.
Our results suggest that a single-dose protocol is superior to a repeat-dose protocol due to a comparable success rate and more favorable outcomes regarding the need for analgesic drugs.
STUDY FUNDING/COMPETING INTEREST(S): We did not receive funding for this study and we declare no conflict of interest.
ClinicalTrials.gov (NCT02515604).
2 August 2015.
DATE OF FIRST PATIENT'S ENROLMENT: 19 August 2015.
重复使用米索前列醇治疗早期妊娠丢失能否提高治疗成功率？
重复使用米索前列醇不会提高治疗成功率，且与更多止痛药的使用相关。
米索前列醇可减少早期妊娠丢失患者的手术清宫需求，并缩短完全排出的时间。然而，重复使用米索前列醇的影响尚不清楚。
研究设计、规模、持续时间：在一家三级医院进行了一项随机临床试验，招募2015年8月至2016年6月期间因早期妊娠丢失（<12周）前来就医的女性。样本量为160例患者足以检测到治疗成功率下降30%。
参与者/材料、环境、方法：参与者在第1天经阴道给予800μg米索前列醇，然后随机分为两组：单剂量组患者在第8天进行评估。重复剂量组患者在第4天进行评估，必要时给予重复剂量，并安排在第8天进行重新评估。如果在第8天未实现完全排出（子宫内膜厚度>15mm或经阴道超声检查有妊娠囊），参与者接受手术清宫。主要结局为治疗成功，定义为至第8天无需手术干预。
最终分析纳入单剂量组87例参与者和重复剂量组84例参与者，其中41例（48.8%）接受了第二剂。单剂量组67例（77%）患者治疗成功，重复剂量组64例（76%）患者治疗成功（相对危险度0.98；95%置信区间0.83 - 1.16；P = 0.89）。重复剂量组患者报告使用非处方止痛药的情况更多（82.1%对69.0%，P = 0.04）。
局限性、谨慎的理由：本研究未设盲，且我们对完全排出的定义可能存在争议。所有参与者的随访时间并不相同，因为一些人在第4天完全排出，一些人在第8天之前接受了急诊刮宫术。然而，这不应影响主要结局。
我们的结果表明，单剂量方案优于重复剂量方案，因为成功率相当，且在止痛药需求方面有更有利的结果。
研究资金/利益冲突：我们未获得本研究的资金，且声明无利益冲突。
ClinicalTrials.gov（NCT02515604）。
2015年8月2日。
2015年8月19日。
