Management of first-trimester miscarriage: a systematic review and network meta-analysis

Hum Reprod Update. 2019 May 1;25(3):362-374. doi: 10.1093/humupd/dmz002.


Background: First-trimester miscarriage affects up to a quarter of women worldwide. With many competing treatment options available, there is a need for a comprehensive evidence synthesis.

Objectives and rationale: We conducted a systematic review and network meta-analysis to assess the effectiveness and safety of treatment options for first-trimester miscarriage: expectant management (EXP), sharp dilation and curettage (D+C), electric vacuum aspiration (EVAC), manual vacuum aspiration (MVA), misoprostol alone (MISO), mifepristone+misoprostol (MIFE+MISO) and misoprostol plus electric vacuum aspiration (MISO+EVAC).

Search methods: We searched MEDLINE, Embase, CINAHL, AMED and Cochrane Library from inception till June 2018. We included randomized trials of women with first-trimester miscarriage (<14 weeks gestation) and conducted a network meta-analysis generating both direct and mixed evidence on the effectiveness and side effects of available treatment options. The primary outcome was complete evacuation of products of conception. We assessed the risk of bias and the global network inconsistency. We compared the surface under the cumulative ranking curve (SUCRA) for each treatment.

Outcomes: A total of 46 trials (9250 women) were included. The quality of included studies was overall moderate with some studies demonstrating a high risk of bias. We detected unexplained inconsistency in evidence loops involving MIFE+MISO and adjusted for it. EXP had lower effectiveness compared to other treatment options. The effectiveness of medical treatments was similar compared to surgery. Mixed evidence of low confidence suggests increased effectiveness for MIFE+MISO compared to MISO alone (RR 1.49, 95% CI: 1.09-2.03). Side effects were similar among all options. Fewer women needed analgesia following EVAC compared to MISO (RR for MISO 0.43, 95% CI: 0.27-0.68) and in the EXP group compared to EVAC (RR 2.07, 95% CI: 1.25-3.41). MVA had higher ranking (low likelihood) for post-treatment infection and serious complications (SUCRA 87.6 and 79.2%, respectively) with the highest likelihood for post-treatment satisfaction (SUCRA 98%).

Wider implications: Medical treatments for first-trimester miscarriage have similar effectiveness and side effects compared to surgery. The addition of MIFE could increase the effectiveness of MISO and reduce side effects, although evidence is limited due to inconsistency. EXP has lower effectiveness compared to other treatment options.Systematic review registration: Prospero CRD42016048920.

Keywords: effectiveness; first trimester; miscarriage; network meta-analysis; pregnancy loss; systematic review; woman.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Abortifacient Agents, Nonsteroidal / administration & dosage*
  • Abortifacient Agents, Steroidal / administration & dosage*
  • Abortion, Spontaneous / therapy*
  • Female
  • Gestational Age
  • Humans
  • Mifepristone / administration & dosage*
  • Misoprostol / administration & dosage*
  • Network Meta-Analysis
  • Pregnancy
  • Pregnancy Trimester, First
  • Vacuum Curettage / methods*


  • Abortifacient Agents, Nonsteroidal
  • Abortifacient Agents, Steroidal
  • Misoprostol
  • Mifepristone