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Simultaneous compared to interval administration of mifepristone and misoprostol for medical abortion up to 10+0 weeks' gestation: a systematic review with meta-analyses
  1. Mia Schmidt-Hansen1,
  2. Jonathan Lord2,
  3. Elise Hasler1,
  4. Sharon Cameron3
  1. 1 National Guideline Alliance, Royal College of Obstetricians and Gynaecologists, London, UK
  2. 2 Department of Gynaecology, Royal Cornwall Hospitals NHS Trust, Truro, UK
  3. 3 Sexual and Reproductive Health Services, NHS Lothian, Edinburgh, UK
  1. Correspondence to Dr Mia Schmidt-Hansen, National Guideline Alliance, Royal College of Obstetricians and Gynaecologists, London SE1 1SZ, UK; MSchmidt-Hansen{at}


Background Medical abortion with mifepristone and misoprostol usually involves an interval of 36–48 hours between administering these drugs; however, it is possible that the clinical efficacy at early gestations may be maintained when the drugs are taken simultaneously. The objective of this systematic review was to determine the safety and effectiveness of simultaneous compared with interval administration of mifepristone and misoprostol for abortion up to 10+0 weeks’ gestation.

Methods We searched Embase Classic, Embase; Ovid MEDLINE(R) including Daily, and Epub Ahead-of-Print, In-Process & Other Non-Indexed Citations; and Cochrane Library on 11 December 2019. We included randomised controlled trials (RCTs), published in English from 1985, comparing simultaneous to interval administration of mifepristone and misoprostol for early abortion. Risk of bias was assessed using the Cochrane Collaboration checklist for RCTs. Meta-analysis of risk ratios (RRs) using the Mantel-Haenszel method were performed. The quality of the evidence was assessed using GRADE.

Results Meta-analyses of three RCTs (n=1280) showed no differences in ‘ongoing pregnancy’ (RR 1.78, 95% CI 0.38 to 8.36), ‘haemorrhage requiring transfusion or ≥500 mL blood loss’ (RR 0.11, 95% CI 0.01 to 2.03) and ‘incomplete abortion with the need for surgical intervention’ (RR 1.30, 95% CI 0.76 to 2.25) between the interventions. Individual study results showed no difference in patient satisfaction, or ‘need for repeat misoprostol’, although ‘time to onset of bleeding or cramping’ was longer after simultaneous than interval administration. The quality of evidence was very low to moderate.

Conclusion The published data support the use of simultaneous mifepristone and misoprostol for medical abortion up to 9+0 weeks in women who prefer this method of administration.

  • abortion

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  • Contributors SC, JL, EH and MSH conceived and designed the review and wrote the protocol. EH devised and undertook the search strategy. MSH screened the search results, performed the data extraction and ‘risk of bias’ assessment of the included studies, and the overall GRADE ratings. MSH devised and performed the analysis strategy. JL and SC interpreted the results. SC, MSH, EH and JL wrote the first draft of different sections of the full review. All the authors critically revised the first draft of the review and approved the final version.

  • Funding This article presents a systematic review undertaken as part of the 2019 National Institute for Health and Care Excellence (NICE) guideline on abortion care. This work was undertaken by the National Guideline Alliance (NGA) at the Royal College of Obstetricians and Gynaecologists (RCOG), which received funding from NICE. The funding body (NICE) did not play any direct role in the study design; the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. The views expressed in this publication are those of the authors and not necessarily those of the NGA, RCOG or NICE. All researchers involved in this work were independent from the funding body at the time of completing this work.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.