Semin Reprod Med 2022; 40(05/06): 258-263
DOI: 10.1055/s-0042-1760117
Review Article

Medical Abortion before Confirmed Intrauterine Pregnancy: A Systematic Review

Karin Brandell*
1   Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden
2   Södertalje Hospital, Södertalje, Sweden
John J. Reynolds-Wright*
3   MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom
Clare Boerma
4   Family Planning NSW, Newington, Australia
Gillian Gibson
5   Womens Health, Auckland City Hospital, Auckland, New Zealand
Helena Hognert
6   Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, Institution of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden
Heera Tuladhar
7   KIST Medical College Teaching Hospital, Lalitpur, Nepal
Oskari Heikinheimo
8   Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Sharon Cameron
9   NHS Lothian and University of Edinburgh, Edinburgh, United Kingdom
Kristina Gemzell-Danielsson
1   Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden
10   Karolinska University Hospital, Stockholm, Sweden
On Behalf of the VEMA Study Group › Author Affiliations
Funding K.G-D. received funding from the Swedish Research Council and K.B. received funding from European Society for Contraception and Reproductive Health for the clinical trial “VEMA –Very Early Medical Abortion Trial”. K.B. was supported by Region Stockholm (combined residency and PhD training program).


“Very early medical abortion” (VEMA) refers to medical abortion (with mifepristone and misoprostol) before intrauterine pregnancy is visualized on ultrasound. Our aim is to present the current evidence on efficacy, safety (focused on ectopic pregnancies), and how to assess treatment success of VEMA. We conducted a systematic review of studies reporting outcomes of VEMA. The field is small and so our objective was to map all relevant literature, without conducting meta-analysis. We searched PubMed, Medline, and Embase on April 19, 2022. We conducted a narrative synthesis of the evidence. A total of 373 articles were identified. Six articles (representing four observational and one pilot trial) were included in the final review. Across all included studies, treatment efficacy ranged between 91 and 100%. Prevalence of ectopic pregnancy was low and very few cases (n = 2) of ruptures were reported. Most studies used serial serum human chorionic gonadotrophin (s-hCG) levels to determine success of abortion; one study used low sensitivity urine hCG. From the available evidence, VEMA appears to be efficacious and does not appear to cause harm to ectopic pregnancies. Treatment can be assessed with pre- and postabortion s-hCG. Good quality, randomized controlled trial evidence is needed to best inform practice.

* Equal contribution

Supplementary Material

Publication History

Article published online:
10 January 2023

© 2023. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

  • References

  • 1 WHO Guidelines Approved by the Guidelines Review Committee. Abortion Care Guideline. World Health Organization; 2022
  • 2 Kopp Kallner H, Fiala C, Stephansson O, Gemzell-Danielsson K. Home self-administration of vaginal misoprostol for medical abortion at 50-63 days compared with gestation of below 50 days. Hum Reprod 2010; 25 (05) 1153-1157
  • 3 Kopp Kallner H, Gomperts R, Salomonsson E, Johansson M, Marions L, Gemzell-Danielsson K. The efficacy, safety and acceptability of medical termination of pregnancy provided by standard care by doctors or by nurse-midwives: a randomised controlled equivalence trial. BJOG 2015; 122 (04) 510-517
  • 4 Endler M, Lavelanet A, Cleeve A, Ganatra B, Gomperts R, Gemzell-Danielsson K. Telemedicine for medical abortion: a systematic review. BJOG 2019; 126 (09) 1094-1102
  • 5 Oppegaard KS, Qvigstad E, Fiala C, Heikinheimo O, Benson L, Gemzell-Danielsson K. Clinical follow-up compared with self-assessment of outcome after medical abortion: a multicentre, non-inferiority, randomised, controlled trial. Lancet 2015; 385 (9969): 698-704
  • 6 Blum J, Sheldon WR, Ngoc NT. et al. Randomized trial assessing home use of two pregnancy tests for determining early medical abortion outcomes at 3, 7 and 14 days after mifepristone. Contraception 2016; 94 (02) 115-121
  • 7 Fiala C, Bombas T, Parachini M. et al. Management of very early medical abortion - an international survey among providers. Eur J Obstet Gynecol Reprod Biol 2020; 246: 169-176
  • 8 Jar-Allah T, Hognert H, Köcher L. et al. Detection of ectopic pregnancy and serum beta hCG levels in women undergoing very early medical abortion: a retrospective cohort study. Eur J Contracept Reprod Health Care 2022; 27 (03) 240-246
  • 9 Barnhart K, van Mello NM, Bourne T. et al. Pregnancy of unknown location: a consensus statement of nomenclature, definitions, and outcome. Fertil Steril 2011; 95 (03) 857-866
  • 10 Socialstyrelsen. Statistik om aborter 2020. 2021. Accessed December 5, 2022 at:
  • 11 Lidegaard Ø. Medicinsk abortus provocatus – 1. trimester. 2014. Accessed December 5, 2022 at:
  • 12 Queensland Clinical Guidelines. Termination of Pregnancy. Guideline No. MN19.21-V6-R24. 2019, 2022
  • 13 Reynolds-Wright JJ, Johnstone A, McCabe K, Evans E, Cameron S. Telemedicine medical abortion at home under 12 weeks' gestation: a prospective observational cohort study during the COVID-19 pandemic. BMJ Sex Reprod Health 2021; 47 (04) 246-251
  • 14 Aiken A, Lohr PA, Lord J, Ghosh N, Starling J. Effectiveness, safety and acceptability of no-test medical abortion (termination of pregnancy) provided via telemedicine: a national cohort study. BJOG 2021; 128 (09) 1464-1474
  • 15 Arbets- och Referensgruppen för Familjeplanering. Inducerad Abort, Svensk Förening för Obstetrik och Gynekologi, ARG-rapport nr 2018 78.
  • 16 Vayssière C, Gaudineau A, Attali L. et al. Elective abortion: clinical practice guidelines from the French College of Gynecologists and Obstetricians (CNGOF). Eur J Obstet Gynecol Reprod Biol 2018; 222: 95-101
  • 17 Schmidt-Hansen M, Cameron S, Lord J, Hasler E. Initiation of abortion before there is definitive ultrasound evidence of intrauterine pregnancy: a systematic review with meta-analyses. Acta Obstet Gynecol Scand 2020; 99 (04) 451-458
  • 18 Kapp N, Baldwin MK, Rodriguez MI. Efficacy of medical abortion prior to 6 gestational weeks: a systematic review. Contraception 2018; 97 (02) 90-99
  • 19 Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan - a web and mobile app for systematic reviews. Syst Rev 2016; 5 (01) 210
  • 20 Campbell M, McKenzie JE, Sowden A. et al. Synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline. BMJ 2020; 368: l6890
  • 21 Apperloo MJA, Vink P, Oosterbaan-Schram JHG. [Very early medical abortion, a termination of pregnancy before ultrasound evidence: something to aim for in the Netherlands?]. Ned Tijdschr Geneeskd 2021; 165: D5843 [ Zwangerschapsafbreking voordat de zwangerschap echoscopisch zichtbaar is]
  • 22 Schaff EA, Fielding SL, Eisinger S, Stadalius L. Mifepristone and misoprostol for early abortion when no gestational sac is present. Contraception 2001; 63 (05) 251-254
  • 23 Bizjak I, Fiala C, Berggren L. et al. Efficacy and safety of very early medical termination of pregnancy: a cohort study. BJOG 2017; 124 (13) 1993-1999
  • 24 Heller R, Cameron S. Termination of pregnancy at very early gestation without visible yolk sac on ultrasound. J Fam Plann Reprod Health Care 2015; 41 (02) 90-95
  • 25 Goldstone P, Michelson J, Williamson E. Effectiveness of early medical abortion using low-dose mifepristone and buccal misoprostol in women with no defined intrauterine gestational sac. Contraception 2013; 87 (06) 855-858
  • 26 Li CL, Chen DJ, Song LP. et al. Effectiveness and safety of lower doses of mifepristone combined with misoprostol for the termination of ultra-early pregnancy: a dose-ranging randomized controlled trial. Reprod Sci 2015; 22 (06) 706-711
  • 27 Li CL, Song LP, Tang SY. et al. Efficacy, safety, and acceptability of low-dose mifepristone and self-administered misoprostol for ultra-early medical abortion: a randomized controlled trial. Reprod Sci 2017; 24 (05) 731-737
  • 28 Wiebe ER. Methotrexate with or without misoprostol to terminate pregnancies with no gestational sac visible by ultrasound. Int J Gynaecol Obstet 2009; 107 (01) 64-65
  • 29 Barnhart KT. Clinical practice. Ectopic pregnancy. N Engl J Med 2009; 361 (04) 379-387
  • 30 Chu JJ, Devall AJ, Beeson LE. et al. Mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage (MifeMiso): a randomised, double-blind, placebo-controlled trial. Lancet 2020; 396 (10253): 770-778