Randomized Trial of Very Early Medication Abortion

Karin Brandell; Tagrid Jar-Allah; John Reynolds-Wright; Helena Kopp Kallner; Helena Hognert; Frida Gyllenberg; Janina Kaislasuo; Anand Tamang; Heera Tuladhar; Clare Boerma; Karen Schimanski; Gillian Gibson; Mette Løkeland; Pia Teleman; Marie Bixo; Mette Mandrup Kjaer; Ervin Kallfa; Johan Bring; Oskari Heikinheimo; Sharon Cameron; Kristina Gemzell-Danielsson; VEMA (Very Early Medication Abortion) Study Group

doi:10.1056/NEJMoa2401646

Randomized Trial of Very Early Medication Abortion

N Engl J Med. 2024 Nov 7;391(18):1685-1695. doi: 10.1056/NEJMoa2401646.

Authors

Karin Brandell¹, Tagrid Jar-Allah¹, John Reynolds-Wright¹, Helena Kopp Kallner¹, Helena Hognert¹, Frida Gyllenberg¹, Janina Kaislasuo¹, Anand Tamang¹, Heera Tuladhar¹, Clare Boerma¹, Karen Schimanski¹, Gillian Gibson¹, Mette Løkeland¹, Pia Teleman¹, Marie Bixo¹, Mette Mandrup Kjaer¹, Ervin Kallfa¹, Johan Bring¹, Oskari Heikinheimo¹, Sharon Cameron¹, Kristina Gemzell-Danielsson¹; VEMA (Very Early Medication Abortion) Study Group

Collaborators

VEMA (Very Early Medication Abortion) Study Group:
Karin Brandell, Tagrid Jar-Allah, John Reynolds-Wright, Helena Kopp-Kallner, Helena Hognert, Frida Gyllenberg, Janina Kaislasuo, Anand Tamang, Heera Thuladhar, Clare Boerma, Mette Løkeland, Karen Schimanski, Gillian Gibson, Pia Teleman, Marie Bixo, Mette Mandrup Kjaer, Ervin Kallfa, Johan Bring, Oskari Heikinheimo, Sharon Cameron, Deborah Bateson, Kevin Sunde Oppegaard, Christian Fiala, Anette Daberius, Maria Sarberg, Jan Brynhildsen, Cecilia Berger, Gutsaf Rejnö, Helena Kopp Kallner, Marie Bixo, Kerstin Haupt, Lovisa Amelin, Sarah Wallage, Ervin Kalifa, Bhaktabatsal Raut, Rakeshlal Bajracharya, Dipesh Mali, Sajan Kc, Kripa Chhetri, Aruna Karki, Manisha Aryal

Affiliation

¹ From the Department of Women's and Children's Health, Division of Obstetrics and Gynecology (K.B., K.G.-D.), and the Department of Clinical Sciences at Danderyd Hospital (H.K.K.), Karolinska Institutet, and the Department of Obstetrics and Gynecology, Karolinska University Hospital (K.G.-D.), Stockholm, Södertälje Hospital, Södertälje (K.B.), the Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg (T.J.-A., H.H.), the Department of Obstetrics and Gynecology, Skåne University Hospital, Malmö (P.T.), the Department of Clinical Sciences, Lund University Faculty of Medicine, Lund (P.T.), the Department of Clinical Sciences, Obstetrics, and Gynecology, Umeå University, Umeå (M.B.), and Statisticon, Uppsala (J.B.) - all in Sweden; the Centre for Reproductive Health, Institute for Regeneration and Repair, University of Edinburgh, and Chalmers Centre, NHS Lothian - both in Edinburgh (J.R.-W., S.C.); the Departments of Obstetrics and Gynecology (F.G., J.K., O.H.) and General Practice and Primary Health Care (F.G.), University of Helsinki and Helsinki University Hospital, Helsinki, and the Division of Health and Social Services, Wellbeing Services County of Vantaa and Kerava, Vantaa (F.G.) - both in Finland; the Center for Research on Environment, Health, and Population Activities, Kathmandu (A.T.), and KIST Medical College Teaching Hospital, Lalitpur (H.T.) - both in Nepal; Family Planning Australia, Sydney Medical School, University of Sydney, and the School of Public Health, University of Technology Sydney - all in Sydney (C.B.); Women's Health, Auckland City Hospital, Auckland, New Zealand (K.S., G.G.); the Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway (M.L.); and the Department of Obstetrics and Gynecology, Copenhagen University Hospital Hvidovre, Hvidovre (M.M.K.), and the Hospital of Southern Jutland, Aabenraa (E.K.) - both in Denmark.

PMID: 39504520
DOI: 10.1056/NEJMoa2401646

Abstract

Background: Medication abortion, with a combination of mifepristone and misoprostol, is highly effective and safe. However, there is insufficient evidence on efficacy and safety at very early gestations before a pregnancy can be visualized with ultrasonography.

Methods: We conducted a multicenter, noninferiority, randomized, controlled trial involving women requesting medication abortion at up to 42 days of gestation with an unconfirmed intrauterine pregnancy on ultrasound examination (visualized as an empty cavity or a sac-like structure without a yolk sac or embryonic pole). Participants were randomly assigned to either immediate start of abortion (early-start group) or standard-care treatment delayed until intrauterine pregnancy was confirmed (standard group). The primary outcome was complete abortion. The noninferiority margin was set at 3.0 percentage points for the absolute between-group difference.

Results: In total, 1504 women were included at 26 sites in nine countries and were randomly assigned to the early-start group (754 participants) or the standard group (750 participants). In an intention-to-treat analysis, a complete abortion occurred in 676 of 710 participants (95.2%) in the early-start group and in 656 of 688 (95.3%) in the standard group; the absolute between-group difference was -0.1 percentage points (95% confidence interval, -2.4 to 2.1). Ectopic pregnancies occurred in 10 of 741 participants (1.3%) in the early-start group and in 6 of 724 (0.8%) in the standard group, with one rupture before diagnosis (early-start group). Serious adverse events occurred in 12 of 737 participants (1.6%) in the early-start group and in 5 of 718 (0.7%) in the standard group (P = 0.10); the majority were uncomplicated hospitalizations for treatment of ectopic pregnancy or incomplete abortion.

Conclusions: Medication abortion before confirmed intrauterine pregnancy was noninferior to standard, delayed treatment with respect to complete abortion. (Funded by the Swedish Research Council and others; VEMA EudraCT number, 2018-003675-35; ClinicalTrials.gov number, NCT03989869.).

Publication types

Equivalence Trial
Multicenter Study

MeSH terms

Abortifacient Agents, Nonsteroidal* / administration & dosage
Abortifacient Agents, Nonsteroidal* / adverse effects
Abortifacient Agents, Steroidal* / administration & dosage
Abortifacient Agents, Steroidal* / adverse effects
Abortion, Induced* / adverse effects
Abortion, Induced* / methods
Abortion, Induced* / statistics & numerical data
Adult
Female
Gestational Age
Humans
Intention to Treat Analysis / statistics & numerical data
Mifepristone* / administration & dosage
Mifepristone* / adverse effects
Misoprostol* / administration & dosage
Misoprostol* / adverse effects
Pregnancy
Pregnancy Trimester, First* / drug effects
Time-to-Treatment
Ultrasonography, Prenatal
Young Adult

Randomized Trial of Very Early Medication Abortion

Authors

Collaborators

Affiliation

Abstract

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MeSH terms

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