Immediate versus delayed insertion of an etonogestrel releasing implant at medical abortion-a randomized controlled equivalence trial.
Does a progestin releasing subdermal contraceptive implant affect the efficacy of medical abortion if inserted at the same visit as the progesterone receptor modulator, mifepristone, at medical abortion?



A etonogestrel releasing subdermal implant inserted on the day of mifepristone did not impair the efficacy of the medical abortion compared with routine insertion at 2-4 weeks after the abortion.



The etonogestrel releasing subdermal implant is one of the most effective long acting reversible contraceptive methods. The effect of timing of placement on the efficacy of mifepristone and impact on prevention of subsequent unintended pregnancy is not known.



This multicentre, randomized controlled, equivalence trial with recruitment between 13 October 2013 and 17 October 2015 included a total of 551 women with pregnancies below 64 days gestation opting for the etonogestrel releasing subdermal implant as postabortion contraception. Women were randomized to either insertion at 1 hour after mifepristone intake (immediate) or at follow-up 2-4 weeks later (delayed insertion). An equivalence design was used due to advantages for women such as fewer visits to the clinic with immediate insertion. The primary outcome was the percentage of women with complete abortion not requiring surgical intervention within 1 month. Secondary outcomes included insertion rates, pregnancy and repeat abortion rates during 6 months follow-up. Analysis was per protocol and by intention to treat.



Women aged 18 years and older who had requested medical termination of a pregnancy up to 63 days of gestation and opted for an etonogestrel releasing contraceptive implant were recruited in outpatient family planning clinics in six hospitals in Sweden and Scotland.



Efficacy of medical abortion was 259/275 (94.2%) in the immediate insertion group and 239/249 (96%) in the routine insertion group with a risk difference of 1.8% (95% CI -0.4 to 4.1%), which was within the ±5% margin of equivalence. The insertion rate was 275/277 (98.9%) in the immediate group compared to 187/261 (71.6%) women in the routine group (P < 0.001). At 6 months of follow-up significantly fewer women in the immediate group had become pregnant again (2/277, 0.8%) compared to the routine group (10/261, 3.8%) P = 0.018.



For the main outcome loss to follow-up data was minimized through access to patient records. Efforts were made to reduce loss to follow-up also for secondary outcomes. The results of the sensitivity analysis did not differ from the intention to treat or per protocol analysis.



Guidelines on postabortion contraception should be amended to include insertion of the etonogestrel releasing implant at the time of mifepristone intake for medical abortion up to and including a gestation of 63 days.



This study was funded by the Swedish Research Council (2012-2844), Stockholm City County and Karolinska Institutet (ALF). The contraceptive implants were provided by Merck and supplied by MSD Sweden. HKK and KGD have received honorariums for giving lectures for MSD/Merck and have participated in the national (HKK and KGD) and international (KGD) medical advisory boards for MSD/Merck. The other authors have nothing to declare.



ClinicalTrials number NCT01920022.



06 August 2013.



13 October 2013.
Department of Obstetrics and Gynecology, Sahlgrenska Academy at Gothenburg University, Sahlgrenska University Hospital, 416 85 Gothenburg, Sweden.
Helena
H
Hognert
Department of Clinical Sciences at Danderyd Hospital, Karolinska Institutet, 171 77 Stockholm, Sweden Helena.kopp-kallner@ki.se Kristina.gemzell@ki.se.|Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, 171 76 Stockholm, Sweden.
Helena
H
Kopp Kallner
National Health Service, Lothian, Chalmers Centre, 2a Chalmers Street, Edinburgh EH3 9ES, UK.
Sharon
S
Cameron
Department of Obstetrics and Gynecology at Stockholm South General Hospital, 118 83 Stockholm, Sweden.
Christina
C
Nyrelli
Department Obstetrics and Gynecology, Örebro University Hospital, Södra Grev Rosengatan, 701 85 Örebro, Sweden.
Izabella
I
Jawad
Department of Obstetrics and Gynaecology, University of Edinburgh, 51 Little France Crescent Edinburgh, EH16 5SU, UK.
Rebecca
R
Heller
Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, 171 76 Stockholm, Sweden.
Annette
A
Aronsson
Department of Obstetrics and Gynecology, Sahlgrenska Academy at Gothenburg University, Sahlgrenska University Hospital, 416 85 Gothenburg, Sweden.
Ingela
I
Lindh
Department of Clinical Science and Education, Karolinska Institutet, 171 77 Stockholm, Sweden.
Lina
L
Benson
Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, 171 76 Stockholm, Sweden Helena.kopp-kallner@ki.se Kristina.gemzell@ki.se.
Kristina
K
Gemzell-Danielsson
D000021:Abortifacient Agents, Steroidal / Q000627:therapeutic use*; D000028:Abortion, Induced / Q000379:methods*; D000293:Adolescent; D000328:Adult; D003267:Contraception / Q000379:methods*; D003271:Contraceptive Agents, Female / Q000008:administration & dosage* / Q000627:therapeutic use; D017135:Desogestrel / Q000008:administration & dosage* / Q000627:therapeutic use; D004343:Drug Implants; D004347:Drug Interactions; D005260:Female; D006801:Humans; D015735:Mifepristone / Q000627:therapeutic use*; D011247:Pregnancy; D049168:Pregnancy, Unplanned; D013997:Time Factors; D055815:Young Adult
D000021:Abortifacient Agents, Steroidal; D003271:Contraceptive Agents, Female; D004343:Drug Implants; C044815:etonogestrel; D015735:Mifepristone; D017135:Desogestrel
LARC; abortion; contraceptive implant; etonogestrel; termination of pregnancy; unintended pregnancy; unwanted pregnancy