Comparison of vaginal and sublingual misoprostol for second trimester abortion: randomized controlled equivalence trial.
BACKGROUND
To identify an effective misoprostol-only regimen for the termination of second trimester pregnancy, we compared sublingual and vaginal administration of multiple doses of misoprostol in a randomized, placebo-controlled equivalence trial.


METHODS
Six hundred and eighty-one healthy pregnant women requesting medical abortion at 13-20 weeks' gestation were randomly assigned within 11 gynaecological centres in seven countries into two treatment groups: 400 microg of misoprostol administered either sublingually or vaginally every 3 h up to five doses, followed by sublingual administration of 400 microg misoprostol every 3 h up to five doses if abortion had not occurred at 24 h after the start of treatment. We chose 10% as the margin of equivalence. The primary end-point was the efficacy of the treatments to terminate pregnancy in 24 h. Successful abortion within 48 h was also considered as an outcome along with the induction-to-abortion-interval, side effects and women's perceptions on these treatments.


RESULTS
At 24 h, the success (complete or incomplete abortion) rate was 85.9% in the vaginal administration group and 79.8% in the sublingual group (difference: 6.1%, 95% CI: 0.5 to 11.8). Thus, equivalence could not be concluded overall; the difference, however, was driven by the nulliparous women, among whom vaginal administration was clearly superior to sublingual administration (87.3% versus 68.5%), whereas no significant difference was observed between vaginal and sublingual treatments among parous women (84.7% versus 88.5%). The rates of side effects were similar in both groups except for fever, which was more common in the vaginal group. About 70% of women in both groups preferred sublingual administration.


CONCLUSIONS
Equivalence between vaginal and sublingual administration could not be demonstrated overall. Vaginal administration showed a higher effectiveness than sublingual administration in terminating second trimester pregnancies, but this result was mainly driven by nulliparous women. Fever was more prevalent with vaginal administration. Registered with International Standard Randomized Controlled Trial number ISRCTN72965671.
von Hertzen
Helena
H
UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, World Health Organization, 1211 Geneva 27, Switzerland. helena.vonhertzen@gmail.com
Piaggio
Gilda
G
Wojdyla
Daniel
D
Nguyen
Thi My Huong
TM
Marions
Lena
L
Okoev
Georgy
G
Khomassuridze
Archil
A
Kereszturi
Attila
A
Mittal
Suneeta
S
Nair
Rajasekharan
R
Daver
Rekha
R
Pretnar-Darovec
Alenka
A
Dickson
Kim
K
Nguyen
Duc Hinh
DH
Nguyen
Huy Bao
HB
Hoang
Thi Diem Tuyet
TD
Peregoudov
Alexandre
A
D000028:Abortion, Induced / Q000379:methods*; D000282:Administration, Intravaginal; D000286:Administration, Sublingual; D005260:Female; D005865:Gestational Age; D006801:Humans; D016595:Misoprostol / Q000008:administration & dosage* / Q000009:adverse effects; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D016896:Treatment Outcome
D016595:Misoprostol