MISOPROSTOL-ONLY REGIMENS FOR MEDICAL ABORTION Department of Reproductive Health and Research World Health Organization Geneva HELENA VON HERTZEN

HvH FIAPAC MOSCOW OC MISOPROSTOL Synthetic analogue of naturally occurring prostaglandin E 1 Approved in >80 countries (prevention and treatment of gastric and duodenal ulcers; Brazil, Egypt, France also other indications) Safe and well tolerated Tablets can be kept at room temperature when packed in aluminium blisters

HvH FIAPAC MOSCOW OC Mean plasma concentrations of misoprostol acid over time with oral and vaginal administration

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HvH FIAPAC MOSCOW OC INDUCING EARLY ABORTION Oral misoprostol StudyRegimen N Gestational Success age (wks) Rabe et al.(1987) 0.4mg x % 0.2mg x % Norman et al.(1991) 0.2mg – 0.6mg 40 <=8 5% Blanchard et al.(2005) 0.4mg x 4 36 <=839% 0.8mg x 2 24 <=850% 0.8mg x 2 35 <=846%

HvH FIAPAC MOSCOW OC INDUCING EARLY ABORTION Vaginal misoprostol StudyRegimenN Gestational age (wks) Continuing pregnancy Carbonell et al. (1997)0.8mgx3+(48h) 175 <=9 8.0% Carbonell et al. (1999) 0.8mgx3+(24h)720<=7 8.3% % % Carbonell et al. (2001)1.0mgx3 (24h) % Carbonell et al. (2003)0.8mgx3+ (8h) %

HvH FIAPAC MOSCOW OC C OMPARISON OF TWO ROUTES AND TWO INTERVALS OF MISOPROSTOL FOR TERMINATION OF EARLY PREGNANCY: RANDOMIZED, CONTROLLED MULTICENTRE TRIAL 11 centres: Armenia, Cuba, Georgia, India, Mongolia and Viet Nam 2066 women up to 63 days LMP Three doses of 0.8mg misoprostol Group ISublingual, 3-hour interval Group IISublingual, 12-hour interval Group IIIVaginal, 3-hour interval Group IVVaginal, 12-hour interval

HvH FIAPAC MOSCOW OC Baseline characteristics CharacteristicSublingual 3hSublingual 12hVaginal 3h Vaginal 12h (n=517) (n=516) (n=516) (n=517) Age (years) Nulliparity Previous induced abortion Length of pregnancy (days)*, events(%) * Length of pregnancy assessed by ultrasound

HvH FIAPAC MOSCOW OC Outcomes of treatment by group GroupOutcomeNo. ofPercentages excluding casesundetermined cases (95% CI) Sublingual 3-hour, (n=517) Complete abortion (82.5 to 88.8) Continuing pregnancy ( 3.9 to 8.2) Sublingual 12-hour, (n=516) Complete abortion (75.5 to 82.8) Continuing pregnancy ( 6.9 to 12.2)

HvH FIAPAC MOSCOW OC Outcomes of treatment by group GroupOutcomeNo. ofPercentages excluding casesundetermined 1 cases (95% CI) Vaginal 3-hour, (n=516) Complete abortion (83.9 to 90.0) Continuing pregnancy ( 2.5 to 6.1) Vaginal 12-hour, (n=517) Complete abortion (82.1 to 88.5) Continuing pregnancy ( 3.3 to 7.3)

HvH FIAPAC MOSCOW OC Failure to achieve complete abortion* Treatment groupNo. ofPercentagesRR 95% CIDifference 95% CI failures/no. (%) (%) of subjects Sublingual 3-hour71/ (0.8 to 1.5) 1.3(-2.9 to 5.5) Sublingual 12-hour 104/ (1.2 to 2.1)7.8(3.2 to 12.4) Vaginal 3-hour64/ (Reference)0.0(Reference) Vaginal 12-hour 72/ (0.8 to 1.5)1.6(-2.6 to 5.9) * Excluding undetermined cases

HvH FIAPAC MOSCOW OC Failure to achieve complete abortion* Length of pregnancyNo. ofPercentagesRR 95% CIDifference 95% CI (days)**failures/no. (%) (%) of subjects / (Reference) 0.0(Reference) / (0.9 to 1.4) 1.3(-2.4 to 5.0) / (1.0 to 1.7)4.3 (0.2 to 8.4) * Excluding undetermined cases ** Length of pregnancy assessed by ultrasound

HvH FIAPAC MOSCOW OC Failure to abort* Treatment groupNo. ofPercentagesRR 95% CIDifference 95% CI failures/no. (%) (%) of subjects Sublingual 3-hour29/ (0.8 to 2.5) 1.8(-0.9 to 4.4) Sublingual 12-hour 47/ (1.4 to 3.9)5.3 (2.3 to 8.4) Vaginal 3-hour20/ (Reference)0.0(Reference) Vaginal 12-hour25/ (0.7 to 2.2)1.0(-1.6 to 3.6) * Excluding undetermined cases

HvH FIAPAC MOSCOW OC Failure to abort* Length of pregnancyNo. ofPercentagesRR 95% CIDifference 95% CI (days)**failures/no. (%) (%) of subjects / (Reference) 0.0(Reference) / (0.8 to 1.9) 1.1(-1.3 to 3.4) / (1.3 to 2.8) 4.2 (1.4 to 7.1) * Excluding undetermined cases ** Length of pregnancy assessed by ultrasound

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HvH FIAPAC MOSCOW OC Side-effects after 0.8 mg misoprostol in two trials (with and without mifepristone pre- treatment) Side-effectOral/sublingual vaginal Nausea31.1 % / 27.0% 22.5% / 25.9% Vomiting17.8% / 10.0% 6.9% / 6.3% Fever 4.7% / 7.6% 4.3% / 5.6% Pain71.9% / 79.6% 73.3% / 79.7% Figures in red = with mifepristone

HvH FIAPAC MOSCOW OC Efficacy of medical abortion in two trials (with and without mifepristone pre-treatment) RegimenNo. Outcome percentages Mife+O/O 683/740 complete abortion /740 continuing pregnancy 1.2 Mife+V/O 702/741 complete abortion /741 continuing pregnancy 0.1 Mife+V 690/738 complete abortion /738 continuing pregnancy 0.3 Miso V, 3h 434/516 complete abortion /516 continuing pregnancy 4.0