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

2. HvH FIAPAC MOSCOW OC.2005 2 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

3. HvH FIAPAC MOSCOW OC.2005 3 Mean plasma concentrations of misoprostol acid over time with oral and vaginal administration

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5. HvH FIAPAC MOSCOW OC.2005 5 INDUCING EARLY ABORTION Oral misoprostol StudyRegimen N Gestational Success age (wks) Rabe et al.(1987) 0.4mg x 2 100 9 -1211% 0.2mg x 2 100 9 -12 9% 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%

6. HvH FIAPAC MOSCOW OC.2005 6 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% 7-810.4% 8-913.5% Carbonell et al. (2001)1.0mgx3 (24h)3006-9 7.0% Carbonell et al. (2003)0.8mgx3+ (8h)4505-9 9.5%

7. HvH FIAPAC MOSCOW OC.2005 7 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

8. HvH FIAPAC MOSCOW OC.2005 8 Baseline characteristics CharacteristicSublingual 3hSublingual 12hVaginal 3h Vaginal 12h (n=517) (n=516) (n=516) (n=517) Age (years)26.7 5.8 26.7 5.8 26.5 5.726.6 5.4 Nulliparity22142.720139.021241.120639.8 Previous induced abortion 18435.618535.918836.419637.9 Length of pregnancy (days)*, events(%) 29-4924547.424647.724948.323946.2 50-5614427.914628.313726.615129.2 57-6312824.812424.013025.212624.4 * Length of pregnancy assessed by ultrasound

9. HvH FIAPAC MOSCOW OC.2005 9 Outcomes of treatment by group GroupOutcomeNo. ofPercentages excluding casesundetermined cases (95% CI) Sublingual 3-hour, (n=517) Complete abortion 43185.9 (82.5 to 88.8) Continuing pregnancy 29 5.8 ( 3.9 to 8.2) Sublingual 12-hour, (n=516) Complete abortion 39979.3 (75.5 to 82.8) Continuing pregnancy 47 9.3 ( 6.9 to 12.2)

10. HvH FIAPAC MOSCOW OC.2005 10 Outcomes of treatment by group GroupOutcomeNo. ofPercentages excluding casesundetermined 1 cases (95% CI) Vaginal 3-hour, (n=516) Complete abortion 43487.1 (83.9 to 90.0) Continuing pregnancy 20 4.0 ( 2.5 to 6.1) Vaginal 12-hour, (n=517) Complete abortion 42585.5 (82.1 to 88.5) Continuing pregnancy 25 5.0 ( 3.3 to 7.3)

11. HvH FIAPAC MOSCOW OC.2005 11 Failure to achieve complete abortion* Treatment groupNo. ofPercentagesRR 95% CIDifference 95% CI failures/no. (%) (%) of subjects Sublingual 3-hour71/50214.11.1(0.8 to 1.5) 1.3(-2.9 to 5.5) Sublingual 12-hour 104/50320.71.6(1.2 to 2.1)7.8(3.2 to 12.4) Vaginal 3-hour64/49812.9 1(Reference)0.0(Reference) Vaginal 12-hour 72/49714.51.1(0.8 to 1.5)1.6(-2.6 to 5.9) * Excluding undetermined cases

12. HvH FIAPAC MOSCOW OC.2005 12 Failure to achieve complete abortion* Length of pregnancyNo. ofPercentagesRR 95% CIDifference 95% CI (days)**failures/no. (%) (%) of subjects 29-49 132/93514.11(Reference) 0.0(Reference) 50-56 88/57115.41.1(0.9 to 1.4) 1.3(-2.4 to 5.0) 57-63 91/49318.51.3 (1.0 to 1.7)4.3 (0.2 to 8.4) * Excluding undetermined cases ** Length of pregnancy assessed by ultrasound

13. HvH FIAPAC MOSCOW OC.2005 13 Failure to abort* Treatment groupNo. ofPercentagesRR 95% CIDifference 95% CI failures/no. (%) (%) of subjects Sublingual 3-hour29/502 5.81.4(0.8 to 2.5) 1.8(-0.9 to 4.4) Sublingual 12-hour 47/503 9.32.3(1.4 to 3.9)5.3 (2.3 to 8.4) Vaginal 3-hour20/4984.01.0(Reference)0.0(Reference) Vaginal 12-hour25/4975.01.3 (0.7 to 2.2)1.0(-1.6 to 3.6) * Excluding undetermined cases

14. HvH FIAPAC MOSCOW OC.2005 14 Failure to abort* Length of pregnancyNo. ofPercentagesRR 95% CIDifference 95% CI (days)**failures/no. (%) (%) of subjects 29-49 44/9354.7 1(Reference) 0.0(Reference) 50-56 33/5715.81.2 (0.8 to 1.9) 1.1(-1.3 to 3.4) 57-63 44/4938.91.9 (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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21. HvH FIAPAC MOSCOW OC.2005 21 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

22. HvH FIAPAC MOSCOW OC.2005 22 Efficacy of medical abortion in two trials (with and without mifepristone pre-treatment) RegimenNo. Outcome percentages Mife+O/O 683/740 complete abortion 94.5 9/740 continuing pregnancy 1.2 Mife+V/O 702/741 complete abortion 96.6 1/741 continuing pregnancy 0.1 Mife+V 690/738 complete abortion 95.4 2/738 continuing pregnancy 0.3 Miso V, 3h 434/516 complete abortion 87.1 20/516 continuing pregnancy 4.0