1. II-trimester abortion with Mifepristone Kristina Gemzell Danielsson, Dept of Obst. & Gyn Karolinska University Hospital / Institute, Stockholm, Sweden FIAPAC, Moscow, October 2005

2. II-timester abortion, K Gemzell Danielsson Legal abortion in Sweden Since 1975 ”free abortion” until 18 weeks Thereafter only with permission from the National Board of Health and Welfare on special indications until 22 weeks About 30 000 abortions, 90 000 births/ year

3. II-timester abortion, K Gemzell Danielsson The Swedish abortion act Has a limited influence on the number of abortions Has a profound influence on the conditions under which the abortion is performed Has a significant effect on women’s health A liberal abortion law is a prerequisite for the development of safe abortion methods

4. II-timester abortion, K Gemzell Danielsson Year Pregnancy length (weeks) -1213 -1617-2021- 24 1964 10%27,9%54,9%7.4%17.0 weeks Källa: Rätten till abort SOU 1971:58 och EPC Socialstyrelsen -1112-1718+ 2002 93,3%6.0%0,7% 8,1 weeks Mean Percentages of abortions in relation to pregnancy week

5. II-timester abortion, K Gemzell Danielsson Mifepristone abortion in Sweden 1992: up to 63 days 1994: II-trimester abortion –600 mg mifepristone followed by gemeprost 1mg/ 3h –2003: 600 mg mifepristone followed by a suitable prostaglandin analogue

6. II-timester abortion, K Gemzell Danielsson II-trimester abortion 1996 to 1998 197 consecutive abortions in 192 women Regimen: –600 mg mifepristone –24 to 48 h later gemeprost 1mg every 6 hours x 4 –If no abortion within 24 h, I mg gemeprost / 3 h Curettage routinely performed up to 18 weeks, thereafter when needed Gemzell Danielsson K & Östlund 2000

7. II-timester abortion, K Gemzell Danielsson Demography Median age: 30 (15 to 44) years Median pregnancy length: 17 (14 to 26) weeks Primigravidae: 42 (21.3) % Multigravidae: 155 (78.7) % ( Nulliparous (n=45)) Indications: –Social (n=113) 57.4 % –Chromosomal aberration (n=30) 15.2 %, Foetal malformation (n=34) 17.2%, Missed abortion (n=20) 10.2 %

8. II-timester abortion, K Gemzell Danielsson Results Median numbers of gemeprost (Cervagem): 2 Induction-to-abortion interval: –Primigravidae: 9.0 (1.4-40.5) h vs. –Multigravidae: 7.2 (0-152.5) h (ns) Nulliparous (n=45) 10.6 (2.8-30.6) h vs. Parous (n= 104) 6.0 (0-152.5) h (p<0.001)

9. II-timester abortion, K Gemzell Danielsson Results 96.3 % aborted within 24 h (all women with missed abortion) Significant correlation between pregnancy length and abortion time Narcotic analgesia required by 93 % PCB (n=8) EDA (n=1) One woman required a blood transfusion

10. II-timester abortion, K Gemzell Danielsson II-trimester abortion 200mg mifepristone and gemeprost Case series report 200mg mifepristone followed 36h later by 1 mg gemeprost/6h x4, /3h Median gestational length 16 weeks (12-24 w) Median induction-to-abortion interval 7.8h Surgical evacuation 11.5% Tang OS, Thong KJ, Baird DT, Contraception 2001

11. II-timester abortion, K Gemzell Danielsson II-trimester abortion gemeprost vs.misoprostol orally 50 women 200 mg mifepristone followed by 400  g misoprostol p.o/ 3h or 1 mg gemeprost/ 6h Induction – abortion interval 8.7 vs. 10.8 h (ns) No difference in incidence of side effects Ho et al., 1996 Similar efficacy: El Refaey et al., 1993, Dickinson et al., 1998, Nuutila et al., 1997 Higher efficacy: Wong et al., 1996

12. II-timester abortion, K Gemzell Danielsson II-trimester abortion misoprostol 3h vs. 6h intervals 148 women Misoprostol 400  g vaginally Repeated every 3h vs. 6h Induction-ab interval 15.2 vs.19.0 h (P< 0.01) Abortion within 48 h 90.5 vs. 75.7% (P< 0.02) Fever more common in the 3h group (P = 0.01). Wong et al., 2001

13. II-timester abortion, K Gemzell Danielsson II - trimester abortion oral vs. vaginal misoprostol 142 women: 200 mg mifepristone + misoprostol 400  g oral vs. 200  g vaginal/ 3 h up to x 5 Complete abortion rate: 81.4% vs.75.4% (ns.) Diarrhoea 40 vs. 23.2 % (p= 0.03) Total dose 1734 vs. 812  g (p< 0.0001) Median induction-to-abortion interval: 10.4 vs. 10 h 82% preferred the oral route Ngai et al. 2000

14. II-timester abortion, K Gemzell Danielsson II-trimester abortion 200 mg mifepristone followed 48h later by –Misoprostol 400  g vaginally every 3h vs. –Misoprostol 600  g vaginally + 400  g po/ 3h No significant difference between the groups El-Refaey & Templeton 1995

15. II-timester abortion, K Gemzell Danielsson II-trimester abortion 1000 women, 13-21 weeks Mifepristone 200 mg, after 36-48 h followed by –vaginal misoprostol 800  g (4 tabl Cytotec) followed by –400  g po.(2 tabl Cytotec) every 3h to max 4 doses 97% aborted successfully median dose of misoprostol: 1200  g median induction-to-abortion interval: 6.5 h. 9.4% curettage, > 75 % day cases Ashok & Templeton 1999, 2004

16. II-timester abortion, K Gemzell Danielsson II-trimester abortion sublingual misoprostol Significantly higher acceptance for sublingual administration 400 microg misoprostol/ 3h x 5 vaginal. vs. Sublingual Tang et al., 2004 Higher acceptance for sublingual but more pain, more opiates needed 600 microg sublingual vs. 800 microg vaginal followed by 400 microg /3h sublingual or vaginal Hamoda et al., 2005

17. II-timester abortion, K Gemzell Danielsson Effect of the time interval between mifepristone and the prostaglandin No difference in induction to abortion time with mifepristone administered 24, 36 or 48 h prior to the prostaglandin Urquhart and Templeton 1990 Effect on uterine contractility maximal at 36 to 48h Bygdeman & Swahn 1985 Ripening effect of mifepristone on cervix, more pronounced at 36 to 48 h Rådestad et al 1988

18. II-timester abortion, K Gemzell Danielsson  The contraindication is unfounded  NSAIDs are prostaglandin synthetase inhibitors  Effect of mifepristone on uterine contractility: , regardless of NSAID administration (Norman et al.,)  No effect on cervical ripening when coadministered with misoprostol (Ho et al)  Efficacy of medical abortion is the same, when NSAIDs prophylaxis is used  Shortened induction-to abortion interval and less misoprostol in nulliparaous Fiala et al Human Reprod 2005 Arguments for the use of NSAIDs

19. II-timester abortion, K Gemzell Danielsson Conclusion Mifepristone in II-trimester abortion Our data confirm the efficacy and safety of mifepristone and gemeprost for II-trimester abortion. Oral misoprostol has been shown to be as effective and safe as gemeprost Vaginal misoprostol is more effective but less accepted than the oral route The combined vaginal-oral regimen is as effective as repeated vaginal misoprostol

20. II-timester abortion, K Gemzell Danielsson II-trimester abortion Mifepristone followed 24-48h later by Misoprostol 800  g (Cytotec R 4 tabl ) vaginally followed by 400  g (Cytotec R 2 tabl) orally every 3h Curettage only in case of incomplete abortion

21. II-timester abortion, K Gemzell Danielsson Pain prophylaxis T Diclofenac 100 mg T Panocod. ® together with the first dose of Cytotec Contraceptive councelling Screening and treatment/ prophylactic antibiotics for STI

22. II-trimester abortion with Mifepristone Kristina Gemzell Danielsson, Dept of Obst. & Gyn Karolinska University Hospital / Institute, Stockholm, Sweden FIAPAC, Moscow, October 2005 kristina.gemzell@kbh.ki.se www.reproductivehealthresearch.org