2. clara bell duvall education fund Medical Abortion with Methotrexate and Misoprostol David Blair Toub, M.D. Department of Obstetrics and Gynecology Pennsylvania Hospital

3. clara bell duvall education fund Historical Perspective 1985 and earlier: Misoprostol 1985 and earlier: Misoprostol 1988: Mifepristone (RU-486) / Sulprostone 1988: Mifepristone (RU-486) / Sulprostone 1994: MTX / Misoprostol 1994: MTX / Misoprostol 1996: RU-486 conditionally approved by FDA 1996: RU-486 conditionally approved by FDA 1997: Misoprostol for early pregnancy failure 1997: Misoprostol for early pregnancy failure

4. clara bell duvall education fund Methotrexate: Applications Molar Pregnancy / GTN Molar Pregnancy / GTN Ectopic Pregnancy Ectopic Pregnancy Cancer Chemotherapy Cancer Chemotherapy Rheumatoid Arthritis Rheumatoid Arthritis Psoriasis Psoriasis First Trimester Abortion First Trimester Abortion

5. clara bell duvall education fund Misoprostol: Applications Peptic Ulcer Disease Peptic Ulcer Disease Induction of Labor Induction of Labor First and Second Trimester Abortion First and Second Trimester Abortion Treatment of Early Pregnancy Failure Treatment of Early Pregnancy Failure

6. clara bell duvall education fund MTX / Misoprostol Abortion: Most Effective in Early Pregnancy Most Effective in Early Pregnancy (≤ 56 days LMP) (≤ 56 days LMP) 90-97% Effective 90-97% Effective Requires Compliant Patient, Several Visits Requires Compliant Patient, Several Visits Not Yet Covered By Most Insurers Not Yet Covered By Most Insurers

7. clara bell duvall education fund MTX / Misoprostol Side Effects: MTX Stomatitis Stomatitis Gastritis Gastritis Alopecia Alopecia Elevated LFT’s Elevated LFT’sMisoprostol Diarrhea Diarrhea Nausea Nausea

8. clara bell duvall education fund Advantages / Disadvantages of Medical Abortion: Advantages Avoids Clinic Harassment Avoids Clinic Harassment Avoids Surgical Risks Avoids Surgical Risks Relatively Inexpensive Relatively Inexpensive Empowers Patient Empowers Patient Extends Abortion Access Extends Abortion Access May Treat Undiagnosed Ectopic Pregnancy (MTX) May Treat Undiagnosed Ectopic Pregnancy (MTX) Allows Early Termination Allows Early TerminationDisadvantages Multiple Visits Multiple Visits 3-10% Require D+E* 3-10% Require D+E* Not Covered By Insurers Not Covered By Insurers Bleeding May Be Unpredictable Bleeding May Be Unpredictable Must Be Less Than 49- 56 Days From LMP Must Be Less Than 49- 56 Days From LMP *May Be Completed With Karmen Cannula in Office

9. clara bell duvall education fund Advantages / Disadvantages of Suction Curettage: Advantages Brief Procedure Brief Procedure Bleeding and Cramping Relatively Predictable Bleeding and Cramping Relatively Predictable Requires Minimal Visits Requires Minimal Visits Covered By Many Insurers Covered By Many Insurers Safe; High Success Rate Safe; High Success RateDisadvantages Infrequent (But Occasioally Serious) Surgical Risks Infrequent (But Occasioally Serious) Surgical Risks More Often Performed in Targeted Outpatient Clinics More Often Performed in Targeted Outpatient Clinics Availability Limited Availability Limited At Times Restricted to ≥ 8 Weeks LMP At Times Restricted to ≥ 8 Weeks LMP

10. clara bell duvall education fund Patient Selection: ≤ 56 Days LMP ≤ 56 Days LMP Compliant, with Reliable Phone Contact Compliant, with Reliable Phone Contact No h/o Blood Dyscrasia, Liver Disease No h/o Blood Dyscrasia, Liver Disease No Significant Contraindications to D+E No Significant Contraindications to D+E

11. clara bell duvall education fund Misoprostol Alone is a Weak Abortifacient: 400 mcg misoprostol PO, ≤56 days LMP (Norman et al, 1991) Percent

12. clara bell duvall education fund MTX / Misoprostol vs Misoprostol Percent Complete Abortion (Crenin and Vittinghoff JAMA 272:1190-1195, 1994)

13. clara bell duvall education fund Abortion Rates by Misoprostol Routine (+IM MTX): (Schaff, et. al. 1996) Percent Abortion

14. clara bell duvall education fund Evidence-Based Medicine: Class I – At Least One Proper RCT Class I – At Least One Proper RCT Class II – Cohort Studies or Nonrandomized Trial Class II – Cohort Studies or Nonrandomized Trial Class III – Case Reports Class III – Case Reports A – Good Evidence Exists A – Good Evidence Exists B – Fair Evidence Exists B – Fair Evidence Exists C – Insufficient Evidence C – Insufficient Evidence

15. clara bell duvall education fund Grimes: Evidence-Based Summary 800 mcg Misoprostol on Day 7 > Day 3 (IA) 800 mcg Misoprostol on Day 7 > Day 3 (IA) MTX + Misoprostol > Misoprostol (IA) MTX + Misoprostol > Misoprostol (IA) 800 mcg Misoprostol pv > 600 mcg po (IIB) 800 mcg Misoprostol pv > 600 mcg po (IIB) MTX Alone Effective But Slow (IIIA) MTX Alone Effective But Slow (IIIA) Regimen Less Effective > 56 Days LMP (IIIA) Regimen Less Effective > 56 Days LMP (IIIA)

16. clara bell duvall education fund Suggested Protocol

17. clara bell duvall education fund Patient Experiences: (Adapted From Creinin and Park, 1995) 86 MTX/Misoprostol Patients, <56 Days LMP 86 MTX/Misoprostol Patients, <56 Days LMP 85/86 (99%) Completed Questionnaires 85/86 (99%) Completed Questionnaires 48% Had Previous D+E 48% Had Previous D+E 49% Cited Negative Experience with D+E 49% Cited Negative Experience with D+E 67/86 (79%) – Medical Abortion “Positive” 67/86 (79%) – Medical Abortion “Positive” 12/86 (14%) – Negative Experience 12/86 (14%) – Negative Experience 89% Would Choose Medical Abortion Again 89% Would Choose Medical Abortion Again

18. clara bell duvall education fund Conclusions: Medical Abortion with MTX and Misoprostol is Effective for Early (≤ 56 Days LMP) Gestations Medical Abortion with MTX and Misoprostol is Effective for Early (≤ 56 Days LMP) Gestations The Timing and Route of Misoprostol Administration Influences Success Rates The Timing and Route of Misoprostol Administration Influences Success Rates Patient Satisfaction is Generally Favorable Patient Satisfaction is Generally Favorable MTX and Misoprostol is an Available Alternative to Progesterone Antagonists (e.g. RU-486) MTX and Misoprostol is an Available Alternative to Progesterone Antagonists (e.g. RU-486)

19. clara bell duvall education fund Future Dimensions: Increase Availability of Medical Abortion Increase Availability of Medical Abortion Establish Absolute Upper Gestational Age Limit Establish Absolute Upper Gestational Age Limit Compare RU-486 with MTX Compare RU-486 with MTX Work with Insurers to Establish Coverage Work with Insurers to Establish Coverage

20. clara bell duvall education fund Thank You!

21. clara bell duvall education fund