1. Ibis Reproductive Health1 Medication Abortion A training module for health professionals

2. Ibis Reproductive Health2 Ibis Reproductive Health aims to improve womens reproductive health, choices, and autonomy worldwide. Our work includes clinical and social science research, policy analysis, and evidence- based advocacy.

3. Ibis Reproductive Health3 Objectives Define medication abortion Identify current medication abortion methods and present Mechanisms of action Regimens, efficacy, and safety Eligibility requirements and contraindications Side effects and complications Provide general information on medication abortion methods Outline references and resources

4. Ibis Reproductive Health4 What is medication abortion? Medication abortion, also known as non-aspiration or non-surgical abortion, refers to a family of safe and effective methods for terminating an early unwanted pregnancy. Through the use of a drug or combination of drugs that are administered orally, vaginally, and/or intramuscularly, medication abortion first causes the pregnancy to terminate and then causes the uterus to expel the products of conception.

5. Ibis Reproductive Health5 Why medication abortion? Non-aspiration or non-surgical abortion is commonly referred to as medical abortion. However, this phrase has led to confusion among both providers and the public, as the term medical is often associated with physician-based practices and/or medical necessity. Medication abortion more accurately represents the family of safe and effective drug-based methods that can terminate an unwanted pregnancy and will be used throughout this presentation.

6. Ibis Reproductive Health6 Methods of medication abortion Mifepristone and misoprostol Methotrexate and misoprostol Misoprostol alone Medication abortion methods can be used throughout early pregnancy (63 days gestation)

7. Ibis Reproductive Health7 Medication abortion Methods of action of the medications Mifepristone Anti-progestin that blocks the action of progesterone Alters the uteral lining Methotrexate Anti-metabolite Interferes with DNA synthesis and cell growth Misoprostol Prostaglandin E 1 analog Stimulates uterine contractions and induces cervical softening

8. Ibis Reproductive Health8 Medication abortion Additional uses of the medications Mifepristone Labor induction (under investigation) Infertility treatment (under investigation) Methotrexate Treatment of neoplastic diseases Treatment of rheumatoid arthritis Misoprostol Prevention of gastric ulcers Obstetric and gynecologic indications

9. Ibis Reproductive Health9 Mifepristone/misoprostol regimen

10. Ibis Reproductive Health10 Mifepristone Worldwide approval

11. Ibis Reproductive Health11 Mifepristone/misoprostol regimen General protocol Day 1 (Clinic) Clinician counsels the woman, takes a medical history and performs an exam and lab tests Mifepristone is orally administered Day 2-4 (Home or clinic) Misoprostol is administered Day 7-14 (Clinic) Patient returns to the clinic for follow-up Clinician assesses for the completion of the abortion

12. Ibis Reproductive Health12 Mifepristone/misoprostol regimens Comparison of protocols French RegimenUS: FDA RegimenEvidence-Based Regimen Mifepristone Dosage600 mg (Day 1) 200 mg (Day 1) Misoprostol Dosage400 µg, PO Or 1mg gemeprost, PV 400 µg, PO400 µg, PO or 800 µg, PV Gestational Limit 49 days 63 days Location of misoprostol administration At medical office/clinic At medical office/clinic or at home Timing of misoprostol administration Day 2 or 3Day 3Day 2, 3, or 4 Timing of initial follow- up examination Day 10 to 14Day 14Day 4 to 14 Number of clinic visits required Three or more Two or more

13. Ibis Reproductive Health13 Mifepristone/misoprostol regimen Efficacy and safety Approximately 95% of women will have a successful abortion when using mifepristone/misoprostol within 49 days gestation Completion rates appear to decline slightly with increasing durations of pregnancy after 56 days gestation Approximately 67% of women will have a complete abortion within four hours of using misoprostol Approximately 90% of women will have a complete abortion within 24 hours of using misoprostol.

14. Ibis Reproductive Health14 Mifepristone/misoprostol regimen Eligibility for use Non-ectopic pregnancy of 63 days gestation Absence of contraindications Willingness to undergo vacuum aspiration or dilation and curettage (D&C), if indicated

15. Ibis Reproductive Health15 Mifepristone/misoprostol regimen Contraindications to use Confirmed or suspected ectopic (extra-uterine) pregnancy Allergy to either mifepristone or misoprostol Presence of an intrauterine device (IUD) Chronic systemic use of corticosteroids Chronic adrenal failure Coagulopathy or current therapy with anticoagulants Inherited porphyria

16. Ibis Reproductive Health16 Mifepristone/misoprostol regimen Side effects Effects of abortion process Cramping Often described as similar to menstrual cramps Vaginal bleeding Median bleeding time 9-13 days Often described as similar to a heavy period or spontaneous miscarriage Common side effects Nausea Vomiting Diarrhea Headache Dizziness Fever, chills, hot flashes, warmth

17. Ibis Reproductive Health17 Mifepristone/misoprostol regimen Complications Type of complicationPercentage of women Continued pregnancy1%-5% Incomplete abortion requiring aspiration 1% Hemorrhage requiring aspiration 1%-2% Hemorrhage requiring transfusion 0.1%

18. Ibis Reproductive Health18 Mifepristone/misoprostol regimen Summary Millions of women worldwide have safely used mifepristone/misoprostol Mifepristone/misoprostol is more than 95% effective in terminating early pregnancies Mifepristone/misoprostol is widely acceptable to both patients and providers

19. Ibis Reproductive Health19 Methotrexate/misoprostol regimen

20. Ibis Reproductive Health20 Methotrexate Worldwide availability

21. Ibis Reproductive Health21 Methotrexate/misoprostol regimen Evidence-based protocol Day 1 (Clinic) Clinician counsels the woman, takes a medical history and performs an exam and lab tests. Methotrexate is administered either orally (50 mg) or intramuscularly (50 mg/m2) Day 3-7 (Home) Misoprostol is self-administered vaginally at home. Day 8 (Clinic) Clinician performs a vaginal ultrasound to determine if the abortion is complete. If abortion is complete (75% of women) no further visits are required. If the abortion is incomplete additional misoprostol is given and patient returns On Day 15 if cardiac activity is detected On Day 28-45 if no cardiac activity is detected on ultrasound

22. Ibis Reproductive Health22 Methotrexate/misoprostol regimen Evidence-based protocol continued Day 15 (Clinic, if necessary) Patient is assessed for continued pregnancy. If cardiac activity is detected, a aspiration termination is performed. If no cardiac activity is detected, patient returns in three weeks. Day 28-45 (Clinic, if necessary) The patient is assessed for continued pregnancy. If the abortion is incomplete (5% of cases), a aspiration termination is performed.

23. Ibis Reproductive Health23 Methotrexate/misoprostol regimen Efficacy and safety Approximately 95% of women will have a complete abortion when using methotrexate/misoprostol up to 49 days gestation. Medication abortion completion rates decline with increasing gestational age Approximately 20% of patients using methotrexate/misoprostol will experience a complete abortion three to four weeks after misoprostol administration.

24. Ibis Reproductive Health24 Methotrexate/misoprostol regimen Eligibility for use Pregnancy of 49 days gestation Methotrexate/misoprostol is preferable for women with ectopic pregnancies Absence of contraindications Willingness to undergo vacuum aspiration or dilation and curettage (D&C), if indicated

25. Ibis Reproductive Health25 Methotrexate/misoprostol regimen Contraindications to use Allergy to either methotrexate or misoprostol Presence of an intrauterine device (IUD) Coagulopathy or current severe anemia Acute or chronic renal or hepatic disease Acute inflammatory bowel disease Uncontrolled seizure disorders.

26. Ibis Reproductive Health26 Methotrexate/misoprostol regimen Side Effects Effects of abortion process Cramping Often described as similar to menstrual cramps Vaginal bleeding Median bleeding time 2-3 weeks Often described as similar to a heavy period or spontaneous miscarriage Common side effects Nausea Vomiting Diarrhea Headache Dizziness Fever, chills, hot flashes, warmth Oral ulcers Fetal malformations

27. Ibis Reproductive Health27 Methotrexate/misoprostol regimen Complications (49 days gestation) Type of complicationPercentage of women Continued pregnancy3-5% Incomplete abortion requiring aspiration 3-5% Hemorrhage requiring aspiration 1%-2% Hemorrhage requiring transfusion 0.1%-0.5%

28. Ibis Reproductive Health28 Methotrexate/misoprostol regimen Summary Methotrexate/misoprostol is approximately 95% effective in terminating pregnancies 49 days gestation Methotrexate/misoprostol is the preferred medication abortion method for confirmed or suspected ectopic pregnancies Methotrexate/misoprostol is widely acceptable to both patients and providers

29. Ibis Reproductive Health29 Misoprostol-only regimen

30. Ibis Reproductive Health30 Misoprostol Worldwide availability

31. Ibis Reproductive Health31 Misoprostol-only regimen Evidence-based protocols No consensus exists on optimal protocol Various regimens, dosing schedules and routes of administration are currently under investigation Most commonly used protocol Vaginal administration of 800 µg of misoprostol If abortion fails, misoprostol dose is repeated every 24 hours, up to three doses

32. Ibis Reproductive Health32 Misoprostol-only regimen Efficacy and Safety Efficacy varies widely (65%-93%) Efficacy varies by route of administration, dose, dosing schedule, and gestational age Misoprostol-only regimens are not as effective as either mifepristone/misoprostol or methotrexate/misoprostol regimens

33. Ibis Reproductive Health33 Misoprostol-only regimen Eligibility for use Non-ectopic pregnancy of 63 days gestation Absence of contraindications Willingness to undergo vacuum aspiration or dilation and curettage (D&C), if indicated Lack of access to either mifepristone or methotrexate

34. Ibis Reproductive Health34 Misoprostol-only regimen Contraindications for use Confirmed or suspected ectopic pregnancy Allergy to misoprostol Presence of an intrauterine device (IUD) Uncontrolled seizure disorder Inflammatory bowel disease

35. Ibis Reproductive Health35 Misoprostol-only regimen Side effects Effects of abortion process Cramping Often described as similar to menstrual cramps Often described as more severe than the cramping of either mifepristone/misoprostol or methotrexate/misoprostol regimens Vaginal bleeding Median bleeding time 2 weeks Often described as similar to a heavy period or spontaneous miscarriage Common side effects Nausea Vomiting Diarrhea Headache Dizziness Fever and chills Rashes Pelvic pain Fetal malformations

36. Ibis Reproductive Health36 Misoprostol-only regimen Complications Approximately 10%-35% of women will require an aspiration intervention Misoprostol-only regimen is less effective in terminating early pregnancy than when used in combination with either mifepristone or methotrexate

37. Ibis Reproductive Health37 Misoprostol-only regimen Summary Misoprostol used in conjunction with either mifepristone or methotrexate is more effective at terminating early pregnancy than misoprostol alone Efficacy varies widely Optimal regimen has yet to be determined Misoprostol-only regimen is an important alternative for women who do not have access to other medical or aspiration abortion methods

38. Ibis Reproductive Health38 Medication abortion: General issues

39. Ibis Reproductive Health39 Medication abortion Comparing the three regimens RegimenAdvantagesDisadvantages Mifepristone/ misoprostol High efficacy (95%) Can be used through 63 days gestation Abortion typically occurs within hours of misoprostol administration Mifepristone is often expensive Mifepristone is not available in many countries Can not be used to treat ectopic pregnancies Methotrexate/ misoprostol High efficacy (90%-95%) Can be used through 56 days gestation Often less expensive than mifepristone Treats ectopic pregnancies Abortion can occur over a four week period May cause fetal abnormalities in continued pregnancies Efficacy decreases after 49 days gestation Misoprostol-onlyCan be used through 63 days gestation Widely available worldwide Often very inexpensive Stable at room temperature Efficacy is variable (65%-90%) Regimen is currently under investigation May cause fetal anomalies in continued pregnancies Can not be used to treat ectopic pregnancies

40. Ibis Reproductive Health40 Medication abortion Special considerations for early pregnancy termination Determine eligibility for medication abortion Diagnose and accurately date of early pregnancy Discuss medical and aspiration options Inform patients of potential side effects, complications, and follow-up requirements Provide adequate follow-up and post abortion care Aspiration intervention, if necessary Family planning services

41. Ibis Reproductive Health41 Methods for determining gestational age For all medication abortion methods, accurate pregnancy dating is important Methods for determining gestation age include Last menstrual period Bimanual examination Serum β-hCG testing Ultrasound

42. Ibis Reproductive Health42 Alternatives to medication abortion Aspiration abortion Types of aspiration abortion Manual vacuum aspiration Dilation and curettage (D&C) Aspiration procedure Cannula is inserted into the uterus Uterine contents are emptied through suction Can be used throughout the first trimester Highly effective (>99%) in terminating pregnancy

43. Ibis Reproductive Health43 Medication abortion vs. aspiration abortion Advantages and disadvantages MethodAdvantagesDisadvantages Medication abortionUsed early during pregnancy Resembles a natural miscarriage Often considered more private Usually avoids aspiration intervention Anesthesia not required High success rates (for mifepristone/misoprostol and methotrexate/misoprostol regimens) Often requires at least two clinic visits Takes days, sometimes weeks to complete Efficacy decreases at later gestational ages Women may see blood clots and the products of conception Mifepristone and/or methotrexate may not be available Mifepristone can be expensive Aspiration abortionHigh success rate (>99%) May require only one clinic visit Procedure completed within minutes Sedation is available Involves an invasive procedure May not be available very early in pregnancy Often considered to be less private Quality of facilities may vary significantly

44. Ibis Reproductive Health44 Medication abortion Conditions requiring clinical assessment and/or intervention Fever Excessive or prolonged bleeding Incomplete abortion Retained fetal tissue Persistent gestational sac on ultrasound Continued pregnancy

45. Ibis Reproductive Health45 Medication abortion regimens Acceptability Generally well-accepted by patients who report High satisfaction Desire to use the method again Intention to recommend method to a friend or relative Both mifepristone/misoprostol and methotrexate/misoprostol regimens are well- accepted by providers

46. Ibis Reproductive Health46 Medication abortion regimens Best and worst reported features Women report the best features as Ability to avoid surgery and anesthesia Perception that the process is more natural Privacy Convenience Women report the worst features as Length and degree of bleeding Number of clinic visits Uncertainty as to whether or not the procedure had resulted in a complete abortion.

47. Ibis Reproductive Health47 Medication abortion Future directions for research and clinical practice Expand worldwide access to medication abortion medications Establish optimal misoprostol-only regimens Expand programs to educate women, health professionals, and policy makers about medication abortion Train health professionals in medication abortion provision

48. Ibis Reproductive Health48 Medication Abortion Conclusions Medication abortion regimens have been used by millions of women worldwide to safely and effective terminate early pregnancy Medication abortion regimens expand pregnancy termination options for women and health professionals Medication abortion regimens are highly acceptable to both women and providers Future research is needed to improve regimens and expand services

49. Ibis Reproductive Health49 Medication Abortion References and resources The Alan Guttmacher Institute: www.agi-usa.orgwww.agi-usa.org This site provides numerous studies on abortion in the US and worldwide. American College of Obstetricians and Gynecologists: www.acog.orgwww.acog.org This website provides information on the medical management of abortion and resources on practice guidelines. Ibis Reproductive Health: www.ibisreproductivehealth.orgwww.ibisreproductivehealth.org The home page of Ibis Reproductive Health, this site provides information on the organization and contains a database of articles published by staff. Ibis also provides educational materials on medication abortion in English, Arabic, French, and Spanish. IPAS: www.ipas.orgwww.ipas.org IPAS manufactures and distributes manual vacuum aspiration equipment and trains providers in early abortion techniques worldwide. National Abortion Federation: www.earlyoptions.orgwww.earlyoptions.org This site provides medication abortion educational materials for both providers and patients. Population Council: www.popcouncil.orgwww.popcouncil.org The Population Council provides information on reproductive health issues worldwide, including publications on medication abortion methods and acceptability.