1. Medical abortion with mifepristone and misoprostol: overview
Dr. Rodica Comendant,
ICMA Operations Coordinator
Bangkok, Thailand, March 2012

2. Outlines Definition of MA, what is known, the use in the world
The actual trends in MA
The regimens for weeks, 2nd trimester
Misoprostol alone regimen
Alternative ways for follow up

3. What is medical abortion?
A way of inducing termination of pregnancy with medicines (pills)
A “non-surgical” abortion
The regimen for first trimester medical abortion, consists of two drugs, included in 2005 on the WHO Essential Medicines list: mifepristone followed 1–3 days later by misoprostol
“Medical abortion” is the use of drugs to terminate a pregnancy. It is sometimes also called non-surgical abortion.
The regimen for first trimester medical abortion consists of two drugs, included in 2005 on the WHO Essential Medicines list:
mifepristone (an anti-progestogen that blocks progesterone, the hormone necessary to sustain a pregnancy),
followed 1–3 days later by misoprostol (a prostaglandin that makes the uterus contract).

4. Why medical abortion is important?
Medical abortion can make abortion:
earlier,
more accessible,
safer,
less traumatic,
less medicalised and less expensive.
There is no medical reason for adolescents do not have medical abortion.
It has increased access to safe abortion and reduced maternal mortality, including in legally restricted settings.

5. What we know today about MA?
Registered in 50 countries (2011)
Use by million women outside of China
Use by more than 22 million women in China
Good efficacy : 92-97%
Extremely good safety record, lower risk of infection and trauma than surgery
Women like the method very much (it’s private, natural and similar to menstruation)
Safety: No long term consequences
Medical abortion doesn’t affect women’s ability to become pregnant or have a child in the future
Women can become pregnant again within three weeks of having MA

6. What is mifepristone? How does it work?
Antiprogestin compound
Discovered in 1980 in Russel Uklaaf laboratory
First clinical trial in 1982, Geneva
Binds to progesterone receptor to block action of progesterone
Increases endogenous prostaglandins
Increases uterine contractility and sensitivity to prostaglandins
Decidua and trophoblast separate
Cervix softens and dilates, facilitating abortion
GHP
From DH:
Progesterone during pregnancy:
Inhibits contractility of myometrium
Inhibits secretion of prostaglandins in endometrium
Maintains closed cervix
The inhibition or blocking of receptors:
Detachment of the embryo, drop in BHCG, luteolysis
Increase in contractility of the myometrium directly affected by mifepristone as well as increase in the synthesis of prostaglandins in the endometrium
Opening and softening of the cervix (without increase of prostaglandin in the cervical tissue). Flux of water and leucocytes.
Mifepristone alone: 80% abortion rate

9. What is misoprostol? How does misoprostol work?
Prostaglandin E1 analogue, approved for prevention and treatment of gastric ulcers
Drug causes contractions of smooth muscles of the uterus -> empties the uterus
Drug can soften the cervix -> increases dilation for interuterine procedures, facilitates expulsions

10. Widely available (over 80 countries)
Inexpensive (~ $0.35 per 200 mcg)
Simple to administer
No refrigeration needed: stable at ambient temperatures
Misoprostol is increasingly used for a variety of ob/gyn indications

11. Mechanism of Action in MA: Mifepristone + Misoprostol
Rhythmic
Uterine
Contractions
Progesterone Blockade
Decidual
Necrosis
Cervical
Ripening
Detachment
Expulsion
Abortion
© Lisa Penalver

12. Misoprostol: routes of administration
Oral Rapid absorption (peak 30 mins) Levels fall sharply in 1-2 hours
Vaginal Peak later (80 mins) but lower Higher levels longer in plasma
Buccal Later, lower peak, sustained levels (similar to vaginal)
Sublingual Rapid absorption, high peak levels, sustained levels
Rectal Lower peak but higher levels longer than oral

13. Vaginal, oral and sublingual pharmacokinetics
Misoprostol: routes of administration:
Oral Rapid absorption (peak 30 mins) Levels fall sharply in 1-2 hours
Vaginal Peak later (80 mins) but lower Higher levels longer in plasma
Buccal Later, lower peak, sustained levels (similar to vaginal)
Sublingual Rapid absorption, high peak levels, sustained levels
Rectal Lower peak but higher levels longer than oral
Tang, et al, 2002

14. Contraindications to method
Suspected ectopic pregnancy (rule out)
IUD in place (take out)
Chronic adrenal failure
Current long term corticosteroids
Known allergy to the medications
Clotting disorder/anticoagulant therapy
Inherited porphyria
Mifepristone is not an effective treatment for ectopic pregnancy; suspicion of ectopic pregnancy demands further investigation and, if confirmed, immediate treatment

15. Gastrointestinal side effects Fever, chills Dizziness, headache
Expected side effects: go away within several hours and don’t need serious medical treatment
Pain, cramping
Bleeding
Gastrointestinal side effects
Fever, chills
Dizziness, headache
Counselling is very important!!!

16. Safety of MA
Uterine blood loss in surgical or medical abortion is the same
With medical bleeding lasts more days
MA, complication (heavy bleeding) per 1000 women (PPF, USA, ). Mortality 1,1 per (one death)
France ~ abortion, no one death
Hemorrage:
- Aspiration to stop bleeding(0,4-2%)
- Transfusion (0,2%)
(Early surgical abortion: 0,1%)
Infection: medical - 0,09-0,5% (surgical %)
Incomplete :Persistence of gestational sac
or retention (2,9%)
(surgical : 2-

17. Safety of Medical Abortion
Medical Abortion Early Surgical abortion
Transfusion:
0,2% ,1%
Aspiration to stop bleeding (0,4-2%)
Infection
0,09-0,5% %
3-5% incomplete abortion, 1-3% ongoing pregnancy,

18. French regimen (early 90es), for 49 days LMP
Visit 1: Patient eligibility, counseling (!)
Swallow 3 tabs mifepristone
Visit 2: hr
Oral Misoprostol (400 µg)
3-4 hour monitoring in clinic
Visit 3: days
Follow-up visit

19. Recommended mifepristone plus misoprostol regimens (WHO 2012)
Up to 9 completed weeks (63 days) LMP
200 mg mifepristone followed after hours by
800 µg misoprostol, administered vaginally, sublingually or buccally
Or, for up to 7 completed weeks (49 days)
400 µg oral misoprostol.
Regimen Innovations and actual trends in MA: de-medicalisation
200 mg vs. 600 mg mifepristone
Different doses and routes of misoprostol administration
Home use of misoprostol
Use after 49 days LMP, use in weeks
Timing of misoprostol
Alternative follow-up, etc, etc.

20. Home Use of Misoprostol
Overwhelmingly preferred choice in U.S.
98-99% (n = 4345) Schaff, 1998, 1999, 2000
Similar preference in developing countries:
Vietnam 80% (n =112) Elul, et al., 2000
Tunisia 87% (n =191) Elul, et al., 2000
Home administration recently approved in France, in many EU countries

21. Is misoprostol in clinic needed for safety reasons?
No serious adverse events in 4 hours post-misoprostol in clinic – 1059 patients in 4 developing countries
Pop Council trial in 2121 U.S. women: 4 transfusions, none during clinic waiting time
Schaff study of 2295 women: no interventions required within 4 hours of misoprostol

22. Regimens in later first trimester: 10-12 weeks LMP
Beginning to be more widely used
200mg mifepristone orally followed after 36–48 hours by 800 µg vaginal misoprostol, administered in a health facility.
A maximum of 4 further doses of misoprostol 400 µg may be administered at 3-hourly intervals, vaginally or orally.(WHO, 2012)
A clinic-based procedure that takes several hours to a day
Many women prefer the faster surgical approach, especially when that is offered as a rapid outpatient procedure

23. Regimens for second trimester: 12-21 weeks
200 mg mifepristone followed after hours by
400 µg oral or 800 µg vaginal misoprostol followed by 400 µg vaginal or sublingual misoprostol every 3 hours up to a maximum of 5 doses, administered in a health facility.
After 24 weeks gestation, the dose of misoprostol should be reduced. (WHO, 2012)

24. Alternative follow-up: checklists
Clark et al. Ob & Gyn 2010, N=>3000 : simple checklist works
Simple checklist identified all ongoing pregnancies
Checklist also identified all women needing any other additional care for their medical abortion 24

25. A semi-quantitative pregnancy test + the checklist
The semi-quantitative pregnancy test is an accurate alternative method of follow-up
The semi-quantitative pregnancy test correctly identified all ongoing pregnancies
The acceptability and feasibility of using simple semi-quantitative pregnancy tests with a simple checklist are now under the research 25

26. The routine use of ultrasound – not needed!
Total of 4484 women seeking MA in US
Women provided their LMP + vaginal exam
The estimations were compared to ultrasound data
Conclusion: LMP and physical exam, without use of ultrasound are highlely efective for early MA
H. Bracken, W. Clark, etc. Alternative to routine ultrasound for eligibility assessment
prior to early termination of pregnancy with mifepristone-misoprostol, BJOG, 2011

27. MA safely provided by mead-level providers (the Lancet, 2011)
A study in Nepal, 1295 women, randomly assigned to receive the care to a doctor or to a mead-level providers
Similar safety and effectiveness

28. Misoprostol alone for abortion
Induced abortion (0-12 weeks): 800g vaginally 12-hrly
Missed abortion (0-12 weeks)800g vaginally 3-hrly OR
600g sublingually 3-hrly
Incomplete abortion (0-12 weeks)600g orally stat.
Induced abortion (13-24 weeks)400g vaginally 3-hrly x5
Weeks A & Faundes A. International Journal
of Gynecology and Obstetrics 2007;99:S156-9.

29. Misoprostol alone versus mifepristone+misoprostol regimen
A study in Vietnam, 400 women
Randomized to two groups: two doses of 800 mcg buccal miso or 200 mife+800 mcg miso
In miso group the efficacy 76,2%, in mife+miso – 96,5%
Ongoing pregnancy in miso group -16,6%
In mife+miso group – 1,5%
Published in Contraception, 2010

30. Thank you!
Questions?