Medical abortion with Medical abortion with mifepristone and misoprostol: mifepristone and misoprostol:

overviewoverview

Dr. Rodica Comendant,

ICMA Operations CoordinatorBangkok, Thailand, March 2012

Outlines• Definition of MA, what is known, the use in

the world

• The actual trends in MA

• The regimens for 10-12 weeks, 2nd trimester

• Misoprostol alone regimen

• Alternative ways for follow up

What is medical abortion?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

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.

What we know today about MA?

• Registered in 50 countries (2011) • Use by 2.5 - 3 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)

What is mifepristone? 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

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

RhythmicUterine

Contractions

Progesterone Blockade

DecidualNecrosis

CervicalRipening

Detachment Expulsion

Abortion

Mechanism of Action in MA:Mifepristone + Misoprostol

© Lisa Penalver

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

Vaginal, oral and sublingual pharmacokinetics

Tang, et al, 2002

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

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

Safety of MA

• Uterine blood loss in surgical or medical abortion is the same

• With medical bleeding lasts more days• 95.000 MA, complication (heavy bleeding)

- 2.2 per 1000 women (PPF, USA, 2001-2005). Mortality 1,1 per 100.000(one death)

• France ~1000.000 abortion, no one death

Safety of Medical Abortion

Medical Abortion Early Surgical abortion

Transfusion:

0,2% 0,1%Aspiration to stop bleeding (0,4-2%)

Infection

0,09-0,5% 0.2-5.4%

French regimen (early 90es), for 49 days LMP

Visit 1: Patient eligibility, counseling (!)

Swallow 3 tabs mifepristone

Visit 2: +36-48 hr

Oral Misoprostol (400 µg)

3-4 hour monitoring in clinic

Visit 3: +10-12 days

Follow-up visit

Recommended mifepristone plus misoprostol regimens (WHO 2012)

Up to 9 completed weeks (63 days) LMP

• 200 mg mifepristone followed after 24-48 hours by

• 800 µg misoprostol, administered vaginally, sublingually or buccally

Or, for up to 7 completed weeks (49 days)

• 400 µg oral misoprostol.

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

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

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

Regimens for second trimester: 12-21 weeks

• 200 mg mifepristone followed after 36-48 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)

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

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

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

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

Misoprostol alone for abortion

• Induced abortion (0-12 weeks): 800g vaginally 12-hrly

• Missed abortion (0-12 weeks)800g vaginally 3-hrly

OR • 600g sublingually 3-hrly• Incomplete abortion (0-12 weeks)600g orally

stat.• Induced abortion (13-24 weeks)400g

vaginally 3-hrly x5

Weeks A & Faundes A. International Journal

of Gynecology and Obstetrics 2007;99:S156-9.

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

Thank you!

Questions?