Background
Medical abortion as an alternative to surgical
termination of pregnancy, is safe, effective and offers certain
advantages over surgical abortion including avoidance of surgery
and anaesthesia and allowing a very early pregnancy termination.
It permits greater privacy and a degree of personal
control by women. In several European countries, it is now a method
preferred by majority of women, when given a choice. The method
involves use of pharmacological agents capable of inducing abortion
by causing uterine contractions. These include prostaglandins, anti-
metabolites such as methotrexate and antiprogesterones such as mifepristone.
QUESTIONS TO BE ANSWERED
The group needed to decide on :
A. What should be the combination, route of administration and dosage
schedule of drugs used?
B. What monitoring is required during the process of abortion?
C. What is the role of Anti-D?
D. Is analgesia required?
E. Is there a need to administer prophylactic antibiotics? VIEWS
OF THE GROUP
The group discussed the most appropriate technology for medical abortion
including the drug combination, dosage schedule and mode of administration;
the need for medical supervision, Anti- D, analgesia and antibiotics.
A. Drug Regimen
Extensive research has been done on drugs being used for medical
abortion in Europe and USA over the last 20 years to establish the
safest and effective dosage.
The widely-practised protocols include :
1. Mifepristone Regimen
a) French Protocol
Mifepristone 600 mg orally on day one (D1), followed 48 hours later
by Misoprostol 400 µg orally on day three with follow-up between
Day 12-20. Success rate is 92% for pregnancy < 49 days and 77%
to 83% for pregnancy < 63 days.
| Mode
of Action of Medical Methods of Abortion |
Each class
of medical abortion drugs has a unique mechanism of action,
and they can each cause complete abortion on their own.
Mifepristone : an antiprogesterone,
binds to the progesterone receptor with an affinity equal
to progesterone; however, it does not activate the receptor
and thus acts as an antiprogestin. During early pregnancy,
mifepristone alters the decidua, resulting in trophoblast
separation. Mifepristone has no direct effect on trophoblast.
In addition, it softens the cervix to allow expulsion of pregnancy.
It also increases uterine lining prostaglandin release, and
enhances uterine sensitivity to administered prostaglandin.
Methotrexate : an antimetabolite,
blocks dihydrofolate reductase, an enzyme necessary for DNA
synthesis, thus inhibiting growth of such rapidly dividing
cells as placental trophoblastic cells. Methotrexate must
also be followed by a uterotonic such misoprostol, to increase
uterine contractions and cause expulsion of the products of
conception.
Misoprostol : A prostaglandin E1
analogue binds to myometrial cells to cause strong myometrial
contractions leading to expulsion of pregnancy. It also causes
cervical ripening with softening and dilatation of cervix.
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b.) WHO Protocol
With reduced mifepristone dose having
equal efficacy as high dose.
• Mifepristone 200 mg orally on D1 followed 48 hours later
by misoprostol 400 µg orally on D3. Success Rate: 89.1% for
pregnancy < 35 days
• Mifepristone 200 mg orally on D1, followed 48 hours later
by misoprostol 800µg vaginally on D3. Success Rate - 98.5%
for pregnancy < 49 days and 96.5% for pregnancy 50 to 63 days
• Lately, the regimen of 800 µg vaginal misoprostol
has been modified with up to 2 doses of misoprostol, the second
being 400 µg orally or vaginally.
c) Gemeprost Regimen (UK)
It has been approved for pregnancy up to 63 days.
• Mifepristone 600 mg orally on D1, followed 48 hours later
by gemeprost 1 mg vaginal pessary on D3.
• Mifepristone 200 mg orally on D1, followed 48 hours later
by gemeprost 0.5 mg vaginal pessary on D3.
2. Methotrexate Regimen
It has been approved for pregnancy termination up to 56 days of
amenorrhoea in some countries
The combination of ethotrexate and misoprostol takes longer to
effect abortion than mifepristone and misoprostol.
• Methotrexate 50 mg/m2 intramuscularly on D1, followed 3-7
days later by misoprostol 800 µg vaginally at home.
• Methotrexate 25-50 mg orally on D1, followed 3-7 days later
by 800 µg misoprostol vaginally.
Follow-up visit is scheduled one week after misoprostol to confirm
complete abortion. Success rate is 90% for pregnancy < 56 days.
3. Misprostol only Regimen
• 800 µg vaginal misoprostol every 24 hours, for a maximum
of 3 doses. Success rate is 84-88%for gestation up to 63 days and
93% when misoprostol is moistened with saline before vaginal insertion.
It results in longer and better contractility with minimal side-effects.
• 600 µg vaginal misoprostol every 8 hours, for a maximum
of 3 doses over 24 hours. Success rate is 64% for gestation up to
56 days.
• 1000 µg vaginal misoprostol every 24 hours,
for a maximum of 3 doses. Success rate is 93% for gestation up to
63 days.
Final recommendation from the group for first trimester
pregnancy termination up to 56 days is mifepristone 200 mg orally
on D1 followed 48 hours later by 400 µg misoprostol vaginally
or orally.
Vaginal misoprostol is more effective and has fewer side-effects.
There is no need for repeat dose of misoprostol.
B. Monitoring
Clinical monitoring of vital parameters (temperature, pulse, blood
pressure) and watch for any specific complaints (bleeding, pain, expulsion
of products of conception). It is required for 30 minutes after mifepristone
and for 4 hours after misoprostol administration. Four hours waiting
period is kept because 57% of patients abort within this period. A
vaginal examination is done before sending the women home to ensure
that abortion is not imminent. This will prevent a crises situation
on the way.. C.
Role of Anti-D
All patients with Rh-negative blood group should be given 50 µg
anti D along with mifepristone administration on Day 1. There is
no need to administer anti-D in early (< 6 weeks) first trimester
termination of pregnancy.
In India, 50µg of Rh Immunoglobulin is not available, thus
100 µg injection is given only if pregnancy is beyond 6 weeks.
D.
Need for Analgesia
Cramping pain and abdominal discomfort are the most common side-effects
of medical abortion using mifepristone and misoprostol. Medication
for pain management should always be offered. Pain typically follows
3-6 hours after use of misoprostol, for whichpatient can be given
analgesics if required. The common analgesics being used are paracetamol
500 mg and codeine 10 mg orally or injection Morphine 10 mg intra-muscularly.
Some researchers feel that they would inhibit the action of prostaglandins.
Therefore, they do not use Non Steroidal Anti Inflammatory Drugs
(NSAIDs). In fact, NSAIDS are PG Synthesis Inhibitors. They do not
block the action of PGs but they do inhibit synthesis of new PGs.
Therefore, NSAIDS can be given for the purpose of pain relief in
patients undergoing medical abortion.
E. Role
of Antibiotics
Abortion-care should encompass a strategy for minimizing the risk
of post-abortion infective morbidity. Appropriate strategies include
antibiotic prophylaxis or screening for lower genital tract organisms
with treatment of positive cases.
Uterine infection and endometritis are rare complications of medical
abortion as it involves noinstrumentation of cervix or uterine cavity.
Majority study reports show no infection. Infection is rarely seen
in isolated cases (0.09- 0.5%). Therefore, there is no rationale
to support prophylactic use of antibiotics with medical abortion.
In women with lower genital tract infection, treatment can be started
with Metronidazole 1gm and Doxycycline 100 mg twice daily for 7
days. Nulliparous women, women opting for home administration of
drugs and women with genital problems may be offerred prophylactic
antibiotics.
F. Unresolved Issues
• Decision regarding the drug combination and dosage schedule
for second trimester pregnancytermination
• Sublingual administration of misoprostol is under trial
to prove its efficacy
• Research is under way to use misoprostol only regimen for
pregnancy termination as it is likely reduce the cost.
| RECOMMENDATIONS |
1. Recommended
drug combination and dosage schedule to be used for pregnancy
termination up to 56 days is mifepristone 200mg orally on
D1 followed 48 hours later by misoprostol 400 µg orally/
vaginally (moistened) on D3 with a scheduled follow-up visit
on D15 to check for completeness of abortion.
2. Vaginal misoprostol is preferable and moistening of vaginal
tablet with water or normal saline increases the efficacy
of the drug.
3. Clinical monitoring of the patient is required for 30 minutes
and 4 hours after mifepristone and misoprostol administration,
respectively.
4. Anti D 100 µg should be given on D1 of Mifepristone
administration in Rh-negative patients undergoing termination
for pregnancy more than 6 week.
5. Paracetamol and codeine or NSAIDS can be given for pain
relief.
6. Antibiotics need not be administered in patients undergoing
medical abortion unless instrumentation of cervix or uterus
is required. In women with lower genital tract infection,
treatment can be started with Metronidazole 1gm stat and Doxycycline
100mg twice daily for 7 days.
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