Transcript MEDICAL ABORTION

Issues in Early
Medical Abortion
Mitchell Creinin, MD
Professor
Director of Gynecologic Specialties
Director of Family Planning
University of Pittsburgh
Pittsburgh, PA
USA
Objectives
•
•
•
•
Very early surgical abortion
Home use of misoprostol
Shortening the interval between
mifepristone and misoprostol
Follow-up intervals shorter than two
weeks
Medical Abortion
Early pregnancy termination
(usually before 9 weeks
gestation) performed without
primary surgical intervention
and resulting from the use of
abortion-inducing medications
Early surgical abortion
MVA
•
•
•
•
•
Manual vacuum
aspirator with locking
valve
Portable and reusable
Generates vacuum
equivalent to electric
pump
Efficacy same as electric
vacuum (98–99%)
Semi-flexible plastic
cannula
Early Abortion with Vacuum
Aspiration
Date
N
Paul et al.
2002
1,132
(MVA+EVA)
<6
98%
Creinin &
Edwards
1997
2,399 MVA
<6
99%
Hemlin &
Möller
2001
91 MVA
<8
98%
Laufe
1977
12,888
“About 6”
98%
Author
Gestational Efficacy
Age
Paul ME, et al. Am J Obstet Gynecol 2002;187:407-11.
Creinin MD, Edwards J. Curr Prob Obstet Gynecol Fertil 1997;20:6-32.
Hemlin J, Möller B. Acta Obstet Gynecol Scand 2001;80:563-7.
Laufe LE. Stud Fam Plann 1977;8:253-6.
Early Abortion with MVA
Methods
• 2,399 MVA procedures
• <6 weeks LMP, high sens UCG , vaginal sono
• Meticulous inspection of products of conception
immediately after MVA
Results
• 99.2% effective in terminating pregnancy
• 6 repeat aspirations (0.25%)
• 14 ectopic pregnancies (0.6%) diagnosed & treated
Creinin MD, Edwards J. Curr Prob Obstet Gynecol Fertil 1997;20:6-32.
Mifepristone abortion
Can we provide this regimen in an
easier fashion and with less cost?
Variations:
• mifepristone dose
• non-oral misoprostol
go together
• gestational age limits
• timing of misoprostol - dependent on route
• easier follow-up
Objectives
•
•
•
•
Very early surgical abortion
Home use of misoprostol
Shortening the interval between
mifepristone and misoprostol
Follow-up intervals shorter than two
weeks
Home use of misoprostol
• Majority
of trials in North America
High acceptability
• High efficacy
•
• Allowed
in the regulatory labeling for
mifepristone in the U.S.
• Standard of care in North America
Home use of misoprostol
•
Early studies of mifepristone and vaginal
misoprostol in U.S.
•
•
•
Women allowed choice of returning
Only 3 (1.9%) of 158 women asked the clinician to
place the misoprostol.
Initial follow-up studies in the U.S.
•
•
>4300 women with home use of vaginal misoprostol
90% home use acceptable; no difference by
•
•
•
prior abortion experience
gestational age
time between MIF and MIS (1, 2 or 3 days)
Schaff et al. Contraception 1999;59:1-6.
Schaff et al. Contraception 2000;61:41-6.
Schaff et al. JAMA 2000;284:1948-53 .
Home use of misoprostol
•
•
Adverse events in the hours after MIS
4/4365 women (0.1%) had emergencies:
•
Two emergent aspiration for heavy bleeding
•
•
One vasovagal reaction to cramping
•
•
neither required a blood transfusion.
treated with intravenous fluids.
One syncopal episode while bleeding
•
fell and broke her nose.
Schaff et al. Contraception 1999;59:1-6.
Schaff et al. Contraception 2000;61:41-6.
Schaff et al. JAMA 2000;284:1948-53 .
Home use in Europe
•
U.K.
•
•
•
•
•
•
49 women up to 56 days
Lived within 12 miles of facility
Sublingual MIS at home
Contacted at 4 hour intervals by RN
98% -- no trouble with the regimen
(1 woman came to hospital after MIS)
93% -- would use it at home again
Hamoda et al. J Fam Plann Reprod Health Care 2005;31:189-92.
Home use in Europe
•
Sweden and France
130 women up to 49 days
• oral MIS at home
• 98% -- no trouble with the regimen
• 98% -- would use it at home again
•
•
In 2004, Sweden changed its regulatory
guidelines to allow medical abortion at
home up to 63 days gestation.
Fiala et al. Contraception 2004;70:387-92.
Clark et al. Eur J Contracept Reprod Health Care 2005;10:184-91.
Objectives
•
•
•
•
Very early surgical abortion
Home use of misoprostol
Shortening the interval between
mifepristone and misoprostol
Follow-up intervals shorter than two
weeks
Mifepristone Actions
Progesterone Blockade
Decidual
Necrosis
Rhythmic
Uterine
Contractions
Detachment
Cervical
Softening
Expulsion
Abortion
>18 hours for mifepristone effects
Shortened interval overview
•
Oral misoprostol
24-36 hours  effective with 800 mcg dose
• 6-8 hours  doesn’t work
•
•
Vaginal misoprostol
•
•
•
•
24 hours
6-8 hours
<15 minutes
Buccal misoprostol
•
24 hours
Timing of Misoprostol Dosing
2,255 women <56 days gestation
Mifepristone 200 mg PO, misoprostol 800 mcg PV
Interval randomized  24, 48 or 72 hours
• Complete medical abortion
•
•
•
•
•
•
•
98% (95% CI 97, 99%) in the 24 hour group;
98% (95% CI 97, 99%) in the 48 hour group;
96% (95% CI 95, 97%) in the 72 hour group.
Time waiting for expulsion acceptable
•
•
•
86% in the 24 hour group;
79% in the 48 hour group;
76% in the 72 hour group (p=0.0001).
Schaff EA et al. JAMA 2000;284:1948-53.
Medical abortion in One Day
1,080 women enrolled at 4 centers (4/02 6/03)
• Women received mifepristone 200 mg followed
•
•
•
6 to 8 hours later OR
23 to 25 hours later
by misoprostol 800 mcg vaginally
• Follow-up 7 (+ 1) days and 14 (+ 2) days after
mifepristone
• Repeat misoprostol dose at first follow-up if no
expulsion
Creinin MD,after
et al. Obstet
Gynecol 2004;103:851-9.
• Follow-up phone call 5 weeks
mifepristone
Abortion outcome (%)
23-25 hours
(n=531)
6-8 hours
(n=525)
Complete abortion
TOTAL
with 1 dose misoprostol
98 (97, 99)
97 (95, 98)
96 (94, 97)
95 (93, 97)
<49 days gestation
50-56 days gestation
57-63 days gestation
98 (96, 100)
98 (94, 99)
98 (94, 100)
97 (94, 99)
94 (89, 98)
95 (90, 98)
Creinin MD, et al. Obstet Gynecol 2004;103:851-9.
Medical Abortion at the Same Time
1,128 women enrolled at 4 centers (4/04 – 5/06)
• Women received mifepristone 200 mg followed
•
•
•
within 15 minutes OR
23 to 25 hours later
by misoprostol 800 mcg vaginally
• Follow-up 7 (+ 1) days and 14 (+ 2) days after
mifepristone
• Repeat misoprostol dose at first follow-up if no
expulsion
• Follow-up phone call 5 weeks after mifepristone
Creinin MD, et al. Obstet Gynecol 2007;109:885-94.
Abortion outcome (%)
23-25 hours
(n=546)
witihin 15 min
(n=554)
Complete abortion
TOTAL
with 1 dose misoprostol
97 (95, 98)
94 (92, 96)
95 (93, 97)
91 (88, 93)
<49 days gestation
50-56 days gestation
57-63 days gestation
98 (96, 99)
95 (91, 98)
97 (92, 99)
96 (92, 98)
94 (90, 97)
95 (90, 98)
Creinin MD, et al. Obstet Gynecol 2007;109:885-94.
Questioning results
UK study
• Randomized trial
• 450 women up to 63 days gestation
•
•
•
•
6 hour interval (n=225)  stayed in clinic
36-48 hours (n=225)  went home and returned for
misoprostol
Complete abortion rates
•
•
89% in 6 hour group
96% in 36-48 hour group
Guest J et al. BJOG 2007;114:207-15 .
Why a difference?
•
•
Smaller study (450 vs. 1056)
Ultrasound use
•
U.S. study
Sonography at 7 days
• Assess if sac present
• If present, repeat dose of misoprostol and return in one week.
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•
U.K. study
•
•
•
Sonography at 2-7 days
Assess for a gestational sac and also for evidence of “nonviable
products of conception.”
If present, could have a suction aspiration or more misoprostol;
however, women who wanted another dose of misoprostol were
required to remain under observation for 4-6 hours with a followup in one week.
Creinin MD et al. Obstet Gynecol 2004;103:851-9.
Guest J et al. BJOG 2007;114:207-15 .
Why a difference?
•
Protocol biases results
•
success rate with a single dose of MIS in 6-8 h group
•
•
•
Incomplete abortion rates
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•
•
U.S. study = 2%
U.K. study = 4%
Aspiration for persistent sac
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•
•
U.S. study = 95%
U.K. study = 79%
U.S. study = 0.6%
U.K. study = 4%
Increased interventions in U.K. women b/o
management schema
Creinin MD et al. Obstet Gynecol 2004;103:851-9.
Guest J et al. BJOG 2007;114:207-15 .
Differences in continuing
(viable) pregnancy rate
Schaff et al (2000)
< 49 d
50-56 d
57-63 d
Creinin et al (2004)
< 49 d
50-56 d
57-63 d
Creinin et al (2007)
< 49 d
50-56 d
57-63 d
interval
rate
interval
rate
48h
0.2%
0.4%
1.0%
6-8h
0
0
0.8%
24h
0
0.6%
0
<15 min
0.4%
1.3%
0.8%
24h
0.4%
0
0
Schaff EA, et al. Contraception 2000, 61:41-6.
Creinin MD, et al. Obstet Gynecol 2004;103:851-9
Creinin MD, et al. Obstet Gynecol 2007;109:885-94.
Mifepristone Actions
Progesterone Blockade
Decidual
Necrosis
Rhythmic
Uterine
Contractions
Detachment
Cervical
Softening
Expulsion
Abortion
WHAT REALLY IS IMPORTANT?
Objectives
•
•
•
•
Very early surgical abortion
Home use of misoprostol
Shortening the interval between
mifepristone and misoprostol
Follow-up intervals shorter than two
weeks
Shorter Follow-up Intervals
•
•
Most studies include follow-up at 1-7 days
following treatment
Earlier follow-up with transvaginal
ultrasound
 compare to standard regimen
Follow-up
No studies validate this practice
• Does earlier evaluation result in high rates
of later intervention?
• What is the best way to use ultrasound?
Follow-up
2 U.S. trials followed subjects who had not had a
suction aspiration for 5 weeks after treatment
Study
Women for 5 week follow-up
(no known aspiration)
#1
1,060
#2
1,103
Women contacted
829 (88%)
974 (78%)
Aspiration since last visit
(includes aspiration at
5 week follow-up)
14 (1.7%)
13 (1.3%)
Creinin MD, et al. Obstet Gynecol 2004;103:851-9.
Creinin MD, et al. Obstet Gynecol 2007;109:885-94.
Post-abortion uterus
transverse
longitudinal
Is follow-up exam necessary?
Is the ultrasound examination necessary to
evaluate for expulsion?
• Is a clinical examination necessary to evaluate
for expulsion?
•
•
Clinician and patient both feel pregnancy is
expelled:
•
•
Happens in 95% of treatments
They are right 99% of time
Rossi et al. Contraception 2004;70:313-7.
Mifepristone regimens
•
•
•
•
•
Acceptable alternatives to the
Standard Regimen
Mifepristone 200 mg mifepristone
Home administration of misoprostol
Misoprostol 800 mcg vaginally through 63 days
gestation 0-72 hours after the mifepristone
Misoprostol 800 mcg buccally through 63 days
gestation 24-48 hours after the mifepristone
Follow-up within 1 week using ultrasound
Etienne-Emile Baulieu
"Choice is freedom,
science cannot and
must not dictate our
beliefs. But science
can provide choices.”
1991
Mifepristone and Buccal
Misoprostol
•
•
•
Mifepristone 200 mg
Misoprostol 800 mcg buccally or orally 1-2
days later
Follow-up 7-14 days after misoprostol
•
•
If no expulsion, aspiration or additional
misoprostol
966 women up to 63 days gestation
Dzuba et al (submitted for publication)
Mifepristone and buccal
misoprostol
Complete abortion
TOTAL*
oral
(n=546)
buccal
(n=554)
91 (88, 94)
96 (94, 98)
<42 days gestation
98 (92 ,100) 99 (93, 100)
42-49 days gestation
95 (89, 98) 97 (92, 99)
50-56 days gestation* 89 (81, 94) 96 (89, 99)
57-63 days gestation* 85 (77, 91) 95 (89, 98)
*p<.05
Dzuba et al (submitted for publication)
Mifepristone and buccal
misoprostol
16
Percentage
12
Buccal Failure
Oral Failure
Buccal Ongoing
Oral Ongoing
8
4
0
?42
43-49
50-56
57-63
Gestational age (days)
Dzuba et al (submitted for publication)
Buccal misoprostol at same time
Mifepristone 200 mg and misoprostol 800 mcg buccally
gestational
age (days)
N
expulsion at
24 hours after
misoprostol*
abortion
rate at
2 weeks
<49
40
50-56
40
57-63
40
29
73% (56, 85%)
27/39
69% (52, 83%)
29
73% (56, 85%)
39
98% (87, 100%)
37/37
100% (91, 100%)
37/39
95% (83, 99%)
*1, 1, and 2 subjects, respectively, had an aspiration for incomplete
abortion.
Lohr PA, et al. Contraception 2007;76:215-20.
Buccal misoprostol at same time
115 subjects (96%) completed the post-treatment
questionnaire.
Would choose medical abortion again
Recommend medical abortion to a friend
Disliked some part of the buccal misoprostol
taste objectionable
buccal retention uncomfortable
oral irritation, numbness, or oral ulcers
did not work
91%
97%
72%
43%
30%
10%
6%
Lohr PA, et al. Contraception 2007;76:215-20.