ASPIRIN PLUS HEPARIN

OR ASPIRIN ALONE IN
WOMAN WITH
RECURRENT
MISCARRIAGE
Fasilitator :
Dr. Abram Siregar Sp.OG
By :
Yafet Yanri Sirupang (04-136)
 BACKGROUND

Aspirin and low-molecular-

weight Heparin
PRESCRIBED

Women with unexplained

recurrent miscarriage
GOAL

Improving the rate of live births

 Approximately 1% of all women
trying to conceive

RECCURENT
MISCARRIAGE

Defined as 3 previous miscarriages

when recurrent miscarriage is defined as 2
previous miscarriages, the proportion rises to 5%.
 Aspirin combined with
low-molecular-weight heparin

Which would improve the

live-birth rate among women with
unexplained Aspirin alone
recurrent miscarriage in this
study??

Compared with placebo

 METHODS
Study Population
• Evaluated patients at 3 university hospitals
and 5 teaching hospitals in the Netherlands,
February 2004 - January 2008.
• Women 18 - 42 years → unexplained
recurrent miscarriage , attempting to
conceive, or pregnant with a gestational age
≤ 6 weeks.
• Previous miscarriage → pregnancy loss at a
gestational age of ≤ 20 weeks.
• Recurrent miscarriage → ≥ 2 miscarriages
(ACOG)
 Study Design and Treatment Regimen

• Aspirin in the form of • LMWH in the form

calcium carbasalate of nadroparin
• 100 mg daily dose • subcutaneously at a
• equivalent to 80 mg of daily dose of 2850
acetylsalicylic acid IU
• Aspirin or placebo • Initiated when a
- started at the time of
randomization
viable intrauterine
- continued → 36 weeks pregnancy was
GA confirmed on USG,
- stopped → miscarriage, - starting at 6 weeks of
a diagnosis of ectopic gestation,
pregnancy, or - continued throughout
premature delivery.
pregnancy
Outcome Measures
• The primary outcome : live births.
• Secondary outcomes :
- miscarriage,
- IUFD (fetal death after 20 weeks of gestation),
- and obstetrical complications such :
1. preeclampsia,
2. the HELLP syndrome (hemolysis, elevated liver
enzymes, and a low platelet count),
3. IUGR (birth weight below the 10th percentile for
gestational age and sex),
4. placental abruption, and
5. premature delivery.
 RESULT

A total of 364 women

were enrolled, with
- 123 the combination Combinat
121 123 ion
therapy group, Aspirin
- 120 the aspirin only group 120 Only
- 121 to the placebo Plasebo
 364 women underwent
randomization

became
27.1% pregnant
(299)
82.1% No 299 women became
pregnant pregnant
(65)
Live
birth
167
(65.9%)
197
No Live
Birth
(34.1%)
 Outcomes
The proportions of women who gave
birth to a live infant Live-birth rates did
not different
Combinatio
significantly
54.5% n therapy among the three
57.0%
(54.5%) study groups.
Aspirin only
(50.8%)
50.8% Placebo
(57.0%))
• In analyses involving women who
became pregnant, live-birth rates also
did not different significantly among the
three groups, with rates of
- 69.1% in the combination-therapy
group,
- 61.6% in the aspirin-only group, and
- 67.0% in the placebo group
 Combination
Placebo Therapy

swellin
g

- Itching

Increased tendency significantly more common

the combination-therapy group
 Conclusion
• Neither aspirin combined with heparin
(nadroparin ) or aspirin alone improved the
chance of a live birth in women with a history of
unexplained recurrent miscarriage.
• Live-birth rates were 54.5% in the combination
therapy group, 50.8% in the aspirin-only group,
and 57.0% in the placebo group. Among women
who became pregnant, these rates were 69.1%,
61.6%, and 67.0%, respectively.
• Side effects, most notably an increased
tendency to bruise and swelling or itching at the
injection site, occurred in almost half the women
in the combination therapy group.
• The hypothesis that women with
unexplained recurrent miscarriage might
benefit from aspirin, heparin, or both was
based on a presumption that this condition
might be caused by thrombosis in decidual
vessels.

• Likewise, we found no significant benefits

in other subgroups, including women with
inherited thrombophilia (who might be
most likely to benefit from treatment with
heparin or aspirin
• In conclusion, our findings do not
support the hypothesis that either
combination therapy with aspirin
and Heparin (nadroparin) or aspirin
alone improves the chance of a
live birth for women with
unexplained recurrent miscarriage.
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THANK YOU