NDK, скептицизма ти по отношение на имунотерапията споделят и водещите специалисти по IVF, както личи от становището на The Practice Committee of the American Society for Reproductive Medicine. (За тази комисия вече съм писала в съседната тема
ин витро и имунология )
Заключението е леко притеснително...
Intravenous immunoglobulin (IVIG) and recurrent
spontaneous pregnancy lossThe Practice Committee of the American Society for Reproductive Medicine
American Society for Reproductive Medicine, Birmingham, Alabama
BACKGROUND
Some cases of unexplained recurrent spontaneous pregnancy
loss have been proposed to arise from an undefined immu-
nological barrier to normal placentation. One proposed treat-
ment, active immunization with allogeneic leukocytes, ben-
efits only 8% to 10% of treated couples, who cannot be
selected by means of diagnostic testing (1). Another treat-
ment, passive immunization with intravenous immunoglob-
ulin (IVIG), was promising in uncontrolled trials (2). IVIG,
which is human IgG prepared from pooled plasma, has a
diverse antibody profile because thousands of donors con-
tribute to the pool (3). IVIG treatment has now been evalu-
ated in five randomized controlled trials (RCTs) (4–8). This
document addresses the effectiveness of IVIG and the clin-
ical implications of related publications.
SOURCES
A current literature search located five RCTs which assessed
IVIG treatment for recurrent spontaneous pregnancy loss
(RSPL). In the studies, eligible couples had at least three
(5–8),or at least two(4),previous abortions. Two trials were
limited to women with primary RSPL (no live births) (5, 8 ),
one involved only women with secondary RSPL (at least one
live birth) (6), and two trials included both primary and
secondary RSPL(4,7). Required investigations included but
were not limited to, hysterosalpingogram and/or hysteros-
copy, luteal progesterone and/or endometrial biopsy and
karyotype.
Exclusion criteria were IgA deficiency (5– 8 ), lupus (6– 8 ),
age over 39 years (5), age over 42 years ( 8 ), and presence of
anti-cardiolipin antibody (4, 7, 8 ). All studies described the
randomization methods, all made use of a control treatment
that could maintain blinding, and al lstudies provided data on
delivery after 28 weeks and newborn status. For this state-
ment success is defined as live birth at or after 28 weeks.
IVIG therapy was initiated before conception in two trials
(4–7), and during the first trimester in three trials (5, 6, 8 );
and continued until the first or second trimester.
Committee Opinion
Reviewed June 2006.
Published October 1998
No reprints will be available.
Correspondenceto:PracticeCommittee,AmericanSocetyforReproductive
Medicine, 1209 Montgomery Highway, Birmingham, Alabama 35216.
METHODS
The relevant RCTs were examined for estimates of the
relative likelihood of live birth in IVIG-treated and control-
treated couples. The results for all randomized patients who
conceived were included in the meta-analysis. Statistical
techniques were used to estimate the average treatment ef-
fect with its 95% confidence limits and a heterogeneity
statistic (9).RESULTS
The five randomized controlled trials reported on 121 IVIG-
treated patients and 125 placebo-treated patients. The aggre-
gate live birth rate was 62% (95% CI 53, 71) in the IVIG
group and 54% (95% CI 45, 62) in the placebo-treated
controls.
The individual RCT results were as follows.
- In the German multicenter trial, 20/33 IVIG-treated pa-
tients and 21/31 albumin-treated patients were successful.
IVIG was no more effective than the albumin placebo
(relative risk 0.89 95% CI 0.61, 1.35) (5).
- In the American trial, 18/29 IVIG-treated and 11/32
albumin-treated patients were successful. IVIG was 1.66
fold (95% CI 0.93, 2.94) more effective than placebo (4).
- In the Danish trial among women with secondary RSPL,
9/17 IVIG-treated patients and 5/17 albumin-treated had a
live birth after 28 weeks. IVIG was 1.80 fold (95% CI
0.69, 5.13) more effective than placebo (6).
- In the Canadian trial 12/20 IVIG-treated patients and
10/21 placebo-treated delivered after 28 weeks. IVIG was
ineffective in primary RSPL and 1.81 fold (95% CI 0.29,
11.3) more effective than placebo in secondary RSPL (7).
DISCUSSION
The effectiveness of IVIG as a treatment for recurrent spon-
taneous pregnancy loss remains unproven. IVIG does not
prevent further losses among women with primary recurrent
spontaneous pregnancy loss. A potential effect has been
demonstrated in the less prevalent problem of secondary
recurrent spontaneous pregnancy loss. The published data
are insufficient, however, to exclude the possibility that the
treatment also has no value in the latter condition.
Severe side effects of IVIG are rare in well-selected pa-
tients. Mild side effects including fever, malaise, myalgia
and headache occur in 4% of patients (3). Severe reactions
are encountered in IgA deficient patients; the prevalence of
IgA deficiency is1per1000. Nephrotoxicity ,alopecia, asep-
tic meningitis and retinal necrosis are rare but serious side-
effects (3). The potential for harm from immunotherapy
during pregnancy cannot be excluded, and potential risk of
using a preparation derived from pooled plasma cannot be
assessed from currently available data.
IVIG treatment is expensive. The cost ranges from $7,000
to $14,000 for a single course of therapy.
CONCLUSIONIVIG as a treatment for recurrent pregnancy loss should be
evaluated in patients who are informed, consenting partici-
pants in an institutional review board approved randomized
clinical trial. For the management of recurrent spontaneous
pregnancy loss IVIG is an experimental treatment.REFERENCES
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collaborative observational study and meta-analysis on allogenic leuko-
cyte immunotherapy for recurrent spontaneous abortion. Am J Reprod
Immunol 1994;32:55–72.
2. Coulam CB, Krysa LW, Bustillo M. Intravenous immunoglobulin for in
vitro fertilization failure. Hum Reprod 1994;9:2265–9.
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Neurol 1993;50:135–6.
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1072–7.
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Lauritsen JG, et al. Placebo-controlled trial of treatment of unexplained
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