Use of intravenous immunoglobulin for treatment of recurrent miscarriage: a systematic review

Hutton, Brian; Sharma, Ritu; Fergusson, Dean; Tinmouth, Alan; Hébert, Paul C.; Jamieson, J. P. S.; Walker, Mark

doi:10.1111/j.1471-0528.2006.01201.x

Cited by 127 publications

(103 citation statements)

References 22 publications

(46 reference statements)

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“…There is also empirical evidence for benefit in patients with recurrent spontaneous abortion if secondary or associated with autoantibodies or elevated natural killer (NK)-lineage cells in blood [2][3][4]. In vitro fertilization failure may also be prevented in patients who have immune abnormalities [2].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

CD200-dependent and nonCD200-dependant pathways of NK cell suppression by human IVIG

Clark

Wong

Banwatt

et al. 2008

J Assist Reprod Genet

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Section: Introductionmentioning

confidence: 99%

“…In vitro fertilization failure may also be prevented in patients who have immune abnormalities [2]. Suppression of blood NK cell activity has been proposed as an important effect, and different IVIGs may differ in potency both in vitro and in vivo [3][4][5]. However, the mechanism of IVIG suppression of NK-type cells is uncharacterized.…”

Section: Introductionmentioning

confidence: 99%

CD200-dependent and nonCD200-dependant pathways of NK cell suppression by human IVIG

Clark

Wong

Banwatt

et al. 2008

J Assist Reprod Genet

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“…Hutton et al, in a meta-analysis of placebo-controlled trials of IVIg in RM, found that the OR of achieving a live birth in primary and secondary RM was 0·66 and 2·71, respectively, suggesting that IVIg may be effective in secondary RM patients, but not primary RM patients [16]. A recent meta-analysis of five placebo-controlled studies (Christiansen et al, unpublished data) found that the OR for an unsuccessful pregnancy in secondary RM patients was 0·74 bs_bs_banner Clinical and Experimental Immunology IMMUNOMODUL ATION…”

mentioning

confidence: 99%

Advances of intravenous immunoglobulin G in modulation of anti-fetal immunity in selected at-risk populations: science and therapeutics

Christiansen

2014

Clin Exp Immunol

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Recurrent miscarriage (RM) is the occurrence of three or more consecutive miscarriages before gestational week 20 and is a condition that affects 1-3% of women [1]. RM can be classified into two categories: primary RM (no prior live birth) or secondary RM (three or more consecutive miscarriages following a live birth). In addition to genetic and anatomical factors causing RM, many studies have suggested that signs of autoimmunity and dysregulation of natural killer (NK) cell immunity characterize women with RM.Approximately 25 years ago, the first pilot studies on the use of intravenous immunoglobulin (IVIg) for the treatment of RM were conducted and reported a live birth rate of 80-82% [2,3], which provided support to warrant further investigation in placebo-controlled trials. In 2006, a Cochrane review of IVIg treatment for RM in eight placebo-controlled trials with 303 RM patients was conducted, concluding that IVIg did not increase live birth rates when compared to placebo [odds ratio (OR) = 0·98; 95% confidence interval (CI) = 0·61-1·58] [4]. However, this review did not differentiate between primary and secondary RM patients. Separate analysis of these two subsets of RM patients may be necessary, as several studies have observed that secondary RM is a condition dominated by immunological risk factors when compared to primary RM, suggesting large heterogeneity between these two subgroups.Tumour necrosis factor (TNF)-α is a cytokine involved in the immune system's inflammatory response. Piosik et al. analysed peripheral blood samples of RM patients taken at gestational week 5, and found that TNF-α levels were increased significantly in secondary RM patients compared to primary RM patients (P = 0·042) [1]. This indicates that secondary RM is a condition with an increased proinflammatory response in early pregnancy.More evidence of the role of immunological factors in secondary RM has been reported in studies that have shown associations between secondary RM patients with specific maternal human leucocyte antigen (HLA) polymorphisms. Kruse et al. found that there was a significantly higher prevalence of the HLA-DRB1*03 allele in secondary RM patients compared with controls (OR = 1·8; 95% CI = 1·3-2·5) [5], whereas the allele was not increased in patients with primary RM. A previous pregnancy with a boy can be a risk factor for secondary RM. In general, maternal immune recognition of male-specific minor histocompatibility (HY) antigens expressed in male fetal and trophoblast cells is well tolerated, resulting in a live birth. However, pregnancy with a boy may prime the mother's HY immunity. Nielsen et al. found that maternal carriage of HLA class II alleles that restrict anti-HY antigen responses reduces the chances of a live birth in secondary RM patients with a firstborn boy compared with a firstborn girl (OR = 0·17; 95% CI = 0·1-0·4; P = 0·0001) [6]. In another study, the prevalence of a 14 base pair insertion in exon 8 of the HLA-G gene was found to be increased significantly in secondary RM patients, compa...

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“…7,[93][94][95][96][97] Recent meta-analysis reported a significant increase in live births following IVIg use in women with secondary recurrent miscarriage although overall live birth rate was not improved. 98 We have reported that IVIg treatment significantly improved reproductive outcome in women with aPL who were refractory to anticoagulation treatment or elevated NK cell levels. 99,100 In addition, IVIg treatment has been reported to be effective in RPL women with aPL with catastrophic APS.…”

Section: The Epitopes Of Apl and Treatment Outcomementioning

confidence: 92%

Management of Women with Recurrent Pregnancy Losses and Antiphospholipid Antibody Syndrome

Kwak‐Kim

Agcaoili

Aleta

et al. 2013

American J Rep Immunol

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Antiphospholipid antibodies (aPL) have been associated with recurrent pregnancy losses (RPL) and other obstetrical complications. The diagnostic criteria for the classical antiphospholipid antibody syndrome (APS) have been utilized for the detection of obstetrical APS in women with RPL. However, laboratory findings and immunopathology of obstetrical APS are significantly different from those of classical APS. In addition, many women with RPL who have positive aPL do not have symptoms consistent with the current APS criteria. The induction of a proinflammatory immune response from trophoblasts and complement activation by aPL rather than thromboembolic changes has been reported as a major immunopathological feature of obstetrical APS. Heparin treatment has been reported to be effective in prevention of early pregnancy loss with APS but not for the late pregnancy loss or complications. The complex effects of heparin may explain the limited efficacy of heparin treatment in RPL. New diagnostic criteria for obstetrical APS are needed urgently, and new therapeutic approaches should be explored further.

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Use of intravenous immunoglobulin for treatment of recurrent miscarriage: a systematic review

Cited by 127 publications

References 22 publications

CD200-dependent and nonCD200-dependant pathways of NK cell suppression by human IVIG

CD200-dependent and nonCD200-dependant pathways of NK cell suppression by human IVIG

Advances of intravenous immunoglobulin G in modulation of anti-fetal immunity in selected at-risk populations: science and therapeutics

Management of Women with Recurrent Pregnancy Losses and Antiphospholipid Antibody Syndrome

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