The effectiveness of IVIG therapy in pregnancy and live birth rate of women with recurrent implantation failure (RIF): A systematic review and meta-analysis

Abdolmohammadi-Vahid, Samaneh; Pashazadeh, Fariba; Pourmoghaddam, Zahra; Aghebati‐Maleki, Leili; Abdollahi‐Fard, Sedigheh; Yousefi, Mehdi

doi:10.1016/j.jri.2019.07.006

Cited by 35 publications

(26 citation statements)

References 29 publications

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“…However, if the treatment started before conception, the results were better. Similar outcomes were encountered by Abdolmohammadi-Vahid et al [130] in four clinical trials. More well designed clinical trials, including monitoring NK cell cytotoxic and tolerogenic responses, are required.…”

Section: Intravenous Immunoglobulins (Ivig)supporting

confidence: 86%

“…Two exciting issues have not been well described in this treatment. First, it is believed that intravenous immunoglobulins would decrease the number of antibodies against their own ligands and decrease autoimmune responses [127][128][129][130][131]. Yet, it is unclear if IVIg may enhance antibody-dependent cellular cytotoxicity on NK cells.…”

Section: Intravenous Immunoglobulins (Ivig)mentioning

confidence: 99%

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A Brief Analysis of Tissue-Resident NK Cells in Pregnancy and Endometrial Diseases: The Importance of Pharmacologic Modulation

Garmendia

Sanctis

2021

Immuno

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NK cells are lymphocytes involved in the innate and adaptative immune response. These cells are located in peripheral blood and tissues with ample functions, from immune vigilant to tolerogenic reactions. In the endometrium, NK cell populations vary depending on age, hormones, and inflammation. When pregnancy occurs, tissue-resident NK cells and conventional NK cells are recruited to protect the fetus, a tolerogenic response. On the contrary, in the inflamed endometrium, various inflammatory cells down-regulate NK tolerance and impair embryo implantation. Therefore, NK cells’ pharmacological modulation is difficult to achieve. Several strategies have been used, from progesterone, lipid emulsions to steroids; the success has not been as expected. However, new therapeutic approaches have been proposed to decrease the endometrial inflammatory burden and increase pregnancy success based on understanding NK cell physiology.

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Section: Intravenous Immunoglobulins (Ivig)supporting

confidence: 86%

Section: Intravenous Immunoglobulins (Ivig)mentioning

confidence: 99%

A Brief Analysis of Tissue-Resident NK Cells in Pregnancy and Endometrial Diseases: The Importance of Pharmacologic Modulation

Garmendia

Sanctis

2021

Immuno

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“…Intravenous immunoglobulin (IVIG) is used at low doses as replacement therapy in patients with primary immunodeficiencies, while at high doses it is a potent immunomodulator to reduce morbidity in hyperinflammatory conditions such as Kawasaki disease (KD) and in autoimmune diseases such as immune thrombocytopenia [reviewed in ( 1 )]. IVIG is also used in women with recurrent miscarriage or implantation failure to enable full-term pregnancy ( 2 , 3 ). In patients with KD, high dose (2 g/kg) IVIG infusion results in remarkable reduction of fever and laboratory indicators of inflammation such as C-reactive protein ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

High Dose Intravenous IgG Therapy Modulates Multiple NK Cell and T Cell Functions in Patients With Immune Dysregulation

et al. 2021

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Intravenous immunoglobulin (IVIG) is an effective immunomodulatory treatment for immune dysregulation diseases. However, the mechanisms by which it reduces systemic inflammation are not well understood. NK cell cytotoxicity is decreased by IVIG in women with reduced fertility, but IVIG effects on NK cells in immune dysregulation are less clear. We hypothesized that IVIG modulation of lymphocyte function, especially in NK cells, is important for resolution of inflammation. Our aim was to identify IVIG-induced changes in a cohort of patients with Kawasaki disease (KD) and those that occur broadly in pediatric patients with various immune dysregulatory diseases. Peripheral blood mononuclear cells (PBMCs) of patients with KD or autoimmune/inflammatory diseases were phenotyped pre and post high dose IVIG treatment by flow cytometry. In KD patients, after IVIG infusion Treg cell frequency and the proportion of activated CD25+ immunoregulatory CD56bright NK cells was increased, and multiple lymphocyte subsets showed increased expression of the lymphoid tissue homing receptor CD62L. Importantly, IVIG treatment decreased the frequency of cells expressing the degranulation marker CD107a among cytotoxic CD56dim NK cells, which was reflected in a significant reduction in target cell killing and in decreased production of multiple pro-inflammatory mediators. Interestingly, the activating receptor CD336 was expressed on a higher proportion of CD56bright NK cells after IVIG in both KD and autoimmune/inflammatory patients while other NK receptors were increased differentially in each cohort. In autoimmune/inflammatory patients IVIG induced the proliferation marker CD71 on a higher percentage of CD56dim NK cells, and in contrast to KD patients, CD107a+ cells were increased in this subset. Furthermore, when PBMCs were stimulated ex vivo with IL-2 or Candida antigen in autologous plasma, more of the CD4+ T cells of KD patients expressed CD25 after IVIG therapy but fewer cytotoxic T cells were degranulated based on CD107a expression. In summary, IVIG treatment in patients with immune dysregulation has multiple effects, especially on NK cell subsets and CD4+ T cells, which are compatible with promoting resolution of inflammation. These novel findings provide insight into the immunomodulatory actions of IVIG in autoimmune and inflammatory conditions.

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“…However, there was no significant difference in the miscarriage rate between the IVIG group and controls. The authors concluded that IVIG might be a beneficial therapeutic strategy in RIF patients with relevant immunological disturbances, 72 and large RCTs to verify these findings are needed.…”

Section: Meta‐analyses For Ivig For Rifmentioning

confidence: 99%

A systemic review of intravenous immunoglobulin G treatment in women with recurrent implantation failures and recurrent pregnancy losses

Saab

Seshadri

Huang

et al. 2021

American J Rep Immunol

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Over the last few decades, the advancement in reproductive technologies and protocols to improve embryo quality through culture techniques and genetic testing to eliminate chromosomally abnormal embryos resulted in better pregnancy rates and outcomes after fertility treatments. Unfortunately, some patients still struggle with recurrent implantation failures (RIFs) and recurrent pregnancy losses (RPLs). Immune etiologies have been attributed to play an important role in some of those patients. Maintaining a pre‐conceptional anti‐inflammatory environment for implantation and pregnancy continuation yields superior results. Intravenous immunoglobulin G (IVIG) treatment has been reported to enhance reproductive outcome in patients with RIF and RPL with immune dysregulations. In this systemic review, we analyzed outcomes of IVIG trials for RIF and RPL, its mechanism of action, dosing, administration, side‐effects, and evidence for its use in women with RIF and RPL.

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The effectiveness of IVIG therapy in pregnancy and live birth rate of women with recurrent implantation failure (RIF): A systematic review and meta-analysis

Cited by 35 publications

References 29 publications

A Brief Analysis of Tissue-Resident NK Cells in Pregnancy and Endometrial Diseases: The Importance of Pharmacologic Modulation

A Brief Analysis of Tissue-Resident NK Cells in Pregnancy and Endometrial Diseases: The Importance of Pharmacologic Modulation

High Dose Intravenous IgG Therapy Modulates Multiple NK Cell and T Cell Functions in Patients With Immune Dysregulation

A systemic review of intravenous immunoglobulin G treatment in women with recurrent implantation failures and recurrent pregnancy losses

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