Common variable immune deficiency and treatment with intravenous immunoglobulin during pregnancy

Brinker, Kimberly; Silk, Howard J.

doi:10.1016/j.anai.2012.04.014

Cited by 14 publications

(5 citation statements)

References 6 publications

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“…Immune dysregulation causing defective establishment or early loss of fetal alloantigen tolerance has been proposed as a mechanism of RPL, 20,21 leading to the use of immunomodulatory treatments in such patients. 22 Amongst these, IVIg is a leading candidate 23 because of its favorable safety profile during pregnancy 9,10 and broad immunomodulatory potential. 24 The exact mechanisms by which IVIg can reverse an abortive phenotype are still being elucidated (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

“…IVIg is polyclonal immunoglobulin G (IgG) preparation pooled from donor plasma that been used for over 40 years as an off-label treatment for patients with uRPL. IVIg is well tolerated by an obstetric population 9,10 and acts by multiple mechanisms to decrease inflammation and promote a tolerogenic immune environment (Figure 1). 11 Despite initial success in small cohorts, IVIg has failed to show a consistent beneficial effect for RPL in a randomized controlled trial (RCT) setting (Table 1).…”

Section: Introductionmentioning

confidence: 99%

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Intravenous immunoglobulin use in patients with unexplained recurrent pregnancy loss

Banjar

Kadour

Khoudja

et al. 2023

American J Rep Immunol

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Problem Recurrent pregnancy loss (RPL) affects up to 4% of couples attempting to conceive. RPL is unexplained in over 50% of cases and no effective treatments exist. Due to the immune system's pivotal role during implantation and pregnancy, immune‐mediated RPL may be suspected and immunomodulatory treatments like intravenous immunoglobulin (IVIg) have been administered but remain controversial. The goal of our study was to evaluate our center's 6 year‐outcomes and to develop a framework for IVIg use in RPL. Method of the study Retrospective, single‐center cohort study. All patients having received IVIg for unexplained RPL at the McGill Reproductive Immunology Clinic (MRIC) from January 2014 to December 2020 were included if maternal age was <42 years, body mass index (BMI) < 35 kg/m2, non‐smoker and having had ≥3 consecutive RPL despite previous treatment with aspirin and progesterone. IVIg 0.6–0.8 g/kg was given prior to conception and monthly during pregnancy until 16–20 weeks’ gestation. We compared IVIg treated patient's outcomes to a separate “natural history cohort”. This cohort was composed of patients consulting at the McGill recurrent pregnancy loss clinic and the MRIC over a 2‐year period (January 2020 to December 2021) with similar inclusion criteria as the treatment cohort but did not receive IVIg or other immunomodulatory treatments. The association of IVIg with outcomes (compared to no IVIg) was evaluated among the groups of patients with primary RPL and secondary RPL. The primary outcome was live birth rate (LBR), secondary outcomes included IVIg safety, obstetrical, and neonatal complications. Results Among 169 patients with unexplained RPL that were included in the study, 111 had primary RPL (38 exposed to IVIg and 83 controls) and 58 had secondary RPL (nine exposed to IVIG and 49 controls). Among patients with primary RPL (n = 111), the LBR was 64.3% (18/28) among patient exposed to IVIg compared to 43.4% (36/83) in controls (p = 0.079); regression analysis adjusting for BMI and number of previous miscarriages showed benefit favoring the use of IVIg (OR = 3.27, CI 95% (1.15–10.2), p = 0.03) when evaluating for live birth. In the subgroup of patients with ≥5 previous RPL and primary RPL (n = 31), IVIg was associated with higher LBR compared to control (10/15 (66.7%) vs. 3/16 (18.8%); p = 0.0113) but not the in the sub‐group of patients with <5 miscarriages and primary RPL (8/13 (61.5%) vs. 33/67 (49.3%); p = 0.548). IVIG treatment did not improve LBR in patients with secondary RPL in our study (3/9 (33.3%) vs. 23/49 (47%); p = 0.495). There were no serious adverse events in the IVIg treatment group, obstetrical/neonatal complications were similar between groups. Conclusion IVIg may be an effective treatment for patients with RPL if appropriately used in specific groups of patients. IVIg is a blood product and subject to shortages especially with unrestricted off‐label use. We propose considering IVIg in well‐selected patients with high order RPL who have failed standard medical therapy. ...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intravenous immunoglobulin use in patients with unexplained recurrent pregnancy loss

Banjar

Kadour

Khoudja

et al. 2023

American J Rep Immunol

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“…Despite these promising results, it is too early to recommend routine administration of IVIg for RIF patients. IVIg is safe during pregnancy (14,15), but a minority of patients will experience moderate to severe headache or infusion reaction post treatment; risks of anaphylaxis, aseptic meningitis, hemolytic anemia and blood borne pathogen transmission are possible, albeit extremely rare (42…”

Section: Discussionmentioning

confidence: 99%

“…IVIg is a plasmaderived product that contains polyclonal immunoglobulin G and is used in clinic to treat patients with humoral immune de ciency and autoimmune diseases ( 13)). It is safe and well tolerated in pregnancy, even at high doses (14,15). As an immune modulator, the effects of IVIg are multipronged (16), reducing both innate and adaptive immune responses while possibly improving immune tolerance required for successful implantation.…”

Section: Study Design and Settingmentioning

confidence: 99%

IVIg for recurrent implantation failure: the right treatment for the right patient?

Peero,

Banjar,

Khoudja

et al. 2023

Preprint

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The effectiveness of intravenous immunoglobulin (IVIg) for patients with unexplained recurrent implantation failure (uRIF) remains debated. The objective of this study was to evaluate outcomes in patients with uRIF treated with intravenous immunoglobulin (IVIg) compared to a separate cohort of uRIF patients not receiving IVIg within our center. We performed a retrospective cohort study defining uRIF as \(\ge\) 3 unexplained previously failed high quality blastocyst transfer failures in patients with a body mass index < 35, aged < 42, non-smoking, with >7mm type I endometrium at time of transfers. Primary outcomes included live birth, miscarriage, or transfer failure. We documented IVIg side effects and maternal/fetal outcomes. Logistic regression analysis was used to assess for association of IVIg exposure with outcomes and adjust for confounders. The study included 143 patients, with a 2:1 ratio of controls to patients receiving IVIg treatment. The baseline characteristics were similar between groups. There was higher live birth rate (LBR) in patients receiving IVIg (32/49; 65.3%) compared to controls (32/94; 34%); p < 0.001). When stratifying patients into moderate and severe uRIF (respectively 3–4 and \(\ge\) 5 previous good quality blastocyst transfer failures), only patients with severe uRIF benefited from IVIg (LBR (20/29 (69%) versus 5/25 (20%) for controls, p = 0.0004). In the logistic regression analysis, IVIg was associated with a higher odds of live birth (OR 3.64; 95% CI: 1.78–7.67; p = 0.0004). There were no serious adverse events with IVIg. In conclusion, it is reasonable to consider IVIg in well selected patients with \(\ge\) 5 previous unexplained, high quality blastocyst transfer failures. A well-designed randomized controlled trial is needed to confirm these findings.

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“…In addition, advanced age ( ‡65 years) is associated with increased risk of side effects. The correlation between pregnancy and adverse events is controversial; yet, a recent study found no significant correlation [81]. A significantly higher anti-IgA IgG level in CVID compared to other primary antibody deficiencies is reported, increasing the susceptibility to adverse reactions, suggesting a significant correlation between serum anti-IgA antibody and the occurrence of adverse reactions [82].…”

Section: Immunoglobulin Replacement Therapymentioning

confidence: 99%

Primary immunodeficiencies: a decade of shifting paradigms, the current status and the emergence of cutting-edge therapies and diagnostics

Ebadi

Aghamohammadi

Rezaei

2014

Expert Review of Clinical Immunology

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A shift has occurred in the diagnostic and therapeutic modalities considered for patients with primary immunodeficiency diseases (PIDs). Early diagnosis remains the mainstay in appropriate management and remarkably influences the prognosis. More specific diagnostic tests as well as therapeutic modalities have been introduced in the last few decades. Nonetheless, the importance of a thorough history taking and physical examination should not be neglected. Novel diagnostic modalities including genetic sequencing have led to the recognition of previously unknown defects underlying PIDs. In addition, newborn screening is being advocated as an imperative diagnostic test. In terms of treatment, hematopoietic stem cell transplantation is considered the optimal treatment modality for many cases and has dramatically improved the outcome. Gene transfer into hematopoietic stem cells prior to transplantation has improved the efficacy of hematopoietic stem cell transplantation. In this article, the latest advances made in terms of diagnosis and treatment of PIDs are reviewed.

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Common variable immune deficiency and treatment with intravenous immunoglobulin during pregnancy

Cited by 14 publications

References 6 publications

Intravenous immunoglobulin use in patients with unexplained recurrent pregnancy loss

Intravenous immunoglobulin use in patients with unexplained recurrent pregnancy loss

IVIg for recurrent implantation failure: the right treatment for the right patient?

Primary immunodeficiencies: a decade of shifting paradigms, the current status and the emergence of cutting-edge therapies and diagnostics

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