Intravenous immunoglobulin treatment for secondary recurrent miscarriage: a randomised, double‐blind, placebo‐controlled trial

Christiansen, Ole Bjarne; Larsen, Elisabeth; Egerup, Pia; Lunoee, L.; Egestad, Lisbeth Kofoed; Nielsen, Henriette Svarre

doi:10.1111/1471-0528.13192

Cited by 82 publications

(80 citation statements)

References 34 publications

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“…In the largest placebo-controlled trial that included 82 women with unexplained secondary RPL, LBRs were comparable between IVIg (54.8%) and placebo (50%) 135. A recent meta-analysis of 11 randomized trials in women with URPL also showed no difference in LBR between IVIg and placebo (RR: 0.92, 95% confidence interval [CI]: 0.75–1.12, P =0.42) 136.…”

Section: Unexplained Rpl (Urpl)mentioning

confidence: 96%

Recurrent pregnancy loss: current perspectives

Hachem

Crepaux

May‐Panloup

et al. 2017

IJWH

356

209

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Recurrent pregnancy loss is an important reproductive health issue, affecting 2%–5% of couples. Common established causes include uterine anomalies, antiphospholipid syndrome, hormonal and metabolic disorders, and cytogenetic abnormalities. Other etiologies have been proposed but are still considered controversial, such as chronic endometritis, inherited thrombophilias, luteal phase deficiency, and high sperm DNA fragmentation levels. Over the years, evidence-based treatments such as surgical correction of uterine anomalies or aspirin and heparin for antiphospholipid syndrome have improved the outcomes for couples with recurrent pregnancy loss. However, almost half of the cases remain unexplained and are empirically treated using progesterone supplementation, anticoagulation, and/or immunomodulatory treatments. Regardless of the cause, the long-term prognosis of couples with recurrent pregnancy loss is good, and most eventually achieve a healthy live birth. However, multiple pregnancy losses can have a significant psychological toll on affected couples, and many efforts are being made to improve treatments and decrease the time needed to achieve a successful pregnancy. This article reviews the established and controversial etiologies, and the recommended therapeutic strategies, with a special focus on unexplained recurrent pregnancy losses and the empiric treatments used nowadays. It also discusses the current role of preimplantation genetic testing in the management of recurrent pregnancy loss.

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Section: Unexplained Rpl (Urpl)mentioning

confidence: 96%

Recurrent pregnancy loss: current perspectives

Hachem

Crepaux

May‐Panloup

et al. 2017

IJWH

356

209

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“…[28][29][30] The immunosuppressive properties of IVIG could induce downregulation of B-cell function, 31 and involve in the anti-idiotypic suppression of autoantibodies, 32 prevention of Fc receptormediated phagocytosis, 33 increase of regulatory function of T cells, 34 obstruct of complement fixation, 35 and regulation and alteration of cytokine and cytokine receptor expressions, signaling and functions. 37 One meta-analysis described that IVIG caused to considerably increased live birth rate in RM women with immune anomalies. The trials are very heterogeneous, particularly in terms of the number of previous miscarriages experienced by the women and the IVIg dosages.…”

Section: Discussionmentioning

confidence: 99%

Intravenous immunoglobulin G treatment increases live birth rate in women with recurrent miscarriage and modulates regulatory and exhausted regulatory T cells frequency and function

Jafarzadeh

Ahmadi

Dolati

et al. 2018

J of Cellular Biochemistry

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Exhausted T cells and regulatory T (Treg) cells have been recently proposed to be new risk factors for recurrent miscarriage (RM). Intravenous immunoglobulin G (IVIG) treatment reported to modulate various immune cells. In this study, the effects of IVIG on the frequency and function of exhausted T cells, exhausted Tregs, and Treg cells, as well as pregnancy outcome in women with unexplained RM (URM), were investigated. Ninety‐four pregnant women with RM were enrolled. At the time of positive pregnancy, blood samples were drawn. Forty‐four patients with URM were included as IVIG receiving treated group and received 400 mg/kg of IVIG and the rest fifty patients were considered as a control group and received no IVIG administration. IVIG was given intravenously every 4 weeks during 32 weeks of gestation. Blood samples of patients were collected after the latest administration. Exhausted T cells, exhausted Tregs, and Treg cells were evaluated pre‐ and posttreatment in both groups. IVIG induced a significant decrease in the frequency of exhausted Tregs population and function as well as a significant increase in Treg cells population, however, IVIG failed to affect population and the function of exhausted T cells. Pregnancy outcome was successful in IVIG treated women (86.3%) and were significantly different (P = 0.0006) in compared with the untreated URM subjects (42%). Therefore, employing of IVIG increases Treg cells and diminishes exhausted Tregs responses in RM patients with cellular immune anomalies throughout the pregnancy. Immunemodulatory effects of IVIG are probably associated with successful pregnancy outcome.

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“…After systematic evaluation, more than half of cases of RPL were classified as unexplained [27]. Several meta-analyses of randomized clinical trials of IVIG therapy for unexplained RPL failed to prove its effectiveness [202128]. …”

Section: The Validity Of Ivig Therapy For Each Indicationmentioning

confidence: 99%

“…Even though a meta-analysis of IVIG for women with RPL and randomized controlled trials have not demonstrated a beneficial effect [192021], IVIG is commonly prescribed for women with reproductive failure. However, there is no consensus on the indication and treatment protocol for IVIG in those women.…”

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confidence: 99%