Experience in <scp>IVI</scp>g Therapy for Selected Women with Recurrent Reproductive Failure and <scp>NK</scp> Cell Expansion

Ramos-Medina, Rocío; García-Segovia, Áurea; Gil, Juana; Carbone, J.; Cruz, A. Aguarón de la; Seyfferth, Ansgar; Alonso, Bárbara; Alonso, Jorge; León, Juan Antonio; Alecsandru, Diana; Meliá, Elena; Albornoz, Elena Carrillo de; Ordoñez, Daniel; Santillan, Isabel; Verdú, Victoria; Morales, José María García Ruiz de; López-Hoyos, Marcos; A, Larios; Sampalo, Almudena; Caballero, Pedro; Quintana, Luis Ortiz; Fernández‐Cruz, Eduardo; Sánchez-Ramón, Silvia

doi:10.1111/aji.12217

Cited by 57 publications

(64 citation statements)

References 35 publications

(53 reference statements)

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“…Intravenous immunoglobulin (IVIG) seems to act through a multitude of mechanisms that include reducing the activity of NK cells, increasing the activity of suppressor T cells, elimination of immune complexes, down-regulation of stimulatory receptors, and upregulation of inhibitory receptors on the surface of different immune cells 85,86. Such as for VD, several studies have indicated that treatment with IVIG in RPL patients may improve pregnancy outcomes through an immunological effect [87][88][89]. However, this studies are underpowered for definitive conclusions and ESHRE Guidelines considered that IVIG cannot be recommended for clinical use at this moment.…”

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confidence: 99%

Recurrent pregnancy loss and vitamin D: A review of the literature

Gonçalves

Braga

et al. 2018

American J Rep Immunol

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Recurrent pregnancy loss (RPL) affects approximately 1%-2% of reproductive women. Auto- and cellular immune responses seem to be associated with RPL. Vitamin D (VD) has been shown to play a role in the modulation of the immune system. Effects of VD deficiency (VDD) in pregnancy have been associated with preeclampsia, gestational diabetes, fetal growth restriction, preterm labor, and sporadic spontaneous abortion (SA). We systematically reviewed articles that studied women with 2 or more SA and its association with VD. Eleven studies were included. Studies reported a high prevalence of VD insufficiency (VDI) or VDD in women with RPL and suggested that this could be associated with immunological dysregulation and consequently with RPL. Immunological benefits were reported in the peripheral blood of women with RPL after VD exposure. Thus, it is possible to speculate a beneficial role for VD supplementation in RPL. It seems that there are not differences in the vitamin D receptor (VDR) and CYP27B1 expression in endometrium of women with RPL but, in villous and decidual tissues, RPL women seem to have a decreased expression of VDR and, perhaps, a decreased expression of CYP27B1. Further randomized controlled studies are required to investigate the association between VDD or VDI and RPL.

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confidence: 99%

Recurrent pregnancy loss and vitamin D: A review of the literature

Gonçalves

Braga

et al. 2018

American J Rep Immunol

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“…Based on these results, IVIg was used in patients with RPLs or RIFs with these cellular immune abnormalities and many observational studies reported favorable pregnancy outcomes . The authors' previous study also demonstrated a significantly higher live birth rate using IVIg with women with unexplained RPLs and with cellular immune abnormalities (n = 49), as compared with that of IVIg non‐using women with unexplained RPLs and with cellular immune abnormalities (n = 39) who were reported in other studies (81.6% vs 30.8%) . The authors treated 189 patients with RPLs with or without IVIg, according to their etiologies: known conventional etiologies, thrombophilia, including APS, and cellular immune abnormalities, including the peripheral NK cell proportion and its cytotoxicity, and the Th1/Th2 ratio.…”

Section: Effect Of IV Immunoglobulin G Use In Reproductive Failurementioning

confidence: 93%

Immune modulation of i.v. immunoglobulin in women with reproductive failure

Han

Lee

2018

Reprod Medicine & Biology

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BackgroundThe mechanism of maternal immune tolerance of the semi‐allogenic fetus has been explored extensively. The immune reaction to defend from invasion by pathogenic microorganisms should be maintained during pregnancy. An imbalance between the immune tolerance to the fetus and immune activation to the pathogenic organisms is associated with poor pregnancy outcomes. This emphasizes that the immune mechanism of successful reproduction is not just immune suppression, but adequate immune modulation.MethodsIn this review, the action of i.v. immunoglobulin G (IVIg) on the immune system and its efficacy in reproductive failure (RF) was summarized. Also suggested is the indication of IVIg therapy for women with RF.Main findings (Results)Based on the mechanism of the immune regulation of IVIg and following confirmation of the immune modulation effects of it in various aberrant immune parameters in patients with RF, it is obvious that IVIg is effective in recurrent pregnancy losses and repeated implantation failures with immunologic disturbances.ConclusionThe authors recommend IVIg therapy in patients with RF with aberrant cellular immunologic parameters, including a high natural killer cell proportion and its cytotoxicity or elevated T helper 1 to T helper 2 ratio, based on each clinic's cut‐off values. Further clinical studies about the safety of IVIg in the fetus and its efficacy in other immunologic abnormalities of RF are needed.

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“…Subsequently, Winger et al [60] reported that IVIG significantly improved IVF success rates in subfertile women with increased Th1/Th2 ratios and/or NK cell levels as compared to those who did not undergo the treatment. Another observational study reported that IVIG treatment improved clinical pregnancy and live-birth rates in selected RPL and RIF patients with immunologic alterations [61]. …”

Section: The Validity Of Ivig Therapy For Each Indicationmentioning

confidence: 99%