Immunotherapy to improve pregnancy outcome in women with abnormal natural killer cell levels/activity and recurrent miscarriage or implantation failure: A systematic review and meta-analysis

Woon, Ee Von; Day, Andrea; Bracewell‐Milnes, Timothy; Male, Victoria; Johnson, Mark R.

doi:10.1016/j.jri.2020.103189

Cited by 30 publications

(27 citation statements)

References 86 publications

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“…Overall, this study demonstrates that prednisolone alters decidualized hESF and altered decidual-trophoblast interactions. The clinical consequences of these changes are unknown, however, as all available data suggests that corticosteroid administration has no beneficial effect for IVF (Kaye et al, 2017;Mohammadi Yeganeh et al, 2018), RPL (Tang et al, 2013;Cooper et al, 2019;Woon et al, 2020), or repeated implantation failure (Siristatidis et al, 2018) and the emerging evidence that corticosteroid use during pregnancy may be associated with poor obstetrical outcomes (Boyd et al, 2015;Bandoli et al, 2017), offlabel use of corticosteroids, in particular prednisolone, during the period of decidualization (secretory phase of the menstrual cycle and the 1st trimester), should be carefully considered.…”

Section: Discussionmentioning

confidence: 99%

“…Prednisolone is used an off-label therapy for RPL to reduce uterine Natural Killer (uNK) cell numbers (Dimitriadis et al, 2020). The reported efficacy of prednisolone at preventing miscarriage in women with a history of idiopathic miscarriage is highly variable between studies (Tang et al, 2013;Gomaa et al, 2014;Dan et al, 2015;Cooper et al, 2019) however, the most recent systematic review and meta-analysis found that prednisolone administration did not improve miscarriage rates or pregnancy outcome (Woon et al, 2020). Concerningly, there is emerging evidence linking corticosteroid use to preeclampsia incidence in women (Boyd et al, 2015;Bandoli et al, 2017) and dexamethasone treatment in pregnant rats induces the development of PE features (Zhang et al, 2016(Zhang et al, , 2018, however, most studies investigating the role of prednisolone in RPL are not sufficiently powered to identify rare pregnancy outcomes such as preeclampsia.…”

Section: Introductionmentioning

confidence: 99%

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Prednisolone Alters Endometrial Decidual Cells and Affects Decidual-Trophoblast Interactions

Grbac

Varshney³

et al. 2021

Front. Cell Dev. Biol.

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Poor pregnancy outcomes such as recurrent pregnancy loss (RPL) and preeclampsia are associated with impaired decidualization and abnormal trophoblast invasion. Emerging evidence suggests that use of corticosteroids, including prednisolone affects fertility by altering uterine function and may be associated with preeclampsia incidence. In this study, using primary and gestational-age appropriate tissue, we aimed to define the effect of prednisolone on human endometrial stromal fibroblast (hESF) decidualization and determine whether hESF decidualization in the presence of prednisolone would alter hESF regulation of trophoblast function. We found that prednisolone treatment reduced hESF cytokine expression (IL6, IL11, IL18, LIF, and LIFR) but had no effect on hESF expression or secretion of the classic markers of decidualization [prolactin (PRL) and IGFBP1]. Using proteomics we determined that prednisolone altered decidualized hESF protein production, enriching hESF proteins associated with acetylation and mitrochondria. Conditioned media from hESF decidualized in the presence of prednisolone significantly enhanced trophoblast outgrowth and trophoblast mRNA expression of cell motility gene PLCG1 and reduced trophoblast production of PGF. Prednisolone treatment during the menstrual cycle and 1st trimester of pregnancy might alter decidual interactions with other cells, including invasive trophoblast.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prednisolone Alters Endometrial Decidual Cells and Affects Decidual-Trophoblast Interactions

Grbac

Varshney³

et al. 2021

Front. Cell Dev. Biol.

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“…In the immune test positive group, IVIG treatment had a significantly higher success rate than that of immune test positive controls (57.6% vs. 21.7%, p < 0.05) 43 . A recent meta‐analysis of the non‐RCT IVIG studies focused on women with an abnormal level of NK cells showed LB in favor of the intervention (RR 2.57, 95% CI 1.79–3.69, p < 0.05) 44 . It was concluded that there might be some benefit of immunotherapy for women with NK cell pathology; however, due to the significant heterogeneity (I 2 = 62%), it is regarded as the paucity of high‐quality evidence.…”

Section: Ivig For Women With Rpl and Immune Abnormalitiesmentioning

confidence: 98%

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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“…Perhaps, due to this diversity, the first meta-analysis in the field, including studies assessing NK cell biology prior IVF treatment, showed no significant difference in NK cell count and activity between fertile and infertile women (Seshadri and Sunkara, 2014). Emerging evidence now put in doubt the initial notion that NK cell density and activity may predict RIF (Donoghue et al, 2019;, while a recent meta-analysis highlights that studies reporting interventions based on NK status are heterogeneous and lack the quality to produce solid evidence (Woon et al, 2020).…”

Section: Immunological Disordersmentioning

confidence: 99%

Approaches to Improve Endometrial Receptivity in Case of Repeated Implantation Failures

Makrigiannakis

Makrygiannakis

Vrekoussis

2021

Front. Cell Dev. Biol.

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Repeated implantation failures are a constant challenge in reproductive medicine with a significant impact both on health providers and on infertile couples. Several approaches have been proposed so far as effective; however, accumulative data have clarified that most of the treatment options do not have the evidence base for a generalized application to be suggested by the relevant societies. Implantation failures are attributed to either poor quality embryos or to defected endometrial receptivity. The current review aims to summarize in a systematic way all the new trends in managing RIF via interference with endometrial receptivity. The authors focus mainly, but not exclusively, on endometrial injury prior to embryo transfer and endometrial priming with autologous cells or biological agents. To this direction, a systematic search of the Pubmed database has been conducted taking into account the emerged evidence of the last two decades. All the suggested interventions are herein presented and analyzed in terms of reproductive outcomes. It is evident that properly powered and designed randomized trials are needed to support a new standard approach in RIF treatment that will safely be incorporated in national and international guidelines.

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Immunotherapy to improve pregnancy outcome in women with abnormal natural killer cell levels/activity and recurrent miscarriage or implantation failure: A systematic review and meta-analysis

Cited by 30 publications

References 86 publications

Prednisolone Alters Endometrial Decidual Cells and Affects Decidual-Trophoblast Interactions

Prednisolone Alters Endometrial Decidual Cells and Affects Decidual-Trophoblast Interactions

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

Approaches to Improve Endometrial Receptivity in Case of Repeated Implantation Failures

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