The Role of Uterine Natural Killer Cells on Recurrent Miscarriage and Recurrent Implantation Failure: From Pathophysiology to Treatment

Uterine natural killer (uNK) cells constitute a unique uterine leucocyte subpopulation facilitating implantation and maintaining pregnancy. Herein, we critically analyze current evidence regarding the role of uNK cells in the events entailed in recurrent implantation failure (RIF) and recurrent misc...

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Bibliographic Details
Published in:Biomedicines 2021-10, Vol.9 (10), p.1425
Main Authors: Sfakianoudis, Konstantinos, Rapani, Anna, Grigoriadis, Sokratis, Pantou, Agni, Maziotis, Evangelos, Kokkini, Georgia, Tsirligkani, Chrysanthi, Bolaris, Stamatis, Nikolettos, Konstantinos, Chronopoulou, Margarita, Pantos, Konstantinos, Simopoulou, Mara
Format: Article
Language:English
Subjects:
assisted reproduction
Biological activity
Cytotoxicity
Embryos
Endometrium
Gene expression
Glucocorticoids
Hypotheses
Implantation
Infertility
Intravenous administration
Localization
Miscarriage
Natural killer cells
Pathophysiology
Physiology
Pregnancy
recurrent implantation failure
recurrent miscarriages
Review
Therapeutic applications
uterine natural killer cells
Uterus
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Summary:Uterine natural killer (uNK) cells constitute a unique uterine leucocyte subpopulation facilitating implantation and maintaining pregnancy. Herein, we critically analyze current evidence regarding the role of uNK cells in the events entailed in recurrent implantation failure (RIF) and recurrent miscarriages (RM). Data suggest an association between RIF and RM with abnormally elevated uNK cells’ numbers, as well as with a defective biological activity leading to cytotoxicity. However, other studies do not concur on these associations. Robust data suggesting a definitive causative relationship between uNK cells and RIF and RM is missing. Considering the possibility of uNK cells involvement on RIF and RM pathophysiology, possible treatments including glucocorticoids, intralipids, and intravenous immunoglobulin administration have been proposed towards addressing uNK related RIF and RM. When considering clinical routine practice, this study indicated that solid evidence is required to report on efficiency and safety of these treatments as there are recommendations that clearly advise against their employment. In conclusion, defining a causative relationship between uNK and RIF–RM pathologies certainly merits investigation. Future studies should serve as a prerequisite prior to proposing the use of uNK as a biomarker or prior to targeting uNK cells for therapeutic purposes addressing RIF and RM.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines9101425