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Biomedicines
Volume 9
Issue 10
10.3390/biomedicines9101425
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Review

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

by
Konstantinos Sfakianoudis
1,
Anna Rapani
2,
Sokratis Grigoriadis
2,3,
Agni Pantou
1,2,
Evangelos Maziotis
2,3,
Georgia Kokkini
2,
Chrysanthi Tsirligkani
2,
Stamatis Bolaris
4,
Konstantinos Nikolettos
5,
Margarita Chronopoulou
1,
Konstantinos Pantos
1,† and
Mara Simopoulou
2,3,*,†
1
Centre for Human Reproduction, Genesis Athens Clinic, 14-16, Papanikoli, 15232 Athens, Greece
2
Laboratory of Physiology, Medical School, National and Kapodistrian University of Athens, 75, Mikras Asias, 11527 Athens, Greece
3
Assisted Conception Unit, Second Department of Obstetrics and Gynecology, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, 76, Vasilisis Sofias Avenue, 11528 Athens, Greece
4
Assisted Conception Unit, General-Maternity District Hospital "Elena Venizelou", Elenas Venizelou Avenue, 11521 Athens, Greece
5
Assisted Reproduction Unit of Thrace “Embryokosmogenesis”, Apalos, 68132 Alexandroupoli, Greece
*
Author to whom correspondence should be addressed.
†
Considered jointed last authors.
Biomedicines 2021, 9(10), 1425; https://doi.org/10.3390/biomedicines9101425
Submission received: 23 August 2021 / Revised: 27 September 2021 / Accepted: 5 October 2021 / Published: 9 October 2021
(This article belongs to the Section Molecular and Translational Medicine)
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Abstract

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.
Keywords: uterine natural killer cells; assisted reproduction; recurrent implantation failure; recurrent miscarriages; implantation; pregnancy; glucocorticoids; intralipids; intravenous immunoglobulin uterine natural killer cells; assisted reproduction; recurrent implantation failure; recurrent miscarriages; implantation; pregnancy; glucocorticoids; intralipids; intravenous immunoglobulin

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MDPI and ACS Style

Sfakianoudis, K.; Rapani, A.; Grigoriadis, S.; Pantou, A.; Maziotis, E.; Kokkini, G.; Tsirligkani, C.; Bolaris, S.; Nikolettos, K.; Chronopoulou, M.; et al. The Role of Uterine Natural Killer Cells on Recurrent Miscarriage and Recurrent Implantation Failure: From Pathophysiology to Treatment. Biomedicines 2021, 9, 1425. https://doi.org/10.3390/biomedicines9101425

AMA Style

Sfakianoudis K, Rapani A, Grigoriadis S, Pantou A, Maziotis E, Kokkini G, Tsirligkani C, Bolaris S, Nikolettos K, Chronopoulou M, et al. The Role of Uterine Natural Killer Cells on Recurrent Miscarriage and Recurrent Implantation Failure: From Pathophysiology to Treatment. Biomedicines. 2021; 9(10):1425. https://doi.org/10.3390/biomedicines9101425

Chicago/Turabian Style

Sfakianoudis, Konstantinos, Anna Rapani, Sokratis Grigoriadis, Agni Pantou, Evangelos Maziotis, Georgia Kokkini, Chrysanthi Tsirligkani, Stamatis Bolaris, Konstantinos Nikolettos, Margarita Chronopoulou, and et al. 2021. "The Role of Uterine Natural Killer Cells on Recurrent Miscarriage and Recurrent Implantation Failure: From Pathophysiology to Treatment" Biomedicines 9, no. 10: 1425. https://doi.org/10.3390/biomedicines9101425

APA Style

Sfakianoudis, K., Rapani, A., Grigoriadis, S., Pantou, A., Maziotis, E., Kokkini, G., Tsirligkani, C., Bolaris, S., Nikolettos, K., Chronopoulou, M., Pantos, K., & Simopoulou, M. (2021). The Role of Uterine Natural Killer Cells on Recurrent Miscarriage and Recurrent Implantation Failure: From Pathophysiology to Treatment. Biomedicines, 9(10), 1425. https://doi.org/10.3390/biomedicines9101425

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