Peripheral blood NK-cells in women with unsuccessful attempts of assisted reproduction: quantity, subpopulation composition and activation markers


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Abstract

Objective: To study the subpopulation composition of lymphocytes, quantity, subpopulation composition and activation markers of peripheral blood natural killer cells (pbNK cells) in women with unsuccessful attempts of assisted reproductive technologies (ART). Materials and methods: The main group consisted of 60 women with the previous history of one or more unsuccessful ART attempts who were subdivided into groups as patients with primary and secondary infertility. The patients with secondary infertility were divided into those who had a history of miscarriage and those who did not have it. The control group included 15 healthy fertile women. The study was carried out in the 2nd phase of the menstrual cycle (day 19-22). Subpopulation composition of peripheral blood lymphocytes, subpopulation composition of pbNK cells, their activated forms expressing receptors CD107a and NKG2D were determined using flow cytofluorimetric method. Results: The patients of the main group in comparison with the control group demonstrated a decline in the relative number of B-lymphocytes (p<0.05), number of CD16+CD107a+pbNK cells (p<0.01) and lower CD107a receptor expression (MFI) (p<0.01). The patients of the main group showed an inverse correlation between the number of pregnancies and the absolute pbNK cell count (rs=-0.55; p<0.01), as well as a direct correlation with MFI CD16+CD107a+ pbNK cells (rs=0.41; p<0.01). The threshold values associated with the absence of pregnancy were more than 0.312 k/μL for pbNK cells. The patients of the main group with primary infertility in comparison with those with secondary infertility had a decrease in the relative number of T-helpers (p<0.05), an increase in the absolute number of pbNK cells, as well as the number of NKG2D+CD56dimCD16brigh and NKG2D+CD56brighlCD16dim of pbNK cells (p<0.05). The patients who had secondary infertility and a history of miscarriage showed a decrease in the number of CD56dimCD16brighl and CD56brighlCD16dim of pbNK cells (p<0.05) and an increase in the number of CD56dimCD16dim of pbNK cells (p<0.05) compared to the patients who had no history of miscarriage. Conclusion: Depending on primary or secondary infertility as well as the presence of miscarriage in the patient’s history, the changes in pbNK cell parameters of the patients with unsuccessful ART attempts may reflect the immunological characteristics of the impaired mechanisms of implantation or termination of pregnancy in the early stages.

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About the authors

Valeriya A. Zagaynova

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproduction

Email: zagaynovav.al.52@mail.ru
Junior Researcher, obstetrician-gynecologist at the Department of Assisted Reproductive Technologies

Igor Yu. Kogan

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproduction

Email: ikogan@mail.ru
Dr. Med. Sci., Director; Professor at the Department of Obstetrics, Gynecology and Reproduction, Faculty of Medicine

Sergey A. Selkov

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproduction

Merited Scholar of the Russian Federation, Dr. Med. Sci., Professor, Head of the Department of Immunology and Intercellular Interactions

Olesya N. Bespalova

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproduction

Dr. Med. Sci

Inna O. Krikheli

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproduction

PhD, Senior Researcher, obstetrician-gynecologist

Valentina A. Mikhailova

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproduction

PhD., Senior Researcher at the Laboratory of Intercellular Interactions, Department of Immunology and Intercellular Interactions

Alina A. Davydova

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproduction

Junior Researcher at the Laboratory of Intercellular Interactions, Department of Immunology and Intercellular Interactions

Yulia P. Milyutina

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproduction

PhD, Senior Researcher at Biochemistry Group

Dmitry I. Sokolov

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproduction; I.P. Pavlov First Saint Petersburg State Medical University, Ministry of Health of Russia

Dr. Bio. Sci., Head of the Laboratory of Intercellular Interactions, Department of Immunology and Intercellular Interactions; Associate Professor at the Department of Immunology

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