Establishment of Cut-off Values for Uterine and Peripheral Blood Natural Killer Cells During the Peri-implantation Period in Fertile Controls and Women with Unexplained Recurrent Implantation Failure

Neeta Singh; Yogita  Dogra; Pawan  Kumar; Sandeep  Mathur; Ashok Sharma; Garima Patel

doi:10.18502/jri.v24i4.14152

Neeta Singh All India Institute of Medical Sciences, New Delhi, India
Yogita Dogra Arriva IVF Superspeciality Centre Shimla Himachal Pradesh, Himachal Pradesh, India
Pawan Kumar All India Institute of Medical Sciences, New Delhi, India
Sandeep Mathur All India Institute of Medical Sciences, New Delhi, India
Ashok Sharma All India Institute of Medical Sciences, New Delhi, India
Garima Patel All India Institute of Medical Sciences, New Delhi, India

DOI: https://doi.org/10.18502/jri.v24i4.14152

Keywords: CD56 antigen, Endometrium, Immunohistochemistry, Natural killer cells, Recurrent miscarriage.

Abstract

Background: The purpose of the study was to determine the cut-off values for peripheral and uterine natural killer (pNK, uNK) cells in fertile controls and in women with recurrent implantation failure (RIF).

Methods: In this study, 50 women with RIF and 50 fertile controls were enrolled. Midluteal endometrial biopsy samples from both cases and controls were obtained for CD 56+ cell immunohistochemistry labeling to identify uNK cells. Peripheral venous blood was also taken during the biopsy to detect pNK cells in peripheral blood mononuclear cells using flow cytometry. Cut-off values were obtained from fertile controls. Using a non-parametric Mann-Whitney U-test, the medians of the data sets were compared.

Results: The median values for uNK and pNK cell levels in the control group were 7% and 11.6%, respectively. The median value for uNK cells in RIF patients was 9%, which was higher than the one in controls but not statistically significant (p-value of 0.689). The median pNK levels (11.6% vs. 12.4%) were comparable between the RIF group and the controls. Moreover, it was found that 68% of individuals had uNK cell counts below the reference value, while 32% had excessive levels exceeding 7%. Additionally, only 51.4% of the RIF group had increased pNK cells.

Conclusion: The pNK cell cut-off values need to be used with caution because there was no difference between fertile controls and RIF women. If immunotherapy is recommended for RIF women, uNK cell testing should be used as the preferred approach.