Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Oct-Dec;24(4):248-256.
doi: 10.18502/jri.v24i4.14152.

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  1 , Yogita Dogra  2 , Pawan Kumar  1 , Sandeep Mathur  1 , Ashok Sharma  1 , Garima Patel  1
Affiliations

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 et al. J Reprod Infertil. 2023 Oct-Dec.

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.

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

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Box and Whisker plot depicting median and range of values for uNK cells in controls and subjects
Figure 2.
Figure 2.
Box and Whisker plot depicting median and range of values for pNK cells in controls and subjects
Figure 3.
Figure 3.
Photomicrograph depicting immunostaining of periimplantation endometrium from fertile control women and women with RIF. CD 56 (brown stain) in normal endometrium (A) CD 56 (brown stain) in endometrium from RIF woman (B). IHC (200X)
Figure 4.
Figure 4.
A) Flow cytometry dot plots showing pNK cell levels (CD 16+ CD 56+) in RIF subjects and B) control population
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Polanski LT, Baumgarten MN, Quenby S, Brosens J, Campbell BK, Raine-Fenning NJ. What exactly do we mean by “recurrent implantation failure”? a systematic review and opinion. Reprod Biomed Online. 2014;28(4):409–23. - PubMed
    1. Laufer N, Simon A. Recurrent implantation failure: current update and clinical approach to an ongoing challenge. Fertil Steril. 2012;97(5):1019–20. - PubMed
    1. Tuckerman E, Laird SM, Prakash A, Li TC. Prognostic value of the measurement of uterine natural killer cells in the endometrium of women with recurrent miscarriage. Hum Reprod. 2007;22(8):2208–13. - PubMed
    1. Tuckerman E, Mariee N, Prakash A, Li TC, Laird S. Uterine natural killer cells in peri-implantation endometrium from women with repeated implantation failure after IVF. J Reprod Immunol. 2010;87(1–2): 60–6. - PubMed
    1. Tang AW, Alfirevic Z, Quenby S. Natural killer cells and pregnancy outcomes in women with recurrent miscarriage and infertility: a systematic review. Hum Reprod. 2011;26(8):1971–80. - PubMed

LinkOut - more resources