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Natural killer cells, miscarriage, and infertility. BMJ

Department of Pathology, University of Cambridge, Cambridge CB2 1QP.
BMJ (online) (Impact Factor: 17.45). 12/2004; 329(7477):1283-5. DOI: 10.1136/bmj.329.7477.1283
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    • "After the 20th week of gestation they are present in low numbers and they are not easily detectable in term decidua (Trundley and Moffett, 2004). uNK cells are supposed to play a role in controlling trophoblast invasion and in the maintenance of pregnancy (Moffett et al., 2004). Regardless of their supportive role in the initiation and maintenance of pregnancy, over-activity or increased numbers of uNK cells has been proposed to be one of the key factors triggering early pregnancy loss (Karami et al., 2012). "

    Full-text · Dataset · Nov 2015
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    • "It may be assumed that in favorable immune phenotype the function of immune system improves as a whole, i.e., the processes of migration of immunocompetent cells are more correct in both their quantity and quality, especially those of natural killers, into organs of the reproductive system on the basis of optimized cytokine regulation that creates optimal conditions for relatively autonomic regulation in the reproductive system. Phenotypically and functionally decidual NK cells are different from NK cells in peripheral blood and may be regarded as a separate lymphoid subset [30]. Migration of peripheral NK cells through the human endothelial and stromal decidual cells is possible because of chemokines support [31]. "
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    ABSTRACT: Immune markers that may predict IVF failure and successful implantation and pregnancy were studied. Favorable immune parameters were selected based on 90% of data of women who got pregnant and had uneventful pregnancy course and outcome in present IVF cycle. Immune phenotype and NK cell activity of peripheral blood of 123 women with multiple IVF failure were studied by flow cytometry. Some parameters that were out of favorable borders (elevated expression of CD56, CD158a in T lymphocytes, decreased levels of CD4 T lymphocytes, up-regulated expression of HLA DR in CD8+ T cells and NK cells, elevated number of NK cells and increased NK cytotoxicity, increased and decreased expression of CD158a and CD8 in NK cells) were considered to be immune deviations (ID) potentially predictive for IVF failure. In women with 0-1 ID implantation rate (IR) was 50.9% (27/53), with two ID - 42.8% (12/28), with three and more ID - 21.4% (9/42). IR in group with three ID was lower than in group with 0-1 ID (p<0.01, OR=3.8, CI: 1.52-9.48) and in group with two ID (p<0.05). Live birth rate (LBR) in women with 0-1 ID was 33.9%, with two ID - 28.5%, with three and more ID - 9.5%. LBR in group with three ID was lower than in group with 0-1 ID (p<0.01, OR=4.8, CI: 1.52-15.8) and in group with two ID (p<0.05). The absence or single ID seems to be more favorable for successful IVF program. Combination of ID may predict implantation failure to a greater degree than isolated ID. Multiple immune deviations form unfavorable "immune phenotype" for implantation and pregnancy development. Copyright © 2014. Published by Elsevier B.V. KEYWORDS: Favorable immune phenotype; IVF; Implantation; Pregnancy
    Full-text · Article · Oct 2014 · Immunology Letters
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    • "Full manuscripts were obtained for the remaining 35 articles for detailed evaluation and following scrutiny, 13 studies were excluded. Three studies were excluded as they were reviews (Moffet et al., 2004; Kwak-Kim et al., 2005; Rai et al., 2005). Five studies were excluded for question one evaluating NK cell levels in infertile women versus controls for the following reasons: three studies had insufficient data for analysis (Lukassen et al., 2004; Baczkowski and Kurzawa, 2007; Lynch et al., 2007) and two studies measured various markers of NK cells (Matsubayashi et al., 2001; Ntrivalas et al., 2001). "
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    ABSTRACT: INTRODUCTIONEmbryo implantation is a complex process involving maternal hormonal changes, immune responses and maturational events in the embryo. A pregnancy could fail when these events are not synchronized. It is speculated that in women, an elevation of natural killer (NK) cells may have an effect on reproductive performance, and NK cell levels in blood are currently being used as a diagnostic test to guide the initiation of therapies in patients with infertility.METHODS We conducted a systematic review to evaluate the (i) levels of NK cells in blood and endometrium in infertile versus fertile women, (ii) association between NK cells and IVF outcome, (iii) levels of NK cells in blood and endometrium in women with recurrent miscarriage (RM) versus controls. The following electronic databases were searched: Medline, EMBASE, Cochrane Library, Web of Science and National Research Register.RESULTSA total of 22 studies were included. Meta-analysis of studies that evaluated peripheral and uterine NK (uNK) cell percentages in infertile versus fertile women showed no significant difference between the two groups [standardized mean difference (SMD) -0.33; 95% confidence intervals (CI) -1.06, 0.4; P = 0.37; SMD -1.82; 95% CI -4.80, 1.17; P = 0.23 respectively]. Pooling of studies that reported peripheral NK cells as numbers showed significantly higher NK cell numbers in infertile women compared with fertile controls (SMD 3.16; 95% CI 1.07, 5.24; P = 0.003). Meta-analysis of studies that evaluated the role of NK cells in IVF outcome showed no significant difference in live birth rates in women with elevated NK cells or NK cell activity compared with women without elevated peripheral NK cells or NK cell activity (NK activity assessed using a cytotoxicity assay) (relative risk 0.57; 95% CI 0.06, 5.22; P = 0.62). Meta-analysis of studies that evaluated peripheral NK cell percentages in women with RM versus controls showed significantly higher NK cell percentages in women with RM (SMD 1.36; 95% CI 0.04, 2.69; P = 0.04). Meta-analysis of studies that evaluated peripheral NK cell numbers showed significantly higher NK cell numbers in women with RM compared with controls (SMD 0.81; 95% CI 0.47, 1.16; P < 0.00001). Meta-analysis of studies that evaluated uNK cells showed no significant difference in women with RM compared with controls (SMD 0.40; 95% CI -1.24, 2.04; P = 0.63).CONCLUSIONS Further research is needed before NK cell assessment can be recommended as a diagnostic tool in the context of female infertility or RM. There is no clear explanation as to why the results differ when data for NK cells are expressed as numbers or a percentage. On the basis of current evidence, NK cell analysis and immune therapy should be offered only in the context of clinical research.
    Preview · Article · Nov 2013 · Human Reproduction Update
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