Hum. Reprod. Advance Access originally published online on August 19, 2004
Human Reproduction 2004 19(10):2395-2400; doi:10.1093/humrep/deh378
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An increase in the absolute count of CD56dimCD16+CD69+ NK cells in the peripheral blood is associated with a poorer IVF treatment and pregnancy outcome
1 Lister Fertility Clinic, Lister Hospital, Chelsea Bridge Road, London SW1W 8RH, 2 Immunology Department and 3 Women Health Department, Epsom and St Helier University Hospitals NHS Trust, Surrey, UK
4 To whom correspondence should be addressed. Email: mythum{at}doctors.net.uk
BACKGROUND: Our aim was to evaluate the effect of the absolute count of the activation marker (CD69), IgG Fc receptor (CD16) and inhibitor marker (CD94) expression on peripheral blood natural killer (NK) cells on implantation and miscarriage rates after IVF treatment. METHODS: Prospective observational study of 138 randomly selected women who underwent IVF treatment from December 2002 to September 2003. NK cells were identified as CD56+ (dim + bright) and CD3– by flow cytometry. The absolute counts of the CD69+, CD16+ and CD94+expressing NK cells were recorded and their relation to IVF treatment outcome and miscarriage rate was analysed. RESULTS: The mean (±SD) absolute count of the CD56dimCD16+CD69+ NK cells for women who had a successful ongoing pregnancy was 0.61 x 106/l (±0.31). For those women who failed to achieve a pregnancy, the mean value of the absolute count of CD56dimCD16+D69+ NK cells was significantly (P=0.003) higher at 1.66 x 106/l (±0.52). The absolute count of CD56dimCD16+CD94+ and CD56dimCD16+ NK cells did not show any statistically significant differences between those women with successful and failed IVF treatment. Receiver operating characteristic (ROC) curve analysis was performed to select a CD69 threshold for further statistical analysis. The implantation rate (IR) was significantly lower (13.1%) and miscarriage rate (MR) was significantly higher (66.7%) for women with an absolute CD56dimCD16+CD69+ NK cell count of >1.0 x 106/l compared to women with count below this value (IR 28.2% and MR 16.7%). Further analysis of the absolute count of CD56brightCD69+ and CD56brightCD94+ NK cells did not show any significant difference between those women with successful and failed IVF treatment. CONCLUSIONS: An increase in the absolute count of activated NK cells (CD56dimCD16+CD69+) in the peripheral blood is associated with a reduced rate of embryo implantation in IVF treatment. Furthermore, women with high CD56dimCD16+CD69+ peripheral blood NK cell absolute count, who are able to achieve pregnancy, have a significantly higher miscarriage rate.
Key words: activation markers/CD69/flow cytometry/IVF/natural killer cells
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