OBJECTIVE: To assess the uterine NK(uNK)cell subpopulation in the peri-implantation endometrium in prospective surrogate and in women with implantation failure
To correlate uterine NK cell density with implatation failure or success
DESIGN: A prospective observational study
MATERIALS AND METHODS: The study was conducted over a period of 1 year at Milann-the fertility centre, Bangalore. Total of 21 prospective surrogates and 87 women with implantation failure were studied. Patients with uterine abnormalities and/or endocrine disorders were excluded. Transvaginal ultrasound was done on day 2/3 of the menses. Natural cycle or Hormone Replacement Therapy (HRT) cycle was followed. Diagnostic hysteroscopy with endometrial biopsy for uNK cell was done on day 5 after ultrasound documentation of ovulation in natural cycle or after 5 days of progesterone therapy in HRT cycle. Flow cytometry was used to assess CD56 and CD3 NK cells in the endometrial biopsies and the percentage was identified by immunocytochemistry. Embryo transfer or Frozen embryo transfer was performed in the subsequent menstrual cycle either in stimulated cycle or HRT cycle. Primary outcome was to find the percentage of uterine NK cells in prospective surrogate with proven fertility so as to create a normogram. Secondary outcome measured was the reproductive outcome in surrogates and in women with implantation failure in relation to percentage of uterine NK cell
RESULTS: The 10th and 90th percentile cut offs for NK cells in surrogates was determined to be 19.58% and 44.3% respectively. Patients with history of implantation failure had a wider distribution of NK cells. 10.5% (versus 9.5% in surrogates) of implantation failure patients had NK cells below the 19.58% cut off. 17.5% (versus 9.5% in surrogates) were found to have NK cell values above 44.3%. However there was no statistically significant difference in terms of implantation failure or success in relation to uNK cell density, both in surrogates and in women with implantation failure.
CONCLUSIONS: Previous studies have implicated both low NK cell activity and high NK cell activities to be associated with implantation failure. The data from our study did not find this correlation. This study proves that increased uterine NK cell number in the secretory phase may not be the sole reason that affects embryo implantation. There is some evidence regarding relationship between maternal uterine natural killer cell immunoglobulin receptor (KIR) genotype and trophoblastic HLA-C(human leukocyte antigen) genotype. Further studies are required to evaluate maternal KIRs along with trophoblastic HLA-C, so the effect of various KIR/HLA-C combinations on miscarriage risk/implantation failure can be analysed.