Natural killer cells and pregnancy outcomes in women with recurrent miscarriage and infertility: a systematic review

BACKGROUND: Peripheral natural killer (pNK) and uterine NK (uNK) cells have been associated with reproductive failure. We systematically reviewed the literature to assess whether numbers or activity of pNK or uNK cells predicted subsequent pregnancy and outcome. METHODS: We searched the electronic MEDLINE database from 1950 to April 2010 for relevant publications by using MeSH terms 'natural killer cells', 'reproduction' and 'pregnancy complications'. We included studies that measured pre-pregnancy pNK and uNK cell numbers or activity in women with recurrent miscarriage (RM) or infertility, and reported subsequent pregnancy outcomes of miscarriage or failure to conceive after assisted reproductive technology (ART). RESULTS: The search identified 783 publications and 12 fulfilled the inclusion criteria. There were too few women entered into the observational studies to assess whether high pNK cell percentages or activity predicted subsequent miscarriage in women with idiopathic RM (numbers: n = 32, OR 17, 95% CI 0.82-350.6, activity: n = 92, OR 2.51, 95% CI 0.16-40.29), or implantation failure (n = 203, OR 1.35, 95% CI 0.28-6.46), or miscarriage in infertile women after ART (n = 79, OR 2.48, 95% CI 0.50-12.32). Similarly, the studies of uNK cells were not large enough to assess whether abnormal uNK cell density predicted subsequent miscarriage in women with idiopathic RM (n = 72, OR 1.33, 95% CI 0.16-11.11). None of the uNK cell studies in women with infertility reported pregnancy outcomes dichotomized for uNK cell numbers. CONCLUSIONS: The prognostic value of measuring pNK or uNK cell parameters remains uncertain. More studies are needed to confirm or refute the role of NK cell assessments as a predictive test for screening women who may benefit from immunotherapy.