Maturation of human ovarian follicles is accompanied by a decrease in the CD56+CD16+ natural killer cell population

ObjectiveTo investigate whether “proangiogenic” CD56+CD16− natural killer (NK) cells, which accumulate in follicular fluid (FF) of patients with a good response to ovarian stimulation, are also present in earlier stages of follicular development.DesignObservational study.SettingAcademic in vitro fertilization (IVF) unit.Patient(s)Patients of similar age and ovarian reserve, undergoing in vitro maturation (IVM; n = 10) or IVF (n = 22) cycles.Intervention(s)None.Main Outcome Measure(s)FF was collected from the first follicle aspirated in each ovary, and flow cytometry was used to define CD56+CD16− “proangiogenic” or CD56+CD16+ “cytotoxic” NK cells.Result(s)FF derived from antral follicles of patients undergoing IVM (maximum diameter 10 mm) showed a slightly higher abundance of “proangiogenic” NK cells compared with FF from preovulatory mature follicles (>18 mm) of patients undergoing IVF (5.4 ± 1.3% vs. 3.0 ± 1.1% of CD45+CD3− cells). Importantly, antral FF contained a significantly higher concentration of “cytotoxic” NK cells (11.4 ± 2.3% vs. 3.7 ± 0.9% of CD45+CD3− cells) compared with FF from mature follicles.Conclusion(s)“Proangiogenic” NK cells accumulate in ovarian follicles from as early as the antral follicular stage. Maturation of follicles is accompanied by a decrease in the population of “cytotoxic” NK cells that may have deleterious effects on follicular maturation.