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

Objective: To 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. Design: Observational study. Setting: Academic 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.