Follicular-phase ovarian follicular fluid and plasma cytokine profiling of natural cycle in vitro fertilization patients

Abstract

To characterize follicular fluid (FF) and systemic cytokine profiles at various time points during the natural-cycle follicular and periovulatory phases. Observational clinical study across two consecutive cycles. Hospital-basedin vitro fertilization program. Ten women undergoing modified natural-cycle invitro fertilization (MNC-IVF). Plasma and follicular fluid (FF) collection. Forty FF cytokine concentrations from individual follicles and plasma from each patient were determined by fluid-phase multiplex immunoassay in two consecutive cycles: 1) tracking cycle-midfollicular or luteal surge; and 2) treatment cycle-periovulatory (at the time of MNC-IVF). Demographic, cycle, and cytokine data were compared with the use of chi-square, paired-scores t test, or Wilcoxon signed ranks tests. Fluctuations in various FF cytokines were evident during the follicular phase: Levels of interleukin (IL) 6 and IL-8 were higher in periovulatory samples, and IL-1 receptor antagonist and vascular endothelial growth factor were elevated earlier in the cycle. Luteal surge profiles were similar to those found in periovulatory samples. Conversely, circulatory cytokine concentrations were more stable during the follicular phase. These findings present an extensive physiologic reference profile of FF cytokines associated with antral folliculogenesis and highlight the compartmentalization of systemic and intraovarian cytokine networks in natural cycles.