Cytokines in older patients undergoing in vitro fertilization:: The relationship to the response to controlled ovarian hyperstimulation

Purpose: Our purpose was to assess the endocrine, autocrine, and paracrine milieu in follicles of older women undergoing stimulated cycles, comparing normal (NR) and low (LR) responses, based on the measurement of interleukin (IL)-1 beta, IL-6, and vascular endothelial growth factor (VEGF) in serum and follicular fluid (FF). Methods: A total of 40 women entered the study, divided into three groups: (1) older patients (>37 years) with NR (age-NR; n = 18); (2) older women with LR (age-LR; n = 11); and (3) normal controls, aged <35 years (control: n = 11). IL-1 beta, IL-6, and VEGF measured in serum (day of ovum pickup) and FF, employing ELISAs. Results: Follicular fluid IL-6 was significantly (P < 0.05) higher in age-LR compared to the other two groups. IL-6 and VEGF showed a 4- to 29-fold increase in FF compared to blood, suggesting the ovary as an additional source of both cytokines. IL-1 beta levels remained unchanged in FF compared to blood and, also, among groups. Conclusions: These data provide further evidence that the endocrine, paracrine, and/or autocrine status in vivo of older patients is different from that of younger women and suggest that cytokines, specifically IL-6, may be involved in the changes observed during senescence within the ovary.