Systemic Inflammation Is Associated with Ovarian Follicular Dynamics during the Human Menstrual Cycle

Background:Ovarian processes and the timing of ovulation are important predictors of both female fertility and reproductive pathology. Multiple waves of antral follicular development have been documented during the menstrual cycle in women. However, the mechanisms underlying the development of follicular waves and their clinical significance are not fully understood. The objective of this study was to examine the relationship between C-reactive protein (CRP) and follicular waves in healthy women. We wanted to determine whether follicular wave dynamics influence systemic inflammation, as ovarian activity increases local inflammatory processes and blood flow. We tested the hypothesis that women with 3 follicular waves would have higher CRP concentrations than those with 2 waves. We further hypothesized that a greater number of major waves (those with a dominant follicle) would be positively associated with CRP.Methods/Principal Findings:Thirty-nine healthy women underwent daily transvaginal ultrasound examinations for one interovulatory interval, as part of an earlier study. Serum was collected every 3 days during the interovulatory interval (IOI). Enzyme-linked immunosorbent assays were conducted to quantify serum CRP concentrations. Women with 3 waves had higher average log CRP concentrations (n = 14, -0.43±0.35) over the IOI than those with 2 waves (n = 25, -0.82±0.47, p = 02). Average log CRP concentrations were greater in women with 3 (0.30±0.31) versus 1 (-0.71±0.55) or 2 (-0.91±0.47) major waves (p = 0.03). Greater average CRP over the IOI was attributed to greater CRP in the follicular, but not the luteal phase, of the IOI.Conclusions/Significance:A greater number of total antral follicular waves, in particular major waves, corresponded to greater serum concentrations of CRP. These findings suggest that women with a greater number of follicular waves exhibit greater tissue remodeling and therefore greater local and systemic inflammation.