OBJECTIVE: Brain-derived neurotrophic factor (BDNF), a neurotrophin responsible for neuronal repair and plasticity in the nervous system, has been identified in human ovarian follicular fluid (FF). Recent studies suggest this growth factor may play a role in the body's response to oxidative stress. We hypothesize that oxidative stress may contribute to ovarian aging and thus we examined FF BDNF levels in women with diminished ovarian reserve.DESIGN: Cross-sectional.MATERIALS AND METHODS: FF from a single 18-20 mm follicle was obtained from 46 women across a range of age (age 21-44) undergoing IVF for varying indications, including unexplained infertility, male-factor infertility and diminished ovarian reserve (DOR, i.e., baseline antral follicle count < 8). FF samples were assayed for BDNF concentration using a commercially available human BDNF ELISA kit (R & D Systems, Minneapolis, MN), and a Dynatech MR 700 multi-plate reader. All samples were run in duplicate. BDNF concentrations were determined by extrapolation from nonlinear regression of data obtained from standard curves. To confirm inter-assay reliability, an internal control of serum was obtained from one individual, frozen in multiple aliquots, and assayed in duplicate on each plate. Spearman correlations and Mann-Whitney tests were performed where appropriate.RESULTS: Median FF BDNF concentration was significantly higher in women with diminished ovarian reserve when compared to donors and subjects with male factor infertility (10.51 ng/dl vs. 7.89 ng/dl, P = 0.052). Interestingly, women with unexplained infertility also had higher median FF BDNF concentrations when compared to donors and subjects with male factor infertility (10.25 ng/dl vs. 7.89 ng/dl, P =0.102), though this did not reach statistical significance. Among 30 patients for whom all data points were available, FF BDNF positively correlated with age (rsp= 0.26, 95%CI -0.04, 0.51), with a stronger and statistically significant correlation among the 16 subjects with DOR (rsp= 0.58, 95%CI 0.10, 0.83).CONCLUSIONS: BDNF is newly emerging as an ovarian growth factor that plays a role in follicular and oocyte development. There is a trend towards higher FF BDNF concentrations in women with DOR and a stronger association between age and BDNF in this subgroup when compared to women undergoing IVF for other indications. This correlation suggests that BDNF may serve as a marker for ovarian aging and appears to be strongly influenced by both chronologic age and ovarian age. OBJECTIVE: Brain-derived neurotrophic factor (BDNF), a neurotrophin responsible for neuronal repair and plasticity in the nervous system, has been identified in human ovarian follicular fluid (FF). Recent studies suggest this growth factor may play a role in the body's response to oxidative stress. We hypothesize that oxidative stress may contribute to ovarian aging and thus we examined FF BDNF levels in women with diminished ovarian reserve. DESIGN: Cross-sectional. MATERIALS AND METHODS: FF from a single 18-20 mm follicle was obtained from 46 women across a range of age (age 21-44) undergoing IVF for varying indications, including unexplained infertility, male-factor infertility and diminished ovarian reserve (DOR, i.e., baseline antral follicle count < 8). FF samples were assayed for BDNF concentration using a commercially available human BDNF ELISA kit (R & D Systems, Minneapolis, MN), and a Dynatech MR 700 multi-plate reader. All samples were run in duplicate. BDNF concentrations were determined by extrapolation from nonlinear regression of data obtained from standard curves. To confirm inter-assay reliability, an internal control of serum was obtained from one individual, frozen in multiple aliquots, and assayed in duplicate on each plate. Spearman correlations and Mann-Whitney tests were performed where appropriate. RESULTS: Median FF BDNF concentration was significantly higher in women with diminished ovarian reserve when compared to donors and subjects with male factor infertility (10.51 ng/dl vs. 7.89 ng/dl, P = 0.052). Interestingly, women with unexplained infertility also had higher median FF BDNF concentrations when compared to donors and subjects with male factor infertility (10.25 ng/dl vs. 7.89 ng/dl, P =0.102), though this did not reach statistical significance. Among 30 patients for whom all data points were available, FF BDNF positively correlated with age (rsp= 0.26, 95%CI -0.04, 0.51), with a stronger and statistically significant correlation among the 16 subjects with DOR (rsp= 0.58, 95%CI 0.10, 0.83). CONCLUSIONS: BDNF is newly emerging as an ovarian growth factor that plays a role in follicular and oocyte development. There is a trend towards higher FF BDNF concentrations in women with DOR and a stronger association between age and BDNF in this subgroup when compared to women undergoing IVF for other indications. This correlation suggests that BDNF may serve as a marker for ovarian aging and appears to be strongly influenced by both chronologic age and ovarian age.