Exploring the role of Brain-Derived Neurotrophic Factor as a biomarker in female infertility: A systematic review and meta-analysis

Brain-derived neurotrophic factor (BDNF) is essential for neuronal survival and development, and is also involved in oogenesis, follicle recruitment, and germ cell survival, which could impact reproduction. However, in humans, the relationship between BDNF levels and infertility remains controversial. The aim of this systematic review and meta-analysis was to explore the available evidence on the variation of BDNF levels in the body fluids of women and men and their interface with different conditions that could affect reproductive functions. Data were independently extracted by 2 reviewers. A systematic search was performed on six databases. Of the 1,735 studies identified, 20 were included in the qualitative synthesis and 15 in the meta-analysis. Meta-analysis was performed for all studies regarding infertility markers, and then, specifically, only for studies that evaluated endometriosis and other cases of infertility. Of the 20 studies included in the systematic review, only 1 evaluated sperm dysfunction in men. Of the 19 studies conducted in women, 13 evaluated endometriosis, 4 evaluated amenorrhea, 1 evaluated premature ovarian failure, and 1 evaluated different outcomes on childbirth. In the meta-analysis, BDNF levels were associated with endometriosis and other conditions that lead to infertility. Our findings confirm that BDNF levels are dysregulated in infertility conditions. However, the analyses showed substantial heterogeneity and, in some cases, evidence of publication bias. Further studies evaluating infertility in men and that include BMI, estrogen levels, and the menstrual cycle phase at the time of collection in women are crucial for obtaining more robust results.