BDNF Val66Met polymorphism is associated with Stage III–IV endometriosis and poor in vitro fertilization outcome

BACKGROUND The recently identified human brain-derived neurotrophic factor (BDNF) Val66Met polymorphism was found to be associated with altered susceptibility to some neuropsychiatric disorders. Interestingly, BDNF together with its receptors TrkB and p75 are extensively expressed in female reproduction system. The aim of this study is to investigate whether the BDNF Val66Met polymorphism plays a role in endometriosis, endometriosis-related infertility and the outcomes of IVF and embryo transfer (IVF–ET). METHODS A case–control study included 425 endometriosis patients and 244 control Chinese Han women. The genotyping of the BDNF Val66Met polymorphism was performed by the fluorescence resonance energy transfer method. The plasma and follicular fluid concentrations of BDNF on the day of oocyte retrieval were measured by ELISA. The general clinical data from the endometriosis-related and tubal obstructed infertile patients treated with IVF–ET were analyzed. RESULTS There was no association between the BDNF Val66Met polymorphism and overall endometriosis (P> 0.05), whereas higher genotype and allele frequencies of the BDNFMet polymorphism were found in the Stage III–IV endometriosis (both P< 0.01) and endometriosis-related infertile patients (both P< 0.05). Moreover, during IVF and embryo transfer (IVF–ET) treatment, fewer mature oocytes (P< 0.05) and lower fertilization rate (P< 0.01) were found in BDNFMet/Met carriers compared with those in BDNFVal/Val carriers with infertility. Follicular-fluid BDNF concentration in BDNFMet/Met carriers was lower compared with that in BDNFVal/Val individuals (P< 0.01). CONCLUSIONS Our results suggest that the BDNFMet single-nucleotide polymorphism might contribute to the increased susceptibility to the Stage III–IV endometriosis and endometriosis-related infertility. Moreover, infertile patients with the BDNFMet/Met genotype had a poorer IVF outcome compared with the BDNFVal/Val genotype individuals, which might in part be due to the decreased BDNF levels in follicular fluids after controlled ovarian hyperstimulation.