TEAS Improves Ovarian Function By Regulating BDNF Content

OBJECTIVE:To observe the effects of transcutaneous electrical acupoint stimulation（TEAS）on brain-derived neurotrophic factor（BDNF）content and Chinese medicine evidence score in patients with liver-depression and kidney-deficiency infertility,to explore the possible mechanism of action of TEAS in improving ovarian function by regulating BDNF content,and to provide theoretical support and experimental basis for the application of TEAS in infertility treatment and the research of BDNF in the field of reproductive medicine.METHODS:172 infertility patients with genotype BDNF Val/Val who met the inclusion criteria for IVF-ET treatment were randomly divided into TEAS treatment group（86 cases）and placebo stimulation group（86 cases）,and TEAS treatment group was given for 2 menstrual cycles before IVF-ET treatment,and placebo stimulation group was given for 2 menstrual cycles before IVF-ET treatment.The TEAS treatment group was given 2 menstrual cycles before IVF-ET treatment,and the placebo stimulation group was given 2 menstrual cycles before IVF-ET treatment.All patients used the early follicular phase long-acting protocol for superovulation.ELISA was performed to detect BDNF concentration in serum on the 3rd day of menstruation,HCG day and follicular fluid on the day of egg collection before and after the intervention in both groups.The mRNA expression levels of two different isoforms of TrkB receptors,TrkB-FL and TrkB-T1,were measured by quantitative PCR,serum hormone levels and ovarian arterial blood flow indexes on the 3rd day of menstruation and HCG day before and after the intervention.Results:1.Serum sex hormone levels and ovarian arterial blood flow indexes:after treatment,serum E2 levels on the 3rd day of menstruation were significantly higher in the TEAS group than before treatment（P<0.05）and significantly higher than in the placebo stimulation group（P<0.05）;FSH levels and S/D values,RI values and PI values in the TEAS group were significantly lower than before treatment（P<0.05）and significantly lower than in the placebo stimulation group（P<0.05）.2.BDNF level and follicular fluid TAC value:serum BDNF level on the 3rd day of menstruation was significantly higher in the TEAS group compared with that before treatment（P<0.05）.After treatment,serum BDNF level on the3rd day of menstruation,serum BDNF level on HCG day and follicular fluid BDNF level on the day of egg retrieval were significantly higher in the TEAS group than in the comfort stimulation treatment group（P<0.05）;follicular fluid TAC was significantly higher than in the comfort stimulation group（P<0.05）.3.Correlation analysis:serum FSH level on the 3rd day of menstruation,ovarian artery S/D,RI and PI values on the 3rd day of menstruation were all negatively correlated with BDNF levels were negatively correlated（P<0.05）,and serum E2 levels on day 3 of menstruation were positively correlated with serum BDNF concentrations（P<0.05）;using the pre-and post-treatment BDNF change values as the dependent variables and including the post-treatment E₂,FSH,S/D,PI,and RI change values,multiple linear regression analysis was performed,and BDNF levels were affected by S/D values（P<0.001）,RI values（P<0.001）,and FSH level（P<0.05）changes were significantly affected.4.TrkB receptor mRNA expression level in granulosa cells of the oocyte:TrkB-T1 mRNA content in granulosa cells of the oocyte of the TEAS group was significantly lower than that of the placebo stimulation group（P<0.05）;TrkB-FL mRNA content was not statistically different（P>0.05）.5.IVF cycle outcome:patients in the TEAS group had less Gn dosage,higher fertilization rate and eugene rate（P<0.05）,and no statistical difference in clinical pregnancy rate（P>0.05）.6.TCM symptom scores:after treatment,the TCM symptom scores of patients in the TEAS group were lower and significantly lower than those of the pre-treatment symptom scores in the comfort stimulation group（P<0.05）;the overall efficiency of TCM symptom efficacy in the TEAS group was significantly higher than that of the comfort stimulation group（P<0.05）.Conclusion:（1）TEAS can regulate HPO axis,increase peripheral serum E2level,decrease FSH level,possibly improve ovarian FSH receptor sensitivity,decrease super ovulation Gn dosage,and improve liver-depression and kidney deficiency symptoms at the same time.（2）TEAS can improve ovarian blood perfusion,increase follicular fluid TAC,improve antioxidant power,improve ovarian microenvironment and reduce granulosa cell apoptosis.Meanwhile,TEAS can increase peripheral serum and follicular fluid BDNF levels,which may regulate TrkB-FL/TrkB-T1 in the ovary by activating the BDNF-TrkB pathway system,thus promoting granulosa cell proliferation and improving oocyte quality.