BDNF基因的Val66Met多态性与子宫内膜异位症性不孕的相关性及对IVF-ET助孕结局的影响

摘要

Objective:To clarify the relationship between the brain-derived neurotrophic factor (BDNF)with single nucleotide polymorphism (SNP,Val/Met) and the female infertility with endometriosis,as well as its effect on the pregnancy outcome of in vitro fertilization-embryo transfer (IVF-ET).Methods:A total of 112 cases with Ⅲ-Ⅳ EMs undergoing IVF-ET from September 2015 to September 2016 were enrolled in the study group,and 109 infertile cases with tubal factors as the control group.The Val66Met polymorphism of BDNF gene was analyzed,and the difference in the pregnancy outcome of IVF-ET was compared between the two groups.Results:① There were no significant differences in age,infertile years,body mass index (BMI),basal follicle stimulating hormone (FSH) and basal estradiol (E2) between the two groups (P＞0.05).②The proportions of Met/Met genotypes and Met allele frequencies in the study group were significantly higher than those in the control group (33.0％ vs.23.9％,P=0.043;58.9％ vs.47.7％,P=0.018).In both groups,the patients with Met/Met genotype had a higher Gn dose than those with the other 2 genotypes,while they had lower number of matured eggs (4.5±3.2 vs.5.2±2.3) and fertilization rate (59.0％ vs.67.0％) (all P＜0.05).③In both groups,the patients with Met/Met genotype had the decreased level of BDNF protein in follicular fluid when compared with those patients with the other 2 genotypes (P＜0.05).However,there was no significant difference in the level of plasm BNDF between menstrual period and hCG day (P＞0.05).Conclusions:The Val66Met polymorphism of BDNF gene is associated with the endometriosis-related infertility.Moreover,this SNP is also related with the poor IVF-ET outcomes in both endometriosis-related and tubal obstructed infertile women.%目的:观察脑源性神经营养因子(BDNF)基因的Val66Met多态性与子宫内膜异位症(EMs)性不孕的相关性,探讨BDNF基因变异对体外受精-胚胎移植(IVF-ET)妊娠结局的影响.方法:收集2015年9月-2016年9月于山东中医药大学第二附属医院生殖医学科就诊,且因Ⅲ～Ⅳ期EMs行IVF-ET的患者112例为观察组,并选取同期因单纯输卵管因素行IVF-ET患者109例为对照组,探讨2组间BDNF基因的Val66Met多态性分型比例,进一步分析2组中不同基因型患者的IVF-ET妊娠结局.结果:①2组患者的年龄、不孕年限、体质量指数(BMI)、基础卵泡刺激素(FSH)和基础雌二醇(E2)水平比较,差异无统计学意义(均P＞0.05).②观察组Met/Met基因型所占比例和Met等位基因频率较对照组显著增高(33.0％ vs.23.9％,P=0.043;58.9％ vs.47.7％,P=0.018);2组中携带Met/Met基因型的患者较携带其他2种基因型患者使用的Gn剂量更高(P＜0.05),但成熟卵数(4.5±3.2 vs.5.2-±2.3)、受精率(59.0％ vs.67.0％)却更低(均P＜0.05).③2组患者中Met/Met基因型者相比于另外2种基因型者卵泡液中的BDNF蛋白水平明显下降(P＜0.05),但月经期和人绒毛膜促性腺激素(hCG)日血浆中BDNF含量差异无统计学意义(P＞0.05).结论:BDNF基因Val66Met多态性与EMs性不孕的发生密切相关,且可能导致患者对IVF-ET治疗的反应性降低.