背景:辅助生殖技术(ART)是治疗不孕症最有效的方法,体外受精-胚胎移植(IVF-ET)后种植失败的发病机制是不孕症的一个难题。女性生殖道中的微生物被认为与妇科和产科疾病有关。然而,其对胚胎着床失败的影响尚不确定。
目的:本研究旨在调查生殖道菌群失调,鉴定生殖道中的不同细菌作为胚胎着床失败的潜在生物标志物,并通过代谢物分析证明其发病机理。
方法:我们通过QIIME2和HUMAnN2比较了239例不育患者和17例健康女性的胚胎植入失败时间,来自生殖道16SrRNA基因和宏基因组的数据。
结果:我们的研究表明,在IVF-ET后,乳酸菌丰度与胚胎着床成功(IS)之间存在很强的正相关性。生殖道微生物群落组成和结构在胚胎着床失败(IF)和健康对照之间显示出实质性差异。此外,我们通过在IS和多次植入失败(MIF)中具有0.913个曲线下面积(AUC)的受试者工作特性(ROC)建立了诊断模型,以AUC=0.784验证其有效性,证明微生物群落改变可以有效区分MIF患者。IVF-ET后另一个独立不育患者的阴道样本的宏基因组功能分析显示,IF患者富含L-赖氨酸合成途径,随着阴道pH值的升高和乳酸菌丰度的降低。
结论:本研究阐明了阴道和子宫内膜液中细菌与胚胎着床失败的几个独立关系,无疑拓宽了对女性生殖健康的认识。
BACKGROUND: Assisted reproductive technology (ART) is the most effective method to treat infertility and the pathogenesis of implantation failure after in vitro fertilization-embryo transfer (IVF-ET) is a challenging filed in infertility. Microbes in the female reproductive tract are considered to be associated with gynecological and obstetric diseases. However, its effects on embryo implantation failure are unsured.
OBJECTIVE: This study aimed to investigate reproductive tract dysbiosis, identify different bacteria in reproductive tract as potential biomarkers of embryo implantation failure and demonstrate the pathogenesis through metabolites analysis.
METHODS: We compared the data from 16S rRNA gene and metagenome in reproductive tracts through QIIME2 and HUMAnN2 by the times of embryo implantation failure on 239 infertile patients and 17 healthy women.
RESULTS: Our study revealed a strong positive correlation between Lactobacillus abundance and embryo implantation success (IS) after IVF-ET. The microbial community composition and structure in reproductive tract showed substantially difference between the embryo implantation failure (IF) and healthy control. Moreover, we established a diagnostic model through receiver operating characteristic (ROC) with 0.913 area under curve (AUC) in IS and multiple implantation failures (MIF), verified its effectiveness with an AUC = 0.784 demonstrating microbial community alterations could efficiently discriminate MIF patients. Metagenome functional analyses of vaginal samples from another independent infertile patients after IVF-ET revealed the L-lysine synthesis pathway enriched in IF patients, along with ascended vaginal pH and decreased Lactobacillus abundance.
CONCLUSIONS: This study clarifies several independent relationships of bacteria in vagina and endometrial fluid on embryo implantation failure and undoubtedly broadens the understanding about female reproductive health.