Recurrent implantation failure (RIF) refers to repeated failure to become pregnant after transferring embryos with normal morphology. However, the pathogenesis of RIF remains unrevealed, especially for those without any pathological features. In this study, we characterized the vaginal microbiota and metabolomes of patients with unexplained RIF, while patients who achieved clinical pregnancy in the first frozen embryo transfer (FET) cycle were used as controls. Based on 16S rRNA gene sequencing of the vaginal microbiota, the vaginal Lactobacillus showed a significant positive correlation with the pregnancy rate, and the RIF group presented higher microbial α-diversity than the control group (P value = 0.016). The metabolomic profile identified 2,507 metabolites, of which 37 were significantly different between the two groups (P value < 0.05, variable importance for the projection [VIP] > 1). Among them, 2′,3-cyclic UMP and inositol phosphate were the top two metabolites that were higher in the RIF group, while glycerophospholipids and benzopyran were important metabolites that were lower in the RIF group. A lack of lysobisphosphatidic acid and prostaglandin metabolized from glycerophospholipids will lead to deferred implantation and embryo crowding. Benzopyran, as a selective estrogen receptor modulator, may affect the outcome of pregnancy. All of the changes in metabolite profiles may result in or from the differential microbiota compositions in RIF patients. In conclusion, significant differences were presented in the vaginal microbiota and metabolomes between patients with unexplained RIF and women who became pregnant in the first FET cycle. For the first time, this study elaborates the possible pathogenesis of RIF by investigating the vaginal microbiota and metabolites in RIF patients.

中文翻译：

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反复着床失败女性阴道微生物群和相关代谢组的变化。


复发性着床失败（RIF）是指移植形态正常的胚胎后反复未能怀孕。然而，RIF 的发病机制仍不清楚，特别是对于那些没有任何病理特征的患者。在这项研究中，我们对不明原因 RIF 患者的阴道微生物群和代谢组进行了特征分析，同时将在第一个冷冻胚胎移植 (FET) 周期中实现临床妊娠的患者用作对照。基于阴道菌群16S rRNA基因测序结果显示，阴道乳酸菌与妊娠率呈显着正相关，且RIF组的微生物α多样性高于对照组（ P值=0.016）。代谢组学特征鉴定出 2,507 种代谢物，其中 37 种代谢物在两组之间存在显着差异（ P值 < 0.05，预测的可变重要性 [VIP] > 1）。其中，2',3-环UMP和磷酸肌醇是RIF组中较高的前两种代谢物，而甘油磷脂和苯并吡喃是RIF组中较低的重要代谢物。缺乏由甘油磷脂代谢的溶血双磷脂酸和前列腺素将导致延迟着床和胚胎拥挤。苯并吡喃作为选择性雌激素受体调节剂，可能会影响妊娠结果。代谢物谱的所有变化都可能是 RIF 患者微生物群组成差异的结果。总之，不明原因 RIF 患者和在第一个 FET 周期怀孕的女性之间的阴道微生物群和代谢组存在显着差异。 本研究首次通过研究 RIF 患者的阴道微生物群和代谢物来阐述 RIF 可能的发病机制。