阴道微生物组对胚胎植入影响的研究

Study on the effect of vaginal microbiota on embryo implantation

目的:探索不明原因反复着床失败(RIF)与第一周期IVF成功妊娠患者的阴道微生物组的差异。方法:不明原因RIF患者15例为实验组(RIF组),以同期第一周期IVF成功妊娠患者15例为对照组。取卵日采集阴道分泌物,提取总基因组DNA,对16S rDNA V3～V4区基因扩增,经Illumina Miseq测序后,比较两组阴道微生物组的丰度和结构。定义阴道乳杆菌丰度>90%为乳杆菌主导(LD)患者,乳杆菌丰度≤90%为非乳杆菌主导(NLD),比较两者临床妊娠率的差异。结果:对照组乳杆菌占(91.60±19.73)%。RIF组阴道微生物多样性显著增加(P<0.01),乳杆菌丰度显著降至(71.10±31.12)%(P<0.05),13个菌属丰度显著增加(P<0.05),包括1个需氧菌丛毛单胞菌,普氏菌、厌氧链球菌、吲哚嗜胨菌和韦荣球菌等12个厌氧菌。LD和NLD患者的临床妊娠率分别为68.42%及18.18%,差异有统计学意义(P<0.05)。结论:RIF组阴道微生物多样性增加,厌氧菌和需氧菌丰度升高,乳杆菌丰度降低。阴道乳杆菌丰度与IVF临床妊娠率相关,乳杆菌主导者具有较高的临床妊娠率。

Objective:To explore the differences in vaginal microbiota between patients with unexplained recurrent implantation failure(RIF)and patients with successful pregnancy in first-cycle IVF.Methods:Fifteen patients with unexplained RIF were enrolled in the case group(RIF group),and fifteen patients with successful pregnancy in the first IVF cycle during the same period were included in the control group.The vaginal swabs were collected on the day of ovum retrival.The total DNA were extracted for amplifying the 16 S rDNA V3~V4 region and sequencing by Illumina Miseq.The abundance and structure of vaginal microbiota were analyzed and compared in both groups.Defite patients with vaginal Lactobacillus abundance >90% as Lactobacillus-dominated(LD) and vaginal Lactobacillus abundance≤90% as non-Lactobacillus-dominated(NLD),compare the clinic pregnancy rate between them.Results:Lactobacillus was the most represented genus in the control group accounted for(91.60±19.73)%.The diversity of vaginal microbiota in RIF group was significantly increased(P<0.01),which showed Lactobacillus abundance was significantly reduced to(71.10±31.12)%(P<0.05),and the abundance of an aerobic bacterium Comamonas and 12 anaerobic bacteria,such as Prevotella,Anaerococcus,Peptoniphilus and Veillonella were statistically increased(P<0.05),and the difference was statistically significant.The clinical pregnancy rates of LD and NLD patients were 68.42% and 18.18%,respectively,and the difference was statistically significant(P<0.05).Conclusion:In RIF group,the diversity of vaginal microbiota was increased,the abundance of aerobic and anaerobic bacteria was increased,and the abundance of Lactobacillus was reduced.Patients with Lactobacillus-dominated in vaginal microbiota had a higher clinical pregnancy rate.