Impact of female reproductive tract microbiota and cytokine disorders on recurrent implantation failure
Objective To explore the changes in the functional composition of genital tract microbiota in patients with recurrent implantation failure(RIF)and its relationship with cytokines related to immune regulation.Methods This was a case-control study.The study included patients from the Reproductive Medicine Center of Peking University Third Hospital,enrolled from August 2020 to January 2021.The enrolled patients were divided into control group(n=20)and the RIF group(n=15).The study examined the expression of flora and cytokines in vaginal and uterine lavage fluid by 16S rRNA sequencing and MSD electrochemiluminescence.Spearman analysis was used to observe the correlation between flora and differently expressional cytokines.Results Compared with control group,there were statistically significant differences in the Shannon index of vaginal microbiota and uterine lavage fluid microbiota in the RIF group(P= 0.032,P=0.015).There was a statistically significant difference in β diversity of the bacterial community in uterine lavage fluid(P=0.020).The expression level of monocyte chemotactic protein-4(MCP-4)in the RIF group[(3.39±1.23)ng/L]was significantly higher than that in control group[(1.07±0.31)ng/L,P=0.044],while the expression level of interleukin(IL)-17A[(1.12±0.29)ng/L]was significantly lower than that in control group[(2.70±0.52)ng/L,P=0.040].The expression levels of interferon(IFN)-γ[(4.70±2.10)ng/L],IL-10[(0.20±0.10)ng/L],tumor necrosis factor-α[(0.84±0.13)ng/L],and IL-5[(0.35±0.05)ng/L]in the RIF group in the uterine lavage were significantly higher than those in control group[(0.97±0.30)ng/L,P=0.049;(0.05±0.01)ng/L,P=0.009;(0.56±0.07)ng/L,P=0.045;(0.23±0.03)ng/L,P=0.029].Correlation analysis revealed significant correlations between vaginal flora and MCP-4(r=-0.42,P=0.025),and in the microbial community of uterine cavity lavage fluid,there was a significant positive correlation between the Muribaculaceae genus and IL-5(r=0.51,P=0.017).Conversely,the Vulcaniibacterium genus,Cupriavidus genus,and Anoxybacillus genus exhibited a significantly negative correlation with IL-5(r=-0.55,P=0.010;r=-0.62,P=0.003;r=-0.45,P=0.041).Additionally,the genera Anoxybacillus,Geobacillus,Thermus,and Meiothermus showed a significantly negative correlation with IFN-γ(r=-0.43,P=0.015;r=-0.38,P= 0.035;r=-0.39,P=0.029;r=-0.38,P=0.035).Conclusion The reproductive tract microbiota and corresponding cytokines in RIF patients are disrupted,and there is a correlation between the microbiota and cytokines.
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