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.

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.

Objectives:To investigate whether adjuvant treatment with growth hormone (GH) can improve the pregnancy outcomes of patients with fresh embryo transfer after repeated implantation failures (RIF).Methods:This retrospective cohort study was performed in patients who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) fresh transfer cycle and were expected RIF from January 2016 to December 2020 in Reproductive Medicine Center, Department of Obstetrics and Gynecology, Peking University Third Hospital. Using SPSS26.0, a 1∶1 propensity score matching was conducted based on age, body mass index (BMI), infertility factors, and antral follicle count with a caliper value of 0.015. The data obtained were then divided into GH treatment group ( n=552) and non-GH treatment group ( n=552). The controlled ovarian stimulation outcomes, implantation rate, clinical pregnancy rate, and live birth rate were compared between the two groups. Results:The implantation rate, the clinical pregnancy rate and the live birth rate of RIF patients in GH treatment group and non-GH treatment group were not significantly different (all P>0.05). Furthermore, analysis of various groups based on ovulation induction protocols similarly indicated no statistically significant differences in live birth rate, implantation rate, and clinical pregnancy rate between the two groups (all P>0.05). Logistic regression also indicated that GH adjuvant therapy has no effect on the live birth rate in RIF patients ( OR=1.035, 95% CI: 0.720-1.487, P=0.854). Conclusion:Adjuvant GH treatment may not improve the live birth rate of fresh embryo transfer in RIF patients.

Objectives:To investigate whether adjuvant treatment with growth hormone (GH) can improve the pregnancy outcomes of patients with fresh embryo transfer after repeated implantation failures (RIF).Methods:This retrospective cohort study was performed in patients who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) fresh transfer cycle and were expected RIF from January 2016 to December 2020 in Reproductive Medicine Center, Department of Obstetrics and Gynecology, Peking University Third Hospital. Using SPSS26.0, a 1∶1 propensity score matching was conducted based on age, body mass index (BMI), infertility factors, and antral follicle count with a caliper value of 0.015. The data obtained were then divided into GH treatment group ( n=552) and non-GH treatment group ( n=552). The controlled ovarian stimulation outcomes, implantation rate, clinical pregnancy rate, and live birth rate were compared between the two groups. Results:The implantation rate, the clinical pregnancy rate and the live birth rate of RIF patients in GH treatment group and non-GH treatment group were not significantly different (all P>0.05). Furthermore, analysis of various groups based on ovulation induction protocols similarly indicated no statistically significant differences in live birth rate, implantation rate, and clinical pregnancy rate between the two groups (all P>0.05). Logistic regression also indicated that GH adjuvant therapy has no effect on the live birth rate in RIF patients ( OR=1.035, 95% CI: 0.720-1.487, P=0.854). Conclusion:Adjuvant GH treatment may not improve the live birth rate of fresh embryo transfer in RIF patients.

Female reproductive tract microbiota refers to the collection of microorganisms in female reproductive tract, its dynamics, function and interactions with host have been investigated in depth. In recent years, the advancement of next-generation sequencing and metagenomic sequencing and other technologies has transformed researches on reproductive tract microbial community, unveiling its possible impact on reproduction function. Furthermore, abnormal reproductive tract microbiota may predispose to infertility, miscarriage, premature rupture of membranes, premature delivery and other diseases. Here we review the current literature that focuses on female reproductive tract microbiota and highlight its possible role on female fertility.

Female reproductive tract microbiota refers to the collection of microorganisms in female reproductive tract, its dynamics, function and interactions with host have been investigated in depth. In recent years, the advancement of next-generation sequencing and metagenomic sequencing and other technologies has transformed researches on reproductive tract microbial community, unveiling its possible impact on reproduction function. Furthermore, abnormal reproductive tract microbiota may predispose to infertility, miscarriage, premature rupture of membranes, premature delivery and other diseases. Here we review the current literature that focuses on female reproductive tract microbiota and highlight its possible role on female fertility.