scholarly journals Characterization of Microbiota in Endometrial Fluid and Vaginal Secretions in Infertile Women with Repeated Implantation Failure

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Kotaro Kitaya ◽  
Yoko Nagai ◽  
Wataru Arai ◽  
Yoshiyuki Sakuraba ◽  
Tomomoto Ishikawa

Studies suggest that persisting intrauterine bacterial infectious conditions such as chronic endometritis potentially impair the embryo implantation process. The microbial environment in the female reproductive tract, however, remains largely undetermined in infertile patients with a history of repeated implantation failure (RIF). Using next-generation sequencing, we aimed to characterize the microbiota in the endometrial fluid (EF) and vaginal secretions (VS) in women with RIF. Twenty-eight infertile women with a history of RIF and eighteen infertile women undergoing the first in vitro fertilization-embryo transfer attempt (the control group) were enrolled in the study. On days 6-8 in the luteal phase of the natural, oocyte-pickup, or hormone replacement cycle, the paired EF and VS samples were obtained separately. Extracted genomic DNA was pyrosequenced for the V4 region of 16S ribosomal RNA using a next-generation sequencer. The EF microbiota had higher α-diversity and broader bacterial species than the VS microbiota both in the RIF and control groups. The analysis of the UniFrac distance matrices between EF and VS also revealed significantly different clustering. Additionally, the EF microbiota, but not the VS microbiota, showed significant variation in community composition between the RIF group and the control group. Burkholderia species were not detected in the EF microbiota of any samples in the control group but were detectable in a quarter of the RIF group. To our best knowledge, this is the first study investigating the microbiota in the paired EF and VS samples in infertile women with RIF.

2020 ◽  
Author(s):  
Takuhiko Ichiyama ◽  
Keiji Kuroda ◽  
Yoko Nagai ◽  
Daichi Urushiyama ◽  
Motoharu Ono ◽  
...  

Abstract Background: Repeated implantation failure (RIF) is estimated to occur in 15%–20% of infertile women undergoing in vitro fertilization-embryo transfer (IVF-ET). Molecular identification recently confirmed that the uterine microbiota may have implications for reproductive and obstetrical outcomes. One hundred forty-five women who had been diagnosed with RIF were enrolled in the study. Twenty-one healthy women were also enrolled as controls. We investigated their vaginal and endometrial microbiotas using 16S rRNA gene sequencing and compared the microbiota profiles in the patients with RIF and controls.Results: The endometrial microbiotas had higher α-diversities than did the vaginal microbiotas (p<0.001 in both patients with RIF and healthy women). The microbiota profiles showed that vaginal and endometrial samples in patients with RIF had significantly higher levels of 5 and 14 bacterial genera, respectively, than those in healthy women. These genera included Atopobium, Gardnerella, Prevotella and Megasphaera. Vaginal Lactobacillus rates in patients with RIF were significantly lower at 76.4 ± 38.9% compared with those of the controls at 91.8 ± 22.7% (p=0.018), but endometrial Lactobacillus rates did not significantly differ between the RIF patients and controls (56.2 ± 36.4% and 58.8 ± 37.0%, respectively, p=0.79) Conclusions: Impaired microbiota communities containing specific bacteria in both the endometrium and vagina were associated with implantation failure. The Lactobacillus rate in the vagina, but not the endometrium, may be a biomarker for RIF.Trial registration: UMIN Clinical Trials Registry, UMIN000031731, Registered 15 March 2018; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000036121


2020 ◽  
Author(s):  
Ying Ni ◽  
Chenye Tong ◽  
Limin Huang ◽  
Wenjie Zhou ◽  
Aijun Zhang

Abstract Background: The objective of this study was to investigate the current status of fertility quality of life (QoL) and explore the influencing factors for infertile women with repeated implantation failure (RIF).Methods: The sample consisted of 137 infertile women with RIF who were under treatment from January 2019 to December 2019 in the Reproductive Medical Center of Ruijin Hospital, affiliated with Shanghai Jiaotong University School of Medicine in China. A general information questionnaire, FertiQoL scale, perceived social support scale (PSSS), self-rating anxiety scale (SAS), and self-rating depression scale (SDS) were used to analyse the fertility QoL and related factors of RIF patients.Results: The total fertility QoL score of RIF patients was 60.44 ± 11.60. The results of multivariate regression analysis showed that residence, financial difficulties, male infertility, BMI index, depression, and family social support were the main factors that influenced the fertility QoL of RIF patients (adjusted R2 = 0.762).Conclusion: Based on the results of this study, RIF patients’ psychological status must be addressed. Corresponding interventions such as building a sound family and social support system, creating a good medical environment and offering diverse health education should be provided to improve the fertility QoL of RIF patients.


2020 ◽  
Author(s):  
Aihua He ◽  
Yangyun Zou ◽  
Cheng Wan ◽  
Jing Zhao ◽  
Qiong Zhang ◽  
...  

Abstract Background: Window of implantation (WOI) displacement was known as one of endometrial origin leading to embryo implantation failure, especially for repeated implantation failure (RIF). A accurately prediction tool of endometrial receptivity (ER) is extraordinary needed to precisely guide the successful embryo implantation. We aimed to establish an RNA-seq based endometrial receptivity test tool (rsERT) using transcriptomic biomarkers, and to evaluate the benefit of personalized embryo transfer (pET) guided by this tool in patients with repeated implantation failure (RIF).Methods: Two-phase strategy including tool establishment with retrospective data and benefit evaluation with prospective, nonrandomized controlled trial. In the first phase, the rsERT was established by sequencing and analyzing the RNA of endometrial tissues from 50 infertile patients with normal window of implantation (WOI) timing. In the second phase, 142 patients with RIF were recruited and grouped by patient self-selection (experimental group, n=56; control group, n=86). pET guided by rsERT in the experimental group, and conventional ET in the control group. Results: The rsERT, comprising 175 biomarker genes, showed an average accuracy of 98.4% by using 10-fold cross-validation. IPR of experimental group (50.0%) was significantly improved compared to that (23.7%) of control group (RR, 2.107; 95% CI, 1.159 to 3.830; P = 0.017) when transferring day 3 embryos. Although not statistically different, IPR of experimental group (63.6%) was still 20 percentage points higher than that (40.7%) of control group (RR, 1.562; 95% CI, 0.898 to 2.718; P = 0.111) when transferring blastocyst. Regression analysis can precisely predict the optimal WOI time by using all samples as training dataset (R2= 0.92).Conclusions: The rsERT was developed to accurately predict WOI period and significantly improve pregnancy outcomes of patients with RIF, indicating the clinical potential of rsERT-guided pET. Optimization of the model made it possible to predict the optimal WOI by one-point sampling.Trial registration: Chinese Clinical Trial Registry: ChiCTR-DDD-17013375. Registered 14 November 2017, http://www.chictr.org.cn/index.aspx


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ying Ni ◽  
Chenye Tong ◽  
Limin Huang ◽  
Wenjie Zhou ◽  
Aijun Zhang

Abstract Background The objective of this study was to investigate the current status of fertility quality of life (QoL) and explore the influencing factors for infertile women with repeated implantation failure (RIF). Methods The sample consisted of 137 infertile women with RIF who were under treatment from January 2019 to December 2019 in the Reproductive Medical Center of Ruijin Hospital, affiliated with Shanghai Jiaotong University School of Medicine in China. A general information questionnaire, FertiQoL scale, perceived social support scale (PSSS), self-rating anxiety scale (SAS), and self-rating depression scale (SDS) were used to analyse the fertility QoL and related factors of RIF patients. Results The total fertility QoL score of RIF patients was 60.44 ± 11.60. The results of multivariate regression analysis showed that residence, financial difficulties, male infertility, BMI index, depression, and family social support were the main factors that influenced the fertility QoL of RIF patients (adjusted R2 = 0.762). Conclusion Based on the results of this study, RIF patients’ psychological status must be addressed. Corresponding interventions such as building a sound family and social support system, creating a good medical environment and offering diverse health education should be provided to improve the fertility QoL of RIF patients.


2020 ◽  
Author(s):  
Mingxia Gao ◽  
Yue Kang ◽  
Bin Li ◽  
Shuang Fan ◽  
Xuehong Zhang

AbstractObjectiveThis study applied the public genetic databases high-throughput gene expression omnibus (GEO) database to compare the difference of gene screening between the repeated implantation failure (RIF) patients and women with normal endometrium. This study aims to provide additional information for the diagnosis and treatment in RIF patients through the gene set enrichment analysis and the construction of protein–protein interactions (PPIs) network.MethodThe human endometrial microarray data of RIF and normal control group were obtained from the GEO database provided by the National Center for Biotechnology Information (NCBI). The analysis and the review of differential gene screening, gene ontology (GO) pathway analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and PPIs network construction were carried out.Result273 genes with differential expression, 87 up-regulated and 186 down-regulated genes, were obtained through differential gene analysis. 50 genes with the most significant differential expression fold change were screened for subsequent analysis. KEGG results indicated that the top three related pathways were cancer pathway, MAPK signaling pathway, and homologous recombination pathway when the relevant pathways were sequenced according to the correlation size. GO analysis showed that differentially expressed genes were involved in protein phosphorylation, complement activation, and other biological processes. PPIs analysis demonstrated that targeted genes show high correlation to the endometrial receptivity, including PAEP, CXCL14, HOXB3, CD55, and VEGFA, all were down-regulated in RIF endometrial tissues compared to the control group, and these genes also influenced and regulated each other.ConclusionThrough public databases and bioinformatics, several factors in endometrial receptivity that affect RIF directly and indirectly were found. In particular, the immune and angiogenesis factors stood out the most. The different genes which regulate the immune response and angiogenesis response may become new targeted treatment for RIF.


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