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Introduction: Alterations in microbiota composition have been implicated in a variety of human diseases. Patients with adenomyosis present immune dysregulation leading to a persistent chronic inflammatory response. In this context, the hypothesis that alterations in the microbiota may be involved in the pathogenesis of adenomyosis, by affecting the epigenetic, immunologic, and biochemical functions of the host, has recently been postulated. The aim of the present study was to compare the microbiota composition in the vagina, endometrium, and gut of individuals with and without adenomyosis. Material and Methods: Cross‐sectional study including 38 adenomyosis patients and 46 controls, performed between September 2021 and October 2022 in a university hospital‐based research center. The diagnosis of adenomyosis was based on sonographic criteria. Fecal, vaginal, and endometrial samples were collected. Study of the microbiota using 16S rRNA gene sequencing. Results: Patients with adenomyosis exhibited a significant reduction in the gut microbial alpha diversity compared with healthy controls (Chao1 p = 0.012, Fisher p = 0.005, Observed species p = 0.005). Beta‐diversity analysis showed significant differences in the compositions of both gut and vaginal microbiota between adenomyosis patients and the control group (Adonis p‐value = 0.001; R2 = 0.03 and Adonis p‐value = 0.034; R2 = 0.04 respectively). Specific bacterial taxa were found to be either overrepresented (Rhodospirillales, Ruminococcus gauvreauii group, Ruminococcaceae, and Actinomyces) or underrepresented in the gut and endometrial microbiota of adenomyosis patients compared with controls. Distinct microbiota profiles were identified among patients with internal and external adenomyosis phenotypes. Conclusions: The study revealed reduced gut microbiota diversity in adenomyosis patients, accompanied by distinct compositions in gut and vaginal microbiota compared with controls. Overrepresented or underrepresented bacterial taxa were noted in the gut and endometrial microbiota of adenomyosis patients, with variations in microbiota profiles among those with internal and external adenomyosis phenotypes. These findings suggest a potential association between microbiota and adenomyosis, indicating the need for further research to comprehensively understand the implications of these differences. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic endometritis (CE) is associated with poor reproductive outcomes, yet the role of endometrial microbiota in patients with recurrent implantation failure (RIF) and CE remains unclear. This study aims to characterize endometrial microbiota in RIF patients with CE and assess its implications for reproductive outcomes. Methods In this prospective study, we enrolled RIF patients both with and without CE. Endometrial and cervical samples were collected for 16 S rRNA gene sequencing. Microbiota composition was compared between groups using diversity indices, phylum, and genus-level analysis. Canonical correlation analysis (CCA) and Spearman’s correlation coefficients were used to assess relationships between CE, reproductive outcomes, and microbiota. Predictive functional profiling was performed to evaluate metabolic pathways associated with CE. Results Endometrial microbiota in CE patients exhibited greater diversity and evenness compared to non-CE patients. Principal coordinates analysis (PCoA) revealed distinct clustering between CE and non-CE groups. Linear discriminant analysis (LDA) identified Proteobacteria, Aminicenantales, and Chloroflexaceae as characteristic of CE, while Lactobacillus, Acinetobacter, Herbaspirillum, Ralstonia, Shewanela, and Micrococcaceae were associated with non-CE. CCA demonstrated associations between CE, adverse reproductive outcomes, and specific bacterial taxa. Microbial metabolic pathways significantly differed between CE and non-CE groups, with enrichment in pathways related to cofactors, vitamins, secondary metabolites, and the immune system in CE patients. Conclusion RIF patients with CE exhibit distinct endometrial microbiota compositions associated with adverse reproductive outcomes. The increased microbial diversity and altered metabolic pathways in CE suggest a potential correlation with reproductive outcomes, although further studies are necessary to elucidate the causal relationship between microbiota alterations and fertility. Modulating the endometrial microbiome may represent a novel therapeutic strategy to improve IVF outcomes in patients with CE.

Background: Chronic endometritis (CE) is associated with poor reproductive outcomes, yet the role of endometrial microbiota in patients with recurrent implantation failure (RIF) and CE remains unclear. This study aims to characterize endometrial microbiota in RIF patients with CE and assess its implications for reproductive outcomes. Methods: In this prospective study, we enrolled RIF patients both with and without CE. Endometrial and cervical samples were collected for 16 S rRNA gene sequencing. Microbiota composition was compared between groups using diversity indices, phylum, and genus-level analysis. Canonical correlation analysis (CCA) and Spearman's correlation coefficients were used to assess relationships between CE, reproductive outcomes, and microbiota. Predictive functional profiling was performed to evaluate metabolic pathways associated with CE. Results: Endometrial microbiota in CE patients exhibited greater diversity and evenness compared to non-CE patients. Principal coordinates analysis (PCoA) revealed distinct clustering between CE and non-CE groups. Linear discriminant analysis (LDA) identified Proteobacteria, Aminicenantales, and Chloroflexaceae as characteristic of CE, while Lactobacillus, Acinetobacter, Herbaspirillum, Ralstonia, Shewanela, and Micrococcaceae were associated with non-CE. CCA demonstrated associations between CE, adverse reproductive outcomes, and specific bacterial taxa. Microbial metabolic pathways significantly differed between CE and non-CE groups, with enrichment in pathways related to cofactors, vitamins, secondary metabolites, and the immune system in CE patients. Conclusion: RIF patients with CE exhibit distinct endometrial microbiota compositions associated with adverse reproductive outcomes. The increased microbial diversity and altered metabolic pathways in CE suggest a potential correlation with reproductive outcomes, although further studies are necessary to elucidate the causal relationship between microbiota alterations and fertility. Modulating the endometrial microbiome may represent a novel therapeutic strategy to improve IVF outcomes in patients with CE. [ABSTRACT FROM AUTHOR]

Introduction: The potential role of the endometrial microbiota in the pathogenesis of endometrial polyps (EPs) warrants further investigation, given the current landscape of limited and inconclusive research findings. We aimed to explore the microecological characteristics of the uterine cavity in patients with EPs and investigate the potential of endometrial microbiota species as novel biomarkers for identifying EPs. Methods: Endometrial samples were collected from 225 patients who underwent hysteroscopies, of whom 167 had EPs, whereas 58 had nonhyperproliferative endometrium status. The endometrial microbiota was assessed using 16S rRNA gene sequencing. We characterized the endometrial microbiota and identified microbial biomarkers for predicting EPs. Results: The endometrial microbial diversity and composition were significantly different between the EP and control groups. Predictive functional analyses of the endometrial microbiota demonstrated significant alterations in pathways involved in sphingolipid metabolism, steroid hormone biosynthesis, and apoptosis between the two groups. Moreover, a classification model based on endometrial microbial ASV-based biomarkers along with the presence of abnormal uterine bleeding symptoms achieved powerful classification potential in identifying EPs in both the discovery and validation cohorts. Conclusion: Our study indicates a potential association between altered endometrial microbiota and EPs. Endometrial microbiota-based biomarkers may prove valuable for the diagnosis of EPs. Clinical trial registration: Chinese Clinical Trial Registry (ChiCTR2100052746). [ABSTRACT FROM AUTHOR]

An increasing number of studies in recent years have focused on the association between female endometrial microbiota and fertility. Once the endometrial microflora microecology is unbalanced, it will cause a series of endometrial lesions, thereby destroying endometrial receptivity, affecting embryo implantation, resulting in embryo implantation or implantation failure. Among them, the most concerned is the positive significance of lactobacillus-led microbiota on reproductive outcome. Although the relationship between endometrial microbiota and reproductive outcome has not reached a consensus, most studies recognize the positive impact of lactobacillus-led microbiota on reproductive outcome. In this review, the relationship between lactobacillus-dominated microbiota and reproductive outcome is reviewed. [ABSTRACT FROM AUTHOR]

Purpose: This prospective study investigates the correlation between vaginal microecology and pregnancy outcomes and explores their impact on endometrial microbiota composition during frozen embryo transfer (FET) cycles. Additionally, the impact of transvaginal Lactobacillus supplementation on reproductive outcomes in patients with previous failed cycles was assessed. Methods: A total of 379 patients undergoing FET at a reproductive medicine center were categorized into clinical pregnancy (CP), miscarriage (MISC), and non-pregnant (NP) groups. Vaginal specimens were collected for microecological evaluation prior to embryo transfer. Endometrial microbiota samples were obtained during embryo transfer for 16S rRNA gene sequencing analysis to assess endometrial microbiota composition. Vaginal microecological indicators, including pH, Lactobacillus dominance, and leukocyte esterase activity, were measured. Transvaginal Lactobacillus supplementation was investigated in 60 patients with previous failed cycles. Results: Vaginal microecology significantly correlated with pregnancy outcomes, with normal microecology associated with a higher clinical pregnancy rate. Vaginal pH and leukocyte esterase activity were significantly associated with clinical pregnancy. Furthermore, vaginal microecological differences significantly impacted endometrial microbiota composition. However, no significant differences were observed in endometrial microbiota composition among the CP, MISC, and NP groups. Notably, transvaginal Lactobacillus supplementation increased the clinical pregnancy rate without affecting the miscarriage rate. Conclusion: This study highlights that normal vaginal microecology, characterized by lower pH and leukocyte esterase negativity, is associated with a higher likelihood of clinical pregnancy following FET. Importantly, vaginal microecological differences influence endometrial microbiota composition. Moreover, transvaginal Lactobacillus supplementation appears promising in improving clinical pregnancy rates in patients with previous failed cycles. These findings contribute to a better understanding of the interplay between vaginal and endometrial microbiota and offer potential interventions to enhance reproductive success in assisted reproductive technologies. [ABSTRACT FROM AUTHOR]

The human endometrium is a dynamic entity that plays a pivotal role in mediating the complex interplay between the mother and developing embryo. Endometrial disruption can lead to pregnancy loss, impacting both maternal physical and psychological health. Recent research suggests that the endometrial microbiota may play a role in this, although the exact mechanisms are still being explored, aided by recent technological advancements and our growing understanding of host immune responses. Suboptimal or dysbiotic vaginal microbiota, characterized by increased microbial diversity and reduced Lactobacillus dominance, has been associated with various adverse reproductive events, including miscarriage. However, the mechanisms linking the lower reproductive tract microbiota with pregnancy loss remain unclear. Recent observational studies implicate a potential microbial continuum between the vaginal and endometrial niche in patients with pregnancy loss; however, transcervical sampling of the low biomass endometrium is highly prone to cross-contamination, which is often not controlled for. In this review, we explore emerging evidence supporting the theory that a dysbiotic endometrial microbiota may modulate key inflammatory pathways required for successful embryo implantation and pregnancy development. We also highlight that a greater understanding of the endometrial microbiota, its relationship with the local endometrial microenvironment, and potential interventions remain a focus for future research. [ABSTRACT FROM AUTHOR]

The uterine microbiota has been the subject of increasing study, but its interaction with the local immune system remains unclear. Successful embryo implantation relies on endometrial receptivity, which is pivotal for immunological tolerance to fetal antigens and precise regulation of inflammatory mediators. Emerging data suggest a dynamic interplay between endometrial microflora and the immune system, making dysbiosis a potential determinant of pregnancy outcomes. Imbalances in the regulation of immune cells in the endometrium and decidua have been associated with infertility, miscarriage, and obstetric complications. A thorough comprehension of the immune system in the female reproductive tract shows potential for improving women's health and pregnancy outcomes. The objective of this study was to evaluate the patterns of endometrial microbiota in patients with recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL) and to explore their implications for endometrial immune cells and chronic endometritis (CE). Immune cells in biopsies from 107 RIF and 93 RPL patients were examined using flow cytometry. The endometrial microbial composition was analyzed using real-time polymerase chain reaction (RT-PCR). The research uncovered disrupted endometrial microbiota in most women with RIF and RPL, which was often associated with significant effects on lymphocytes, T cells, and uNK cells. [ABSTRACT FROM AUTHOR]

An isolate of a bacterium recovered from an endometrial biopsy failed to be identified by MALDI-TOF mass spectrometry and was subjected to 16S rRNA sequencing. The obtained sequence was compared by BLASTn against the NCBI database, which revealed that the most closely related species was Cellulomonas hominis and Cellulomonas pakistanensis, with 98.85% and 98.45% identity, respectively. Phenotypic characterisation and genome sequencing were performed. The isolate was facultative anaerobic, gram-positive, motile, non-spore forming, and rod-shaped. Cell wall fatty acid profiling revealed that 12-methyl-tetradecanoic acid was the most abundant fatty acid (36%). The genome size was 4.25 Mbp with a G + C content of 74.8 mol%. Genomic comparison of species closely related to this strain showed that all digital DNA–DNA hybridisation (dDDH) and mean orthologous nucleotide identity (OrthoANI) values were below published species thresholds (70% and 95–96%, respectively). Based on these data, we conclude that this isolate represents a new bacterial species belonging to the family Cellulomonadaceae and the phylum Actinomycetota. We propose the name Cellulomonas endometrii sp. nov. The type strain is Marseille-Q7820T (= CSUR Q7820 = CECT 30716). [ABSTRACT FROM AUTHOR]

In recent years, the study of the human microbiome has surged, shedding light on potential connections between microbiome composition and various diseases. One specific area of intense interest within this research is the female reproductive tract, as it holds the potential to influence the process of embryo implantation. Advanced sequencing technologies have delivered unprecedented insights into the microbial communities, also known as microbiota, residing in the female reproductive tract. However, their efficacy encounters significant challenges when analyzing low-biomass microbiota, such as those present in the endometrium. These molecular techniques are susceptible to contamination from laboratory reagents and extraction kits, leading to sequencing bias that can significantly alter the perceived taxonomy of a sample. Consequently, investigating the microbiota of the upper female reproductive tract necessitates the exploration of alternative methods. In this context, the current review delves into the application of culturomics in unraveling the upper female reproductive tract microbiota. While culturomics holds value in research, its transition to routine clinical practice appears remote, at least in the foreseeable future. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The primary objective of our study was to compare the endometrial microbiota profiles of women with unexplained infertility and fertile women. STUDY DESIGN: In this case control study a total of 15 patients with unexplained infertility and 15 patients who had a live birth in the last two years with proven fertility were recruited. Endometrial samples were collected and analyzed through next-generation sequencing of the bacteria-specific 16S ribosome gene. RESULTS: Lactobacillus species represented the majority of the microbiome profile in both groups. The median percentage of the endometrial Lactobacillus between infertile patients and fertile patients was not statistically significant (p=0.9). Groups were divided into two categories: Lactobasillus dominant (Lactobacillus spp.> 90%, LD) and Non-Lactobacillus dominant (NLD). Lactobacillus dominance was detected in six of nine patients (66.7%) in the study group and four of nine patients (44.5%) in the control group, and no significant difference was observed between them (p=0.64). CONCLUSION: According to our study results, no significant difference was observed between the endometrial microbiota profile of infertile and fertile patients. Further studies with larger sample sizes are needed to characterize the endometrial microbiota and its impact on reproduction. [ABSTRACT FROM AUTHOR]

Contrary to popular belief, we have known for many years that the endometrium is not a sterile environment and is considered to be a low-biomass milieu compared to the vagina. Numerous trials and studies have attempted to establish a valid sampling method and assess its physiological composition, but no consensus has been reached. Many factors, such as ethnicity, age and inflammation, can influence the microbiome. Moreover, it possesses a higher alpha-diversity and, therefore, contains more diverse bacteria than the vagina. For instance, Lactobacillus has been shown to be a predominant genus in the vaginal microbiome of healthy women. Consequently, even if a majority of scientists postulate that a predominance of Lactobacillus inside the uterus improves reproductive outcomes, vaginal contamination by these bacteria during sampling cannot be ruled out. Certain pathologies, such as chronic endometritis, have been identified as inflammation perpetrators that hinder the embryo implantation process. This pro-inflammatory climate created by dysbiosis of the endometrial microbiota could induce secondary inflammatory mediators via Toll-like receptors, creating an environment conducive to the development of endometriosis and even promoting carcinogenesis. However, studies to this day have focused on small populations. In addition, there is no clearly defined healthy uterine composition yet. At most, only a few taxa have been identified as pathogenic. As sampling and analysis methods become increasingly precise, we can expect the endometrial microbiota to be incorporated into future diagnostic tools and treatments for women's health. [ABSTRACT FROM AUTHOR]

For decades, the endometrium was considered to be a sterile environment. However, now this concept is disputed, and there is growing evidence that microbiota composition might affect endometrial receptivity. Routine clinical management of infertility is still limited to a microbiological assessment of the lower reproductive tract. The purpose of this study was to compare the abundance of various bacterial, fungal, and viral species, qualitatively and quantitatively, in vaginal, cervical, and endometrial biomaterial of infertile patients. A total of 300 samples from 100 infertile patients of a private assisted reproduction clinic were analyzed. A broad real-time polymerase chain reaction panel was used to identify 28 relevant microbial taxa as well as three members of the Herpesviridae family. All patients underwent endometrial biopsy for further histopathological evaluation. Analysis of the microbial diversity (within the boundaries of the detection panel) revealed that Shannon indexes in the cervix and vagina were similar (1.4 × 10−2 (1.6 × 10−3 – 6.5 × 10−1) vs 1.9 × 10−2 (2.3 × 10−3 – 5.3 × 10−1), respectively, p = 0.502), whereas endometrial indexes differed significantly from both regions (0 (0 – 1.4 × 10−1), p < 0.0001). Surprisingly, 17 microbial and viral taxa were detected in at least one sample. Endometrium exhibited a quite distinct microbiological profile, being different at the detection rates of 14 taxa (p < 0.05). Remarkably, 4% and 2% of endometrial samples were positive for Cytomegalovirus and Candida spp., respectively, while these were undetectable in corresponding cervical and vaginal samples. Prevalence of the Gardnerella vaginalis + Prevotella bivia + Porphyromonas spp. group in endometrium was associated with a low abundance of Lactobacillus spp. (p = 0.039). No noteworthy associations were identified between various microbiota characteristics and clinical parameters, such as chronic endometritis, uterine polyps and adhesions, endometriosis, and a history of sexually transmitted infections. These findings indicate that the microbiological profile of the endometrium is unique, and the analysis of the lower reproductive tract should supplement, rather than be a substitute for it. [ABSTRACT FROM AUTHOR]

Endometrial receptivity (ER) is a key factor required for the successful implantation of the embryo. However, the evaluation of ER is challenging, as a nondisruptive sampling of endometrial biomaterial by conventional methods is only possible outside of the embryo transfer (ET) cycle. We propose a novel approach for the assessment of ER—microbiological and cytokine profiling of menstrual blood aspirated directly from the uterine cavity at the beginning of the cryo-ET cycle. The aim of the pilot study was to evaluate its prognostic potential regarding the outcome of the in vitro fertilization procedure. Samples collected from a cohort of 42 patients undergoing cryo-ET were analyzed by a multiplex immunoassay (48 various cytokines, chemokines, and growth factors) and a real-time PCR assay (28 relevant microbial taxa and 3 members of the Herpesviridae family). Significant differences between groups of patients who achieved and did not achieve pregnancy were observed for G-CSF, GRO-α, IL-6, IL-9, MCP-1, M-CSF, SDF-1α, TNF-β, TRAIL, SCF, IP-10, and MIG (p < 0.05), whereas microbial profiles were not associated with the outcome of cryo-ET. It appeared that levels of IP-10 and SCGF-β were significantly lower (p < 0.05), in patients with endometriosis. Menstrual blood may provide great opportunities to noninvasively investigate various parameters of the endometrium. [ABSTRACT FROM AUTHOR]

The uterine microbiota has been the subject of increasing study, but its interaction with the local immune system remains unclear. Successful embryo implantation relies on endometrial receptivity, which is pivotal for immunological tolerance to fetal antigens and precise regulation of inflammatory mediators. Emerging data suggest a dynamic interplay between endometrial microflora and the immune system, making dysbiosis a potential determinant of pregnancy outcomes. Imbalances in the regulation of immune cells in the endometrium and decidua have been associated with infertility, miscarriage, and obstetric complications. A thorough comprehension of the immune system in the female reproductive tract shows potential for improving women’s health and pregnancy outcomes. The objective of this study was to evaluate the patterns of endometrial microbiota in patients with recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL) and to explore their implications for endometrial immune cells and chronic endometritis (CE). Immune cells in biopsies from 107 RIF and 93 RPL patients were examined using flow cytometry. The endometrial microbial composition was analyzed using real-time polymerase chain reaction (RT-PCR). The research uncovered disrupted endometrial microbiota in most women with RIF and RPL, which was often associated with significant effects on lymphocytes, T cells, and uNK cells.

Purpose: A Lactobacillus-dominated microbiota in the endometrium was reported to be associated with favorable reproductive outcomes. We investigated in this study whether 16S ribosomal RNA (rRNA) gene sequencing analysis of the uterine microbiome improves pregnancy outcomes. Methods: This prospective cohort study recruited a total of 195 women with recurrent implantation failure (RIF) between March 2019 and April 2021 in our fertility center. Analysis of the endometrial microbiota by 16S rRNA gene sequencing was suggested for all patients who had three or more failed embryo transfers (ETs). One hundred and thirty-one patients underwent microbial 16S rRNA gene sequencing (study group) before additional transfers, while 64 patients proceeded to ET without that analysis (control group). The primary outcome was to compare the cumulative clinical pregnancy rate of two additional ETs. Main results: An endometrial microbiota considered abnormal was detected in 30 patients (22.9%). All but one of these 30 patients received antibiotics according to the bacterial genus detected in their sample, followed by treatment with probiotics. As a result, the cumulative clinical pregnancy rate (study group: 64.5% vs. control group: 33.3%, p = 0.005) and the ongoing pregnancy rate (study group: 48.9% vs. control group: 32.8%, p = 0.028) were significantly increased in the study group compared to the control group. Conclusion: Personalized treatment recommendations based on the microbial 16S rRNA gene sequencing of the uterine microbiota can improve IVF outcomes of patients with RIF. Trial registration: The University Hospital Medical Information Network (UMIN) Clinical Trial Registry: UMIN000036050 (date of registration: March 1, 2019). [ABSTRACT FROM AUTHOR]

Recurrent implantation failure (RIF) is a major limiting factor in the success rates of in-vitro fertilisation despite the remarkable clinical and technological advancement made at improving assisted reproductive technology. The primary purpose of the endometrium is to provide a receptive site for the implantation of the blastocyst and support its growth and subsequent development. Endometrial pathologies such as endometrial polyps, adenomyosis, Asherman's syndrome, chronic endometritis, and congenital Müllerian ducts defect negatively influence the integrity and receptivity of the endometrium, as well as the implantation of the embryo. This review highlights the implications of these endometrial pathologies and their association with RIF. [ABSTRACT FROM AUTHOR]

Contrary to popular belief, we have known for many years that the endometrium is not a sterile environment and is considered to be a low-biomass milieu compared to the vagina. Numerous trials and studies have attempted to establish a valid sampling method and assess its physiological composition, but no consensus has been reached. Many factors, such as ethnicity, age and inflammation, can influence the microbiome. Moreover, it possesses a higher alpha-diversity and, therefore, contains more diverse bacteria than the vagina. For instance, Lactobacillus has been shown to be a predominant genus in the vaginal microbiome of healthy women. Consequently, even if a majority of scientists postulate that a predominance of Lactobacillus inside the uterus improves reproductive outcomes, vaginal contamination by these bacteria during sampling cannot be ruled out. Certain pathologies, such as chronic endometritis, have been identified as inflammation perpetrators that hinder the embryo implantation process. This pro-inflammatory climate created by dysbiosis of the endometrial microbiota could induce secondary inflammatory mediators via Toll-like receptors, creating an environment conducive to the development of endometriosis and even promoting carcinogenesis. However, studies to this day have focused on small populations. In addition, there is no clearly defined healthy uterine composition yet. At most, only a few taxa have been identified as pathogenic. As sampling and analysis methods become increasingly precise, we can expect the endometrial microbiota to be incorporated into future diagnostic tools and treatments for women’s health.

The uterus is the core place for breeding new life. The balance and imbalance of uterine microecology can directly affect or even dominate the female reproductive health. Emerging data demonstrate that endometrial microbiota, endometrium and immunity play an irreplaceable role in regulating uterine microecology, forming a dynamic iron triangle relationship. Up to nowadays, it remains unclear how the three factors affect and interact with each other, which is also a frontier topic in the emerging field of reproductive tract microecology. From this new perspective, we aim to clarify the relationship and mechanism of the interaction of these three factors, especially their pairwise interactions. Finally, the limitations and future perspectives of the current studies are summarized. In general, these three factors have a dynamic relationship of mutual dependence, promotion and restriction under the physiological or pathological conditions of uterus, among which the regulatory mechanism of microbiota and immunity plays a role of bridge. These findings can provide new insights and measures for the regulation of uterine microecology, the prevention and treatment of endometrial diseases, and the further multi-disciplinary integration between microbiology, immunology and reproductive medicine. [ABSTRACT FROM AUTHOR]

Progress in medicine depends on new technologies and countercurrent concepts that translate to practice to solve long-standing problems. The application of transcriptomics to endometrial biology enables an objective identification of the personalized period during which the maternal endometrium is receptive to an embryo, known as the window of implantation. Likewise, 16S rRNA gene sequencing of microorganisms allows the identification of commensal microbes colonizing the endometrium, linking their composition with reproductive outcomes in patients undergoing IVF. Together, this knowledge underscores the clinical implication of endometrial factor testing for personalizing reproductive care. With such exciting developments and more to come, the era of generalized medicine for the endometrial factor will come to an end and will be replaced by individualized care to improve outcomes. [ABSTRACT FROM AUTHOR]

An abnormal endometrial microbiota has been suggested to impair the process of embryo implantation, thus leading to repeated implantation failure (RIF) in women undergoing in vitro fertilization (IVF). However, the molecular mechanisms linking uterine microbiota and IVF out-comes are still an open question. The aim of this cohort study was to outline the relationship between endometrial microbiota, inflammation and IVF outcomes. To this purpose, endometrial microbiota and selected components of the "cytokine network" were analyzed in women presenting RIF and divided between eubiosis and dysbiosis groups, according to the percentage of endometrial lactobacilli (≥90% or <90%, respectively). The Dysbiosis group presented significantly higher tissue concentrations of the inflammatory markers (IL-6, IL-1β, HIF-1α and COX-2) and significantly lower levels of the anti-inflammatory/well-being factors, IL-10 and IGF-1, with respect to women with eubiosis. Moreover, the Lactobacillus percentage was negatively related to the concentrations of the inflammatory molecules and positively related to IL-10/IGF-1. Interestingly, the number of IVF attempts was directly related to the levels of the inflammatory factors COX-2, IL-1β and HIF-1α in the eubiosis group. Overall, endometrial dysbiosis was demonstrated to be associated with inflammation-related endometrial changes affecting the process of embryo implantation, underlining the importance of assessing uterine microbiota in patients undergoing IVF. [ABSTRACT FROM AUTHOR]

Introduction: The endometrial microbiota has been linked to several gynecological disorders, including infertility. It has been shown that the microbial profile of endometrium could have a role in fertilization and pregnancy outcomes. In this study we aim to assess the microbial community of endometrial tissue (ET) and endometrial fluid (EF) samples in women receiving in vitro fertilization (IVF) treatment. We also search for possible associations between chronic endometritis (CE) and endometrial microbiota. Material and methods: This was a cohort study involving 25 women aged between 28 and 42 years with both primary and secondary infertility and with at least one IVF failure. The ET and EF sample collection was carried out between September 2016 and November 2018. Each of the participants provided two types of samples—tissue and fluid samples (50 samples in total). A 16S rRNA sequencing was performed on both of the sample types for microbial profile evaluation. CE was diagnosed based on a CD138 immunohistochemistry where CE diagnosis was confirmed in the presence of one or more plasma cells. Microbial profiles of women with and without CE were compared in both sample types separately. Results: We report no differences in the microbial composition and alpha diversity (pObserved = 0.07, pShannon = 0.65, pInverse Simpson = 0.59) between the EF and ET samples of IVF patients. We show that the abundance of the genus Lactobacillus influences the variation in microbial beta diversity between and fluid samples (r2 = 0.34; false discovery rate [FDR] <9.9 × 10−5). We report that 32% (8/25) of the participants had differences in Lactobacillus dominance in the paired samples and these samples also present a different microbial diversity (pShannon = 0.06, FDRweighted UniFrac = 0.01). These results suggest that the microbial differences between ET and fluid samples are driven by the abundance of genus Lactobacillus. The microbiome of CE and without CE (ie non‐CE) women in our sample set of IVF patients was similar. Conclusions: Our findings show that genus Lactobacillus dominance is an important factor influencing the microbial composition of ET and fluid samples. [ABSTRACT FROM AUTHOR]

The article highlights modern ideas about the role of the endometrium in the genesis of reproductive failures. A crucial place of chronic endometritis in the structure of the endometrial infertility factor in endometriosis is noted. Given the frequent association of chronic endometritis and endometriosis, common features of these diseases have been identified. The characteristic of endometrial microbiota in infertility, chronic endometritis and endometriosis is given. An extremely important area of scientific research is precisely the interaction between the microbiota of the endometrium and its immunity, and not just the confirmation of the presence of microorganisms in the endometrium. The modern aspects of the etiology and pathogenesis of chronic endometritis and endometriosis are described. The main pathogenetic determinants of chronic endometritis are the failure of adaptation mechanisms to the constant effects of microbes and, as a consequence, the decrease and inferiority of the immune response and the development of autoimmune reactions. The modern paradigm for the development and progression of endometriosis involves the presence of bacterial contamination of the endometrium and the abdominal cavity, which in turn becomes a trigger for genetically-epigenetic modifications of cells, launching different cascades that underlie reproductive function disorders. The pathogenetically significant relationship between chronic endometritis and endometriosis is highlighted. It was revealed that chronic endometritis can be both a cause and a consequence of endometriosis. Disorders of the endometrial receptivity in chronic endometritis associated with endometriosis, their importance in the implementation of endometrial infertility are described. The important role of the microbiome in the formation of reproductive disorders is noted.

Objective: To investigate the Interaction between chronic endometritis (CE) caused endometrial microbiota disorder and endometrial immune environment change in recurrent implantation failure (RIF). Method: Transcriptome sequencing analysis of the endometrial of 112 patients was preform by using High-Throughput Sequencing. The endometrial microbiota of 43 patients was analyzed by using 16s rRNA sequencing technology. Result: In host endometrium, CD4 T cell and macrophage exhibited significant differences abundance between CE and non-CE patients. The enrichment analysis indicated differentially expressed genes mainly enriched in immune-related functional terms. Phyllobacterium and Sphingomonas were significantly high infiltration in CE patients, and active in pathways related to carbohydrate metabolism and/or fat metabolism. The increased synthesis of lipopolysaccharide, an important immunomodulator, was the result of microbial disorders in the endometrium. Conclusion: The composition of endometrial microorganisms in CE and non-CE patients were significantly different. Phyllobacterium and Sphingomonas mainly regulated immune cells by interfering with the process of carbohydrate metabolism and/or fat metabolism in the endometrium. CE endometrial microorganisms might regulate Th17 response and the ratio of Th1 to Th17 through lipopolysaccharide (LPS). [ABSTRACT FROM AUTHOR]

Incidence rates for endometrial cancer (EC) are rising, particularly in postmenopausal and obese women. Low levels of gonadal circulating estrogen observed in post-menopausal women can adversely impact a diverse range of physiological factors, with clinical implications for brain cognition, gut health, the female reproductive tract and other aspects of women's health. Endometrial microbiota interplay in the uterus. Several studies demonstrated that asymptomatic women harbour commensal microbial communities in their uterus, and that the uterine microbiome seems to be altered in women who suffer gynaecological pathologies such EC. We need larger studies to further confirm an association of certain microorganisms in women with EC compared to our healthy women in our office. However, there are large gaps in knowledge regarding the association between the gut microbiome and gynecologic cancers, and research characterizing the reproductive tract microbiome is insufficient. This review aims to shed light on the role of the gut microbiota in estrogen-modulated disease, the bi-directional relationship between the metabolic profile (including estrogen levels) and gut microbiota in estrogen-driven disease will also be discussed. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the Interaction between chronic endometritis (CE) caused endometrial microbiota disorder and endometrial immune environment change in recurrent implantation failure (RIF).MethodTranscriptome sequencing analysis of the endometrial of 112 patients was preform by using High-Throughput Sequencing. The endometrial microbiota of 43 patients was analyzed by using 16s rRNA sequencing technology.ResultIn host endometrium, CD4 T cell and macrophage exhibited significant differences abundance between CE and non-CE patients. The enrichment analysis indicated differentially expressed genes mainly enriched in immune-related functional terms. Phyllobacterium and Sphingomonas were significantly high infiltration in CE patients, and active in pathways related to carbohydrate metabolism and/or fat metabolism. The increased synthesis of lipopolysaccharide, an important immunomodulator, was the result of microbial disorders in the endometrium.ConclusionThe composition of endometrial microorganisms in CE and non-CE patients were significantly different. Phyllobacterium and Sphingomonas mainly regulated immune cells by interfering with the process of carbohydrate metabolism and/or fat metabolism in the endometrium. CE endometrial microorganisms might regulate Th17 response and the ratio of Th1 to Th17 through lipopolysaccharide (LPS).

Introduction: The potential role of the endometrial microbiota in the pathogenesis of endometrial polyps (EPs) warrants further investigation, given the current landscape of limited and inconclusive research findings. We aimed to explore the microecological characteristics of the uterine cavity in patients with EPs and investigate the potential of endometrial microbiota species as novel biomarkers for identifying EPs., Methods: Endometrial samples were collected from 225 patients who underwent hysteroscopies, of whom 167 had EPs, whereas 58 had non- hyperproliferative endometrium status. The endometrial microbiota was assessed using 16S rRNA gene sequencing. We characterized the endometrial microbiota and identified microbial biomarkers for predicting EPs., Results: The endometrial microbial diversity and composition were significantly different between the EP and control groups. Predictive functional analyses of the endometrial microbiota demonstrated significant alterations in pathways involved in sphingolipid metabolism, steroid hormone biosynthesis, and apoptosis between the two groups. Moreover, a classification model based on endometrial microbial ASV-based biomarkers along with the presence of abnormal uterine bleeding symptoms achieved powerful classification potential in identifying EPs in both the discovery and validation cohorts., Conclusion: Our study indicates a potential association between altered endometrial microbiota and EPs. Endometrial microbiota-based biomarkers may prove valuable for the diagnosis of EPs., Clinical Trial Registration: Chinese Clinical Trial Registry (ChiCTR2100052746)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Liao, Xu and Wang.)

Abstract Purpose The present study aimed to analyze the endometrial and vaginal microbiome among a Japanese infertile population by sequencing and the impact of the endometrial and vaginal environment on implantation. Methods In total, 102 infertile (79 in vitro fertilization [IVF] and 23 non‐IVF) patients and seven healthy volunteers were recruited from August to December, 2017. Endometrial fluid and vaginal discharge samples for sequencing were collected by using an intrauterine insemination catheter. The bacterial status of the endometrium and vagina were analyzed. Results The Lactobacillus‐dominated microbiota (>90% Lactobacillus spp.) in the endometrium vs vagina was 38% (30/79) vs 44.3% (44/79) in the IVF patients, 73.9% (17/23) vs 73.9% (17/23) in the non‐IVF patients, and 85.7% (6/7) vs 85.7% (6/7) in the healthy volunteers. The percentage of endometrial Lactobacillus in the healthy volunteers was highly stable within the same menstrual cycle and even in the following cycle. The major taxonomies were Gardnerella, Streptococcus, Atopobium, Bifidobacterium, Sneathia, Prevotella, and Staphylococcus. Fifteen patients achieved pregnancy by a single vitrified‐warmed blastocyst transfer during this study; the median percentage of Lactobacillus in the pregnant women was 96.45 ± 33.61%. Conclusion A considerable percentage of non‐Lactobacillus‐dominated (NLD) microbiota was found in the endometrium of Japanese infertile women. Increasing the endometrial level of the Lactobacilli to >90% might favor the implantation outcome of NLD infertile patients.

Yin and yang is a concept of dualism in Chinese philosophy, describing how opposite or contrary forces may be complementary, interconnected and interdependent, and how they may give rise to each other as they interrelate with one another. In line with this, modern clinical research and business can definitely be described as yin and yang. With the increasing need for funding, researchers at a very early stage during the development of a new concept may be forced or tempted to enter the business world. Furthermore, researchers are encouraged and supported by their own universities to collaborate with possible future business partners, not only to acquire funding, but also to explore potential patenting. This collaboration between the business world and research can definitely be very fruitful and provide benefit for both parties, patients and society as a whole, but it may also introduce the risk of premature materialization. [ABSTRACT FROM AUTHOR]

Investigation of the microbial community in the female reproductive tract with the use of sequencing techniques has revealed that endometrial samples obtained through a transvaginal catheter are dominated by Lactobacillus species. Dysbiotic changes in the endometrial microbiota may be associated with implantation failure or early spontaneous abortion in patients who undergo assisted reproductive technology treatment. Whether or not there is an endometrial microbiota in early pregnancy is unknown. Herein we describe, the human endometrial microbiota in a patient who subsequently had an 8th week spontaneous clinical miscarriage with euploid embryos in the next cycle and, for the first time, during a successful pregnancy in which the endometrial fluid was sampled at 4 weeks of gestation. The microbial profile found on the endometrial sample before the spontaneous abortion had higher bacterial diversity and lower Lactobacillus abundance than the endometrial fluid from the healthy pregnancy. Functional metagenomics detected different Lactobacillus species between the 2 samples. Lactobacillus crispatus was present in the endometrium before the spontaneous abortion, as were other bacteria involved in dysbiosis, which had an unstable functional pattern characterized by transposases and insertion elements. Lactobacillus iners was the most prevalent microbe found in the endometrium during early pregnancy; its presence was associated with defense mechanisms and basal functions. These novel observations prompt future investigations to understand the potential implications of microbiology on healthy and pathologic human pregnancy. [ABSTRACT FROM AUTHOR]

The dysbiosis of the intestinal microbiome is associated with various diseases. It is important to understand the factors that influence the intestinal microbiome and the microbiome regulation strategies to increase therapeutic responses. Endometriosis affects about 10% of women of childbearing age. Among those affected by endometriosis, up to 50% of them suffer from chronic pelvic pain and / or infertility. Endometriosis is characterized by inflammation and oestrogen dependence. Endometriosis is a condition that affects fertility, creates a state of "congestion" with an excessive growth of the endometrial tissue in many other areas of the body. The microbiota plays a role in the occurrence of endometriosis by affecting the epigenetic, immunological and / or biochemical functions of the host. Intestinal bacteria are involved in the oestrogen metabolism. The oestrogen-microbiome link (or the stroboloma) helps explain where the excess oestrogen comes from. Endometriosis appears to be associated with the increased presence of Proteobacteria, Enterobacteriaceae, Streptococcus spp. and Escherichia coli in various areas occupied by the microbiome. Further studies are needed to analyse the association between endometriosis and microbiota. Endometriosis is influenced by diet. [ABSTRACT FROM AUTHOR]

There is a suggested pathophysiology associated with endometrial microbiota in cases where repeated implantation failure of high-quality embryos is observed. However, there is a suspected association between endometrial microbiota and the pathogenesis of implantation failure. However, there is still a lack of agreement on the fundamental composition of the physiological microbiome within the uterine cavity. This is primarily due to various limitations in the studies conducted, including small sample sizes and variations in experimental designs. As a result, the impact of bacterial communities in the endometrium on human reproduction is still a subject of debate. In this discourse, we undertake a comprehensive examination of the existing body of research pertaining to the uterine microbiota and its intricate interplay with the process of embryo implantation. • There is a suspected association between endometrial microbiota and the pathogenesis of implantation failure. • Impact of bacterial communities in the endometrium on human reproduction is still a subject of debate. • This knowledge is crucial for comprehending the factors that influence fertility and the maintenance of a successful pregnancy. [ABSTRACT FROM AUTHOR]

Pregnancy is characterized by maternal adaptations that are necessary to create a welcoming and hospitable environment for the fetus. Studies have highlighted how the microbiota modulates several networks in humans through complex molecular interactions and how dysbiosis (defined as quantitative and qualitative alterations of the microbiota communities) is related to human pathologies including gynecological diseases. This review analyzed how maternal uterine, vaginal, and gut microbiomes could impact on fetus health during the gestational period. We evaluated the role of a dysbiotic microbiota in preterm birth, chorioamnionitis, gestational diabetes mellitus and pre-eclampsia. For many years it has been hypothesized that newborns were sterile organisms but in the past few years this paradigm has been questioned through the demonstration of the presence of microbes in the placenta and meconium. In the future, we should go deeper into the concept of in utero colonization to better understand the role of microbiota through the phases of pregnancy. Numerous studies in the literature have already showed interesting results regarding the role of microbiota in pregnancy. This evidence gives us the hope that microbiota modulation could be a novel strategy to reduce the morbidity and mortality related to pregnancy complications in the future.

Technical advances in massive parallel sequencing have allowed the characterization of the whole reproductive tract microbiome in all the compartments beyond the vagina. The microbiota in the uterine cavity seem to be a continuum from the microbiota in the vagina, but several works have reported significant differences between vaginal and endometrial microbiota, highlighting the relevance of assessing the upper genital tract microbiota to better understand the potential roles of bacteria in the physiological and pathological processes taking place in the uterine cavity, including embryo implantation, pregnancy maintenance, and other gynecological diseases. However, the study of the endometrial microbiota, as with other low-biomass microbiota, presents important hurdles because, due to the small amount of starting material, they are easily contaminated by exogenous bacterial DNA. For this reason, careful and appropriate investigation of the endometrial microbiota is of outstanding importance to detect uterine dysbiosis that may impact the reproductive function. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The present study aimed to analyze the endometrial and vaginal microbiome among a Japanese infertile population by sequencing and the impact of the endometrial and vaginal environment on implantation. Methods: In total, 102 infertile (79 in vitro fertilization [IVF] and 23 non‐IVF) patients and seven healthy volunteers were recruited from August to December, 2017. Endometrial fluid and vaginal discharge samples for sequencing were collected by using an intrauterine insemination catheter. The bacterial status of the endometrium and vagina were analyzed. Results: The Lactobacillus‐dominated microbiota (>90% Lactobacillus spp.) in the endometrium vs vagina was 38% (30/79) vs 44.3% (44/79) in the IVF patients, 73.9% (17/23) vs 73.9% (17/23) in the non‐IVF patients, and 85.7% (6/7) vs 85.7% (6/7) in the healthy volunteers. The percentage of endometrial Lactobacillus in the healthy volunteers was highly stable within the same menstrual cycle and even in the following cycle. The major taxonomies were Gardnerella, Streptococcus, Atopobium, Bifidobacterium, Sneathia, Prevotella, and Staphylococcus. Fifteen patients achieved pregnancy by a single vitrified‐warmed blastocyst transfer during this study; the median percentage of Lactobacillus in the pregnant women was 96.45 ± 33.61%. Conclusion: A considerable percentage of non‐Lactobacillus‐dominated (NLD) microbiota was found in the endometrium of Japanese infertile women. Increasing the endometrial level of the Lactobacilli to >90% might favor the implantation outcome of NLD infertile patients. [ABSTRACT FROM AUTHOR]

Investigation of the microbial community in the female reproductive tract has revealed that the replacement of a community dominated by Lactobacillus with pathogenic bacteria may be associated with implantation failure or early spontaneous abortion in patients undergoing assisted reproductive technology (ART) treatment. Herein we describe taxonomically and functionally the endometrial microbiome of an infertile patient with repeated reproductive failures (involving an ectopic pregnancy and two clinical miscarriages). The microbiological follow-up is presented over 18-month in which the microbiota was evaluated in six endometrial fluid samples. The microbial profile of 16S rRNA gene sequencing showed a persistent infection with Gardnerella and other bacterial taxa such as Atopobium and Bifidobacterium. In addition, taxonomic and functional analysis by whole metagenome sequencing in the endometrial fluid sample collected before one clinical miscarriage suggested the presence of multiple Gardnerella vaginalis clades with a greater abundance of clade 4, usually associated with metronidazole resistance. These results revealed a persistent G. vaginalis endometrial colonization presenting genetic features consistent with antimicrobial resistance, biofilm formation, and other virulence factors, which could be related to the reproductive failure observed.

Detection of bacteria with molecular techniques has enabled the study of low biomass microbiomes in tissues and organs previously considered sterile, such as the endometrium. Subsequently, an abnormal endometrial microbiota has been associated with implantation failure, pregnancy loss, and other gynecological and obstetrical conditions. Further investigation of the reproductive tract microbiome will allow for a better understanding of bacterial communities' role in both physiology and pathophysiology, which in turn impacts the ability to achieve pregnancy and maintain a healthy pregnancy. Here we review the current literature that surrounds the endometrial microbiome and highlight the importance of assessing it as a future tool for improving reproductive outcomes in infertile patients. [ABSTRACT FROM AUTHOR]

Embryo implantation is a key step in human reproduction, and the endometrium plays a key role in this process. Changes in the receptive state of the endometrium are one of the main reasons for embryo implantation failure. However, the mechanism underlying the altered endometrial receptivity remains unclear. In this study, we recruited 140 women undergoing assisted reproductive technology and divided them into a shifting group and a normal group based on their embryo implantation window results. Endometrial transcriptome data suggested that changes in the remodeling process of decidual spiral arterioles and changes in the immune environment might be important mechanisms of implantation window shift. The functional enrichment analysis results also suggested that the changes in microbiota had an important role in the changes in endometrial status. The endometrial functionally active microbial profiles were obtained based on previously validated metatranscriptomic analysis pipelines. Combining host gene expression information, immune cell abundance information and functionally active microbial abundance and activity information, we found that Treponema succinifaciens, Fusobacterium sp. oral taxon 203 and other potentially harmful species may over-activate Eicosapentaenoic acid (EPA) biosynthesis Thus, the balance of the immune environment of the endometrium is disrupted, resulting in the shift of the implantation window and the failure of embryo implantation. • Endometrial microbes were closely associated with decreased endometrial receptivity. • The disruption of endometrial immune balance is an important reason for the decline of endometrial receptivity. • The potentially harmful species might damage the immune environment balance of the endometrium by over activating the biosynthesis of EPA, leading to the deviation of the implantation window. [ABSTRACT FROM AUTHOR]

To investigate the association between the pregnancy outcomes of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) patients with repeated implantation failure (RIF) and their endometrial microbiota profiles. One hundred and forty-one RIF patients were recruited in this retrospective study. Endometrial tissues were sampled using a disposable sterile endometrium sampler. Comprehensive next-generation sequencing techniques were used to detect the endometrial bacteria status, and the pregnancy outcomes were analyzed. Endometrial pathogenic bacteria were detected in 125 patients (88.70%, the pathogenic group) while no relevant pathogen was found in the remaining 16 (11.30%, the no-pathogen group). All the 125 patients received the treatment of oral antibiotics for 14 days. Clinical pregnancy rates and ongoing pregnancy rates were higher in the pathogenic group than in the no-pathogen group without statistical significance (50.40% vs. 37.50%, P ＞0.05; 42.40% vs. 25%, P ＞0.05). In the endometrium of most RIF patients existed pathogenic bacteria, among which Streptococcus , Staphylococcus , Neisseria , and Klebsiella were most frequently observed, and the sensitive antibiotic therapy might improve clinical outcomes of the RIF patients in subsequent embryo transfer cycles. • Pathogenic bacteria were detected in the endometrium of most patients suffering from repeated implantation failure. • Among the pathogens , Streptococcus , Staphylococcus , Neisseria , and Klebsiella were most frequently observed. • The sensitive antibiotic therapy improved clinical outcomes in the subsequent embryo transfer cycle. [ABSTRACT FROM AUTHOR]

Background: Bacterial cells in the human body account for 1-3% of total body weight and are at least equal in number to human cells. Recent research has focused on understanding how the different bacterial communities in the body (eg, gut, respiratory, skin, and vaginal microbiomes) predispose to health and disease. The microbiota of the reproductive tract has been inferred from the vaginal bacterial communities, and the uterus has been classically considered a sterile cavity. However, while the vaginal microbiota has been investigated in depth, there is a paucity of consistent data regarding the existence of an endometrial microbiota and its possible impact in reproductive function.Objective: This study sought to test the existence of an endometrial microbiota that differs from that in the vagina, assess its hormonal regulation, and analyze the impact of the endometrial microbial community on reproductive outcome in infertile patients undergoing in vitro fertilization.Study Design: To identify the existence of an endometrial microbiota, paired samples of endometrial fluid and vaginal aspirates were obtained simultaneously from 13 fertile women in prereceptive and receptive phases within the same menstrual cycle (total samples analyzed n = 52). To investigate the hormonal regulation of the endometrial microbiota during the acquisition of endometrial receptivity, endometrial fluid was collected at prereceptive and receptive phases within the same cycle from 22 fertile women (n = 44). Finally, the reproductive impact of an altered endometrial microbiota in endometrial fluid was assessed by implantation, ongoing pregnancy, and live birth rates in 35 infertile patients undergoing in vitro fertilization (total samples n = 41) with a receptive endometrium diagnosed using the endometrial receptivity array. Genomic DNA was obtained either from endometrial fluid or vaginal aspirate and sequenced by 454 pyrosequencing of the V3-V5 region of the 16S ribosomal RNA (rRNA) gene; the resulting sequences were taxonomically assigned using QIIME. Data analysis was performed using R packages. The χ2 test, Student t test, and analysis of variance were used for statistical analyses.Results: When bacterial communities from paired endometrial fluid and vaginal aspirate samples within the same subjects were interrogated, different bacterial communities were detected between the uterine cavity and the vagina of some subjects. Based on its composition, the microbiota in the endometrial fluid, comprising up to 191 operational taxonomic units, was defined as a Lactobacillus-dominated microbiota (>90% Lactobacillus spp.) or a non-Lactobacillus-dominated microbiota (<90% Lactobacillus spp. with >10% of other bacteria). Although the endometrial microbiota was not hormonally regulated during the acquisition of endometrial receptivity, the presence of a non-Lactobacillus-dominated microbiota in a receptive endometrium was associated with significant decreases in implantation [60.7% vs 23.1% (P = .02)], pregnancy [70.6% vs 33.3% (P = .03)], ongoing pregnancy [58.8% vs 13.3% (P = .02)], and live birth [58.8% vs 6.7% (P = .002)] rates.Conclusion: Our results demonstrate the existence of an endometrial microbiota that is highly stable during the acquisition of endometrial receptivity. However, pathological modification of its profile is associated with poor reproductive outcomes for in vitro fertilization patients. This finding adds a novel microbiological dimension to the reproductive process. [ABSTRACT FROM AUTHOR]

Introduction: The endometrial microbiota plays an essential role in the health of the female reproductive system. However, the interactions between the microbes in the endometrium and their effects on adenomyosis remain obscure., Materials and Methods: We profile endometrial samples from 38 women with ( n =21) or without ( n =17) adenomyosis to characterize the composition of the microbial community and its potential function in adenomyosis using 5R 16S rRNA gene sequencing., Results: The microbiota profiles of patients with adenomyosis were different from the control group without adenomyosis. Furthermore, analysis identified Lactobacillus zeae, Burkholderia cepacia, Weissella confusa, Prevotella copri, and Citrobacter freundii as potential biomarkers for adenomyosis. In addition, Citrobacter freundii, Prevotella copri , and Burkholderia cepacia had the most significant diagnostic value for adenomyosis. PICRUSt results identified 30 differentially regulated pathways between the two groups of patients. In particular, we found that protein export, glycolysis/gluconeogenesis, alanine, aspartate, and glutamate metabolism were upregulated in adenomyosis. Our results clarify the relationship between the endometrial microbiota and adenomyosis., Discussion: The endometrial microbiota of adenomyosis exhibits a unique structure and Citrobacter freundii, Prevotella copri , and Burkholderia cepacia were identified as potential pathogenic microorganisms associated with adenomyosis. Our findings suggest that changes in the endometrial microbiota of patients with adenomyosis are of potential value for determining the occurrence, progression, early of diagnosis, and treatment oadenomyosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lin, Duan, Wang, Guo, Wang, Chang, Chen, Shen, Shou and Zhou.)