Endometrial preparation protocols did not impact pregnancy outcomes of patients with cured chronic endometritis.

RESEARCH QUESTION: Do endometrial preparation protocols have an effect on pregnancy outcomes in patients with cured chronic endometritis? DESIGN: A retrospective study was conducted on 3721 infertile patients from December 2018 to August 2020. Endometrial tissues obtained during the proliferative phase were immunostained for CD138. The presence of CD138-positive cells within the stromal cells indicated chronic endometritis. All patients diagnosed with chronic endometritis received oral antibiotics. Patients underwent endometrial preparation and frozen embryo transfer once chronic endometritis was cured. This study compared various endometrial preparation protocols to assess their effects on pregnancy outcomes. Additionally, it aimed to investigate differences in pregnancy outcomes between patients without chronic endometritis and patients with cured chronic endometritis while following the same endometrial preparation protocol. RESULTS: Almost no differences in pregnancy outcomes were observed between natural cycle, hormone replacement therapy (HRT) and gonadotrophin-releasing hormone agonist-HRT (GnRH agonist-HRT) protocols in patients without chronic endometritis and patients with cured chronic endometritis. The only notable difference was that, among women without chronic endometritis, the early miscarriage rate was higher for the GnRH agonist-HRT protocol (25.8%) compared with the natural cycle (17.4%) and HRT (17.7%) protocols (P = 0.025). However, this difference was not significant after adjusting for confounders (adjusted OR 1.383, 95% CI 0.931-2.055). The live birth rate, clinical pregnancy rate, early miscarriage rate, ectopic pregnancy rate and ongoing pregnancy rate did not differ significantly (P > 0.05) between patients without chronic endometritis and patients with cured chronic endometritis who underwent natural cycle, HRT and GnRH agonist-HRT protocols. CONCLUSION: Endometrial preparation protocols had no impact on pregnancy outcomes in patients with cured chronic endometritis.

Antibiotic cured chronic endometritis remains a risk factor for early pregnancy loss in the subsequent frozen euploid embryo transfer.

RESEARCH QUESTION: Do patients with antibiotic-cured chronic endometritis (CCE) have a comparable pregnancy outcome to those with non-chronic endometritis (NCE) in the subsequent frozen embryo transfer (FET) cycle? DESIGN: A retrospective cohort analysis included 833 patients in their first FET cycles with single euploid embryo transfer. Chronic endometritis (≥5 CD138+ plasma cells per high-power field [CD138+/HPF]) was treated with standard antibiotic therapy. Patients were classified into two groups: the NCE group (n = 611, <5 CD138+/HPF) and the CCE group (n = 222, ≥5 CD138+/HPF and cured after antibiotic treatment). Pregnancy outcomes were compared. NCE group was divided into subgroup 1 (CD138+/HPF = 0) and subgroup 2 (CD138+/HPF = 1-4) for further analysis. RESULTS: The rate of early pregnancy loss (EPL), incorporating all losses before 10 weeks' gestation, was significantly higher in the CCE group than the NCE group (21.2% versus 14.2%, P = 0.016), and the difference was statistically significant (adjusted odds ratio [AOR] 1.68, 95% confidence interval [CI] 1.11-2.55). No significant differences were observed between the two groups with regard to other pregnancy outcomes. In the subgroup analysis, the EPL rate and biochemical pregnancy rate were significantly higher in subgroup 2 than subgroup 1 (17.2% versus 9.4%, AOR 2.21, 95% CI 1.30-3.74; 12.2% versus 6.9%, AOR 2.01, 95% CI 1.09-3.68). CONCLUSIONS: Chronic endometritis cured by standard antibiotic therapy remains a risk factor for EPL in FET cycles, although no differences were found in live birth rates between patients with CCE or with NCE.

Chronic endometritis and the endometrial microbiota: implications for reproductive success in patients with recurrent implantation failure.

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.

Prevalence and risk factors for chronic endometritis in patients with adenomyosis and infertility: a retrospective cohort study.

BACKGROUND: To explore the incidence of chronic endometritis (CE) in patients with infertility and different forms of adenomyosis and analyze potential high-risk factors for infection. METHODS: This retrospective cohort study included 154 patients with infertility in the Liuzhou Maternity and Child Healthcare Hospital. Among them, 77 patients with adenomyosis were divided into four subgroups based on magnetic resonance imaging (MRI): internal, exterior, intramural, and full-thickness. Meanwhile, 77 patients did not have adenomyosis. Hysteroscopy and endometrial biopsy were performed in the proliferative phase. The main outcome measures were the morphology of the endometrium, syndecan-1 (CD138) immunohistochemical staining, clinical characteristics, and prevalence of CE in the adenomyosis subgroups. RESULTS: In comparison to the non-adenomyosis group, the adenomyosis group had significantly higher body mass index (BMI) and CA125 levels. The menstrual cycle in the adenomyosis group was significantly shorter, and menarche was significantly earlier. In comparison to the non-adenomyosis group, the adenomyosis group had a significantly higher diagnostic rate of CE (75.3% vs. 46.8% according to hysteroscopy and 74.0% vs. 33.8% according to histopathology, both with p < .050). The incidence of CE was significantly lower in patients with internal adenomyosis when compared with the other three subgroups. Increased BMI contributed to a higher risk of CE. CONCLUSIONS: The prevalence of CE was significantly higher in patients with adenomyosis and infertility. The differences in the incidence of CE are closely associated with the classification of adenomyosis. When patients with infertility are diagnosed with adenomyosis, it is recommended to identify the subtype and screen for endometritis.

Antibiotics improve reproductive outcomes after frozen-thaw embryo transfer for chronic endometritis treatment, especially in those with repeated implantation failure.

PURPOSE: To investigate the impact of antibiotic treatment for chronic endometritis (CE) on the pregnancy outcome of frozen-thawed embryo transfer (FET) cycles and the relevant clinical risk factors associated with CE. METHODS: A retrospective cohort analysis was conducted on 1352 patients who underwent hysteroscopy and diagnostic curettage at Nanjing Maternal and Child Health Hospital from July 2020 to December 2021. All patients underwent CD138 immunohistochemical (IHC) testing to diagnose CE, and a subset of them underwent FET after hysteroscopy. Patient histories were collected, and reproductive prognosis was followed up. RESULTS: Out of 1088 patients, 443 (40.7%) were diagnosed with CE. Univariate and multivariate binary logistic regression analyses revealed that parity ≥ 2, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, hydrosalpinx, endometrial polyps, a history of ≥ 2 uterine operations, and RIF were significantly associated with an elevated risk of CE (P < 0.05). Analysis of the effect of CE on pregnancy outcomes in FET cycles after antibiotic treatment indicated that treated CE patients exhibited a significantly lower miscarriage rate (8.7%) and early miscarriage rate (2.9%) than untreated non-CE patients (20.2%, 16.8%). Moreover, the singleton live birth rate (45.5%) was significantly higher in treated CE patients than in untreated non-CE patients (32.7%). Survival analysis revealed a statistically significant difference in the first clinical pregnancy time between treated CE and untreated non-CE patients after hysteroscopy (P = 0.0019). Stratified analysis based on the presence of recurrent implantation failure (RIF) demonstrated that in the RIF group, treated CE patients were more likely to achieve clinical pregnancy than untreated non-CE patients (P = 0.0021). Among hysteroscopy-positive patients, no significant difference was noted in pregnancy outcomes between the treatment and control groups (P > 0.05). CONCLUSION: Infertile patients with a history of parity ≥ 2, hydrosalpinx, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, endometrial polyps, a history of ≥ 2 uterine operations, and RIF are at an increased risk of CE; these patients should be recommended to undergo hysteroscopy combined with CD138 examination before embryo transfer. Antibiotic treatment can improve the reproductive outcomes of FET in patients with CE, especially those with RIF.

Chronic endometritis multiplies the recurrence risk of endometrial polyps after transcervical resection of endometrial polyps: a prospective study.

BACKGROUND: To investigate the impact of chronic endometritis (CE) on the recurrence of endometrial polyps (EPs) in premenopausal women after transcervical resection of endometrial polyps (TCRP). METHODS: This prospective study enrolled 507 women who underwent TCRP between January 1, 2022 and December 31, 2022. The patients were divided into a CE group (n = 133) and non-CE group (n = 374) based on the expression of CD138 in the endometrium. The EP recurrence rate at 1 year after TCRP was compared between the CE and non-CE groups and between groups with mild CE and severe CE. The impact of CD138 expression by resected EPs on EP recurrence also was investigated. RESULTS: The EP recurrence rate at 1 year post-TCRP was higher in the CE group than in the non-CE group (25.6% vs. 10.4%) and also higher in the severe CE group than in the mild CE group (34.5% vs. 18.7%). Additionally, the EP recurrence rate was higher among patients with CD138-expressing EPs than among those with EPs lacking CD138 expression (30.5% vs. 6.5%). The odds ratio (OR) for EP recurrence in the CE cohort compared with the non-CE cohort was 3.10 (95% confidence interval [CI] 1.84-5.23) after adjustment for EP number and precautions against EP recurrence. The ORs for EP recurrence in patients with mild CE and severe CE were 2.21 (95%CI 1.11-4.40) and 4.32 (95%CI 2.26-8.26), respectively. Similarly, the OR for EP recurrence in cases with CD138-expressing EPs relative to cases with EPs lacking CD138 expression was 6.22 (95%CI 3.59-10.80) after adjustment for EP number and precautions against EP recurrence. CONCLUSIONS: CE multiplied the recurrence rate of EPs in premenopausal women after TCRP, and this effect positively correlated with CE severity. CD138 expression by EPs also was associated with a higher risk for EP recurrence.

Variation in diagnostic methods, criteria, and treatment for chronic endometritis: A nationwide survey in Japan.

AIM: To investigate variation in the diagnosis and treatment of chronic endometritis (CE) at the national level in Japan. METHODS: We performed a nationwide survey targeting all assisted reproductive technology (ART) facilities across Japan between 2021 and 2022. Diagnostic methods, criteria, and first- and second-line treatment protocols for CE were collected via a questionnaire. RESULTS: Among 616 ART facilities, 437 responded to the survey (response rate: 70.9%) of which 339 (77.6%) implemented diagnosis and treatment of CE. In the diagnosis of CE, 214 (63.1%) facilities used CD138 immunohistochemical staining of endometrial tissue, while hysteroscopy was the most frequently used as an adjunct diagnostic method (241 facilities, 71.1%). The most frequent cutoff value of CD138-positive cells for diagnosing CE was 3-5 cells/20 high-power fields (50%), but 7.9% (17 facilities) and 5.1% (11 facilities) used cutoff values of 1 and 2 cells, respectively. The most common first- and second-line treatment methods were doxycycline (210 facilities, 61.9%) and ciprofloxacin + metronidazole (164 facilities, 48.0%), respectively. CONCLUSIONS: There is considerable variation in the number of CD138-positive cells used for diagnosing CE. Establishing unified diagnostic criteria and therapeutic methods for CE is essential to provide standardized medicine for CE at the national level.

Evaluation of Lipopolysaccharide and Interleukin-6 as Useful Screening Tool for Chronic Endometritis.

Universal diagnostic criteria for chronic endometritis (CE) have not been established due to differences in study design among researchers and a lack of typical clinical cases. Lipopolysaccharides (LPSs) have been reported to cause inflammation in the reproductive systems of several animals. This study aimed to elucidate the influence of LPS in the pathogenesis of CE in humans. We investigated whether LPS affected cytokine production and cell proliferation in the endometrium using in vivo and in vitro experiments. LPS concentrations were analyzed between control and CE patients using endometrial tissues. LPS administration stimulated the proliferation of EM-E6/E7 cells derived from human endometrial cells. High LPS concentrations were detected in CE patients. LPS concentration was found to correlate with IL-6 gene expression in the endometrium. Inflammation signaling evoked by LPS led to the onset of CE, since LPS stimulates inflammatory responses and cell cycles in the endometrium. We identified LPS and IL-6 as suitable candidate markers for the diagnosis of CE.

Chronic endometritis - a constantly discussed issue in infertile women.

OBJECTIVE: A review of current knowledge on the pathophysiology, diagnostic and treatment options for chronic endometritis in infertile women. METHODS AND RESULTS: One of the major causes of failed in vitro fertilization (IVF) is undiagnosed intrauterine pathologies, including chronic inflammation of the uterine mucosa - chronic endometritis. However, some authors relativize the negative impact of chronic endometritis on reproductive outcomes. The etiopathogenesis of chronic endometritis is due to qualitative and quantitative changes in the endometrial microbiome with abnormal multiplication of microorganisms naturally occurring in the uterine cavity or vagina. There is no uniform consensus on the most common pathogen causing chronic endometritis. It is characterized by infiltration of plasma cells into the endometrial stroma outside the menstrual cycle, accompanied by hyperaemia and endometrial oedema. Clinical symptoms are very mild or absent. The diagnosis of chronic endometritis is often difficult because there is no specific clinical or laboratory diagnostic method. The following investigative options are commonly used for the diagnosis of chronic endometritis: diagnostic hysteroscopy, histopathological examination of the endometrium including CD 138 immunohistochemistry and culture from the uterine cavity. However, standardised international hysteroscopic and histopathological criteria for accurate diagnosis of chronic endometritis are still lacking. Empirically administered antibiotic therapy improves the success rate of pregnancy and delivery of a viable foetus in infertile patients with proven chronic endometritis. In addition to reviewing the current knowledge of chronic endometritis, this article discusses the importance of hysteroscopy in the diagnostic process. CONCLUSION: Chronic endometritis is often a clinically silent disease with negative impact on reproduction in infertile women. Although there are still many unresolved issues, the introduction of hysteroscopy into the diagnostic process is important for clinical practice; however, hysteroscopy even in combination with histological examination of the endometrium, often does not allow an unequivocal diagnosis of chronic endometritis. Further prospective randomised studies in a selected group of women with proven chronic endometritis and repeated failure to implant proven euploid embryos should refine this knowledge.

Bridging the Diagnostic Gap between Histopathologic and Hysteroscopic Chronic Endometritis with Deep Learning Models.

Chronic endometritis (CE) is an inflammatory pathologic condition of the uterine mucosa characterized by unusual infiltration of CD138(+) endometrial stromal plasmacytes (ESPCs). CE is often identified in infertile women with unexplained etiology, tubal factors, endometriosis, repeated implantation failure, and recurrent pregnancy loss. Diagnosis of CE has traditionally relied on endometrial biopsy and histopathologic/immunohistochemistrical detection of ESPCs. Endometrial biopsy, however, is a somewhat painful procedure for the subjects and does not allow us to grasp the whole picture of this mucosal tissue. Meanwhile, fluid hysteroscopy has been recently adopted as a less-invasive diagnostic modality for CE. We launched the ARCHIPELAGO (ARChival Hysteroscopic Image-based Prediction for histopathologic chronic Endometritis in infertile women using deep LeArninG mOdel) study to construct the hysteroscopic CE finding-based prediction tools for histopathologic CE. The development of these deep learning-based novel models and computer-aided detection/diagnosis systems potentially benefits infertile women suffering from this elusive disease.

Pregravid preparation of women with chronic endometritis in IVF cycles.

OBJECTIVE: Aim: of our study was to improve the pregravid preparation of women with chronic endometritis to develop individual approaches to overcoming infertility, taking into account the state of endometrium. PATIENTS AND METHODS: Materials and Methods: The study included 90 women (main group, n=90), 28 to 38 years with an anatomically normal uterus and chronic endometritis (CE). Patients were divided into 2 groups: group I - 45 women with CE who received conventional treatment; group II - 45 women with CE who received pregravid preparation by subendometrial injections of Platelet-Rich Plasma (PRP). RESULTS: Results: At the first stage of study, the ART statistical reports from 2015 to 2022 were analyzed at the Medical Center of Reproductive Health ≪Damia≫, (Ivano-Frankivsk). Analysis of the vaginal flora parameters before treatment at the first stage revealed the presence of conditionally pathogenic flora in culture from the cervical canal (Candida albicans - 2.4%, Escherihia coli - 4.8%, Staphylococcus epidermidis - 6.2% Enterococcus faecalis - 6.9%), and was evidence of a possible recurrence of inflammation during gestation. In the age category, the groups of patients were homogeneous, with no significant differences by the level of AMH and the level of CD 138. Biochemical pregnancy be present in 20 patients (44.4%) of group I and 28 (62.2%) of group II. Fertility within a year after the end of therapy was restored with the proposed method of therapy in most women (51.1%), in the comparison group this number was 11.1% lower. Pregnancy rate between the groups (I and II) did not differ significantly. The number of live births in group II - 19 births (42.2%) - was 2 times higher than I group (9 (20.0%), P<0.05). The most common complication for women in the comparison groups was early pregnancy loss. Among 18 (40.0%) clinical pregnancies of group I, 8 women (17.8%) had early miscarriage, 1 ectopic pregnancy (2.2%), while in group II clinical pregnancy be present in 23 women (51.1%). The number of terminated pregnancies was two times lower than in the first group (8.9% vs. 17.8%, P<0.05). CONCLUSION: Conclusions: Chronic endometritis is one of the main causes of pregnancy loss after in vitro fertilization. Patients of the second group were treated with the proposed method of subendometrial injections with Platelet-Rich Plasma (PRP), prepared from autologous blood, is an effective method of preparing the endometrium for embryo transfer and can increase the number of live births in patients with chronic endometritis.

If CE affects infertile women's outcomes after surgery?

OBJECTIVE: To investigate the prevalence of chronic endometritis (CE) in infertile patients and whether it affects spontaneous pregnancy after reproductive surgery in infertile patients. MATERIALS AND METHODS: In this study, we collected clinical information on infertility patients who underwent reproductive surgery at the Reproductive Medicine Centre of the Second Hospital of Lanzhou University from 2021.1 to 2022.8. All patients underwent laparoscopic and hysteroscopic surgery. Tubal lubrication was performed concurrently with endometrial sample collection and pathological examination. The specimens were immunohistochemically stained with CD38 and CD138, and those who tested positive at the same time were diagnosed with chronic endometritis. As of 2023.9, the patients were followed up by telephone to determine whether chronic endometritis impacted postoperative pregnancy. OUTCOME: A total of 81 patients were finally included in the study. Of these, 25 were in the chronic endometritis group, and 56 were in the non-chronic endometritis group. There were no appreciable differences between the two groups' demographic statistics. Furthermore, neither the bilateral appendages nor the uterus's intraoperative conditions showed a statistically significant difference. Patients in the chronic endometritis group had a longer time to conception from the time of surgery (7 (6.00-11.75) vs. 10 (6.50-16.00), p = 0.467) and a lower rate of spontaneous pregnancies (8/25 = 32.00 % vs. 28/55 = 50.00 %, p = 0.132) than patients with non-chronic endometritis. Among the patients who had successful spontaneous pregnancies after surgery, approximately 77.14 % had live births and 22.86 % had miscarriages, and the live birth rate between the two groups was not significantly different. (21/28 = 75.00 % vs 7/8 = 87.50 %, p = 0.651) CONCLUSION: Chronic endometritis affects approximately 31.82% of infertile patients, and following reproductive surgery, it has no discernible impact on spontaneous pregnancy.

Prevalence of chronic endometritis in infertile women undergoing hysteroscopy and its association with intrauterine abnormalities: A Cross-Sectional study.

OBJECTIVE: Chronic endometritis (CE) is an inflammatory condition with several different risk factors. We aimed to examine whether intrauterine abnormalities, such as endometrial polyps, submucosal myomas, intrauterine adhesions, or a septate uterus, were associated with an increased likelihood of developing chronic endometritis. METHODS: A cross-sectional study was conducted on 335 infertile women who underwent hysteroscopy surgery at the Ayatollah Taleghani Hospital Infertility Center, affiliated by Shahid Beheshti University of Medical Sciences, in 2022. All participants in the study underwent hysteroscopic surgery, which allowed for direct visualization of the intrauterine cavity, and endometrial biopsies were taken for further analysis. To characterize endometritis, plasma cell infiltration was assessed. Patients with ≥5 plasma cells observed in 10 high-power fields were defined as having chronic endometritis. RESULTS: Endometritis was observed in 51.3% of the patients, totaling 172 individuals. Logistic regression analysis revealed that patients with endometrial polyps had 5.2 times higher odds of developing endometritis compared to patients without polyps (95% CI = 2.9, 9.2) (p-value <0.001). Similarly, patients with intrauterine adhesions had a significant increase in the odds of endometritis (OR = 4.6, 95% CI = 2.1, 10.1) (p-value <0.001). CONCLUSIONS: Treatment or removal of endometrial abnormalities through hysteroscopic procedures may help to reduce the risk of chronic endometritis and improve fertility outcomes. Further research is necessary.

Impact of Diagnosis and Treatment of Chronic Endometritis on Outcomes Before Starting Assisted Reproductive Technology: A Retrospective Study.

This study aimed to investigate the effect of diagnosis and treatment of chronic endometritis (CE) on the outcome of assisted reproductive technology (ART) with or without repeated implantation failure (RIF). This retrospective analysis included patients who underwent pathological examination for diagnosis of CE at Yamagata University Hospital. The examination was performed for all patients planned for ART with or without RIF. Patients who were examined within 6 months of the first oocyte retrieval or embryo transfer were included. We counted the number of CD138-positive cells within the endometrial stroma in patients' specimens and analyzed the patients' clinical information. Clinical rates of pregnancy and implantation were determined. A total of 80 women met the inclusion criteria: 13 CE-negative patients (17.3%) and 67 CE-positive patients (83.7%). A significant decrease was noted in the CD138-positive cell count between the first biopsy and second biopsy after CE treatment (p < 0.001). In addition, no significant differences were noted in ongoing pregnancy rates between the CE-negative patients and those who underwent CE treatment. The CD138-positive cell counts at first biopsy tended to be lower in each pregnancy group than in the non-pregnancy group. For patients planned to undergo ART, examination for diagnosis of CE with or without RIF could be considered. Pathological CD138-positive cell counts were considered useful for CE diagnosis and treatment decision-making. The study findings suggest the efficacy of antimicrobial agents in CE treatment, contributing to improved pregnancy outcomes.

Expression of HOXA10 and HOXA11 in the endometrium of infertile patients with chronic endometritis.

OBJECTIVE: The study aimed to evaluate the impact of CE on the expression of HOXA10 and HOXA11 during the late proliferative phase in the endometrium of infertile women. METHODS: A prospective, translational cohort study was conducted in partnership with the Hospital Universitário Antônio Pedro in Niterói and the Clínica Ginendo in Rio de Janeiro after approval by the Ethics Committee. The patients were selected to participate in the study after showing an indication for hysteroscopy. All participants were divided into three groups: infertile women with endometritis (n=10), infertile women without endometritis (n=17) and fertile women without endometritis (n=10). At hysteroscopy, two endometrial samples were obtaneid, with one sent for histopathological examination per the gynecologist's request and the other used for immunohistochemistry procedures to evaluate the expression of CD138, HOXA10 and HOXA11. CD138 was used to confirm the diagnosis of CE. The analysis of HOXA10 and HOXA11 was performed using the HScoring method for immunohistochemistry with polyclonal antibodies. RESULTS: Women with and without endometritis had lower HOXA10 and HOXA11 expression values than women in the control group (fertile women without endometritis). CONCLUSIONS: The expression of HOXA10 and HOXA11 during the proliferative phase is not significantly different between infertile women with endometritis and infertile women without endometritis. Translational studies with a larger number of patients should be performed.

Clinical utility of office hysteroscopy following failed in vitro fertilization-embryo transfer: A retrospective cohort study.

OBJECTIVE: Despite its widespread use, in vitro fertilization (IVF) outcomes are challenged by implantation failure, largely due to factors such as embryo quality and endometrial receptivity. In this study, we investigated the clinical effect of office hysteroscopy (OH) on the subsequent frozen-thawed embryo transfer (FET) in infertile women who experienced a failed IVF-embryo transfer (IVF-ET) cycle. METHODS: We included 577 infertile women who underwent OH because of a history of failed ET between October 2019 and September 2021. During OH, visible endometrial polyps (EPs) were diagnosed and removed by curette or biopsy forceps; chronic endometritis (CE) was diagnosed by histopathology and immunohistochemistry and treated with oral doxycycline (0.2 g/d) for 14 days. According to the hysteroscopic findings and endometrial pathology with immunohistochemistry, patients were divided into three groups: group A (n = 161) had CE with or without EPs, group B (n = 156) had EPs only, and group C (n = 260) had no CE or EPs. RESULTS: In the following FET cycle, the implantation rates were 47%, 51%, and 45% (P = 0.411); the clinical pregnancy rates were 56%, 62%, and 55% (P = 0.436); the live birth rates were 45%, 51%, and 42% (P = 0.205); and the miscarriage rates were 18%, 16%, and 22% (P = 0.497) in groups A, B, and C, respectively. There were no significant differences among groups (P > 0.05). CONCLUSION: OH is helpful for diagnosis and treatment of abnormal intrauterine environment in women with a failed IVF cycle and further improves their pregnancy outcome in the following FET.

Risk factors of chronic endometritis in women who have undergone hysteroscopy: a prospective nested case-control study.

There is limited research on risk factors for chronic endometritis regarding reproductive history and clinical symptoms. Thus, this nested case-control study identified risk factors for chronic endometritis in women who have undergone hysteroscopy. Endometrial tissue sections were obtained from 502 women with intrauterine disorders who underwent hysteroscopy. Chronic endometritis was diagnosed via CD138 immunostaining. The women were divided into two groups: 271 women without chronic endometritis and 231 women with chronic endometritis. The prevalence of chronic endometritis was 46%. Univariate logistic regression revealed that prolonged menstruation and intermenstrual bleeding were associated with chronic endometritis, and subsequent multivariate logistic regression analyses showed that these were further independently associated. With univariable logistic regression, the gravidity and abortion history were correlated with chronic endometritis; however, no significant correlation was found with the adjusted odds ratio (OR) of 0.74 (95% confidence interval [CI] 0.46-1.19) or 0.76 (95% CI 0.58-1.11), respectively. No significant correlation was found between caesarean section history and the rates of chronic endometritis. No significant difference was found in all other variables between the three groups with > 5, ≤ 5 plasma cells and in a unknown group. Prolonged menstruation and intermenstrual bleeding were risk factors associated with chronic endometritis. Chronic endometritis should be considered and CD138 immunohistochemical examination should be recommended in women with these symptoms.

Vaginal microbiome dysbiosis as a novel noninvasive biomarker for detection of chronic endometritis in infertile women.

OBJECTIVE: To identify the vaginal microbial signature in women with chronic endometritis (CE) and investigate the potential of vaginal microbiome characterization as a novel diagnostic tools for CE. METHODS: A cross-sectional study was conducted to compare the characteristics of the vaginal microbiome in 98 women who underwent endometrial biopsy for routine clinical inspection of infertility (49 women diagnosed with CE and 49 with non-CE). The vaginal microbiome was analyzed using 16S ribosomal RNA gene amplicon sequencing. The study included an analysis of diversity, bacterial abundance, and microbial function. In addition, microbial markers were identified, and a CE classifier was developed. RESULTS: The relative abundances of genera, including Bifidobacterium, Prevotella and Gardnerella, were found to be different between the two groups. Analysis of the Kyoto Encyclopedia of Genes and Genomes pathways reported differential expression in metabolism-related pathways in the two groups. We identified four microbial markers of CE (Enterobacter, Prevotella, Faecalibacterium, and Phascolarctobacterium) and developed a predictive classifier for diagnosing CE, achieving an area under the curve of 83.26%. CONCLUSION: The results of the current study revealed that, compared with the non-CE controls, patients with CE have a different vaginal microbiota, highlighting the diagnostic significance of the vaginal microbiome as a promising noninvasive biomarker in detecting CE.

Construction of deep learning-based convolutional neural network model for automatic detection of fluid hysteroscopic endometrial micropolyps in infertile women with chronic endometritis.

OBJECTIVE(S): Chronic endometritis (CE) is a localized mucosal inflammatory disorder associated with female infertility of unknown etiology, endometriosis, tubal factors, repeated implantation failure, and recurrent pregnancy loss, along with atypical uterine bleeding and iron deficiency anemia. Diagnosis of CE has traditionally relied on endometrial biopsy and detection of CD138(+) endometrial stromal plasmacytes. To develop a less invasive diagnostic system for CE, we aimed to construct a deep learning-based convolutional neural network (CNN) model for the automatic detection of endometrial micropolyps (EMiP), a fluid hysteroscopy (F-HSC) finding recognized as tiny protrusive lesions that are closely related to this disease. STUDY DESIGN: This is an in silico study using archival images of F-HSC performed at an infertility center in a private clinic. A total of 244 infertile women undergoing F-HSC on the days 6-12 of the menstrual cycle between April 2019 and December 2021 with histopathologically-confirmed CE with the aid of immunohistochemistry for CD138 were utilized. RESULTS: The archival F-HSC images of 208 women (78 with EMiP and 130 without EMiP) who met the inclusion criteria were finally subjected to analysis. Following preprocessing of the images, half a set was input into a CNN architecture for training, whereas the remaining images were utilized as the test set to evaluate the performance of the model, which was compared with that of the experienced gynecologists. The sensitivity, specificity, accuracy, precision, and F1-score of the CNN model-aided diagnosis were 93.6 %, 92.3 %, 92.8 %, 88.0 %, and 0.907, respectively. The area under the receiver operating characteristic curves of the CNN model-aided diagnosis (0.930) was at a similar level (p > .05) to the value of conventional diagnosis by three experienced gynecologists (0.927, 0.948, and 0.906). CONCLUSION: These findings indicate that our deep learning-based CNN is capable of recognizing EMiP in F-HSC images and holds promise for further development of the computer-aided diagnostic system for CE.

The timing for embryo transfer after antibiotic therapy for chronic endometritis.

OBJECTIVE: To explore the optimal timing of embryo transfer after the first round treatment of chronic endometritis (CE) in vitro. MATERIALS AND METHODS: A total of 184 patients were recruited from a retrospective analysis of a large university-affiliated reproduction center in 2021. Some people chose to undergo embryo transfer in the same menstrual cycle with the first round of antibiotic treatment (Group 1, n = 29). Others received embryo transfer in the next cycle after the first round of treatment (Group 2, n = 69) or even one cycle later (Group 3，n = 96). RESULTS: Patients in Group 1 got significantly lower biochemical pregnancy rate and clinical pregnancy rate and live birth rate than Group 2 (p < 0.05) and also Group 3 (p < 0.05). Then after comparing the influence factors, we found embryo transfer in the next cycle after antibiotic treatment had a higher clinical pregnancy rate than group 1 (OR = 3.2 p < 0.05) and group 3(OR = 2.5, p < 0.05). The live birth rate in group 2 was higher than group 1(OR = 3.5, p < 0.05). CONCLUSION: These findings illustrate that embryo transfer in the next menstrual cycle is the optimal time. Embryo transfer in the same menstrual cycle with the first round of treatment reduces the pregnancy rate.