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.

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.

Progesterone-independent endometrial mRNA expression in dairy cows with clinical or subclinical endometritis.

Up to 50 % of dairy cows fail to resolve uterine involution and develop chronic clinical (CE) or subclinical endometritis (SE) 21 days after calving. Clinical endometritis is associated with purulent discharge, while SE is not associated with overt clinical signs. Along with numerous knowledge gaps related to its pathogenesis, SE does not allow for a straightforward and effective therapy. Therefore, it is crucial to unravel differences in the expression of genes among healthy, CE, and SE cows. This might contribute to the discovery of new drug candidates and, in consequence, a potentially effective treatment. In the present study, cows between 21 and 28 days postpartum (PP) were examined using vaginoscopy for the presence of vaginal discharge and endometrial cytology for the determination of the endometrial polymorphonuclear cell (PMN) percentage. Next, an endometrial biopsy sample was taken to investigate the expression of 13 selected candidate genes by qPCR. Uterine health status was assigned to healthy (absence of abnormal vaginal discharge and ≤5 % PMN, n = 13), SE (absence of abnormal vaginal discharge and >5 % PMN, n = 30), and CE (mucopurulent or purulent vaginal discharge and >5 % PMN, n = 9). At the same time, a blood sample was collected to assess serum progesterone concentration and to categorize cows as low (≤1 ng/mL) or high (>1 ng/mL) in progesterone. High expression of IL1B, IL6, IL17A, CXCL8, PTGES, PTGS1, PTGS2, and INHBA genes and low expression of FST was noted in the endometrium of CE compared to healthy cows. Increased endometrial INHBA expression was observed in both SE and CE compared to healthy cows. Interestingly, greater expression of PTGES and PRXL2B genes and lower expression of PTGS2 were characteristic of SE versus CE or healthy. Among cows with no overt clinical symptoms of uterine disease (healthy and SE), the endometrial expression of IL1 B, CXCL8, and PTGES was greater in cows with high versus low serum progesterone. Several genes were differentially expressed among healthy, SE, and CE cows indicating different pathways for the development of different uterine diseases. In conclusion, we found progesterone-independent SE markers, which suggests that low endometrial PTGS2 expression may be indicative of an inadequate immune response and thus contribute to the pathogenesis of SE.

Hysteroscopic features suggestive of chronic endometritis: a systematic review.

The purpose of this systematic review is to identify common hysteroscopic findings suggestive of endometritis, chronic or subclinical, based on current scientific evidence. Data sources were MEDLINE, Embase, PubMed and other sources of grey literature. Four (4) authors independently selected studies addressing hysteroscopic detection of CE based on specific and clearly stated hysteroscopic criteria. The diagnosis was confirmed by histologic assessment, as stated in the materials and methods of these studies included. The initial search identified 599 studies, of which 21 met the inclusion criteria. Significant heterogeneity among published studies on Chronic endometritis (CE) remains the main limitation in performing a metanalysis and further analysis of diagnostic accuracy on the subject. Hysteroscopy is an important diagnostic tool in cases of chronic endometritis when accompanied by endometrial biopsies. Clinicians relate hyperaemia and endometrial oedema with chronic endometritis while more than half include micropolyposis as a pathognomonic feature of this subclinical condition. Micropolyps, stromal oedema, haemorrhagic spots, strawberry aspect, and hyperaemia are proposed as adequate indicators of hysteroscopic evidence of CE according to the literature. The impact of CE in long-term reproductive outcomes remain unclear, thus clinicians ought to communicate this to the patients and provide treatment where clinically appropriate. In addition, we present hysteroscopic images of histologically confirmed CE cases that could play the role of a hysteroscopic atlas.

Hysteroscopic versus histopathological agreement in the diagnosis of chronic endometritis: results from a retrospective observational study.

PURPOSE: To evaluate the agreement rate between hysteroscopy and pathological examination in case of chronic endometritis. METHODS: A retrospective observational study carried out at Gynecology and Obstetrics Department, Puerta de Hierro Hospital, Autónoma University of Madrid, Spain, from January 2021 to June 2022 was performed by obtaining data from 115 medical records of women who underwent office hysteroscopies that was compared with the findings of final histological examination of endometrial biopsy. Cohen's kappa index was used to evaluate this agreement rate. In addition, sensitivity, specificity, positive and negative predictive value and diagnostic accuracy were obtained. RESULTS: The agreement between hysteroscopic findings and histological examination showed a modest result with a Cohen's kappa index of 34%. In addition, we obtained a specificity of 70% and a sensitivity of 64%. The positive and negative predictive value were 60.8% and 73.4%, respectively. An excellent agreement rate (100%) between histological and hysteroscopic results was observed in presence of hyperemia and micropolyps. CONCLUSION: Although the sample size is not as large as that of other studies published so far, the first glance of our experience is that hysteroscopic signs are not yet sufficient to make an accurate diagnosis of chronic endometritis, thus requiring a histopathological confirmation to make it.

MicroRNAs in equine Endometritis: A review of pathophysiology and molecular insights for diagnostic and therapeutic strategies.

Endometritis plays an important role in mare infertility. Certain infectious agents interfere with the innate immune system of endometrium, causing a systemic inflammatory response that lasts for a long time and circulates via the blood or cellular degeneration, leading to endometritis due to bacterial endotoxins. Different small, non-coding RNA molecules are involved in many biological functions. For instance, microRNAs (miRNAs) are involved in the post-transcriptional regulation of gene expression. These miRNAs are important regulators of gene expression, primarily via inhibiting transcription and translation processes. This manuscript reviews: (1) pathomorphological findings in equine endometritis, (2) the expression and effects of eca-miR-17, eca-miR-223, eca-miR-200a, eca-miR-155, and eca-miR-205 in endometritis and (3) the therapeutic role of miRNA in equine endometritis. The miRNAs have a vital regulatory role in a wide range of inflammatory diseases by regulating the molecular mechanism of cytokines that cause inflammation through signal pathways. This review emphasizes the demand for cutting-edge genetic technologies and the development of novel pharmaceutical preparations to improve our understanding of the genes encoding by these miRNAs. It also focuses on the efficacy of miRNAs for control, early diagnosis, and prevention of endometritis.

Local and systemic inflammatory response to the intrauterine infusion of enzymes during estrus in water buffaloes with subclinical endometritis.

Our objective was to determine the effects of intrauterine infusion of proteolytic enzymes in buffaloes with subclinical endometritis (SCE) at estrus on the resolution of endometrial inflammation and reproductive performance. Buffaloes at spontaneous estrus (E1) were screened for SCE by endometrial cytology to identify SCE (≥5% PMN, n = 22) and non-SCE (<5% PMNs, n = 14) animals. All buffaloes underwent uterine ultrasonographic examination, low volume uterine lavage (cytokines and acute phase proteins) and blood sampling (cytokines and acute-phase proteins) at E1. On the same day (E1), SCE buffaloes were randomly selected either for intrauterine infusion of proteolytic enzymes (ENY, n = 11) or saline (PC, n = 11). Buffaloes without SCE were kept as untreated control (NC; n = 14). All buffaloes were re-examined and re-sampled during subsequent estrus (E2), inseminated during the following estrus (E3), and assessed for fertility related outcomes. Proteolytic infusion resulted a reduction in uterine PMN (P < 0.01) in SCE buffaloes. The concentrations of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α in uterus, and TNF-α and IL-10 in serum were higher (P < 0.01) at E1 in buffaloes with SCE (PC and ENY) compared to NC. After treatment, uterine IL-1ß and TNF-α (P = 0.02), and serum TNF-α and IL-10 were lower within the animals of ENY group (P < 0.01). Before treatment, buffaloes with SCE had higher concentrations (P < 0.01) of serum and uterine amyloid-A and haptoglobin, which decreased (P < 0.01) after treatment in the ENY group. None of the fertility outcomes differ between the treatment groups. In conclusion, intrauterine infusion of proteolytic enzymes reduced endometrial inflammation; however, did not improve reproductive outcomes.

Establishment and verification of hysteroscopic scoring system for chronic endometritis in infertile patients. / ä¸å­•æ‚£è€ æ ¢æ€§å­å®«å† è†œç‚Žå®«è ”é•œè¯„åˆ†ç³»ç»Ÿçš„æž„å»ºåŠéªŒè¯.

OBJECTIVES: To establish and verify a hysteroscopic scoring system for the diagnosis of chronic endometritis (CE) in infertile patients. METHODS: A total of 238 infertile patients who underwent hysteroscopy and endometrial biopsy in the Reproductive Medicine Center, Shijiazhuang Obstetrics and Gynecology Hospital Affiliated to Hebei Medical University from October 1 to December 31, 2019 were enrolled in the study. According to the results of CD138 immunohistochemistry, the patients were divided into CE group (n=73) and non-CE group (n=165). Univariate and binary logistic regression analyses were used to screen the risk factors of CE and a nomogram was establish for hysteroscopic scoring. Receiver operating characteristic (ROC) curve, calibration curve and Bootstrap resampling method were used to evaluate and verify the system. RESULTS: Univariate and binary logistic regression analyses showed that hyperemia area (HA) degree ≥2, micropolyps, polypoid hyperplasia of endometrium and history of ectopic pregnancy were independent risk factors for CE (all P<0.05). A nomogram was generated to establish a hysteroscopy scoring system based on the above four factors. The area under ROC curve of the hysteroscopy scoring system for predicting CE was 0.801 (95%CI:0.742-0.861), the sensitivity was 74.0% and the specificity was 73.9%. The calibration curve showed that the predicting value of the scoring system was highly consistent with the actual value. In the internal verification, the C-index was 0.7811. The predicting value of the verification group in the calibration curve was basically consistent with the actual value, indicating that the scoring system had good stability. CONCLUSIONS: The hysteroscopic scoring system composed of HA, micropolyp, polypoid hyperplasia of endometrium and history of ectopic pregnancy can effectively and intuitively predict CE, which is conducive to improving the diagnosis of CE.

A Comparative Proteomic Analysis to Explore the Influencing Factors on Endometritis Using LC-MS/MS.

The inflammatory system activated by uterine infection is associated with decreased fertility. Diseases can be detected in advance by identifying biomarkers of several uterine diseases. Escherichia coli is one of the most frequent bacteria that is involved in pathogenic processes in dairy goats. The purpose of this study was to investigate the effect of endotoxin on protein expression in goat endometrial epithelial cells. In this study, the LC-MS/MS approach was employed to investigate the proteome profile of goat endometrial epithelial cells. A total of 1180 proteins were identified in the goat Endometrial Epithelial Cells and LPS-treated goat Endometrial Epithelial Cell groups, of which, 313 differentially expressed proteins were accurately screened. The proteomic results were independently verified by WB, TEM and IF techniques, and the same conclusion was obtained. To conclude, this model is suitable for the further study of infertility caused by endometrial damage caused by endotoxin. These findings may provide useful information for the prevention and treatment of endometritis.

Results of in vitro fertilization after diagnosis and treatment of chronic endometritis.

OBJECTIVE: A significant cause of infertility is the inability of the embryo to implant. Endometritis is one of the major causes affecting embryo implantation. The present study addressed the diagnosis and effects of chronic endometritis (CE) treatment on pregnancy rates after in vitro fertilization (IVF). PATIENTS AND METHODS: We conducted this retrospective study on 578 infertile couples treated with IVF. In 446 couples, we performed a control hysteroscopy with biopsy before IVF. In addition, we examined the visual aspects of the hysteroscopy and the results of the endometrial biopsies, followed by antibiotic therapy if necessary. Finally, the results of IVF were compared. RESULTS: Of the 446 cases studied, we diagnosed 192 (43%) with chronic endometritis, either by direct observation or based on the histopathological result. In addition, the cases diagnosed with CE we treated with a combination of antibiotics. The group diagnosed at CE and subsequently treated with antibiotic therapy had a significantly higher pregnancy rate after IVF (43.2%) than the group without treatment (27.3%). CONCLUSIONS: Hysteroscopic examination of the uterine cavity was particularly important for the success of IVF. The initial CE diagnosis and treatment were an advantage for the cases in which we performed the IVF procedures.

The Impact of Chronic Endometritis on Infertility: Prevalence, Reproductive Outcomes, and the Role of Hysteroscopy as a Screening Tool.

OBJECTIVES: The objective of this study was to examine the prevalence of chronic endometritis (CE) in infertile women, its impact on reproductive outcomes, and the accuracy of hysteroscopy as a screening tool for CE. DESIGN: This was a prospective observational study. PARTICIPANTS: Participants involved in this study were 514 asymptomatic patients with infertility. SETTING: The review was conducted in a tertiary care center. METHODS: The participants underwent a hysteroscopy and endometrial biopsy (EMB). Antibiotics were given for cases of CE. We investigated the prevalence of CE in patients starting assisted reproductive technologies (ART) as a primary outcome. Secondary outcomes were the clinical pregnancy rate (CPR) in the ART cycle after hysteroscopy, EMB, and antibiotic treatment in cases of CE; the cumulative CPR in the subsequent 2 years after hysteroscopy and EMB; the sensitivity and specificity of hysteroscopy as a screening tool compared to EMB as the "gold standard" for diagnosing CE. RESULTS: CE was identified in 2.8% of patients starting ART (11/393). CPRs did not differ significantly between patients with CE and the entire cohort of patients without CE in the subsequent ART cycle (OR: 0.43; 95% CI: 0.09-2.02) or in the 2 years after EMB (OR: 0.56; 95% CI: 0.16-1.97). In a matched control comparison (with matching for age, basal FSH, and cause of infertility), CPR in patients with CE did not differ in the subsequent ART cycle (OR: 0.39; 95% CI: 0.09-1.61); however, their CPR in the 2 years after EMB was significantly lower (OR: 0.22; 95% CI: 0.13-0.38). The sensitivity and specificity of hysteroscopy as a screening tool for diagnosing CE were 8.3% and 90.1%, respectively. LIMITATIONS: Due to our cohort's low CE prevalence, we could not detect significant differences in CPRs. CONCLUSION: CE is rare in our studied population of asymptomatic patients starting ART. Hysteroscopy cannot replace EMB for diagnosing CE.

Xanthogranulomatous endometritis with unilateral salpingo-oophoritis in a postmenopausal woman masquerading as a malignancy.

Xanthogranulomatous endometritis (XGE) is a rare pathological entity which is characterised by sheets of foamy histiocytes and lymphoplasmacytic infiltrates. This condition can mimic endometrial carcinoma. We report a case, clinically suspected as carcinoma of the endometrium/ovary, which was diagnosed as XGE with left salpingo-oophoritis on histopathology.

Effect of different antibiotic therapies on the reproductive outcomes of fresh embryo transfer for chronic endometritis: A retrospective cohort study.

OBJECTIVE: To investigate the reproductive outcomes by comparing two kinds of antibiotic schemes for chronic endometritis (CE) in infertile women's fresh embryo transfer (FET) cycles and identify subgroups of patients with CE who need long-term antibiotics treatment. DESIGN: A retrospective cohort study. SETTING: University-based reproductive medical center. PATIENT(S): A total of 492 women with CD138-positive plasmacytes per 10 high-power fields (CD138+/10HPF). INTERVENTION(S): Hysteroscopy was performed and endometrial biopsy samples were collected in the proliferative phase. Long-term or short-term antibiotics were administrated. After antibiotics treatment, patients underwent in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) and received ET. MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate, clinical pregnancy rate, clinical miscarriage rate. RESULT (S): There were no significant differences in pregnancy outcomes between patients with CD138+/10HPF 1-4 (low-grade CE) who received long-term antibiotic therapy and short-term antibiotics groups. Among women with CD138+/10HPF ≥5 (high-grade CE), live birth rate (48.4% vs. 14.7%, p = .001), clinical pregnancy rate (66.7% vs. 35.3%, p = .002) and ongoing pregnancy rate (59.1% vs. 20.6%, p < .001) in the long-term arm were significantly higher than that in the short-term arm. The clinical miscarriage rate (21.0% vs. 58.3%, p = .013) was statistically lower in the long-term antibiotics group, but no statistical differences were found between the two groups in preterm delivery rate. CONCLUSION: Long-term antibiotics treatment was a sensible choice to improve pregnancy outcomes in women with CD138+/10HPF ≥5 (high-grade CE). The pregnancy outcomes of women with low-grade CE only defined by histological diagnosis were not greatly improved after antibiotic therapy. Therefore, we recommended the proper diagnosis criteria were CD138+/10HPF ≥5 pathologically.

Chronic endometritis - is it time to clarify diagnostic criteria?

Chronic endometritis is a persistent, low-intensity inflammation of endometrial mucosa, characterized by the infiltration of plasma cells into the endometrial stroma This immunological alteration is thought to be a consequence of a bacterial infection. For a long time, chronic endometritis was poorly investigated and rarely considered in clinical practice because it is either asymptomatic or presents with no specific symptoms. Its association with adverse effects on fertility and retrospectively reported effectiveness of antibiotic treatment were the main reasons for a growing interest in this endometrial pathology. Chronic endometritis is now a hot topic in recurrent pregnancy loss and recurrent implantation failure research. Nevertheless, there are still no recommendations to include chronic endometritis investigation in a clinical evaluation of infertile patients. The uncertain role of this condition is an effect of significant differences in study results presented by different research groups. One important reason for these inconsistent findings is a lack of standardised chronic endometritis diagnostic methods. We present a review of the literature, focusing on the currently available chronic endometritis diagnostic techniques. The review is subdivided into three parts concerning the diagnostic accuracy of three main diagnostic modalities. Histopathological examination of endometrial tissue, hysteroscopic evaluation of uterine cavity and identification of the bacterial factor. In conclusion, it is of great importance to establish a consensus on the diagnostic criteria for chronic endometritis. This is the only way to enhance international cooperation and create well-design multicenter studies to evidence the role of this endometrial pathology in infertility.

Significance of multiple myeloma oncogene 1 immunohistochemistry in chronic endometritis detection in patients with recurrent pregnancy losses: an observational study.

The most reliable chronic endometritis diagnosis is based on immunohistochemistry plasma cell identification in endometrial samples. Our study aimed to compare multiple myeloma oncogene 1 (MUM1) and syndecan-1/CD138 immunohistochemistry staining for chronic endometritis diagnosis among patients with recurrent pregnancy loss. We evaluated the presence of endometrial stromal changes. Fifty-four patients with a history of at least two intrauterine pregnancy losses underwent diagnostic hysteroscopy in the follicular phase of the cycle with endometrial aspiration biopsy. In all 54 cases, three successive sections were cut from each paraffin-embedded tissue block for hematoxylin and eosin (H&E), CD138 and MUM1 staining. The goal was to evaluate the level of agreement between the MUM1 and CD138 results and plasma cell detection rate in assessing the endometrial stromal changes. The concordance analysis between CD138 and MUM1 immunohistochemistry staining showed consistent results in 43 of 54 (79.6%) cases. The level of agreement was moderate, based on a Kappa value of 0.60. MUM1 immunostaining was positive for CE in more cases than CD138 staining, and this difference was statistically significant, showing a higher sensitivity of MUM1 in plasma cell detection (p=0.01). Endometrial stromal changes were observed in the majority of cases - 49/54 (90%). Samples without stromal changes were consistently negative for plasma cells using both CD138 and MUM1 staining. We demonstrated that MUM1 staining, used in conjunction with assessing endometrial stromal changes, contributes to a more accurate and comprehensive diagnosis of chronic endometritis.

The effectiveness of intrauterine antibiotic infusion versus oral antibiotic therapy in the treatment of chronic endometritis in patients during IVF (in vitro fertilization) procedures.

BACKGROUND: Chronic Endometritis (CE) is a subtle pathology, likely infectious in most cases, with a negative impact on the female fertility, but often overlooked even among fertility specialists. The purpose of the study is to demonstrate the predominant infectious nature of CE and to find the best therapeutic option by comparing the results of oral antibiotic therapy versus intrauterine antibiotic infusion in patients with CE undergoing IVF procedures. The objective was to compare the cure rate of CE-defined as the percentage of patients without CE at the test of cure, between the two groups and, the hysteroscopic aspect with the positive CD 138 staining. METHODS: This was a prospective, case-control study that took place in a single university fertility clinic, in Oradea, Romania and included 57 patients with CE divided into 2 groups: orally administered antibiotics group who received a combination of antibiotics compared to intrauterine infusion group who received intrauterine infusion of antibiotic. Chronic Endometritis was diagnosed through hysteroscopy and immunohistochemistry for CD 138. Patients in both groups were tested for CE twice to evaluate the cure rate after oral combination antibiotic therapy versus intrauterine infusion of antibiotic. RESULTS: Out of 115 patients with endometrial biopsies 57 tested positive for CE, with a 49.6% chronic endometritis prevalence. Among the group that was administered oral antibiotics, 11 patients (45.83%) experienced CE resolution after triple antibiotic therapy. Of the intrauterine infusion group, 25 patients (89.29%) presented negative results (p 0.0020). The normal hysteroscopic aspect had a similar prevalence in the patients with immunohistochemical positive and negative CD 138. CONCLUSIONS: Our study demonstrated the effectiveness and superiority of intrauterine antibiotic infusion over the use of oral combination antibiotic therapy for CE cure. TRIAL REGISTRATION: ISRCTN17542620/14.09.2022.

A case of discrepancy between three ERA tests in a woman with repeated implantation failure complicated by chronic endometritis.

BACKGROUND: Endometrial receptivity array (ERA) is used to determine the timing of embryo transfer (ET) synchronized with the window of implantation (WOI). The effectiveness and evaluation of ERAs in women with recurrent implantation failure remain controversial. We report the case of a patient with recurrent implantation failure that raises the issue of reproducibility of ERA tests. CASE REPORT: A 36-year-old Japanese woman with secondary infertility who had previously given birth failed to conceive after three frozen-thawed embryo transfer (FET) cycles. An ERA test was conducted to confirm the WOI. The first ERA test was performed 125 h after progesterone exposure. The laboratory reported that the endometrium was in a non-receptive (post-receptive) phase, and recommended retesting 101 h after progesterone exposure. A simultaneous chronic endometritis (CE) test showed a score of 3. After the antibiotics administration to treat CE, the second ERA test was performed after 101 h of progesterone exposure. The laboratory reported that the endometrium had not reached the WOI and estimated the WOI to be 113 ± 3 h after progesterone exposure. The third ERA test was performed 113 h after progesterone exposure. The laboratory reported that the endometrium was in a non-receptive (pre-receptive) phase and estimated the WOI to be 137 ± 3 h after progesterone exposure. A CE test performed at the same time as the second and third ERA tests showed a score of 1 for the collected endometrium. According to the third ERA test results, the vitrified-warmed blastocyst was transferred at 137 h of progesterone exposure. Pregnancy was achieved and the patient had an uncomplicated vaginal delivery at 39 weeks. One year later, another pregnancy was achieved after FET at 137 h of progesterone exposure, and the patient delivered at 33 weeks due to an unexpected membrane rupture. CONCLUSION: Because the results of the ERA test may vary in the presence of CE, CE should be diagnosed simultaneously with or before conducting ERA tests. If CE is diagnosed, ERA testing should be performed after treatment with antimicrobials or other drugs.

Additional dydrogesterone for the treatment of chronic endometritis treated with antibiotic in premenopausal women with endometrial polyps: a retrospective cohort study.

BACKGROUND: To assess the efficacy of dysdrogesterone in the treatment of chronic endometritis (CE) treated with antibiotic in premenopausal women with endometrial polyps (EPs). METHODS: Routine detection of endometrium was simultaneously conducted to determine whether there was CE by syndecan-1 (CD138), while women underwent hysteroscopic polypectomy in our hospital. Antibiotic was given for the treatment of CE. A total of 235 premenopausal women with CE who underwent hysteroscopic polypectomy were enrolled in the retrospective observational study. In the control group, single antibiotic was given for the treatment of CE form January 2016 to December 2018, and in the treatment group additional dydrogesterone was used from January 2019 to November 2020. Comparison of cure rates of CE with different treatment regimens was performed. RESULTS: The cure rates of CE in dydrogesterone and antibiotic combination group and the single antibiotic group were 85.2% and 74.3%, respectively, with overall cure rate of 80.0% (188/235). The combination group showed better effects regarding the cure rate of CE (P < .05). Multivariate analysis confirmed that the cure rate of CE was not affected by age, body mass index, number of EPs, the status of estrogen receptor and the status of progesterone receptor. Conversely, dydrogesterone and endometrial scratching were beneficial factors for cure rate increase with antibiotic treatment. CONCLUSION: Combination of dydrogesterone and antibiotic was more effective for cure rate of CE than antibiotic alone in premenopausal women after hysteroscopic polypectomy. Endometrial scratching also contributed to the cure rate increase with antibiotic treatment.

Comparison Between Gynecological Examination Methods and Sample Collection Techniques for the Diagnosis of Endometritis in Subfertile Mares.

Endometritis is a relevant cause of subfertility in mares. However, the accurate diagnosis, essential for effective treatment, can be difficult due to the variability of results and interpretations resulting from different examination methods and sample collection techniques. The present work compared gynecological evaluation methods and sample collection techniques to diagnose endometritis in subfertile mares. Forty animals with a history of subfertility were selected for gynecological evaluation using clinical methodologies, such as perineal conformation, transrectal palpation and ultrasonography, vaginoscopy, and digital examination of the cervix. In addition, we performed laboratory analyses, including uterine microbiological culture and endometrial cytology and histology, of which the latter is the gold standard for the diagnosis of endometritis. Samples were collected for microbiological culture and endometrial cytological evaluations using three different techniques: a commercial cytobrush/swab collector, low-volume uterine flush, and a new tested technique, by flush the fragment resulting from the endometrial biopsy. Transrectal palpation and ultrasound showed the best results among clinical examinations. However, they were less efficient in laboratory tests of endometrial cytology and uterine microbiological culture, in which the latter showed the highest sensitivity and specificity for endometritis compared with endometrial histology. The use of multiple results from different methods has also proved to be an effective alternative for diagnosis. Among the techniques used to collect endometrial material for cytology and microbiological culture, the most effective and practical in this study was the commercial cytobrush/swab collector.

Bayesian accuracy estimates and fit for purpose thresholds of cytology and culture of endometrial swab samples for detecting endometritis in mares.

The overall aim of this work was to identify the potential impact of misclassification errors associated with routine screening and diagnostic testing for endometritis in mares. Using Bayesian latent class models (BLCM), specific objectives were to: 1) estimate the diagnostic accuracy of cytology and culture of endometrial swab samples to detect endometritis in mares; 2) assess the impact of different cytology thresholds on test accuracy and misclassification costs; and 3) assess the sensitivity (Se) and specificity (Sp) of a diagnostic strategy including both tests interpreted in series and parallel. Diagnostic and pre-breeding endometrial swab samples collected from 3448 mares based at breeding premises located in the South East of England between 2014 and 2020 were retrospectively analysed. Culture results were classified as positive according to three different case definitions: (A) > 90% of the growth colonies were a monoculture; (B) pathogenic or pathogenic and non-pathogenic bacteria were identified; and (C) any growth was observed. Endometrial smears were graded based on the percent of polymorphonuclear cells (PMN) per high power field (HPF). A hierarchical BLCM was fitted using the cross-tabulated results of the three culture case definitions with a cytology threshold fixed at > 0.5% PMN. Fit for purpose cytology thresholds were proposed using a misclassification cost analysis in the context of good antimicrobial stewardship and for varying endometritis prevalence estimates. Median [95% Bayesian credible intervals (BCI)] cytology Se estimates were 6.5% (2.2-11.6), 6.4% (2.2-10.8) and 6.3% (2.2-10.8) for scenario A, B and C, respectively. Median (95% BCI) cytology Sp estimates were 88.8% (83.1-94.8), 88.9% (83.9-93.8) and 88.8% (84.0-93.8) for scenarios A, B and C, respectively. Median (95% BCI) culture Se estimates were 37.5% (29.9-46.0), 42.3% (33.8-51.1) and 46.4% (35.7-55.9) for scenarios A, B and C, respectively. Median (95% BCI) culture Sp estimates were 92.8% (84.3-99.0), 91.5% (82.5-98.0) and 90.8% (80.1-97.4) for scenarios A, B and C, respectively. Regardless of the culture case definition, Se and Sp of cytology (> 0.5% PMN) was lower than previously reported for swab samples in studies using histology as the reference standard test. The misclassification cost term decreased as the cytology threshold increased for all scenarios and all prevalence contexts, suggesting that, regardless of the endometritis prevalence in the population, increasing the cytology threshold would reduce the misclassification costs associated with false positive mares contributing to good antimicrobial stewardship.