Screening of Endometrial Cancer Related to Lynch Syndrome in China by Suction Curettage-Based Cytology and Histology: A Retrospective Study.

Objective: To explore the feasibility of sampling Chinese patients by suction curettage for cytological and histological screening of endometrial cancer related to Lynch syndrome. Methods: This retrospective study enrolled patients who underwent endometrial biopsy at our hospital between May 2018 and January 2019. Endometrial sampling (cytological and micro-histological specimens) was conducted by suction curettage. The gold standard for diagnosis was traditional sharp dilation and curettage (D&C). The sensitivity, specificity, and diagnostic accuracy of cytology, micro-histology, and the combination of cytology and micro-histology were calculated. Additionally, receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic efficiency of three screening methods. Mismatch repair proteins were further detected using immunohistochemistry (IHC) in endometrial cancer. Results: This retrospective finally enrolled 100 patients, which satisfactory samples were obtained from 96 patients for liquid-based cytology and 93 patients for microtissue histology. The concordance rates with D&C, sensitivity, and specificity were 94.8%, 76.9%, and 97.5% for liquid-based cytology, 96.8%, 84.6%, and 98.8% for microtissue histology, and 99.0%, 92.3%, and 100.0% for liquid-based cytology and microtissue histology combined, respectively. The AUC of ROC curves in liquid-based cytology, microtissue histology, and the combined methods for diagnostic ability were 0.873, 0.917, and 0.962, respectively. Absence rates of MLHl, MSH2, MSH6, and PMS2 proteins were 15.3% (2/13), 0% (0/13), 7.7% (1/13), and 15.3% (2/13) in the 13 endometrial cancer samples. Conclusion: Liquid-based cytology and microtissue histology samples from suction curettage combined IHC are useful for endometrial cancer screening.

Deep learning analysis of endometrial histology as a promising tool to predict the chance of pregnancy after frozen embryo transfers.

PURPOSE: Endometrial histology on hematoxylin and eosin (H&E)-stained preparations provides information associated with receptivity. However, traditional histological examination by Noyes' dating method is of limited value as it is prone to subjectivity and is not well correlated with fertility status or pregnancy outcome. This study aims to mitigate the weaknesses of Noyes' dating by analyzing endometrial histology through deep learning (DL) algorithm to predict the chance of pregnancy. METHODS: Endometrial biopsies were taken during the window of receptivity from healthy volunteers in natural menstrual cycles (group A) and infertile patients undergoing mock artificial cycles (group B). H&E staining was performed followed by whole slide image scanning for DL analysis. RESULTS: In a proof-of-concept trial to differentiate group A (n=24) vs. B (n=37), a DL-based binary classifier was trained, cross-validated, and achieved 100% for accuracy. Patients in group B underwent subsequent frozen-thawed embryo transfers (FETs) and were further categorized into "pregnant (n=15)" or "non-pregnant (n=18)" sub-groups based on the outcomes. In the following trial to predict pregnancy outcome in group B, the DL-based binary classifier yielded 77.8% for accuracy. Its performance was further validated by an accuracy of 75% in a "held-out" test set where patients had euploid embryo transfers. Furthermore, the DL model identified histo-characteristics including stromal edema, glandular secretion, and endometrial vascularity as important features related to pregnancy prediction. CONCLUSIONS: DL-based endometrial histology analysis demonstrated its feasibility and robustness in pregnancy prediction for patients undergoing FETs, indicating its value as a prognostic tool in fertility 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.

Effect of Mycobacterium cell wall fraction on endometrial histomorphometry of mares resistant and susceptible to persistent breeding-induced endometritis.

Mycobacterium cell wall fraction (MCWF) is a biological component made up of molecules with immunostimulant properties, which is therapeutically used to modulate persistent breeding-induced endometritis (PBIE). The aim of this study was to analyze the effect of this immunomodulator on the endometrial histological structure during the diestrus of PBIE-resistant and -susceptible mares that either received treatment with MCWF or not. The experiment was conducted with 10 resistant mares (RM) and 9 susceptible mares (SM). In the first estrous cycle of the trial, all mares were inseminated with dead semen as an inflammatory stimulus (Group A); at the next cycle, all mares were inseminated with dead semen and treated with a MCWF commercial immunomodulator (Group B). In both groups, endometrial biopsies were taken on day 7 post-ovulation (diestrus). Endometrial biopsies of untreated-RM (UTRM, n = 6), untreated-SM (UTSM, n = 7) MCWF-treated-RM (TRM, n = 6) and MCWF-treated-SM (TSM, n = 6) were evaluated. They were randomly chosen as representative mares of Group A and B, respectively. The height of lining and glandular epithelia, glandular diameter, glandular density and glandular area were evaluated. The histological structure revealed lymphocytic infiltration and dilated, tortuous glands with some glandular nests, particularly in UTSM. The histomorphometrical results showed no differences (ρ > 0.05) between the analyzed groups. This would indicate that post-service treatment with the MCWF immunomodulator does not modify the endometrial histoarchitecture but, apparently, its action would be mainly based on the stimulation of the cellular and humoral immune responses.

Choice of progestogen for endometrial protection in combination with transdermal estradiol in menopausal women.

Transdermal estradiol (TE) application (using gels, patches or a novel spray) is now a preferred route of hormone therapy (HT) in menopausal women, because various risks such as venous thromboembolism, stroke and unwanted hepatic effects can be reduced compared with oral HT. However, in the presence of an intact uterus, concurrent administration of progestogen is needed for endometrial protection. Due to the variety of progestogens available and differences in their clinical effects, the selection of the most appropriate substance and dosing for individual combination therapy can be difficult. This is especially true for TE gels and the novel spray because no fixed combination products are commercially available, meaning all progestogens must be added separately, and even for patches only two transdermal synthetic progestogens are available. The aim of this review was to summarize data on the endometrial effects of the different progestogens and to provide practical recommendations for the choice of progestogen (type and dosing), with a focus on endometrial protection when using TE, especially when using the novel estradiol (E2) spray.

A comparison between the effects of metformin and megestrol on simple endometrial hyperplasia.

INTRODUCTION: Endometrial hyperplasia is one of the most serious causes of severe abnormal bleeding and also can be a precursor of endometrial carcinoma. OBJECTIVE: The purpose of the present study was to compare the effects of metformin and megestrol on the endometrial hyperplasia. METHODS: The study was performed as a randomized clinical trial on 42 cases of histopathologically confirmed simple endometrial hyperplasia without atypia. The eligible women were randomly assigned into two groups. In metformin group, metformin was prescribed, 500 mg twice a day (1000 mg daily), for a duration of 4 weeks, and then, followed by 1500 mg daily, for 8 more weeks. In the megestrol group, megestrol was prescribed 40 mg daily for 12 weeks. At the end of the duration of the treatment, endometrial sampling was performed and the results were compared between the two groups. RESULTS: The women of the two groups did not have significant difference according to age, BMI and gravidity, parity and history of abortion. Overall, 18 women (81.8%) in metformin group and 12 women (60%) in the megestrol group had normal endometrial histology, after 12 weeks of treatment (p = 0.11). CONCLUSION: Metformin is comparable with megestrol for the treatment of simple endometrial hyperplasia.

Safety and comfort of long-term continuous combined transdermal estrogen and intrauterine levonorgestrel administration for postmenopausal hormone substitution - a review.

OBJECTIVE: To review the endometrial safety and patient acceptability of long-term use of continuous transdermal estrogen substitution combined with intrauterine release of levonorgestrel (LNG) in postmenopausal women. DESIGN: One-hundred and fifty-three women who utilized the regimen for 2 IUD cycles were followed-up for a period of 10 years. Histology of the endometrium was evaluated at the end of this period to assess endometrial safety and the acceptability of the method was assessed based on the replacement rate of the LNG-IUS and continuation of ET. RESULTS: The regimen, administered over a 10-year period, was very well tolerated and the IUD was retained well and no expulsions occurred. The dominant endometrial histologic picture was that of inactive endometrium characterized by glandular atrophy and stroma decidualization (Kurman classification 5b). No cases of endometrial hyperplasia were found. CONCLUSION: The low systemic absorption of LNG could be desirable, thus allowing for maximization of the beneficial effects of ET on organ tissues (e.g. cardiovascular tissues and breast). Repeat LNG-IUS is associated with high patient satisfaction. If started before the age of 60, this regimen could be advised for lifelong prevention of cardiovascular disease and other prevention measures. The LNG-IUS was shown to effectively oppose the secondary effects of systemic estrogen on the endometrium tissue resulting in strong suppression during the entire period of EPT.

The effect of ozonated sterile saline irrigation on the endometrium - A preliminary study.

The objective of this study was to evaluate the effect of sterile ozonated saline endometrial irrigation on sonographic and histological endometrial parameters. This prospective investigation was performed in 12 healthy, ovulating women over three consecutive menstrual cycles: control cycle (endometrial irrigation with 10 cc of normal saline at day 10), no intervention cycle and study cycle (irrigation with 10 cc of sterile ozonated saline at day 10). Endometrial thickness was measured by transvaginal ultrasound at days 10 and 12 of the control and study cycles, and endometrial samplings were obtained from the participants two days after the irrigations (i.e. on day 12) for histological evaluation. Ozonated saline irrigation, compared to normal saline irrigation, resulted in a statistically significant elevation of the columnar epithelial height (30.30 ± 3.04 vs. 25.82 ± 3.28 µm, p < 0.003), increased number of endometrial blood vessels (30.48 ± 11.38 vs. 19.12 ± 8.74, p < 0.005) and increased number of stromal cells (191.30 ± 34.40 vs. 151.29 ± 29.98, p < 0.01). In conclusion, sterile ozonated saline irrigation of the endometrium has a significant favourable effect on various histological endometrial parameters. Further studies are needed to evaluate the effect of these changes on endometrial receptivity and pregnancy rates.

Modelo experimental de endometrite em vacas inoculadas com Escherichia coli inativada por meio de infusão uterina / Endometritis experimental model in cows inoculated with inactivated Escherichia coli by uterine infusion

The aim of this study was to evaluate the endometrial inflammatory response of nine Zebu cows inoculated through uterine infusion with 30 mL of inactivated Escherichia coli suspension (1 x 109 UFC/mL) and nine with 30 mL of sterile phosphate buffered saline. Endometrial biopsies were performed before and after the inoculations during estrus, and ten days later in the diestrus phase. Neutrophilic infiltrates were observed in 88.8% of samples from the E. coli group in estrus phase and demonstrated different degrees of endometrial inflammation. This study characterizes a suitable model for studying endometritis in cattle.(AU)

Effects of Endometrial Ablation on Treatment Planning in Women With Endometrial Cancer.

To evaluate effects of endometrial ablation on the staging and treatment planning of postablation endometrial cancer. After authorization from the institutional review board, we performed a retrospective chart review of patients with a history of endometrial ablation and a subsequent diagnosis of endometrial cancer from July 2006 to December 2013. The information obtained included patient's age at time of cancer diagnosis, pre-ablation endometrial biopsy histology, dilation and curettage histology at time of ablation, endometrial biopsy-to-ablation interval, ablation-to-hysterectomy interval, final pathologic diagnosis, Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) staging, and treatment recommendations for adjuvant therapy. The histopathology was examined by a gynecologic pathologist. The National Comprehensive Cancer Network guidelines were applied to determine need for adjuvant therapy. Six of 490 (1.2%) patients with endometrial cancer were identified to have an antecedent ablation. Mean patient age was 48.2 years (range: 40-53). The time interval from office pre-ablation endometrial sampling to ablation ranged from 1 to 17 months. Four patients (67%) had an undetected endometrial cancer at the time of ablation, despite having benign pre-ablation histology. Following surgical staging, 4 patients (67%) had no evidence of residual carcinoma, and 2 (33%) had evidence of endometrial adenocarcinoma grades 1 to 2. There was no evidence of myometrial invasion in all cases, and a FIGO stage of IA was assigned. No adjuvant therapies were indicated. There have been no documented cancer recurrences, with a follow-up range from 16 to 52 months (average 30.2). Endometrial ablation artifact does not appear to hinder evaluation and treatment planning in the presence of endometrial cancer.