Proliferative Endometrium Research Articles

The effect of the number of endometrial CD138+ cells on the pregnancy outcomes of infertile patients in the proliferative phase

ObjectiveThis study was conducted to determine the influence of the number of CD138+ cells in the proliferative endometrium on pregnancy outcomes.MethodsThis retrospective cohort study was conducted from January to August 2018. A total of 664 infertile women who were not diagnosed with chronic endometritis (CE) and who had not received the respective antibiotic treatment were studied. Immunostaining was performed for the plasmacyte marker CD138. The number of CD138+ cells was compared in the proliferative and mid-luteal phases of the same patients without antibiotic therapy. Infertile patients were separated into three groups based on the number of positive lesions [the number of high power fields (HPFs) containing no less than five CD138+ cells]: 0 (n = 474), 1-2 (n = 125), and ≥3 positive lesions (n = 104). The pregnancy outcomes of the infertile women undergoing in vitro fertilization-embryo transfer (IVF-ET) among the three groups were then compared.ResultsThere was a much higher level of CD138+ cells during proliferation than during the mid-luteal phase (P <0.0001). Pregnancy outcomes did not differ between the groups with 0 and 1-2 positive lesions. However, the ≥3 positive lesions group (P =0.006, P =0.029) had significantly lower ongoing pregnancy and live birth rates compared with the no positive lesion group. Although the 0 and ≥3 positive lesions groups showed a trend toward higher rates of clinical pregnancy (P =0.132), these differences failed to reach statistical significance. After age, body mass index (BMI), and clinical features were adjusted for, the ≥3 positive lesions group showed significantly lower live birth rates (aOR, 1.84; 95%CI, 1.08-3.15; P =0.026), clinical pregnancy (adjusted odds ratio (aOR), 1.78; 95% CI, 1.06-2.95; P =0.028), and ongoing pregnancy (aOR, 1.85; 95% CI, 1.09-3.15; P =0.024). The analysis demonstrated that the smallest number of stromal CD138+ cells suggestive of CE patients requiring treatment was defined as ≥ 3 positive lesions during the proliferation.ConclusionsDifferent diagnostic criteria for CE should be created for the proliferative and mid-luteal phases. The analysis demonstrated that the smallest number of stromal CD138+ cells suggestive of CE patients was defined as ≥ 3 positive lesions during the proliferative phase.

Safety of Fezolinetant for Treatment of Moderate to Severe Vasomotor Symptoms Due to Menopause: Pooled Analysis of Three Randomized Phase 3 Studies.

This study evaluated the safety and tolerability of fezolinetant in women with vasomotor symptoms (VMS) due to menopause in a pooled analysis of data from three 52-week phase 3 studies (SKYLIGHT 1, 2, and 4). SKYLIGHT 1 and 2 were double-blind, placebo-controlled studies where women (≥40 to≤65years), with moderate to severe VMS (minimum average≥7 hot flashes/day) were randomized to once-daily placebo, fezolinetant 30mg or 45mg. After 12weeks, those on placebo were re-randomized to fezolinetant 30mg or 45mg, while those on fezolinetant continued on their assigned dose for 40weeks. SKYLIGHT 4 was a placebo-controlled, double-blind, 52-week safety study. Safety was assessed by frequency of treatment-emergent adverse events (TEAEs) and endometrial events. TEAEs of special interest included liver test elevations and endometrial hyperplasia or cancer or disordered proliferative endometrium. Totals of 952 participants receiving placebo, 1100 receiving fezolinetant 45mg, and 1103 receiving fezolinetant 30mg took≥1 dose of study medication. TEAEs occurred in 55.3%, 62.9%, and 65.4%, respectively; exposure-adjusted results were consistent with these results. Most frequent TEAEs in fezolinetant-treated participants included upper respiratory tract infection (7.7-8.3%), headache (6.8-8.2%), coronavirus disease 2019 (5.8-6.1%), back pain (3.1-3.7%), arthralgia (2.9-3.2%), diarrhea (2.3-3.2%), urinary tract infection (2.9-3.4%), and insomnia (2.0-3.0%). The incidence of drug-related serious TEAEs and associated treatment withdrawals was low. Elevations in liver transaminases occurred in 1.5-2.3% of fezolinetant-treated participants, were typically asymptomatic and transient, resolved on treatment or discontinuation, with no evidence of severe drug-induced liver injury (Hy's law). Endometrial safety results were well within US Food and Drug Administration criteria. Analysis of benign and non-benign neoplasm controlled for exposure demonstrated no increased risk versus placebo. Pooled data confirm the safety and tolerability of fezolinetant over 52weeks. ClinicalTrials.gov identifiers, NCT04003155, NCT04003142, and NCT04003389. Graphical abstract available for this article.

The risk factors and prognostic impact of different benign pathologic types of background endometrium surrounding endometrial polyps.

This retrospective study investigated the prognostic significance and risk factors of benign pathologic types of background endometrium surrounding endometrial polyps (EPs). We assessed 206 patients who underwent hysteroscopic polypectomy and background endometrium biopsy. Patients were categorized into four groups based on the pathologic types of background endometrium: normal proliferative endometrium (NPE), polypoid hyperplastic endometrium (PHE), chronic endometritis (CE), and non-atypical endometrial hyperplasia (NEH). We employed univariable comparisons and multivariable logistic regression analysis to identify risk factors of PHE, CE, and NEH compared to NPE. Abnormal uterine bleeding (AUB) and recurrence of EPs were monitored over a 12-month postoperative follow-up period. Independent risk factors for EPs with a background of CE included a history of genital tract infection (OR = 8.88, 95% CI: 2.95-26.70, P = 0.000), adenomyosis (OR = 13.70, 95% CI: 3.38-55.52, P = 0.000), and hydrosalpinx (OR = 2.23, 95% CI: 1.59-54.09, P = 0.013). Age (OR = 1.18, 95% CI: 1.07-1.30, P = 0.001) and BMI (OR = 1.33, 95% CI: 1.11-1.61, P = 0.003) were significant risk factors for EPs with a background of NEH. Patients with PHE had higher recurrence rates of EPs following 12 months of follow-up. Moreover, background endometrium types PHE, CE, and NEH were associated with poorer control of AUB. Our study underscores the importance of examining the histopathologic characteristics of the background endometrium surrounding EPs, as these benign lesions significantly influence the recurrence and symptomatology of EPs.

Immunohistochemical Analysis of GATA2 Expression in Endometrium and its Relationship with Hormone Receptor Expression in Benign and Premalignant Endometrial Disorders

The GATA gene family encodes highly conserved zinc-finger transcription factors that facilitate the development and function of multiple organ systems including the uterus. In the endometrium, GATA2 functions in a positive autoregulatory loop with the progesterone receptor (PGR) and colocalizes with PGR on chromatin to promote PGR transcriptional programs. GATA2 also has PGR-independent functions that maintain endometrial cell identity, and GATA2 transcripts reportedly are down-regulated in endometrial disorders including endometriosis. This event is accompanied by a reciprocal increase in GATA6. Here, we applied custom anti-GATA2 monoclonal antibodies and performed GATA2 immunohistochemistry (IHC) on patient endometrial tissues corresponding to proliferative, secretory, inactive, and hormone-treated endometrium, as well as endometriosis and endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (EAH/EIN). We also performed IHC for the estrogen receptor, PGR, and GATA6 in relevant groups. The results reveal a tight correlation between GATA2 and PGR expression in the glandular and stromal cells of benign endometrium. GATA2 expression is markedly reduced in stromal but not glandular cells in endometriosis and EAH/EIN. This reduction in GATA2 expression does not lead to a detectable increase in GATA6 expression in endometriosis. Although average glandular GATA2 expression was preserved in endometriosis and EAH/EIN cases, its expression was decoupled from PGR, implying that alternative pathways regulate GATA2 levels in these disorders. Our findings indicate that GATA2 dysregulation is a feature of endometriosis and EAH/EIN, and support a model whereby loss of stromal GATA2 in these disorders contributes to their progesterone insensitivity.

Endometrial pattern in women with abnormal uterine bleeding attending a tertiary care centre of Kathmandu

Background: Abnormal uterine bleeding is one of the most common problems among pre and postmenopausal women. Abnormal uterine bleeding is diagnosed when there is a substantial change in frequency, duration, or amountof bleeding during or between periodsin the absence of any organic pathology. The study was perform to assess the endometrial causes of abnormal uterine bleeding and their incidence in different age groups. Materials and methods: It was a cross sectional and descriptive study carried out at a Manmohan medical College & hospital, over a period of two year from 13th April, 2020 to 15th March, 2022. In the study all the endometrial tissue either obtained by endometrial curettage and biopsy or hysterectomy presenting with abnormal uterine bleeding for more than 3 months were included Results: A total of 88 cases were received during this period, out of which there were 78 endometrial tissue samples and 10 hysterectomy specimens. The patient’s age ranged from 20 years to 73years. The pattern of endometrial biopsy are Proliferative (37.5%) and secretory (20.45%) phase endometrium is the most common pattern seen, followed by disordered proliferative endometrium (13.63%), endometrial hyperplasia without atypia (9.09%), Change consistent with Exogenous Hormone (5.68%), Chronic Endometritis (5.68%), Endometrial Polyp(3.40%), Endometrial Hyperplasia with Atypia(2.27%) and Endometrial Carcinoma (2.27%). Conclusions: Patients with abnormal uterine bleeding show a varying spectrum of endometrial pattern. Cyclic endometrium is commonly seen in the reproductive age group whereas hyperplasia and carcinomas are seen in pre/postmenopausal age group. Endometrial biopsy with histopathological examination is a major diagnostic tool in the evaluation of abnormal uterine bleeding.

Immunohistochemical Investigation of P16 Expression in Curettage Biopsies

Our study aims to investigate the immunohistochemical expression of the P16 molecule, which is involved in the cell cycle and plays a role in developing endometrial cancer in normal epithelium, endometrial polyp, and precursor lesions. A total of 68 patients underwent endometrial sampling for various reasons at the Department of Obstetrics and Gynecology, Faculty of Medicine, Kafkas University, between 2020 and 2021 were included in the study. The selected cases were categorized into four groups: proliferative endometrium, endometrial hyperplasia without atypia, atypical hyperplasia / endometrioid intraepithelial neoplasia (AH / EIN) and endometrial polyp. There were no cases with a diagnosis of endometrial tumors in our study. All patients’ pathology samples were re-evaluated, and P16 immunohistochemistry was applied to tissue samples. Among patients diagnosed with atypical endometrial hyperplasia, 72.7% exhibited moderate P16 protein expression, 18.2% had low expression, and 9.1% had high protein expression. The number of patients diagnosed with AH / EIN had a very low frequency in the study population. Among patients diagnosed with endometrial polyps, 50.0% showed moderate P16 protein expression, 20.0% exhibited low protein expression, and 30.0% had high protein expression. High P16 expression has been reported to be significantly associated with endometrial cancer in the literature. P16 expression is significant in precancerous lesions and stages of cancer development. Larger-scale studies with more cases are needed in this regard.

The Correlation of Hysteroscopy and Histopathology in Evaluating Abnormal Uterine Bleeding: Observations From a Tertiary Care Center.

Abnormal uterine bleeding (AUB) is an important clinical entity, and its subtype, heavy menstrual bleeding (HMB), affects 14%-25% of women of reproductive age, potentially impairing their physical, emotional, social, and material quality of life. However, in addition to prior studies that supported the efficacy of hysteroscopy in identifying AUB, this study determined the overall pattern of abnormalities in AUB and correlated the diagnosis through hysteroscopy and histopathology. Additionally, a comparison of ultrasonography was done in this study. This study helps healthcare providers provide timely diagnosis and, thereby, timely interventions in treating different causes of AUB. This hospital-based prospective observational study was conducted at a tertiary care center, including women aged 20-60 admitted with complaints of AUBbetween September 2022 and June 2024. Participants were selected based on their willingness to participate in the study. A statistical analysis was performed using relevant descriptive statistics andplotting the frequency and percentage. Cohen's kappa was applied to ascertain significant associations and patterns within the dataset. Results: The study included 47 women who were admitted to the hospital for diagnostic hysteroscopy. A majority of clinical symptoms presented as menorrhagia (17, 36.2%). The hemoglobin (g/dL) ranged from 5.9 to 14.7. Overall, on hysteroscopy, 37 (78.7%) women had a normal uterus. On hysteroscopy, 36 (76.6%) participants showed a normal cervical canal and cervix. In terms of histopathology, a majority of the study population (21, 44.7%) had proliferative endometrium. In terms of the correlation between hysteroscopy and histopathology, the two methods agreed in 83% of cases and disagreed in 17% of cases. Thisstudy confirms that hysteroscopy is a crucial tool for assessing patients with AUB, particularly those with a thick endometrium, across all age groups. It does not replace other diagnostic methods; instead, it enhances them. Hysteroscopic-guided biopsy along withhistopathology is now widely regarded as the most reliablemethod and new gold standardfor assessing cases of AUB.

Clinicopathological Aspects of Dilation and Curettage (D&C) Biopsies Taken from Patients Living at High Altitude in Taif, KSA, with a Special Emphasis on Chronic Endometritis.

Chronic endometritis (CE) is a persistent inflammation of the uterine lining. Although it has a minimal clinical presentation, CE adversely affects the reproductive ability of women. The aims of this study were to detect pathological endometrial patterns in D&C biopsies and to evaluate chronic endometritis in patients living in a high-altitude area (1800 m above sea level) in order to determine the clinical pathological features and prevalence. A cross-sectional study conducted at King Faisal Maternity Hospital included 100 samples of D&C biopsies from women complaining of various gynecological symptoms not due to gestational causes. The biopsies underwent tissue processing, H&E staining, and CD138 detection. Blood samples were taken for serological detection of infectious diseases, complete blood count, and chemical parameters. The mean age of women in the study with CE was 48.5 ± 8.5 years, and that of those without CE was 46.9 ± 9.7 years. The most common complaints were abnormal uterine bleeding, accounting for 83%. CE was present in 8% of cases, and there was a nonsignificant difference in hematological parameters between women with CE and those with other pathological diagnoses. There were also nonsignificant differences in chemical parameters, except for FSH and LH levels, which showed a significant difference, with p-values of 0.05 and 0.02, respectively. It can be concluded that the most common gynecological complaint of women in this study was abnormal uterine bleeding. The most commonly diagnosed pathological endometrial disorder in D&C biopsies was disordered proliferative endometrium, followed by endometrial polyps and endometrial hyperplasia. All of these are usually associated with hormonal disturbance, which appeared to be very common in the women in this study. The prevalence of chronic endometritis detected in our study was 8%, which is relatively high.

Assessing the Role of Transvaginal Sonography in Post-menopausal Bleeding: A Less Invasive Approach to Identify Endometrial Carcinoma.

Background Post-menopausal bleeding (PMB) is a very common complaint seen in current practice. Endometrial carcinoma (EC) commonly presents with PMB. Endometrial biopsy is the tool for definitive diagnosis, but it is invasive. Transvaginal sonography (TVS) is a non-invasive tool that can help us in the initial evaluation of such patients. Methods A prospective observational study was conducted on 76 women with PMB. TVS and histopathological study, along with basic evaluation and investigations, were performed on all participants, followed by necessary treatment and follow-up. Data collected were studied and statistically analyzed. Results A maximum of 27.63% (n=21) of patients had endometrial atrophy causing their PMB. Proliferative endometrium was observed in 21.06% (n=16) of cases, 13.15% (n=10) of women had secretory endometrium, 23.68% (n=18) had simple endometrial hyperplasia, 3.94% (n=3) had complex endometrial hyperplasia without atypia, and another 3.94% (n=3)had complex endometrial hyperplasia with atypia. Further classifying, women with benign hyperplasia included 27.63% (n=21) and those with atypical hyperplasia included 3.94% (n=3). Out of the 5.26% (n=4) patients diagnosed with EC on histopathology, TVS identified carcinoma in75% (n=3) cases. This indicates that the sensitivity and specificity of TVS in detecting EC are 75% and 100%, respectively. The positive predictive value (PPV) is 100%, the negative predictive value (NPV) is 98.63%, and the accuracy is 98.68%. Conclusion If the cut-off for endometrial thickness is set at 4 mm, then TVS proves to be an effective and reliable tool for screening and diagnosing EC. It can thus serve as a safe threshold to screen patients with PMB using TVS.

The range of endometrial pathologies in patients with abnormal uterine bleeding at a tertiary care center in central India

Abstract Background: Endometrial disorders are among the most common gynecological conditions globally. Abnormal uterine bleeding (AUB) refers to any irregularity in the timing, volume, or pattern of menstrual blood flow. This study investigates the histopathological spectrum of endometrial changes across various age groups in patients presenting with AUB as their primary symptom. Materials and Methods: The study analyzed 226 endometrial biopsies/specimens collected over two years from patients with AUB as the main complaint. These specimens were processed, and slides stained with hematoxylin and eosin (H&E) were examined to determine the endometrial patterns. A chi-square test assessed the relationship between age and specific endometrial pathologies. Observations and Results: Most of the 226 cases were from perimenopausal women (40–49 years), representing 57% of the total, with proliferative endometrium being the most common pattern (40.9%). About 20% of the cases were in the reproductive age group (<40 years), where typical hyperplasia was the most prevalent pattern (45.7%). Additionally, 23% of the cases involved postmenopausal women (>49 years), with endometrioid carcinoma being the most frequent pattern observed. Other endometrial patterns included disordered proliferative endometrium, endometritis, endometrial polyps, Arias–Stella reaction, and progesterone effects. Conclusion: Patients with AUB present with a wide range of endometrial patterns, from normal cyclic endometrium to malignancies. Histopathological examination remains the gold standard for diagnosing AUB, showing a significant association between endometrial lesions and age.

The Role of Endometrial Sampling before Hysterectomy in Premenopausal Women with Abnormal Uterine Bleeding.

Background/Objectives: An endometrial sampling is recommended for patients experiencing abnormal uterine bleeding above the age of 40 or 45. Valid risk prediction models are needed to accurately assess the risk of endometrial cancer and avoid an unnecessary endometrial biopsy in premenopausal women. We aimed to assess the necessity and usefulness of preoperative endometrial sampling by evaluating premenopausal women who underwent hysterectomy for abnormal uterine bleeding after preoperative endometrial sampling at our clinic. Methods: A retrospective analysis was conducted on 339 patients who underwent preoperative endometrial sampling and subsequently underwent hysterectomy due to abnormal uterine bleeding. Detailed gynecologic examinations, patient histories, and reports of endometrial sampling and hysterectomy were recorded. Cohen's Kappa (κ) statistic was utilized to evaluate the concordance between histopathological results from an endometrial biopsy and hysterectomy. Results: The mean age of the cohort was 47 ± 4 years. Endometrial biopsies predominantly revealed benign findings, with 137 (40.4%) cases showing proliferative endometrium and 2 (0.6%) cases showing endometrial cancer. Following hysterectomy, final pathology indicated proliferative endometrium in 208 (61.4%) cases, with 7 (2.1%) cases showing endometrioid cancer. There was a statistically significant but low level of concordance between histopathological reports of endometrial biopsy and hysterectomy results (Kappa = 0.108; p < 0.001). Significant differences were observed only in the body mass index of patients based on hysterectomy results (p = 0.004). When demographic characteristics were compared with cancer incidence, smoking status and preoperative endometrial biopsy findings showed statistically significant differences (p = 0.042 and p = 0.010, respectively). Conclusions: The concordance between the pathological findings of a preoperative endometrial biopsy and hysterectomy is low. Body mass index is an important differentiating factor between benign histopathologic findings of endometrium and endometrial neoplasia. Moreover, adenomyosis was found to be associated with endometrial cancer cases. The current approach to premenopausal women with abnormal uterine bleeding, which includes a routine endometrial biopsy, warrants re-evaluation by international societies and experts.

Application of strain elastography ultrasound to the endometrium of normal women

BackgroundWhile there is a scarcity of studies utilizing strain elastography (SE) for the endometrium, commonly used gynecologic ultrasound instruments are equipped with built-in elastography modalities, primarily SE. With the objective of facilitating comprehensive examinations for gynecologic patients on a single ultrasound instrument, we undertook this study. Therefore, our aim was to study the value of SE ultrasonography in the assessment of endometrial elasticity in normal women.MethodsThree hundred and twenty normal women were recruited at our hospitals from November 2021 to December 2022. Each volunteer underwent a transvaginal two-dimensional (2D) and SE ultrasound during either the endometrial proliferative or secretory phase. The 2D ultrasound indices obtained included endometrial thickness, echo type (type A, B, and C), and blood flow grading (grades 0, 1, 2, and 3). SE indices obtained included endometrial strain values, myometrial strain values, and endometrial strain ratios. Differences in endometrial ultrasound indices between different menstrual cycles and different age groups were compared.ResultsComparison of 2D ultrasound parameters revealed that endometrial thickness in the proliferative phase endometrium group was smaller than that in the secretory phase endometrium group, with a statistically significant difference. Additionally, there was a statistically significant difference in endometrial echo types between the two groups, while the disparity in endometrial blood flow grading was not significant. Regarding SE parameters, the median and mean values of endometrial strain ratio in the proliferative phase endometrium group were smaller than those in the secretory phase endometrium group, showing a statistically significant difference. However, there were no significant differences observed between the two groups in endometrial strain and myometrial strain in the fundus. Furthermore, there were no significant differences in any of the endometrial ultrasound indices among the different age groups.ConclusionsSE can reflect changes in endometrial stiffness in different menstrual cycles and is an important tool for assessing endometrial softness.

Endometrial Proliferative Phase-Centered View of Transcriptome Dynamics across the Menstrual Cycle.

The endometrium, the inner mucosal lining of the uterus, undergoes complex molecular and cellular changes across the menstrual cycle in preparation for embryo implantation. Transcriptome-wide analyses have mainly been utilized to study endometrial receptivity, the prerequisite for successful implantation, with most studies, so far, comparing the endometrial transcriptomes between (i) secretory and proliferative endometrium or (ii) mid-secretory and early secretory endometrium. In the current study, we provide a complete transcriptome description of the endometrium across the entire menstrual cycle and, for the first time, comprehensively characterize the proliferative phase of the endometrium. Our temporal transcriptome analysis includes five time points including the mid-proliferative, late proliferative (peri-ovulatory phase), early secretory, mid-secretory, and late secretory phases. Thus, we unveil exhaustively the transitions between the consecutive proliferative and secretory phases, highlighting their unique gene expression profiles and possible distinct biological functions. The transcriptome analysis reveals many differentially expressed genes (DEGs) across the menstrual cycle, most of which are phase-specific. As an example of coordinated gene activity, the expression profile of histone-encoding genes within the HIST cluster on chromosome 6 shows an increase in cluster activity during the late proliferative and a decline during the mid-secretory phase. Moreover, numerous DEGs are shared among all phases. In conclusion, in the current study, we delineate the endometrial proliferative phase-centered view of transcriptome dynamics across the menstrual cycle. Our data analysis highlights significant transcriptomic and functional changes occurring during the late proliferative phase-an essential transition point from the proliferative phase to the secretory phase. Future studies should explore how the biology of the late proliferative phase endometrium impacts the achievement of mid-secretory endometrial receptivity or contributes to molecular aberrations leading to embryo implantation failure.

Investigation of Hyaluronan Synthase 2 and CD44 immune reactivity as a biomarker to predict Progesterone-Resistant Endometrial Hyperplasia without atypia: A retrospective case-control study.

In our study, the effect of hyaluronan synthase 2 (HAS2) and CD44 immunoreactivity as a predictive biomarker in the prediction of progesterone-resistant endometrial hyperplasia (EH) cases without atypia was investigated. In this retrospective study, HAS2 and CD44 immunoreactivity in the endometrial tissues of 60 patients diagnosed with EH and treated with progesterone and 20 patients diagnosed with proliferative endometrium (PE) were evaluated. Eighty patients were divided into four groups. Group 1 (G1) (n = 20) = PE group, G2 (n = 20) = EH group without atypia, G3 (n = 20) = group with continued EH with treatment, G4 (n = 20) = EH with treatment without atypia. Intergroup evaluation was done with One-way ANOVA and posthoc tukey test. P < 0.05 values were considered statistically significant. The HAS2 immunoreactivity score of G2 and G3 was higher than G1 and G4. On the other hand, there was no difference between G1 and G4. When G2 and G3 were compared, HAS2 immunoreactivity scores were significantly increased in G3. When CD44 immunoreactivity was compared with G1, a significant increase was detected in G2, G3, and G4. However, CD44 immunoreactivity scores were similar in G2, G3, and G4. HAS2 immunoreactivity may be an immunohistochemical biomarker in predicting EH cases without atypia resistant to progesterone therapy. Since CD44 immunoreactivity is increased in all EH groups without atypia, it is not effective in predicting treatment resistance.

A prospective study of endometrial histopathology in post-menopausal women in Jharkhand.

Postmenopausal bleeding (PMB) refers to any uterine bleeding in a menopausal women. In the early menopausal years, endometrial hyperplasia, polyps and submucosal fibroids are common etiologies of post menopausal bleeding. The most common cause of postmenopausal bleeding is endometrial atrophy, comprises of 60-80%, while endometrial hyperplasia and endometrial cancer contribute to only 11% of Post menopausal bleeding. The aim of study is to analyses histomorphological pattern of endometrium in patients presenting with post-menopausal bleeding in Jharkhand. 103 postmenopausal women presenting to tertiary center of Jharkhand in 2020-22 with bleeding were subjected to endometrial curettage for histopathology. Analysis is based on morphological criteria to assess endometrium. Endometrial histology is of four categories: Proliferative, Secretory, premalignant and carcinoma. The highest incidence of postmenopausal bleeding was noticed in age group of < 60 years and incidence of malignancy was higher after 57 years of age. The majority of patients had parity between 1 and 3 (78.6%). Malignant & premalignant lesions comprises about 22.3% among that 77.7% were due to benign causes. Among the benign causes of postmenopausal bleeding, proliferative endometrium was the commonest finding. Types of hyperplasia encountered were simple hyperplasia without atypia (6.8%), Complex hyperplasia without atypia (3.9%),Complex hyperplasia with atypia (4.8%) and Simple hyperplasia with atypia (4.8%). 21.4% of cases of postmenopausal bleeding were associated with atrophic endometrium. Secretory endometrium seen in 17.5% of women. Endometrial carcinoma accounted for 12.6% of cases of postmenopausal bleeding. Out of these 69.2% were of endometroid type of endometrial carcinoma, 15.3% were of papillary serous carcinoma and 15.3% had clear cell carcinoma. The mean age of patients with endometrium carcinoma was 62.3 years. All cases of endometrial carcinoma were associated with 1 or more risk factor like diabetes/hypertension/Nulligravida. Proliferative Endometrium was a major cause of postmenopausal bleeding. Among the malignant causes, endometrial adenocarcinoma of endometroid type was most frequent with a lower mean age at presentation than other high grade cancers like papillary serous carcinoma & clear cell carcinoma.

The usefulness of p16 and COX-2 expression on the prediction of progression to endometrial cancer.

Endometrial cancer (EC) is the most commonly diagnosed gynecological cancer. Endometrial hyperplasia (EH) is a more common diagnosis than EC. Endometrial hyperplasia is found in approximately 1.5% of all women presenting with abnormal bleeding. Endometrial hyperplasia progresses to EC, and especially, cancer risk increases in cases with atypical hyperplasia. p16, one of the tumor suppressor proteins involved in the cell cycle, and COX-2, one of the key enzymes of prostaglandin synthesis, are important markers for the diagnosis of both EH and EC. There is lack of consensus in the classification, diagnosis and treatment of EH. The subject of changes in the cell cycle in the progression of endometrial pathologies may help to identify and prevent these affected pathways in the treatment stage. The aim of this study is to investigate the expression of p16 and COX-2 during the development of EC from EH. We investigated COX-2 and P16 expressions in patients with proliferative endometrium, complex/simple endometrial hyperplasia and endometrioid adenocarcinoma. p16 expression increased in EH and EC (p<0.001). COX-2 expression was increased in endometrial cancer compared to other groups, but this increase was not found to be statistically significant. Although p16 and COX-2 expression were increased in patients with advanced grade/stage, lymphovascular invasion, and >50% of myometrial invasion, this increase was not statistically significant. More detailed studies are needed to investigate the prognostic significance of the COX-2 molecule. COX-2 might be a potential biomarker for the prognosis of endometrial cancer and a potential therapeutic target for EC treatment. Also, it might be used to prevent the progression of precursor lesions to invasive EC.

Expression and clinical significance of RHCG in endometrial cancer.

Endometrial cancer (EC) is the most common gynecological cancer. Rhesus family, C glycoprotein (RHCG) has been evidenced to be involved in the occurrence and development of various tumors. This study aimed to investigate the expression and clinical significance of RHCG in EC. Bioinformatics analysis was based on the RNAseq counts data from TCGA database, and the prognosis analysis was performed using the Kaplan-Meier method; 4 cases of endometrioid adenocarcinomas samples and 4 cases of normal proliferative endometrium were collected for qPCR and western blot; immunohistochemistry analysis was employed to assess the expression of RHCG in a tissue microarray; the correlation between RHCG and clinicopathological factors was analyzed through Mann-Whitney U test. The lentiviral interference vector was further constructed. The results demonstrated that RHCG was highly expressed in EC tissues, and RHCG was an independent factor affecting the overall survival of patients. Additionally, the expression of RHCG was related to FIGO stage and tumor infiltrate. After interfering with shRHCG, the proliferation activity of EC cells decreased, the migration ability of cells decreased, the apoptosis of cells increased, and the tumor outgrowth was arrested. In summary, RHCG promotes the malignant proliferation and migration of EC, and makes the cells have anti-apoptotic activity. Our study provides a theoretical basis for RHCG to become a potential therapeutic target for EC in the future.

Correlation of Hysteroscopy With Histopathological Findings of the Endometrium in Women With Polycystic Ovary Syndrome (PCOS)-Related Infertility.

Introduction There have been numerous studies on the anovulatory factor, leading to infertility inwomen with polycystic ovary syndrome (PCOS); however, studies on the endometrium factor causing infertility in PCOS women are scarce. While hysteroscopy can accurately diagnose endometrial disorders such as endometrial polyps, it may be ineffective in detecting probable endometrial pathologies due to different hormonal habitats in these patients. Materials and methods Sixty patients with PCOS-related infertility were included in the study. All participants underwent hysteroscopic examination followed by endometrial biopsy and histopathological examination. The clinical and hormonal profiles of two main subgroups, that is, (a) normal endometrium (N), which included proliferative endometriumand secretory endometrium on histology, and (b) disordered endometrium (D), which included disordered endometrium on histology, were compared. Results There was no correlation between hysteroscopic and histopathological findings of PCOS infertile women. In the subgroup analysis of the two main histological types, that is, normal (proliferative and secretory) and disordered (disordered endometrium), age (28.70±4.66 vs. 32.9±5.61, p=0.012) and duration of amenorrhea (5.49±2.43 vs. 7.82±2.93, p=0.008) were significantly higher in the disordered group. There was a statistically nonsignificant higher BMI in the patients of the disordered endometrium group. Conclusion These findings suggest that endometrial biopsy and histopathological evaluation along with hysteroscopy should be desired in women with PCOS-related infertility, especially if they are in the late reproductive age group and have a longer duration of amenorrhea, regardless of endometrial thickening. This approach is essential to diagnose and treat endometrial disorder, which can be an additional cause of infertility, recurrent implantation failure, and recurrent pregnancy loss, in addition to ovulatory dysfunction.

Staining Pattern of Alcian Blue in Endometrial Cytology: Utility in Distinguishing Grade 1-Endometrial Endometrioid Carcinoma from Endometrial Glandular Stromal Breakdown.

In endometrial cytology, differentiating endometrial glandular stromal breakdown (EGBD) from endometrial endometrioid carcinoma (G1-EEC) is often difficult. In this study, we provided a new focus on chondroitin sulfate (CS), a major substrate component of the endometrial stroma, and assessed the diagnostic utility of Alcian Blue (AB) staining in the differential diagnosis in liquid-based cytological (LBC) samples. LBC specimens from 19 patients with a proliferative endometrium, 36 with EGBD, and 30 with G1-EEC who underwent endometrial cytology were stained with AB (pH 1.0), and their reactivity was observed. In addition, immunocytochemical staining of CS and CD31 was performed for five cases each to evaluate their interrelationship with blood vessels. Regarding the 30 G1-EEC cases, at least one of the three representative staining patterns was observed by AB staining: dot-like, microtubular, and finely branched linear patterns. Moreover, the inner portion of the tubular material observed by AB staining expressed CD31. Conversely, in the 36 EGBD cases, only five metaplastic clusters with irregular protrusions and condensed stromal clusters (CSCs) showed a dot-like positive pattern, and background CSCs did not show reactivity to AB staining in any of the cases. Furthermore, the vascular structure expressing CD31 in cell clusters was also unclear. We demonstrated that AB staining shows different staining patterns in G1-EEC and EGBD, reflecting their different tissue structures. Our data provide new insights into endometrial cell diagnosis changes and demonstrate that AB staining is a potential new diagnostic aid tool for the differentiation of G1-EEC from EGBD.

Clinicopathological Analysis of Postmenopausal Bleeding and Endometrium

Highlights: 1. Malignancies in postmenopausal bleeding are not very common, yet it is necessary to evaluate the etiology and implement appropriate treatment strategies.2. The findings of this study highlight the need for early detection of benign, premalignant, or malignant cases to provide more effective management, prevent the development of cancer, and improve the prognosis of the condition. Abstract Bleeding from the genital organ after a year of menopause is called postmenopausal bleeding. The causes may be either benign or malignant, originating from genital (uterine or extrauterine) and extragenital sites. About 3% of postmenopausal women suffer from uterine cancer. This present study aimed to analyze the clinical significance of postmenopausal bleeding concerning the source, associated risk factors, and various endometrial pathologies, including malignant and premalignant conditions. This retrospective study was conducted over four years and featured postmenopausal bleeding patients who met the inclusion criteria. Different causes of bleeding were noted and managed. Data collection on the history, clinical examination, blood test, and endometrial biopsy was performed on women with endometrial bleeding. The collected data were analyzed using standard descriptive statistics and presented using frequency tables. A total of 88 women were admitted, of whom 73 (82.95%) had endometrial bleeding and 15 (17.05%) experienced bleeding from other sites. The endometrial bleeding group mostly consisted of women aged &gt;50–60 years (45.20%). Hypertension (26.03%), diabetes (21.91%), obesity (43.83%), and nulliparous (5.48%) were the risk factors present among the patients. The majority of the patients (41.10%) were within five years of menopause. The transvaginal ultrasound findings indicated that 56.16% of the women had an endometrial thickness of &gt;10 mm, while 9.59% had an endometrial thickness of ≤4 mm. Upon histological investigation, endometrial hyperplasia (34.24%), atrophy (38.36%), and cancer (4.11%) were detected. Furthermore, a prevalence of 16.44% was identified as proliferative endometrium, whereas polyps were found in 6.84% of cases. In conclusion, postmenopausal bleeding is mostly benign, but it may raise concerns about the possibility of malignancy, which can be distressing for women. Disregarding the amount and frequency, postmenopausal bleeding requires a thorough evaluation, primarily because adequate management can prevent the progression of many premalignant cases to be endometrial cancer.