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Sterile inflammation occurs in various chronic diseases due to many nonmicrobe factors. Examples include endometrial hyperplasia (EH), endometriosis, endometrial cancer, and breast cancer, which are all sterile inflammation diseases induced by estrogen imbalances. However, how estrogen‐induced sterile inflammation regulates EH remains unclear. Here, a single‐cell RNA‐Seq is used to show that SHP2 upregulation in endometrial endothelial cells promotes their inflammatory activation and subsequent transendothelial macrophage migration. Independent of the initial estrogen stimulation, IL1β and TNFα from macrophages then create a feedforward loop that enhances endothelial cell activation and IGF1 secretion. This endothelial cell–macrophage interaction sustains sterile endometrial inflammation and facilitates epithelial cell proliferation, even after estradiol withdrawal. The bulk RNA‐Seq results and phosphoproteomic analysis show that endothelial SHP2 mechanistically enhances RIPK1 activity by dephosphorylating RIPK1Tyr380. This event activates downstream activator protein 1 (AP‐1) and instigates the inflammation response. Furthermore, targeting SHP2 using SHP099 (an allosteric inhibitor) or endothelial‐specific SHP2 deletion alleviates endothelial cell activation, macrophage infiltration, and EH progression in mice. Collectively, the findings demonstrate that SHP2 mediates the transition of endothelial activation from estradiol‐driven acute inflammation to macrophage‐amplified chronic inflammation. Targeting sterile inflammation mediated by endothelial cell activation is a promising strategy for nonhormonal intervention in estrogen‐related diseases. [ABSTRACT FROM AUTHOR]

Although obesity is an important risk factor for endometrial intraepithelial neoplasia (EIN) and uterine cancer, little is known about the trends in use of weight-loss therapy for patients with obesity with EIN and uterine cancer. We examined the use of weight-loss therapy among patients with obesity with EIN and uterine cancer. The Merative MarketScan Database was used to identify patients aged 18–70 years who were obese and diagnosed with EIN or uterine cancer. The primary treatment for EIN or uterine cancer was categorized as either primary hysterectomy or hormonal therapy. Nutrition counseling, bariatric surgeries, and weight-management medications were identified as weight-loss therapy. We analyzed trends in the use of any weight-loss therapies with Cochran-Armitage tests. A multivariable logistic regression model was developed to examine factors associated with weight-loss therapy use. Overall, 15,374 patients were identified, including 5561 (36.2%) patients with EIN and obesity, and 9813 (63.8%) patients with uterine cancer and obesity. Weight-loss therapy was utilized within 1 year after diagnosis in 480 (8.6%) patients with EIN and in 802 (8.2%) patients with uterine cancer. Use of any weight-loss therapy after diagnosis of EIN increased from 4.1% in 2009 to 12.6% in 2020 (P <.001), and the use of any weight-loss therapy after diagnosis of uterine cancer increased from 4.9% in 2009 to 11.4% in 2020 (P <.001). In a multivariable regression model, younger age and patients with high comorbidity score were associated with a higher likelihood of using any weight-loss therapy. Use of weight-loss therapy has increased, however there is still a significant underuse of this adjunctive therapy in patients with obesity with EIN or uterine cancer. • Weight-loss therapy among patients with obesity with EIN or uterine cancer has increased over the past decade. • Patients who were treated with primary hormonal therapy were more likely to receive weight-loss therapy. • Use of nutrition counseling and weight-management medication have increased, while bariatric surgery has decreased. [ABSTRACT FROM AUTHOR]

• The prevalence of atypical hyperplasia and endometrial cancer in premenopausal women ≤ 45 years with abnormal bleeding was 4.1% and 1.9%. • Risk factors identified: nulliparity (OR: 4.75, 95% CI [2.11–10.70]), PCOS (OR: 2.72, 95% CI [1.34–5.52]), and multiple polyps (OR: 2.33, 95% CI [1.23–4.41]). • Predicted probabilities of AH or EC increased with the number of risk factors, ranging from 1% to 33.6%. • Predicted probabilities of risk factor combinations may aid clinical decisions on endometrial sampling for patients ≤ 45 years with AUB. To assess the prevalence and risk factors for atypical hyperplasia (AH) or endometrial cancer (EC) in premenopausal women aged ≤ 45 years with abnormal uterine bleeding (AUB). This was a retrospective study of premenopausal patients aged 18 to 45 years who underwent hysteroscopy, dilation and curettage, or pipelle sampling at Inha University Hospital, South Korea, from 2014 to 2023. We used multivariable logistic regression analysis to identify risk factors and calculate the predicted probabilities of AH or EC with various combinations of these factors. Of 821 patients included in the study, 6.0 % were diagnosed with AH or EC. The significant risk factors identified were nulliparity (odds ratio (OR): 4.75, 95 % confidence interval (CI): 2.11–10.70), PCOS (OR: 2.72, 95 % CI: 1.34–5.52), and multiple polyps (OR: 2.33, 95 % CI: 1.23–4.41). The predicted probabilities of developing AH or EC increased with the number of risk factors present, ranging from 1 % to 33.6 %. The predicted probabilities within combinations of risk factors may be considered helpful in making better clinical decisions regarding endometrial sampling for patients ≤ 45 years with AUB. [ABSTRACT FROM AUTHOR]

• This is one of the largest studies focusing on the outcomes and prognosis of IVF treatment in EH patients. • ART is effective in patients with EH who have achieved CR after conservative treatment. • Controlling body weight and choosing ART methods as soon as possible may be beneficial for clinical outcomes. The aim was to analyze the clinical characteristics, controlled ovarian stimulation status, pregnancy outcomes, and major factors influencing live births in patients with endometrial hyperplasia (EH) undergoing IVF/ICSI for assisted reproduction, so as to identify potential intervention measures. Patients with EH who achieved complete remission (CR) after conservative treatment and who were undergoing their first IVF/ICSI cycle were included in this matched-pair study. Patients with normal endometriums were matched at a 1:2 ratio with the control group for the first cycle of controlled ovarian stimulation. Matching was based on age, and reproductive outcomes were analyzed. Among the 263 patients (including 51 cases with atypical endometrial hyperplasia) in the study group, the pregnancy rate after the first controlled ovarian stimulation cycle was 48.67 % (128/263), and the live birth rate was 34.98 % (92/263). Multiple logistic regression analysis revealed that maternal age, body mass index (BMI), and endometrial thickness were significantly associated with live births (P<0.001). Specifically, being aged ≥ 35 years (OR 0.450, 95 % CI 0.223–0.907) and having a BMI≥28 kg/m2 (OR 0.358, 95 % CI 0.161–0.798) were identified as unfavorable factors for a clinical live birth, while an endometrial thickness ≥ 10 mm was found to be a favorable factor. ART is effective in patients with EH who have achieved CR after conservative treatment. Avoiding unnecessary intrauterine procedures, controlling body weight appropriately, and choosing suitable ART methods as soon as possible may be beneficial for clinical outcomes. [ABSTRACT FROM AUTHOR]

• MSI-H/MMRd subtype: less responsive to fertility-sparing treatment; higher recurrence risk. • Patients with MSI-H/MMRd have low spontaneous conception and require assisted reproductive technology. • Cautiously recommend fertility-sparing treatment for MSI-H/MMRd patients. • Emphasize the need for comprehensive counseling. This systematic review and meta-analysis aimed to describe the oncological and reproductive outcomes of patients with MSI-H/MMRd endometrial carcinoma (EC) or atypical endometrial hyperplasia (AEH) undergoing fertility-sparing treatment. The study protocol was registered with the PROSPERO database (No: CRD42024530406). A systematic literature search in major electronic databases (PubMed, Embase, and Cochrane Library) was conducted from January 1, 2013 to August 10, 2024. The primary outcomes were complete remission (CR) rate and recurrence rate. Other outcomes included oncological outcomes in patients with Lynch syndrome and overall patient fertility status. The study included ten retrospective studies summarizing 66 patients with MSI-H/MMRd undergoing fertility-sparing treatment. The publication bias analysis was low. The length of follow-up varied from 3 to 164 months according to the different studies analyzed. After fertility-sparing treatment, 61.8 % of patients achieved CR, and 41.2 % of patients relapsed. Twelve patients were identified with germline mutations in Lynch syndrome, nine (75 %) achieved CR, and seven (77.8 %) relapsed. Only one study with active use of assisted reproductive technology reported a 1-year cumulative pregnancy rate of more than 60 % and more than half live births, while the remaining five studies assessed fertility outcomes and reported only one live birth. EC and AEH patients with the MSI-H/MMRd subtype had a low remission rate and high recurrence rate compared to conservative treatment. Caution is recommended when evaluating fertility-sparing therapy for patients with the MSI-H/MMRd subtype. [ABSTRACT FROM AUTHOR]

• Biopsy for asymptomatic postmenopausal women if endometrial thickness is ≥8 mm. • For 4-8 mm, consider biopsy after evaluating risk factors and blood flow signals. To determine the cutoff value for endometrial thickness (ET) that prompts a biopsy in asymptomatic postmenopausal women with an incidental finding of thickened endometrium, and to develop a risk prediction model. This is a retrospective cohort analysis of the clinical records of the Hysteroscopic Center of Fu Xing Hospital, Capital Medical University, Beijing, China. We collected asymptomatic postmenopausal women who presented with an ET of ≥4 mm (double-layer) as an incidental finding. We stratified the participants into non-malignant and malignant groups based on pathology results and assessed differences between the two groups. A receiver operating characteristic curve (ROC) was used to identify the cutoff value of ET for predicting endometrial malignancy. Logistic regression models were also constructed to predict the risk of malignancy. A total of 581 consecutive eligible cases were included. The optimal cutoff value for ET was 8 mm, with a maximum area under the curve (AUC) of 0.755 (95 % CI: 0.645–0.865). In addition to ET, the regression model incorporated diabetes, blood flow signal, BMI, and hypertension to predict the risk of malignancy. A ROC curve constructed for the model yielded an AUC of 0.834 (95 % CI: 0.744–0.924). It is reasonable to offer hysteroscopy and visually-directed endometrial biopsy for asymptomatic postmenopausal women when ET is 8 mm or above. For those with an ET between 4 and 8 mm, further decision to perform biopsy should be determined on an individual basis, considering risk factors and blood flow signals of the endometrium. [ABSTRACT FROM AUTHOR]

Hormonal contraception (HC) is a well-recognized protection against endometrial cancer (EC) in the general population. It has not been established if this is also applicable to women with Lynch syndrome (LS), a condition associated with a up to 50% lifetime risk of developing EC. The objective of this study was to evaluate if the use of HC influences the incidence of endometrial hyperplasia and EC in women with LS by comparing the histology of annual endometrial biopsies obtained in patients with LS who are using HC versus non-users. This is a retrospective cohort study conducted with endometrial biopsies obtained in women 30 to 50 years of age with LS. The Pearson Chi-square test was performed to compare the prevalence of cancer and hyperplasia in the HC users and in the non-HC users groups. A total of 164 endometrial biopsies obtained among 75 women were suitable for analysis. Among the 86 biopsies obtained in the non-HC group, 81.4% (70/86) were normal. Two cases of endometrial carcinoma (2.3%) and 6 endometrial hyperplasia without atypia were found (7.0%). Among the 78 biopsies performed in patients using HC, 78.2% (61/78) were normal. Three endometrial hyperplasia without atypia (3.8%) and three cases of EC were diagnosed (3.8%). This study suggests that, in women of 30 to 50 years of age with LS, the use of hormonal contraception does not seem to decrease the occurrence of endometrial hyperplasia/carcinoma on annual endometrial histology. [ABSTRACT FROM AUTHOR]

Objective: To present a novel technique for office resection of pedunculated endometrial polyps under ultrasound guidance. Methods: A prospective trial was conducted at an academic center where women with abnormal uterine bleeding (AUB) who were diagnosed an endometrial polyp following saline infusion sonogram (SIS), were offered polyp removal under ultrasound guidance using a universal grasping forceps (2.5 mm × 25 cm). The primary outcome was to evaluate the feasibility of this technique for complete removal of the polyp. The secondary outcomes were to evaluate the patients' pain score, satisfaction score using visual analogue score (VAS), and efficacy of the technique in alleviating symptoms in patients with AUB due to polyps. Results: Thirty patients participated, with a mean age of 54.8 ± 11 years. Average polyp volume was 1.87 cm3 and mean duration for polypectomy was 11 minutes 31 seconds. The median pain score immediately post‐procedure was 5 (0–9). We were unable to complete the procedure in two patients due to patient discomfort and poor visualization. Complete removal of polyp was ensured by checking for a thin endometrial echo at the end of the procedure and by performing SIS at 3‐months post‐procedure. Of the 22 patients who returned for follow‐up, 19 (86.36%) showed no evidence of polyp on SIS and all reported resolution of AUB symptoms. The median satisfaction score at the follow‐up was 10/10. Adequate pathology samples were obtained from all cases, diagnosing malignancy in one and endometrial hyperplasia in one patient. Conclusion: This technique offers safe and effective removal of pedunculated endometrial polyps in an office setting, avoiding the need for general anesthesia. It can be offered as a therapeutic option at the initial point of contact, providing symptom relief and tissue diagnosis while reducing costs and patient visits. [ABSTRACT FROM AUTHOR]

Background: Nesfatin-1 is a neuropeptide that regulates the hypothalamic-pituitary-gonadal axis and may play a role in uterus function. It is co-expressed with other peptides, such as phoenixin, which can influence sex hormone secretion. Our previous research has confirmed that phoenixin-14 is involved in the development of cystic endometrial hyperplasia (CEH) and pyometra in dogs. Therefore, based on the similarities and interactions between these neuropeptides, we hypothesized that nesfatin-1 might also regulate the reproductive system in dogs. This study aimed to determine the expression of nesfatin-1 and its interaction with phoenixin-14 in dogs with CEH or pyometra compared to healthy females, and concerning animals' body condition score (BCS 4–5/9 vs. BCS > 5/9). Results: The analysis of nesfatin-1 in the uterus of bitches consisted of qPCR, western blot and immunofluorescence assays, and ELISAs. The results showed significantly higher nesfatin-1 encoding gene, nucleobindin-2 mRNA (Nucb2) and nesfatin-1 protein expression in overweight females and those suffering from CEH or pyometra compared to healthy animals. The immunoreactivity of nesfatin-1 was elevated in the uteri of bitches with higher BCS > 5/9. Moreover, nesfatin-1 blood concentrations increased in all examined overweight bitches. In the case of phoenixin signals, we found opposite results, regardless of the female body condition score. Conclusion: The etiology of CEH and pyometra are not fully known, although we have expanded the level of knowledge with respect to the possible interaction of nesfatin-1 and phoenixin in female dogs' uteri. They interact oppositely. With increasing female body weight, the expression of nesfatin-1 in the uterus and its peripheral blood concentration increased. However, for female dogs affected by CEH and pyometra, a decreased level of phoenixin-14, irrespective of their body condition score is characteristic. This knowledge could be crucial in the development of biomarkers for these conditions, which may lead to earlier recognition. [ABSTRACT FROM AUTHOR]

AbstractIntroductionMethodsResultsConclusionsThe diagnostic workflow for endometrial carcinoma in postmenopausal asymptomatic women remains an ongoing dilemma. Whereas an ultrasonographic endometrial thickness greater than 4.0 or 5.0 mm is adequate for warranting further investigations in women with postmenopausal vaginal bleeding, there is still no unanimous consensus on what the ideal endometrial thickness cut-off should be, justifying additional inspection through endometrial sampling when bleeding is absent.A comprehensive overview of the most recent literature to summarize the clinical pathway necessary for the diagnostic assessment of a postmenopausal asymptomatic woman with increased ultrasonographic endometrial thickness.An endometrial thickness cut-off between 3.0 and 5.9 mm seems to show the lowest specificity while also reducing the chances of missing malignancy. If endometrial thickness can be a valid starting point, a careful evaluation of the other ultrasonographic endometrial features and a thorough scrutiny of patients’ risk factors are pivotal to standardizing the diagnostic process while avoiding overtreatment. Although preventing unnecessary procedures is crucial, stratifying the risk and proceeding with further investigations (preferably through outpatient or office hysteroscopically-guided targeted biopsies) should be the goal.Closer collaboration between different fields of medicine (ultrasonography, hysteroscopy, and oncology) is strongly encouraged to facilitate early diagnosis of asymptomatic postmenopausal women at risk of developing endometrial malignancy. [ABSTRACT FROM AUTHOR]

Aims: This study aims to examine cases identified with endometrial polyp and carcinoma originating from polyps in patients presenting with gynaecological problems, and to highlight the significance of risk factors contributing to malignancy. Materials and methods: The study comprised 203 patients who visited our clinic between January 2019 and 2024 with various gynaecological problems and were identified with endometrial polyps after a clinical, radiographic, and laboratory assessment. We retrospectively analysed data from 191 benign endometrial polyps and hyperplasia without atypia and 12 patients with endometrial polyps and underlying endometrial hyperplasia with atypia and/or endometrial carcinoma, diagnosed histopathologically after hysteroscopic resection, retrieved from our hospital's electronic archive system. Two hundred three participants were tested in the study, with 191 classifieds with benign tumours and 12 diagnosed with malignant tumours and atypical endometrial hyperplasia (premalignant). Cases were chosen according on consistent criteria for age, BMI, gravida, parity, abortion, educational level, smoking habits, operation history, and co-morbidities. After determining the sample size for the malignant group, patients from the control group were selected to be included in the study. Initially, patients with similar age and BMI distributions were included into the study. Next, the cases were analysed for similarities in gravida, parity, and abortion parameters, and those that matched were chosen. Following this step, the educational status was compared for resemblance, and examples with matching educational status were chosen. Consequently, the study covered a total of 34 patients, with 12 identified with malignant tumours and atypical endometrial hyperplasia (premalignant) and 22 with benign tumours. Two groups of cases were diagnosed with endometrial polyp, and risk factors that may cause the development of endometrial polyp and underlying carcinoma: age, gravida, parity, abortion, education level, smoking, previous operation history, comorbidity, gynaecological complaints, fasting blood sugar, CRP values, haemoglobin, and haematocrit were evaluated in terms of endometrial polyp sizes, endometrial thickness level, and endometrial polyp localization. By examining the pathological risk factors of these cases, particularly during the premenopausal period, the goal is to predict endometrial cancer, the most prevalent gynaecological cancer in women, along with its antecedents, and implement preventive measures proactively. Results: Age, BMI, gravida, parity, number of abortions, educational status, smoking status, operation history, co-morbidity, and complaint variables did not exhibit a statistically significant difference between the groups (p > 0.05). It was revealed that the FBG level, CRP level, Polyp length and Endometrial thickness level of the malignant group were statistically significantly higher than the benign group (p < 0.01) (p < 0.05). Upon analysing the FBG distribution among groups, it is noted that the ODDS ratio is 10.20 for FBG values of 122.5 and above (95% CI: 1.97 – 52.78). Upon analysing the CRP distribution by groups, it is noted that the ODDS ratio is 231 for CRP values of 9.7 and above (95% CI: 13.15 – 4058.67). Upon analysing the distribution of Polyp length based on groups, it was determined that the ODDS ratio is 13.5 for Polyp lengths of 2.25 and above (95% CI: 2.47 – 73.71). Upon analysing the distribution of EM thickness based on groups, it is shown that the ODDS ratio is 5.25 for EM thicknesses of 11 and above (95% CI: 1.09 – 25.21). Conclusion: Endometrial polyps are common benign growths that are typically not seen as cancer precursors but may be linked to cancer in people with advanced age. It is vital to remember that in cases of endometrial polyps, variables such as increasing polyp length, endometrial thickness, fasting glucose level, and elevated CRP levels are significant risk factors for the development of cancer associated with polyps. [ABSTRACT FROM AUTHOR]

Objectives: The most important phase in the endometrial pathologies diagnostics is the histological examination of tissue biopsies obtained under visual hysteroscopic control. However, the unclear visual diagnostics characteristics of subtle focal endometrial pathologies often lead to selection errors regarding suspicious endometrial lesions and to a subsequent false pathological diagnosis/underestimation of precancer or early-stage cancer. Methods: In this study, we investigate the potential of Multimodal Optical Coherence Tomography (MM OCT) to verify suspicious endometrial lesion regions before biopsy collection. We study the polarization (by cross-polarization OCT, CP OCT) and elastic (by compression OCT-elastography, C-OCE) properties of ex vivo endometrial tissue samples in normal conditions (proliferative and secretory phases to the menstrual cycle, atrophic endometrium) with endometrial hyperplasia (non-atypical and endometrial intraepithelial neoplasia) and endometrial cancer subtypes (low-grade, high-grade, clear cell and serous). Results: To the best of our knowledge, this is the first quantitative assessment of relevant OCT parameters (depth-resolved attenuation coefficient in co-[Att(co) values] and cross-[(Att(cross) values] polarizations and Young's elastic modulus [stiffness values]) for the selection of the most objective criteria to identify the clinically significant endometrial pathologies: endometrial intraepithelial neoplasia and endometrial cancer. The study demonstrates the possibility of detecting endometrial pathologies and establishing optimal threshold values of MM OCT criteria for the identification of endometrial cancer using CP OCT (by Att(co) values = 3.69 mm−1, Sensitivity (Se) = 86.1%, Specificity (Sp) = 92.6%; by Att(cross) values = 2.27 mm−1, Se = 86.8%, Sp = 87.0%) and C-OCE (by stiffness values = 122 kPa, Se = 93.2%, Sp = 91.1%). The study also differentiates endometrial intraepithelial neoplasia from non-atypical endometrial hyperplasia and normal endometrium using C-OCE (by stiffness values = 95 kPa, Se = 87.2%, Sp = 90.1%). Conclusions: The results are indicative of the efficacy and potential of clinical implementation of in vivo hysteroscopic-like MM OCT in the diagnosis of endometrial pathologies. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate characteristics of endometrial surveillance in women treated for breast cancer to build a clinical prediction model. Design: A multicentric retrospective cohort study was conducted at two tertiary-care university hospitals from January 2020 to June 2023. Perimenopausal and postmenopausal women treated for breast cancer were categorized into two groups: patients with and without diagnosis of endometrial malignancy (endometrial carcinoma) or premalignancy (atypical endometrial hyperplasia). Characteristics of breast cancer and ultrasonographic and hysteroscopic examinations were compared. A prediction model for endometrial malignancy was built using logistic regression. Predictive accuracy was assessed using the receiver operating characteristic (ROC) curve and goodness of fit using the Hosmer–Lemeshow test. Results: One hundred and thirty-two (28 with premalignancy or malignancy and 104 without malignancy) women were analyzed. A nomogram was produced for prediction model development utilizing the presence and duration in months of abnormal uterine (BL)eeding, ultrasound (US) vascular pattern and echogenicity and (H)ysteroscopic appearance of endometrium (BLUSH) as determined by logistic regression. Sensitivity and specificity were 79.17% and 95.19%, respectively, with an area under ROC curve of 0.965, indicating good accuracy. Good goodness of fit and prediction stability were indicated by the calibration curve and Hosmer–Lemeshow test (χ2 = 26.36; p = 0.999). Conclusions: Breast cancer survivors undergoing endometrial surveillance might benefit from a potentially useful prediction model based on hysteroscopic appearance, ultrasonographic uniformity of endometrium, Doppler flow and presence of abnormal uterine bleeding. [ABSTRACT FROM AUTHOR]

Lynch syndrome, also called hereditary non‐polyposis colorectal cancer, is an autosomal dominant disorder characterized by germline pathogenic mutations in DNA mismatch repair genes—resulting in increased susceptibility to colorectal, endometrial, and other tumors. This case report presents an incidental finding of endometrial cancer with Lynch syndrome during investigation for primary infertility. A 34‐year‐old woman presented to the fertility clinic with unexplained primary infertility. Investigations showed possible endometrial polyp, 13 × 11 mm in size. Hysteroscopic polypectomy and endometrial biopsy revealed complex endometrial hyperplasia amounting to endometroid adenocarcinoma. The case was discussed at the West of Scotland Gynecology‐Oncology MDT meeting—management options including fertility‐sparing treatment or radical surgery were presented to the patient and she opted for the latter. A total laparoscopic hysterectomy with bilateral salpingo‐oophorectomy was performed with pathology results consistent with well‐differentiated endometroid adenocarcinoma Stage 1A. Peritoneal washings showed no malignant cells. Genetic testing confirmed a diagnosis of Lynch syndrome. On further questioning, it was revealed that the patient had a strong family history of colon cancer but had not previously met the criteria for genetic testing. She was referred to colorectal surgeons and underwent colonoscopy. This showed no abnormality; she was therefore scheduled for 2‐yearly colonoscopic surveillance. Synopsis: Asymptomatic presentation of endometrial cancer in a patient found to have Lynch syndrome, discovered incidentally through workup for primary infertility. [ABSTRACT FROM AUTHOR]

Background: Endometrial cancer is the most common malignancy in women in developed countries, and its incidence is increasing annually. Due to the availability and cost‐effectiveness of serum markers of red cell distribution width (RDW), and mean platelet volume (MPV), we decided to investigate these two important markers in patients with endometrial cancer and assess their role in diagnosing the tumor and differentiate it from endometrial hyperplasia and other causes of bleeding. Methods: This is a case‐control study that examined the data of patients who were referred to Al‐Zahra Hospital during 2022–2023 with complaints of abnormal bleeding and underwent diagnostic curettage. Based on the pathology findings, the patients were divided into 3 groups, including endometrial cancer, endometrial hyperplasia, and control. The clinical characteristics and results of MPV and RDW were compared in these three groups. The IBM SPSS Statistics for Windows, Version 21.0. was used for data analysis. Results: In this study, 87 women were examined in three groups endometrial cancer, endometrial hyperplasia, and control with a mean age of 52.70 ± 11.63 years. The results showed that the endometrial cancer group, had higher gravida, underlying disease, history of radiation therapy, anticoagulant therapy, blood transfusion, surgery, and family history of cancer (p < 0.05). Meanwhile, the endometrial cancer group had lower menstrual age and history of using contraceptives than other groups (p < 0.05). In addition, in this study, the results indicated that the levels of MPV and RDW in the endometrial cancer group were significantly higher than in the endometrial hyperplasia and control groups (p < 0.05). Conclusion: Since MPV and RDW are cheap and accessible and can be easily obtained from complete blood count panels, they can be used as suitable diagnostic markers for endometrial cancer. However, conducting comprehensive multicenter prospective studies with a larger sample size can be helpful. [ABSTRACT FROM AUTHOR]

Objective Method Results Conclusion To explore the assisted reproductive outcomes of patients with atypical endometrial hyperplasia (AEH) and early‐stage endometrial cancer (EEC) who achieved complete remission after conservative treatment and to provide reference for clinical selection of appropriate conservative treatment.This retrospective cohort study included seven patients with EEC and 62 patients with AEH who underwent in vitro fertilization or intracytoplasmic sperm injection at the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University between August 2015 and October 2023. The authors divided the participants into two groups based on the type of fertility‐sparing treatment received: the oral medication group and the levonorgestrel‐releasing intrauterine system (LNG‐IUS) group. The primary outcome was the cumulative clinical pregnancy rate. Secondary outcomes included clinical pregnancy rate per transfer cycle, embryo utilization rate, and high‐quality embryo rate.The LNG‐IUS group had a significantly higher rate of usable embryos compared with the oral medication group (80.8% vs 91.1%, P = 0.005) and also had a thinner endometrial thickness on the day of embryo transfer. The cumulative clinical pregnancy rate was higher in the LNG‐IUS group compared with the medication group (46.7% vs 78.9%, P = 0.037), and the difference was statistically significant.For patients with AEH and EEC with fertility needs, the conservative treatment method of LNG‐IUS can achieve better assisted reproductive outcomes. [ABSTRACT FROM AUTHOR]

Background: Around 4% of women receive an endometrial cancer diagnosis before turning 40, mainly those without prior childbirth experience and a strong desire to preserve their ability to conceive. Consequently, for young patients diagnosed with atypical endometrial hyperplasia (AEH) or early endometrial carcinoma (EC), a fertility-preserving approach employing high-dose oral progesterone has been adopted. However, previous research has shown a notable relapse rate. Furthermore, the extended use of substantial oral progesterone doses may hinder ovarian function and raise the risk of weight gain, liver issues, blood clotting, and breast cancer. We previously assessed the clinical effectiveness and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based re-treatment for women with EC and AEH who did not respond to oral progestin therapy but achieved favorable treatment results and reproductive outcomes. Methods: This study will be an open-label, two-armed, randomized, investigator-initiated multicenter trial evaluating the combination of GnRH-a with the levonorgestrel-releasing intrauterine system or the combination of GnRH-a with an aromatase inhibitor (comprising a subcutaneous GnRH-a injection every 4 weeks and daily oral letrozole 2.5 mg). A total of 226 participants will be randomly allocated to one of the two treatment groups in a 1:1 ratio. The primary objective is to determine the effectiveness of GnRH-a-based re-treatment in achieving a complete response (CR) at 24 weeks for patients with AEH or EC. Secondary objectives include assessing the pregnancy rate 12 weeks after treatment, as well as post-treatment pregnancy outcomes and the rate of recurrence. Ethics and dissemination: The protocol received approval from the Institutional Review Board of Peking Union Medical College Hospital and from boards at five other institutions. The trial will adhere to the principles outlined in the World Medical Association's Declaration of Helsinki and follow Good Clinical Practice standards. The trial results will be disseminated through publication in a peer-reviewed journal. Conclusions: Prospective evidence supporting conservative treatment for EC and AEH is limited. There is a need for new approaches that can achieve higher CR rates with fewer side effects. This trial will assess the effectiveness of GnRH-a-based fertility-sparing treatment in obese women and recurrent patients, offering a promising alternative for patients with EC and AEH. Trial registration number: Chinese Clinical Trial Registry ChiCTR2200067099. Registered on December 27, 2022. [ABSTRACT FROM AUTHOR]

Background: Endometrial hyperplasia, characterized by excessive growth leading to endometrial thickening, is commonly observed in the premenopausal period. Its prevalence in postmenopausal women is approximately 15%, peaking between ages 50 and 60. This condition often manifests as abnormal uterine bleeding and can progress to malignancy, with varying risks depending on the type of hyperplasia. Purpose: This study aims to investigate the factors influencing endometrial thickness during the perimenopausal period and raise awareness among healthcare professionals about the importance of evaluating and caring for individuals with endometrial hyperplasia. Methods: Studies examining the association between various factors such as diabetes mellitus, hypertension, age, estrogen replacement therapy, anovulatory disorders, smoking, medications, genetic factors, and endocrine-related proteins and the development of endometrial hyperplasia were reviewed. The literature search encompassed relevant databases, including PubMed, Scopus, and Web of Science. Results: Research findings indicate significant associations between changes in gene expression of several factors and the development of endometrial hyperplasia. Notably, the risk of progression to cancer varies between non-atypical and atypical hyperplasia cases. Factors such as diabetes mellitus, hypertension, age, estrogen replacement therapy, anovulatory disorders, smoking, medications, Lynch syndrome, tamoxifen use, and alterations in gene expression of TNF-α, EGF, IGF-1, IGF-1R, and PTEN have been implicated in the pathogenesis of endometrial hyperplasia. Conclusion: This study underscores the importance of understanding the factors influencing endometrial thickness during the perimenopausal period. It emphasizes the pivotal role of healthcare professionals in evaluating and caring for individuals with this condition. [ABSTRACT FROM AUTHOR]

Background: Obesity is associated with a higher prevalence of endometrial hyperplasia, thereby increasing the risk of endometrial and ovarian cancers. The precise mechanisms linking obesity to endometrial hyperplasia remain unclear, but dysregulation of adipose tissue homeostasis is known to play a significant role. Hypertrophied adipocytes in obese individuals secrete various bioactive substances, including cytokines, growth factors, hormones, and metabolites. Additionally, hyperplastic adipocytes exhibit enhanced aromatase activity, leading to increased estrogen synthesis, which further promotes the development of endometrial hyperplasia. Purpose: The purpose of this study is to explore the anti-inflammatory and anti-proliferative activities of the poly unsaturated fatty acids. Methodology: An extensive literature survey has been performed to identify the role of adipokines and elevated endogenous estrogen levels in activating cell survival signaling pathways, such as PI3K/Akt/mTOR, MEK/ERK1, and JAK–STAT in endometrial cells and their possible role in Endometrial Hyperplasia. Further, the possible beneficial anti-inflammatory and anti-proliferative effects of polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) were explored. Results: Numerous studies suggest the beneficial role of dietary fats, such as EPA, DHA, and AA in modulating the growth of endometrium in obesity-induced endometrial hyperplasia. PUFAs can activate adenosine monophosphate-activated protein kinase (AMPK), which inhibits gluconeogenesis and lipogenesis. It also phosphorylates acetyl-CoA, leading to a decrease in malonyl-CoA, which inhibits mitochondrial CPT1. Additionally, AMPK activation promotes β-oxidation, and PPAR-γ mechanisms by down regulating the NF-kB pathway involved in endometrial hyperplasia. Conclusion: This review sheds light on the potential of PUFAs in mitigating estrogen synthesis, adipokine secretion, and endogenous aromatase activity in obesity induced endometrial hyperplasia. Furthermore, it critically evaluates the role and mechanisms of PUFAs in attenuating obesity-associated endometrial hyperplasia and reducing the risk of ovarian cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a medical condition that causes hormonal disorders in women in their childbearing years. The hormonal imbalance leads to a delayed or even absent menstrual cycle. Women with PCOS mainly suffer from extreme weight gain, facial hair growth, acne, hair loss, skin darkening, and irregular periods, leading to infertility in rare cases. Doctors usually examine ultrasound images and conclude the affected ovary but are incapable of deciding whether it is a normal cyst, PCOS, or cancer cyst manually. OBJECTIVE: To have access to the high-risk crucial PCOS and to detect the condition and the treatment aimed at mitigating health hazards such as endometrial hyperplasia/cancer, infertility, pregnancy complications, and the long-term burden of chronic diseases such as cardiometabolic disorders linked with PCOS. METHODS: The proposed Self-Defined Convolution Neural Network method (SD_CNN) is used to extract the features and machine learning models such as SVM, Random Forest, and Logistic Regression are used to classify PCOS images. The parameter tuning is done with lesser parameters in order to overcome over-fitting issues. The self-defined model predicts the occurrence of the cyst based on the analyzed features and classifies the class labels effectively. RESULTS: The Random Forest Classifier was found to be the most reliable and accurate among Support Vector Machine (SVM) and Logistic Regression (LR), with accuracy being 96.43%. CONCLUSION: The proposed model establishes better trade-off compared to various other approaches and works effectually for PCOS prediction. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of the levonorgestrel intrauterine system (LNG-IUS) versus megestrol acetate (MA) in inducing complete regression among women with atypical endometrial hyperplasia (AEH) who declined hysterectomy. Methods: In this single-center, open-label randomized controlled trial, we included 148 women with AEH who declined hysterectomy. We randomized participants to receive either daily oral MA 160 mg (n=74) or apply LNG-IUS (n=74) and scheduled their follow-up by endometrial sampling at 3, 6, 9, 12, 18, and 24 months. The success rate and duration until complete regression were the primary outcomes. Results: The mean duration until complete regression was 5.52 months (95% confidence interval [CI]=4.85-6.18) for the LNG-IUS group versus 6.87 months (95% CI=6.09-7.64) for the megestrol group (log-rank test p-value=0.011). The cumulative regression rate after 12 months was 91.9% with the LNG-IUS versus 77% with MA (p=0.026). Weight gain in the MA group vs LNG-IUS group after one year (4.7±4 kg vs. 2.7±2.6 kg, 95% CI=0.89-3.12; p=0.001) and after two years of therapy (7.8±5.1 kg vs. 4.1±2.9 kg, 95% CI=2.29-5.06; p<0.001). Conclusion: Compared to MA, the LNG-IUS was more efficacious in treating AEH in women who declined hysterectomy, especially those with moderate/severe obesity, with fewer adverse effects and less weight gain. Extending therapy to 12 months for persistent cases would improve regression rates with reasonable safety. Alternate hysteroscopic and office sampling seemed convenient for follow-up. [ABSTRACT FROM AUTHOR]

Purpose: The objective of the trial was to compare the regression rate of atypical endometrial hyperplasia (AEH) in patients treated with megestrol acetate (MA) vs. levonorgestrel-intrauterine device (LNG-IUS). We also aimed to assess the fertility and pregnancy outcomes in these patients. Methods: The study was a phase II multi-centre randomised controlled trial on the use of MA compared to LNG-IUS in the treatment of AEH conducted from January 2020 to January 2024 in Singapore. Women who were diagnosed with AEH and between 21 and 40 years old were included. The patients were randomised to receive either MA (160 mg orally daily) or LNG-IUS. The primary outcomes assessed were the regression rates at 3 months, 6 months and 9 months of treatment. The secondary outcomes assessed were the side effects, patient acceptability and fertility outcomes. Results: Thirty-six patients completed the trial. The overall regression rate was 88.9% by 9 months. There was no statistically significant difference in the 9-month complete regression rate between MA vs. LNG-IUS. There was also no significant difference in side effects and weight change between both arms. Nineteen patients were actively pursuing fertility after complete regression. There were 8 pregnancies achieved, with resultant 4 live births and 4 miscarriages. Conclusion: Our study confirms a high regression rate of AH with medical treatment. LNG-IUS is a non-inferior treatment compared to megestrol acetate. Successful pregnancy outcomes can be achieved after regression of AEH. Long-term studies of sufficient sample-size are needed to assess for fertility and pregnancy outcomes, risk of recurrence and long-term risk of malignancy. Trial registration number: The study was registered with the Health Science Authority (HSA) (License No.: CTA1900087) on September 5, 2019: https://eservice.hsa.gov.sg/prism/ct%5fr/enquiry.do?action=loadSpecificDetail. The trial was registered retrospectively on ClinicalTrials.gov (ID: NCT05492487) on April 7, 2022: https://clinicaltrials.gov/study/NCT05492487. [ABSTRACT FROM AUTHOR]

Endometrial intraepithelial neoplasia (EIN) and atypical hyperplasia (AH) are recognized precursors for endometrial cancer (EC). Most current guidelines do not recommend the routine surgical evaluation of lymph nodes (LN), although recent studies indicate increased use of sentinel lymph node (SLN) biopsy in patients with a preoperative diagnosis of EIN/AH. We aimed to evaluate the rates of positive LN and its effect on the incidence of upstaging of EIN/AH patients, complications, and adjuvant treatment administration. A systematic review and meta-analysis was conducted in the following databases: MEDLINE(R) using the OvidSP interface and PUBMED, Embase, Web of Science, Clinicaltrials.gov and Cochrane Library. Included were studies investigating lymph node evaluation in patients diagnosed with EIN/AH, presenting results of LN assessment and/or comparisons of hysterectomy results with and without lymph node assessment. This analysis was registered at PROSPERO International prospective register of systematic reviews (CRD42023443598). A total of 447 studies were initially identified through database searching. The current analysis includes 7 studies comprising 1791 atypical endometrial hyperplasia patients who underwent hysterectomy with lymph node assessment. The incidence of positive lymph nodes among those who had undergone any LN evaluation was found to be 1.1% (95% CI 0.3%–2%). The rate of positive LNs was 1.4% (95% CI 0.2%–1.9%) among those who had undergone specifically SLN. 319 (44.3%, 95% CI 34%–54.7%) patients of the patients initially diagnosed with EIN/AH (n = 699), were finally upgraded to EC diagnosis. Fifteen percent of the final EC diagnosed patients were treated with adjuvant treatment. No significant difference regarding complication rates was noticed. Our review indicates that the rate of metastatic LNs is <2% in patients undergoing surgical nodal evaluation for EIN/AH. However, the rate of complication for SLN mapping is low and may have an impact on postoperative therapy decisions in those diagnosed with malignancy. • We found that the rate of metastatic lymph nodes is <2% in patients undergoing surgical nodal evaluation for EIN/AH. • With that said, no significant difference regarding complication rates was noticed and overall complication rates were low. • Lymph node assessment may have an impact on postoperative therapy decisions in those diagnosed with malignancy. [ABSTRACT FROM AUTHOR]

Objective: Levonorgestrel intrauterine system (LNG-IUS) has been widely used in patients with endometrial carcinoma (EC), endometrial hyperplasia without atypical (EH), and atypical endometrial hyperplasia (AEH). The purpose of our Network meta-analysis (NMA) is to evaluate the efficacy of the treatments based on the LNG-IUS in patients with EC and EH with or without atypical. Methods: We examined PubMed, EMBASE, Web of Science and the Cochrane Library up to 22 April 2024 to determine studies reporting treatment outcomes in EC and EH patients receiving LNG-IUS therapy, LNG-IUS + metformin (MET), oral progestins (OP), etc. We used EndNote 9 to select studies, Jadad scale and NOS scale to assess quality, stata(16.0) and R (4.3.1) to analysis the data. Results: Overall, 28 studies involving 3752 patients were included in our NMA. As for EH patients, LNG-IUS (RR 1.21; 95% CrI [1.11, 1.34]) and LNG-IUS + MET (RR 323.57; 95% CrI [1.61, 214,223,188.1])] significantly increased CR rate in comparison with OP. Based on SUCRA, LNG-IUS + OP was the best treatment to improve CR(SUCRA = 67.2%) in patients with EC, whereas LNG-IUS + MET was superior in increasing CR (SUCRA = 99.8%) than any other treatments for EH patients. Besides, the ranking based on SUCRA illustrated that LNG-IUS alone was the best choice to raise CR rates (SUCRA = 76.7%) for AEH patients. In head-to-head meta-analysis, OP has a higher progression rate (RR 4, 95% CI 1.89–8.46, p = 0.062; I2 = 71.3%), a higher nausea rate (RR 1.93, 95% CI 1.24–3.01, p = 0.187; I2 = 40.4%) than LNG-IUS in patients with EH. In contrast, LNG-IUS had a irregular vaginal bleeding rates (RR 0.76, 95% CI 0.64–0.90, p = 0.034; I2 = 77.7%) than OP in EH patients. In addition, as for AEH patients, OP has a higher persistence rate (RR 4.31, 95% CI 1.43–13.00, p = 0.93; I2 = 0.0%) than LNG-IUS. Conclusion: According to the NMA, LNG-IUS related studies are feasible for conservative therapy in patients with EC and EH with or without atypical. Therefore, concerning the curative effect, we recommend LNG-IUS-based treatments as the best conservative therapy for EC and EH patients. However, future studies require large sample sizes and more outcomes to further evaluate the differences of treatment selections based on LNG-IUS. [ABSTRACT FROM AUTHOR]