Pregnancy outcomes in infertile patients with endometrial hyperplasia with or without atypia undergoing in vitro fertilization: the early-follicular long protocol is superior to midluteal long protocol.

Background: Although in vitro fertilization (IVF) in infertile patients with endometrial hyperplasia is common after drug treatment, the pregnancy outcomes are often unsatisfactory. Till date, no studies have reported the outcome of patients with endometrial hyperplasia treated using early-follicular long (EL) protocol and midluteal long (ML) protocol. Objective: To evaluate the pregnancy outcomes and disease prognosis of patients with endometrial hyperplasia with or without atypia undergoing IVF treatment with EL protocol or ML protocol. Methods: This was a retrospective study in university-affiliated reproductive medical center. A total of 138 patients with endometrial hyperplasia undergoing IVF treatment were included to compare the pregnancy outcomes and disease prognosis between EL and ML protocols. We further matched 276 patients with normal endometrium to compare the pregnancy outcomes between patients with endometrial hyperplasia and patients with normal endometrium under different controlled ovarian stimulation (COS) protocol. Results: In patients with endometrial hyperplasia, the clinical pregnancy rate (CPR) and live birth rate (LBR) were significantly higher in EL protocol than in ML protocol (61.8% vs. 43.5%, P=0.032; 50.0% vs. 30.6%, P= 0.022). In the ML protocol, patients with endometrial hyperplasia had significantly lower CPR and LBR than those with normal endometrium (43.5% vs. 59.7%, P=0.037; 30.6% vs. 49.2%, P=0.016). While in the EL protocol, they achieved similar CPR and LBR as patients with normal endometrium (61.8% vs. 69.7%, P=0.232; 50.0% vs. 59.9%, P=0.156). In patients with endometrial hyperplasia, COS protocol was an independent factor affecting clinical pregnancy (adjusted odds ratio [OR] 2.479; 95% confidence interval [CI] 1.154-5.327) and live birth (adjusted OR 2.730; 95% CI 1.249-5.966). After 1-10 years of follow-up, no significant difference was found in the recurrence rate of endometrial lesions between both treatment groups. Conclusions: For patients with endometrial hyperplasia undergoing IVF treatment, the EL protocol is superior to ML protocol, and in the EL protocol, they can achieve similar pregnancy outcomes as patients with normal endometrium.

Predictive factors of endometrial lesions in patients with abnormal uterine bleeding.

PURPOSE: To explore the risk factors of endometrial lesions in patients with abnormal uterine bleeding(AUB) and establish prediction models which can discriminate between different endometrial etiologies of AUB. MATERIAL AND METHODS: We conducted this cross-sectional study in consecutive 778 women with AUB who received ultrasound examination and endometrial histopathological examination. Models were developed to distinguish between normal endometrium and (1) endometrial lesions, (2) endometrial polyps, (3) endometrial hyperplasia without atypia, (4) endometrial atypical hyperplasia and endometrial carcinoma. RESULTS: 274 (35.2%) women had normal endometrium; 504 (64.8%) had endometrial lesions, including 337(43.3%) endometrial polyps, 139(17.9%) endometrial hyperplasia without atypia, 28(3.6%) endometrial atypical hyperplasia and endometrial carcinoma. Age (OR = 1.122, 95%CI 1.002-1.257, P < 0.001), ET (endometrial thickness, OR = 2.702, 95%CI 1.629-4.402, P < 0.001), and CA125(U/ml) (OR = 1.007, 95%CI 1.003-1.021, P < 0.001) are independent risk factors of endometrial lesions in women with AUB. BMI(OR = 1.109, 95%CI 1.067-1.433,P = 0.038), ET(OR = 20.741, 95%CI 16.136-98.842, P < 0.001), age(OR = 1.182, 95%CI1.031-1.433,P = 0.016)、CA125(U/ml) (OR = 1.690, 95%CI 1.506-1.929,P = 0.001), prevalence of hypertension(OR = 1.350, 95%CI 1.051-67.82, P = 0.014) and diabetes(OR = 1.108, 95%CI 1.008-20.194,P = 0.001) were independent risk factors for atypical hyperplasia and endometrial carcinoma in patients with AUB. The model we built could predict atypical hyperplasia and endometrial carcinoma with the sensitivity of 87.5%, specificity of 80.7% and the AUC of 0.921. CONCLUSION: In women with AUB, the new-built model based on age, BMI, endometrial thickness, hypertension, diabetes and CA125 could discriminate reliable between atypical hyperplasia, endometrial carcinoma and normal women. The model may be useful for management of AUB.

Effect of bariatric surgery on endometrial cancer regression as part of fertility sparing treatment.

INTRODUCTION: Obesity is a major risk factor in the development of endometrial cancer (EC) in young patients of reproductive age. Fertility sparing treatment is a viable option for a select group of patients with early EC, and involves systemic and intra-uterine hormonal therapy. Weight loss has been associated with improved outcomes in this group. Bariatric surgery (BS) has been shown to be the most efficient and durable method of weight loss in obese patients. However, there is a paucity of data studying the benefit of BS as part of fertility sparing treatment. METHODS: We present a retrospective case series of five patients who are undergoing fertility sparing treatment for early EC, who also underwent BS for treatment of obesity and related comorbidities. We aim to show early regression of EC for all the patients and also report on the other health benefits of BS. RESULTS: All five patients in the series achieved regression of EC within 6 months of undergoing BS. They also achieved significant weight loss consistent with previous studies, and three patients who had comorbidities related to obesity had remission of these conditions. One of the patients with EC regression also managed to conceive with IVF (In-vitro Fertilisation). CONCLUSION: Patients on fertility sparing treatment for early EC who underwent BS was associated with early regression within 6 months, significant weight loss and resolution of comorbidities. BS could be a promising component of fertility sparing treatment. Long term, prospective studies are required to confirm the benefits reported in this case series.

Endometrial cancer patients understanding and interest in weight loss surgery.

OBJECTIVE: Obesity is a risk factor for endometrial hyperplasia (EH), endometrial intraepithelial neoplasia (EIN), and early type 1 endometrial cancer (EC) in 70%-90% of patients and is often a significant contributor to overall morbidity and mortality due to comorbidities. In 2011, bariatric surgery (BS) with lifestyle modification was identified as an intervention for reduction in overall mortality as well as risk for gynecologic cancers (Tsui et al., 2021). Our aim was to assess awareness of obesity as a risk factor and understanding of BS in an underinsured obese patient population with EC or EH. METHOD: This IRB-approved survey was distributed to patients with type I EC or EH within the past 5 years and a BMI >30. Questions addressed demographics, health habits, cancer and obesity awareness, as well as benefits and concerns about undergoing BS. Information was provided about dietary requirements after BS, and then interest in BS was surveyed. RESULTS: 61.2% of surveyed patients were interested in bariatric surgery for weight loss after receiving education about the procedure. Interest in bariatric surgery was correlated with higher BMI, higher ideal and comfortable weight loss in pounds and higher estimated weight loss that could be obtained with bariatric surgery. Additionally, patients who were interested in BS had better understanding of the risks of obesity with cancer overall. CONCLUSION: Obese patients with history of EC/EIN/EH are aware of hazards associated with excess weight and understand the relationship between EC/EIN/EH diagnosis and obesity, and overall are very interested in BS as a modality to improve their health.

Identifying women 45 years and younger at elevated risk for endometrial hyperplasia or cancer.

OBJECTIVE: To estimate the prevalence of, and identify risk factors associated with, endometrial hyperplasia and/or cancer (EH/EC) in patients ≤45 years old undergoing endometrial sampling for abnormal uterine bleeding (AUB). METHODS: We performed a retrospective cohort study of patients 18-45 years old with AUB who underwent endometrial sampling between 2016 and 2019 within a US-based multi-hospital system using billing code queries. We used multivariable Poisson regression to identify factors associated with EH/EC and calculated prevalence stratified by these factors. We estimated predicted probabilities within combinations of characteristics in order to examine the range of risk in this population. RESULTS: Among 3175 patients, median age was 39 years (interquartile range [IQR]:35-43) and BMI was 29.7 kg/m2 (IQR: 24.2-36.9). Thirty-nine percent were non-Hispanic White, 41% non-Hispanic Black, 9% Hispanic, and 11% Asian/Other/Unknown. BMI and polycystic ovarian syndrome (PCOS) were associated with higher EH/EC risk; non-Hispanic Black race was associated with lower risk. EH/EC prevalence ranged from 2% in BMI <25 to 16% in BMI ≥50 kg/m2 (p-trend <0.001). These prevalence estimates differed by race/ethnicity with the lowest estimates in non-Hispanic Black patients (0.5% BMI <25 vs. 9% BMI ≥50) and highest in Hispanic patients (1.5% BMI <25 vs. 33% BMI ≥50). Accounting for combinations of risk factors, predicted probabilities were highest - 34-36% - among patients with PCOS, diabetes, BMI ≥50, and Hispanic or Asian/Other/Unknown race/ethnicity. CONCLUSIONS: When accounting for combinations of key risk factors, risk of EH/EC in patients ≤45 years old with AUB ranges widely; the more nuanced estimates of risk presented here could help inform clinical decision-making about endometrial sampling in this population.

Comparison of the effect of levonorgestrel-intrauterine system with or without oral megestrol acetate on fertility-preserving treatment in patients with atypical endometrial hyperplasia: A prospective, open-label, randomized controlled phase II study.

OBJECTIVE: To compare the effects of levonorgestrel-intrauterine system (LNG-IUS) with or without oral megestrol acetate (MA) versus MA alone on fertility-preserving treatment in patients with atypical endometrial hyperplasia (AEH). METHODS: This was a single-center phase II study with an open-label, randomized, controlled trial conducted between July 2017 and June 2020 at the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. A total of 180 patients (18-45 years) with primary AEH were randomly assigned (1:1:1) to the MA (N = 60), LNG-IUS (N = 60), or MA + LNG-IUS (N = 60) groups, in which the patients received MA (160 mg orally daily), LNG-IUS, or MA + LNG-IUS (MA 160 mg orally daily plus LNG-IUS), respectively. The primary endpoint was complete response (CR) rate at 16 weeks of treatment. The secondary endpoints were CR rate at 32 weeks of treatment, adverse events, and recurrence and pregnancy rates. All analyses were conducted in a modified intention to treat (ITT) population who underwent randomization and in whom treatment was initiated. RESULTS: The Kaplan-Meier estimate of 16-week CR rates (with 95% confidence interval) were 19.2% (9.0-29.4%) in the MA group, 35.0% (22.8-47.2%) in the LNG-IUS group, and 29.4% (17.2-41.6%) in the MA + LNG-IUS groups. Side effects such as weight gain, increased nocturnal urine, night sweat, insomnia and edema face seemed to occur less frequently in LNG-IUS group compared with MA group. No difference was found among groups regarding second endpoints. CONCLUSIONS: LNG-IUS or LNG-IUS plus MA did not show significant therapeutic benefit compared with MA alone. Further studies including sufficient sample-size are needed to validate these findings due to the underpowered design of this trial. FUNDING: This study was supported by the National Key Research and Development Program of China (Grant No 2019YFC1005200 and 2019YFC1005204), Shanghai Medical Centre of Key Programs for Female Reproductive Diseases (Grant No. 2017ZZ010616), Shanghai sailing program (Grant No. 19YF1404200), and Shen Kang clinical project (SHDC22021219). Trial registrationClinicalTrials.govNCT03241888. https://www. CLINICALTRIALS: gov/ct2/show/NCT03241888?term=NCT03241888&draw=2&rank=1.

The role of hysteroscopy in fertility preservation in endometrial cancer and atypical endometrial hyperplasia: a semi-systematic literature review.

PURPOSE: Endometrial premalignancies are among the common reasons for outpatient gynecology visits among women in reproductive ages. Due to the continued increase in global obesity incidence among them, endometrial malignancies are expected to become even further prevalent. Hence, fertility-sparing interventions are essential and needed. In this semi-systematic literature review, we aimed to investigate the role of hysteroscopy in fertility preservation in endometrial cancer and atypical endometrial hyperplasia. Our secondary goal is to analyze the pregnancy outcomes following fertility preservation. METHODS: We conducted a computed search in PubMed. We included original research articles including hysteroscopic interventions in pre-menopausal patients with endometrial malignancies and premalignancies who underwent fertility-preserving treatments. We collected data on medical treatment, response, pregnancy outcomes, and hysteroscopy. RESULTS: Of the query results (n = 364), our final analysis included 24 studies. Overall, 1186 patients with endometrial premalignancies and endometrial cancer (EC) were included. More than half of the studies were retrospective design. They included almost ten different forms of progestins. Of the reported pregnancies (n = 392), the overall pregnancy rate was 33.1%. The majority of the studies used operative hysteroscopy (87.5%). Only three (12.5%) reported their hysteroscopy technique in detail. Although more than half of the studies did not provide any information on adverse effects due to hysteroscopy, there were no serious adverse effects among the reported ones. CONCLUSION: Hysteroscopic resection may increase the success rate of fertility-preserving treatment of EC and atypical endometrial hyperplasia. The clinical significance of the theoretical concern of the dissemination of cancer is not known. Standardization of the use of hysteroscopy in fertility-preserving treatment is needed.

Endometrial Thickness Measurement as Predictor of Endometrial Hyperplasia and Cancer in Perimenopausal Uterine Bleeding: Cross-Sectional Study.

BACKGROUND: Endometrial thickness (ET) measurement was an alternative method for predicting abnormal endometrial pathology in postmenopausal bleeding. Cut-off value of ET measurement could not be use in perimenopausal bleeding. OBJECTIVE: Aim of this study was to investigate appropriate ET cut-off value for perimenopause women with abnormal uterine bleeding (PEMB) and abnormal endometrial histopathology. MATERIAL AND METHODS: This was a cross-sectional study. PEMB at Bhumibol Adulyadej Hospital between July 2018 and June 2022 were recruited. Subjects who met inclusion criteria underwent ET measurement and endometrial biopsy via endometrial aspirator. Participants who had histopathology report of endometrial hyperplasia and more were classified as the study group. The Control group were subjects with no endometrial hyperplasia or cancer. Demographic and clinical character data were included. Correlation of ET and endometrial histopathology were calculated for statistical significance. RESULTS: A total of 304 cases were included. After exclusion, 254 subjects were recruited for this study. There were 22 and 232 cases in the study and control groups, respectively. The mean age and body mass index (BMI) of participants were 44.7 years old and 27.5 kg/m2, respectively. Prevalence of endometrial hyperplasia and cancer in perimenopausal uterine bleeding were 7.5 (19/254) and 1.2 (3/254) percent, respectively. Endometrial thickness equal to and more than 8 mm was associated with abnormal endometrial histopathology with statistical significance. Age, BMI, nulliparity, anovulatory bleeding history, hypothyroidism, diabetes mellitus and anovulation state of both groups were comparable. CONCLUSIONS: Endometrial thickness equal or more than 8 mm were significantly associated with endometrial hyperplasia or more among perimenopausal women with abnormal uterine bleeding.

Acceptability of bariatric surgery in people with endometrial cancer and atypical hyperplasia: A qualitative study.

OBJECTIVE: In young individuals with obesity, infertility, and endometrial cancer, significant, sustained weight loss through bariatric surgery may result in a durable oncologic and reproductive response. However, it is not known whether bariatric surgery is acceptable to this patient population. We performed a qualitative study to understand the acceptability of bariatric surgery in young individuals with obesity and endometrial cancer or atypical hyperplasia. STUDY DESIGN: All participants were of reproductive age with body mass index [BMI] ≥ 35 and grade 1 endometrial cancer or atypical hyperplasia. Semi-structured interviews were used to explore participant perception of their weight, fertility, and the possibility of bariatric surgery as part of the treatment strategy for their endometrial cancer/atypical hyperplasia. Thematic saturation was reached after 14 interviews. RESULTS: Fourteen participants with a median age of 34 years (range 27-38) and BMI of 42 (33-64) were interviewed. Participants were reluctant to accept bariatric surgery as a treatment option due to 1) lack of knowledge about the procedure, 2) stigma attached to bariatric surgery, and 3) fear of the risks associated with bariatric surgery. Their perception towards their weight, fertility, and cancer diagnosis was characterized by concepts of 'helplessness', 'isolation', 'frustration', and 'guilt'. We observed a significant gap in participant understanding of the complex interplay between their cancer, infertility, and obesity. CONCLUSIONS: More support and resources are required, with patient-oriented counseling focused on the implication of their weight on their cancer diagnosis and fertility, before presenting bariatric surgery as a treatment option.

Does endometriosis increase the risks of endometrial hyperplasia and endometrial cancer?

OBJECTIVE: The risk of developing endometrial hyperplasia after diagnosis of endometriosis has not been determined. Moreover, the risk of endometrial cancer associated with endometriosis is unclear. This nationwide population-based study investigated the associations of endometrial hyperplasia and endometrial cancer with endometriosis, after adjusting for covariates. METHODS: This population-based observational study analyzed data from the Korean National Health Insurance (NHI) database, including 147,869 women who were diagnosed with endometriosis from 2002 to 2017, with each patient matched to 20 control women without endometriosis. Cox proportional hazard regression analyses were performed to estimate the hazard ratios (HRs) of endometrial hyperplasia, endometrial cancer, and mortality from endometrial cancer. RESULTS: Among three million women in this population, 16,377 women were diagnosed with endometrial hyperplasia, and 1795 women were diagnosed with endometrial cancer over 19,931,794 person-years of follow-up. Women with endometriosis were at significantly higher risks of endometrial hyperplasia (adjusted hazard ratio [aHR] 1.85, 95% confidence interval [CI] 1.75-1.95), and endometrial cancer (aHR 1.35, 95% CI 1.12-1.63) were compared with control women after adjustment for covariates. A diagnosis of endometriosis did not affect survival in patients with endometrial cancer. CONCLUSION: The risks of endometrial hyperplasia and endometrial cancer were found to be significantly higher in women with than without endometriosis. The presence of endometriosis did not affect overall survival in women with endometrial cancer. Additional long-term prospective studies with adequate control of confounders are needed.

Rare case of coexisting ovarian Brenner tumour and ovarian stromal hyperplasia presenting with persistent endometrial hyperplasia following treatment with levonorgestrel-intrauterine system.

Endometrial hyperplasia (EH) is a precursor of endometrial cancer. It arises in an environment of unopposed oestrogen. Treatment is based on a combination of weight management, diet and exercise, and the use of progestogens either via a levonogestrel-intrauterine system (LNG-IUS) or orally. The LNG-IUS is the first-line recommendation for EH without atypia. Recurrences are rare, and any recurrences despite prolonged treatment and control of risk factors necessitate a thorough consideration of other oestrogenic sources. This case report presents a rare case of a coexisting ovarian Brenner tumour and ovarian stromal hyperplasia in a menopausal patient in her 50s with recurrent EH despite earlier regression. The above histology may have provided the additional oestrogenic influence. This patient subsequently underwent a definitive hysterectomy and bilateral salpingo-oophorectomy (BSO). It is important to maintain a high index of suspicion for potential oestrogenic influences in cases of refractory EH that are not identifiable on imaging. BSO should be considered at the time of hysterectomy in such cases of unidentified oestrogenic foci.

Trend changes and factor analysis of endometrial hyperplasia in patients with polycystic ovarian syndrome based on the Korean National Health Insurance Database.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with an increased risk of other gynecological disorders, such as endometrial hyperplasia (EH). However, substantial factors in the comorbidity of EH and PCOS remain to be investigated. We analyzed trend changes in PCOS and factors related to the comorbidity of PCOS and EH using data from the Korea National Health Insurance (KNHI) claims database. METHODS: The data for this population-based study of people diagnosed with PCOS or EH in Korea from 2009 to 2016 were collected from the KNHI claims database between 2007 and 2017. We conducted a trend analysis of the prevalence and incidence of PCOS and EH. In addition, we performed a logistic regression analysis to identify risk factors associated with EH incidence in people with PCOS using the matched case-control methodology. RESULTS: The average annual growth rate of the incidence of PCOS was 14.1% from 2009 to 2016, whereas the EH rate increased by only 3.4% annually. Comorbidities, type 2 diabetes, obesity, hypertension, hyperlipidemia, and infertility, increased the risk of EH in PCOS patients. Additionally, the cumulative duration of oral contraceptive & progestin treatment for PCOS correlated highly with the comorbidity of EH and PCOS. CONCLUSIONS: We confirmed the relationship between PCOS and EH using big data suitable for time series analyses of the diagnosis and treatment of diseases. Endometrial evaluation should be done with more caution if oral contraceptives & progestins have been used for a long time.

Metabolic syndrome is an independent risk factor for time to complete remission of fertility-sparing treatment in atypical endometrial hyperplasia and early endometrial carcinoma patients.

OBJECTIVE: Fertility-sparing treatment of atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EC) patients has recently emerged important social health topic. This study is designed to explore the risk factors for time to complete remission (CR) of fertility-sparing treatment in woman with AEH and early EC. METHODS: A retrospective study was designed with clinical data from 106 patients admitted between January 2012 to December 2019. Univariate and multivariate logistic analysis were used to explore independent risk factors for time to CR. These factors were employed in receiver operator characteristic (ROC) curve and the decision curve analysis (DCA) to evaluate predictive accuracy of time to CR. Stratified analysis and interactive analysis was also performed for more in-depth perspective. RESULTS: Univariate analysis showed that fasting blood glucose levels (FBG, OR = 1.6, 95%CI: 0.6-2.5, P = 0.020), metabolic syndrome (MetS, OR = 3.0, 95%CI: 1.1-5.0, P = 0.003), and polycystic ovary syndrome (PCOS, OR = 2.0, 95%CI: 0.5-3.4, P = 0.009) were associated with time to CR. Among these factors, multivariate analysis confirmed MetS (OR = 3.1, 95%CI: 1.0-5.2, P = 0.005) was an independent risk factor. The area under the ROC curve (AUC) of MetS was higher than FBG and PCOS (AUC = 0.723 vs 0.612 and 0.692). The AUC of FBG combined with PCOS was 0.779, and it was improved to 0.840 when MetS was included (P < 0.05). Additionally, MetS played different roles in time to CR in various groups. Moreover, we found high-density lipoprotein (HDL) and MetS had an interactive effect for time to CR. CONCLUSION: MetS is an independent risk factor for time to CR and should be taken seriously in fertility-sparing management of AEH and early EC patients.

A Prospective Cohort Study of Metformin as an Adjuvant Therapy for Infertile Women With Endometrial Complex Hyperplasia/Complex Atypical Hyperplasia and Their Subsequent Assisted Reproductive Technology Outcomes.

Objective: To investigate the adjuvant efficacy of metformin treatment to achieve pathological complete response (CR) in patients with endometrial complex hyperplasia (CH) and complex atypical hyperplasia (CAH), and secondarily, to evaluate their pregnancy outcomes after following assisted reproductive technology (ART). Study Design: This prospective cohort study analyzed 219 patients diagnosed with infertility and CH/CAH from January 2016 to December 2020. Among these patients, 138 were assigned to the control group (progesterone alone) and 81 were assigned to the study group (progesterone+metformin). After 8/12 weeks of therapy, the treatment responses were assessed by histological examination of curettage specimens obtained by hysteroscopy. Once the pathological results indicated CR, the patients were able to receive ART. The ART treatment and follow-up data of these patients were collected and analyzed. Results: 116 patients in the control group achieved CR, compared with 76 patients in the study group. The CR rate in the control group was significantly lower than that in the study group (P=0.034). We then divided the patients into subgroups to compare the treatment responses. In the subgroup analyses, patients with body mass index (BMI) ≥25 kg/m2 and patients with polycystic ovarian syndrome (PCOS) had higher CR rates in the metformin group compared with the control group (P=0.015, P=0.028 respectively). Subsequently, 68 patients in the control group and 47 patients in the study group received an ART cycle. We examined the pregnancy indications and found no significant differences in the clinical pregnancy rate and live birth rate between the two groups (P>0.05). Conclusion: Regression of CH/CAH may be improved by progesterone+metformin compared with progesterone alone. The effect was particularly pronounced in patients with BMI ≥25 kg/m2 and patients with PCOS. Metformin had no obvious effect on subsequent ART outcomes. The trial is registered on the publicly accessible website. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=15372, identifier ChiCTR-ONR-16009078.

Nodal Assessment in Endometrial Atypical Hyperplasia.

OBJECTIVE: Atypical endometrial hyperplasia (AH) is the neoplastic precursor more often associated with endometrial cancer (EC). Nowadays, 25-50% of patients subjected to hysterectomy for preoperative AH are diagnosed with EC at the final pathological analysis. Furthermore, there is no consensus on which preoperative AH patients would benefit from sentinel lymph node mapping. This study aimed to evaluate nodal assessment and preoperative cancer risk factors in preoperative AH patients undergoing nodal surgical staging. METHODS: Patients undergoing surgical treatment for AH were retrospectively included in the analysis. Patients were divided into two groups (AH and EC groups) based on the final surgical pathology. The ESGO/ESTRO/ESP risk classification was used for EC cases. DESIGN: This was a retrospective study. RESULTS: Of the 207 AH patients treated, 152 cases met the inclusion criteria. Among preoperative AH patients with final EC diagnosis, 39 patients were in the low-risk group (25.7%), 8 in the intermediate-risk group (5.3%), 4 in high-intermediate (2.6%), and 3 patients were allocated in the high-risk group (2.0%). Fifty-four total patients underwent nodal surgical staging. Only one nodal micrometastasis (0.7%) was found at ultrastaging. Multivariate analysis showed abnormal uterine bleeding (AUB) (p = 0.01), hypertension (p < 0.01), and endometrial thickness ≥20 mm (p = 0.02) statistically more represented in patients with EC at final surgical analysis. EC risk was 2.9 (95% CI: 1.29-6.48) in AUB, 2.7 (95% CI: 1.06-6.92) in hypertension, and 3.1 (95% CI: 1.19-7.97) in endometrial thickness ≥20 mm cases. LIMITATIONS: The present study has limitations inherent in its retrospective nature. CONCLUSION: The overall risk of nodal metastases in preoperative AH patients was low. Conversely, 9.9% of the preoperative AH patients belonged to the intermediate or high-risk group for EC at the final histological examination. Preoperative cancer risk factors would identify AH patients for whom nodal staging could be suggested.

Prediction of Factors Associated with Abnormal Uterine Bleeding by Transvaginal Ultrasound Combined with Bleeding Pattern.

In order to explore the ability of vaginal ultrasound combined with bleeding pattern to predict factors related to abnormal uterine bleeding (AUB), a total of 205 patients with abnormal uterine bleeding were selected as experimental subjects. According to the corresponding diagnostic criteria, patients were divided into the endometrial polyp group (56 cases), endometrial hyperplasia and canceration group (84 cases), and normal cycle endometrial group (65 cases). The efficiency of the method was determined by comparing the prediction efficiency of the single/joint model. The results showed that there were statistically significant differences in the body mass index, dysmenorrhea, endometrial thickness, diabetes, hypertension, and polycystic ovary syndrome among the three groups, P < 0.05. The sensitivity, specificity, positive predictive value, negative predictive value, and Youden index of endometrial polyp diagnosis were 86.89%, 88.12%, 83.54%, 90.11%, and 0.74, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and JordAn index in diagnosing endometrial hyperplasia and canceration were 96.71%, 98.40%, 96.54%, 98.24%, and 0.96, respectively. In summary, the body mass index, dysmenorrhea, endometrial thickness, diabetes, hypertension, and polycystic ovary syndrome were related factors, and the combination of vaginal ultrasound and bleeding pattern had a stronger predictive power for abnormal uterine bleeding.

Excess Heme Promotes the Migration and Infiltration of Macrophages in Endometrial Hyperplasia Complicated with Abnormal Uterine Bleeding.

In patients, endometrial hyperplasia (EH) is often accompanied by abnormal uterine bleeding (AUB), which is prone to release large amounts of heme. However, the role of excess heme in the migration and infiltration of immune cells in EH complicated by AUB remains unknown. In this study, 45 patients with AUB were divided into three groups: a proliferative phase group (n = 15), a secretory phase group (n = 15) and EH (n = 15). We observed that immune cell subpopulations were significantly different among the three groups, as demonstrated by flow cytometry analysis. Of note, there was a higher infiltration of total immune cells and macrophages in the endometrium of patients with EH. Heme up-regulated the expression of heme oxygenase-1 (HO-1) and nuclear factor erythroid-2-related factor 2 (Nrf2) in endometrial epithelial cells (EECs) in vitro, as well as chemokine (e.g., CCL2, CCL3, CCL5, CXCL8) levels. Additionally, stimulation with heme led to the increased recruitment of THP-1 cells in an indirect EEC-THP-1 co-culture unit. These data suggest that sustained and excessive heme in patients with AUB may recruit macrophages by increasing the levels of several chemokines, contributing to the accumulation and infiltration of macrophages in the endometrium of EH patients, and the key molecules of heme metabolism, HO-1 and Nrf2, are also involved in this regulatory process.

Analysis of IVF/ICSI outcomes in infertile women with early-stage endometrial cancer and atypical endometrial hyperplasia after conservative treatment.

PURPOSE: To investigate the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes and identify factors that might affect live births in patients with early-stage endometrial cancer (EEC) and atypical endometrial hyperplasia (AEH). METHODS: This retrospective study was performed in a tertiary hospital. Patients (n = 123) with EEC or AEH, who underwent IVF/ICSI treatment between January 2010 and December 2019, were divided into a live birth group and a non-live birth group. Clinical characteristics and IVF/ICSI outcomes were assessed. RESULTS: A total of 123 patients (28 with EEC and 95 with AEH) underwent 215 ovarian stimulation cycles, resulting in 121 fresh embryo transfer (ET) and 108 frozen-thawed ET. Among 229 ET cycles, 91 (23.7%) of 384 embryos were implanted and 86 pregnancies were achieved, including five ectopic pregnancies (5.8%), 28 miscarriages (32.6%), and 53 live births (61.6%). The clinical pregnancy and live birth rates in each ET cycle were 37.6% and 23.1%, respectively. Fifty-one patients gave birth to 57 live neonates, and the cumulative live birth rate was 41.46%. Multiple logistic regression analysis showed that maternal age, histological type, thin endometrium, and time after complete remission (CR) to IVF cycle started were significantly associated with live births. CONCLUSIONS: The live birth rate after IVF/ICSI is promising in infertile patients with EEC and AEH. A shorter interval between CR and IVF/ICSI treatment might be a positive factor, while age > 35 years, endometrial thickness < 8 mm on the day of ET, and degree of endometrial lesion progressing into carcinoma can negatively influence IVF/ICSI outcomes.

Role of metformin in functional endometrial hyperplasia and polycystic ovary syndrome involves the regulation of MEG3/miR­223/GLUT4 and SNHG20/miR­4486/GLUT4 signaling.

Metformin (MET) can effectively treat endometrial hyperplasia (EH), and the expression of glucose transporter type 4 insulin­responsive (GLUT4) is closely associated with the development of EH. The present study aimed to verify the effect of MET in functional EH and polycystic ovary syndrome (PCOS). H&E staining was performed to analyze the severity of EH, and immunohistochemistry was performed to evaluate the expression of GLUT4 in the endometrium of PCOS rats. Reverse transcription­quantitative PCR was used to calculate the expression of long non­coding (lnc)RNA­maternally expressed gene 3 (MEG3), lncRNA­small nucleolar RNA host gene 20 (SNHG20), GLUT4 mRNA, microRNA (miR)­223 and miR­4486. Sequence analysis and luciferase assays were performed to explore the regulatory relationship among certain lncRNAs, miRNAs and target genes. EH in PCOS rats was efficiently inhibited by MET administration. The increased expression of GLUT4 in PCOS rats was attenuated by MET treatment. Moreover, the expression levels of lncRNA­MEG3 and lncRNA­SNHG20 were significantly inhibited in the endometrium of PCOS rats. MET treatment also showed remarkable efficiency in restoring the expression of lncRNA­MEG3 and lncRNA­SNHG20. Meanwhile, the expression levels of miR­223 and miR­4486 were notably elevated in the endometrium of PCOS rats, while MET treatment reduced the expression of miR­223 and miR­4486 in PCOS rats. Furthermore, a luciferase assay confirmed the inhibitory relationship between miR­223 and lncRNA­MEG3/GLUT4 expression, as well as between miR­4486 and lncRNA­SNHG20/GLUT4 expression. GLUT4 knockdown restored the decreased viability of HCC­94 cells induced by overexpression of lncRNA­MEG3. To conclude, MET exhibited a therapeutic effect in the treatment of EH by modulating the lncRNA­MEG3/miR­223/GLUT4 and lncRNA­SNHG20/miR­4486/GLUT4 signaling pathways. This work provides mechanistic insight into the development of EH.

Sonoelastography evaluation in the diagnosis of endometrial pathology combined with chronic endometritis in infertile women.

Endometrial pathology, including hyperplastic processes in the structure of reproductive disorders, occupies one of the leading places along with inflammatory diseases of the pelvic organs, contributing to infertility in 80% of cases and irregular menstrual cycle in 40-43%. This study aims to optimize the diagnostic algorithm in patients with endometrial hyperplasia combined with chronic endometritis and determine qualitative indicators of compression sonoelastography in patients with endometrial pathology and infertility. A comprehensive clinical and laboratory examination of 90 infertile patients aged 25 to 45 years with endometrial hyperplasia combined with chronic inflammation, retention cysts, and benign ovarian tumors was carried out. The results of clinical-laboratory and complex ultrasound examination with compression sonoelastography were compared with the data of pathomorphological and immunohistochemical studies. A high percentage of pelvic inflammatory disease (55.0%), benign lesions of the cervix (67.5%), hyperplastic processes of the myometrium (37.5%), an increasing number of polyps by 2.9 times, leiomyomas and adenomyosis - by 2.3 times (p<0.05) was established. In the case of a combination of endometrial hyperplasia and ovarian cysts, a high percentage of comorbidity of gynecological pathology is verified (37.8%), and the use of compression sonoelastography allows to establish class II and class III elastograms in 91.1% of cases which characterize benign endometrial lesions, reduce the number of false-positive results in 95.6% of cases, correctly interpret the nature of pathological changes and increase the sensitivity of ultrasound techniques.