Atypical Endometrial Hyperplasia

SHAPE-ENDO is a single-center, open-label, pilot randomized clinical trial conducted at Hospital Universitari de Bellvitge in Barcelona, Spain. The study will evaluate the feasibility, safety, and acceptability of comparing two treatment strategies in women with atypical endometrial hyperplasia/endometrial intraepithelial neoplasia or low-risk endometrioid endometrial cancer and grade III obesity, defined as BMI ≥40 kg/m². Eligible participants will be randomized in a 1:1 ratio to one of two arms. The control arm will undergo standard immediate surgery according to the institutional clinical protocol. The experimental arm will receive the SHAPE-ENDO multimodal pre-surgical optimization strategy before surgery. The SHAPE-ENDO strategy includes metabolic treatment with semaglutide/Wegovy®, local hormonal therapy with a levonorgestrel-releasing intrauterine device/Mirena® with or without oral medroxyprogesterone acetate/Progevera®, a structured nutritional program, adapted physical exercise, and scheduled oncologic surveillance with clinical evaluation, imaging, and endometrial biopsy with or without hysteroscopy. The experimental strategy will initially last 28 weeks. In participants with clinical, metabolic, or anthropometric benefit, adequate tolerance, and no evidence of tumor progression, the strategy may be extended up to 54 weeks before surgery. The primary objective is to evaluate the feasibility, safety, and acceptability of the randomized trial design. Primary feasibility outcomes include recruitment rate, acceptance of randomization, retention, adherence to the assigned intervention, completion of the SHAPE-ENDO strategy, progression during the optimization period, and the proportion of participants in the experimental arm who reach surgery without tumor progression. Secondary outcomes include perioperative morbidity, histological response in the experimental arm, metabolic and anthropometric changes, quality of life, treatment adherence, safety and tolerability, and exploratory long-term oncologic outcomes including overall survival, recurrence-free survival, and cancer-specific survival.

To investigate the efficacy of weight management plus levonorgestrel intrauterine system (LNG-IUS) or megestrol acetate (MA) in obese patients with endometrial atypical hyperplasia (EAH) asking for conservative therapy.

The overarching objective of this project is to develop a pan-gynecologic cancer detection test using gynecologic (unique endometrial, cervical, and ovarian cancer) cancer-specific methylated DNA markers and high-risk human papilloma virus (HR-HPV) detected in vaginal fluid and/or plasma. This proposal defines Phase II MDM-based cancer detection studies in endometrial cancer (EC) and endometrial hyperplasia with atypia (AEH) in vaginal fluid and 2) ovarian cancer (OC) in plasma and vaginal fluid. Additionally, it defines necessary Phase I MDM-based cancer detection and exploratory aims to test novel cervical cancer (CC) MDMs and test the specificity of cancer-specific MDMs among various common benign gynecologic pathologies.er detection and exploratory aims to test novel cervical cancer MDMs and test the specificity of cancer-specific MDMs among various common benign gynecologic pathologies.

This is a multicenter, prospective, specimen collection study for development and evaluation of tests used to detect endometrial cancer, other cancers, or their causes.

The goal of this clinical trial is to learn if intrauterine injection of "Recombinant Humanized Type III Collagen Lyophilized Fibers" works to treat endometrial cancer or atypical hyperplasia in patients seeking fertility-preserving treatment. It will also learn about the safety of this intervention.The main questions it aims to answer are: 1. Does the combination of recombinant humanized type III collagen and progestin significantly increase the tumor remission rate at 6 months compared to progestin alone? 2. What medical problems do participants have when receiving this treatment (e.g., allergic reactions, abnormal inflammatory markers, or histocompatibility issues)? Researchers will compare "recombinant humanized type III collagen plus progestin (experimental group)" to "high-dose progestin alone (control group)" to see if the combination therapy is more effective for fertility preservation. Participants will: 1. Take high-dose progestin (such as Medroxyprogesterone Acetate or Megestrol Acetate) orally every day. 2. If assigned to the experimental group, receive one intrauterine submucosal injection of collagen via hysteroscopy at months 0, 1, and 2, for a total of 3 injections. 3. Visit the clinic once every 3 months for treatment evaluation and follow-up, which includes hysteroscopic endometrial biopsy, imaging (such as transvaginal ultrasound), and safety tests for relevant biochemical indicators.

To investigate the efficacy of GnRHa plus letrozole in obese progestin-insensitive EEC patients.

To investigate the efficacy of GnRHa plus letrozole vs Diane-35 plus metformin in non-obese progestin-insensitive early-stage endometrial cancer (EEC) and atypical hyperplasia(EAH) patients asking for conservative treatment.

Ultra-S.A.F.E. is a multicenter, ambispective observational study investigating the ultrasound and histological characteristics of patients with atypical endometrial hyperplasia (AEH) or endometrioid endometrial carcinoma (EEC) G1-2 undergoing fertility-sparing treatment (FST). The study aims to describe pre-treatment ultrasound features, evaluate endometrial modifications during treatment, and assess histological and reproductive outcomes. It includes a prospective cohort (new patients recruited at three gynecologic oncology centers) and a retrospective cohort (patients treated conservatively since January 2023). Approximately 50 patients will be enrolled over 24 months, with clinical, ultrasound, and histological data collected. The ultimate goal is to enhance the diagnostic and monitoring role of transvaginal ultrasound (TVUS) in conservative treatment for fertility preservation.

To construct a prediction model of progesterone sensitivity in patients with endometrial cancer treated with fertility preservation

To explore the treatment efficacy of medroxyprogesterone acetate plus atorvastatin in patients with atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EEC) for conservative treatment.

Primary end points: This clinical trial is aimed to analyze the effectiveness of Levonorgestrel-Releasing Intrauterine System (LNG-IUS, Mirena®) in the fertility-sparing treatment of atypical endometrial hyperplasia and early endometrial carcinoma, including pathology response and pregnancy outcome. Second end points: To analyze the appearances of side-effects.