Weight-loss Drug for Fertility-Sparing Treatment of Atypical Hyperplasia and Low-grade Cancer of the Endometrium

Who can take part

Inclusion Criteria: * BMI ≥ 27 * Diagnosis of grade 1 endometrioid endometrial cancer or atypical hyperplasia made by either endometrial biopsy or dilation and curettage * For those with endometrial cancer, clinical FIGO 2009 stage 1A disease without evidence of metastatic disease beyond the uterus and no myometrial invasion by MRI or CT * ECOG status \<2 * Desire for fertility preservation * Ability to understand and willing to sign a written informed consent document Exclusion Criteria: * Evidence of myometrial invasion or extra-uterine disease on imaging * High grade or p53 mutated (p53mut) endometrial cancer * Estrogen receptor negative endometrial cancer (positivity defined as moderate/strong staining\>10%) * Mismatch repair deficient (MMRd) endometrial cancer * History of other malignancies except if curatively treated with no evidence of disease for \>5 years * Previous surgical treatment of obesity * Current use of weight loss medication (no use in last 2 months) * Medical comorbidity with end-organ dysfunction * History of suicide attempts or current suicidal thoughts or behaviours * Currently taking insulin or insulin secretagogue (e.g., sulfonylurea) * Diabetic retinopathy * Gastroparesis or problems with food digestion * History of tachycardia (e.g., sinus tachycardia, supraventricular tachycardia, atrial fibrillation, atrial flutter, or ventricular tachycardia) * Contraindications to pIUD or semaglutide. * Hypersensitive to WEGOVY or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container * Personal or family history of medullary thyroid carcinoma (MTC) * Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) * Pregnant or breast-feeding * Current or recurrent pelvic inflammatory disease * Lower genital tract infection * Postpartum endometritis * Uterine anomalies including fibroids if they distort the uterine cavity * Cervical malignancy * Known or suspected progestin-dependent neoplasia, including breast cancer * Cervicitis * Untreated cervical dysplasia * Active liver disease or dysfunction * Actual benign or malignant liver tumors * Sceptic abortion within the previous three months * Hypersensitivity to levonorgestrel or any of the other ingredients in the formulation or components of MIRENA. * Bacterial endocarditis * Established immunodeficiency * Acute malignancies affecting blood or leukemias * Recent trophoblastic disease while hCG levels are elevated * Previously inserted intrauterine device (IUD) that has not been removed * Conditions associated with increased susceptibility to pelvic infections * Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.

Registry changes

• StatusOct 11, 2026

  NOT_YET_RECRUITING → RECRUITING

• Primary completion dateOct 11, 2026

  2027-02 → 2029-02

• Start dateOct 11, 2026

  2025-08 → 2026-09-17