Weight-loss Drug for Fertility-Sparing Treatment of Atypical Hyperplasia and Grade 1 Cancer of the Endometrium (WE-FiERCE)

Inclusion Criteria: People aged ≥ 18 and ≤ 41 years of age BMI ≥ 27 Diagnosis of grade 1 endometrioid EC or AH Clinical FIGO 2009 stage 1A disease - no evidence of metastatic disease beyond the uterus and no evidence of myometrial invasion by imaging performed (MRI, CT) ECOG status <2 Desire for fertility preservation Have signed an approved informed consent form Exclusion Criteria: Evidence of myometrial invasion or extra-uterine disease on imaging High grade or p53 mutated (p53mut) EC Estrogen receptor (ER) EC Mismatch repair deficient (MMRd) MLH1 with methylation EC History of other malignancies, except if: a. Curatively treated with no evidence of disease for >5 years Previous bariatric surgery Current use of weight loss medication Medical co-morbidity with end-organ dysfunction Unable to understand and participate in the informed consent process Currently pregnant or breastfeeding (negative serum bhCG at screening) Contraindications to progestin intra-uterine device (pIUD) Self-reported change in body weight of >5kg within 90 days before screening Previous treatment with any medication for obesity within 90 days before screening History of chronic pancreatitis or acute pancreatitis within 180 days prior to screening Contraindications to semaglutide Personal or first-degree history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma Anaphylactic reaction to semaglutide