Outcomes of women treated with progestin and metformin for atypical endometrial hyperplasia and early endometrial cancer: a systematic review and meta-analysis.

OBJECTIVE: Progestin therapy is the recommended fertility-sparing management of atypical endometrial hyperplasia or early-stage endometrial cancer in reproductive-aged women. Our objective was to evaluate disease relapse after progestin and metformin versus progestin therapy alone in patients with endometrial hyperplasia or cancer. Our secondary outcomes were disease remission, clinical pregnancy and live birth rate. METHODS: A systematic review of the literature was conducted (MEDLINE, Web of Science, Cochrane Library, CINAHL, LILACS, clinicaltrials.gov) from inception to April 2021. Studies of reproductive-aged women with atypical endometrial hyperplasia or early endometrial cancer who received progestin and metformin or progestin alone for fertility-sparing management, were included in the review. Early endometrial cancer was defined as grade 1, stage 1 disease. Exclusion criteria included women with higher grade endometrial cancer and when conservative management was not for fertility-sparing purposes. Data are presented as odds ratios (ORs) and 95% confidence intervals (CIs) with fixed or random effects meta-analysis. Quality scoring was based on the Newcastle-Ottawa and Jadad scales. RESULTS: In total, 271 reports were identified and six studies met the inclusion criteria. These studies included 621 women; 241 (38.8%) patients received combined therapy and 380 (61.2%) received progestin therapy alone. Relapse rates were lower for progestin and metformin than for progestin therapy alone (pooled OR 0.46, 95% CI 0.24 to 0.91, p=0.03). The remission rates were not different (pooled OR 1.35, 95% CI 0.91 to 2.00, p=0.14). Women who received progestin and metformin achieved pregnancy and live birth rates similar to those who received progestin therapy only (pooled OR 1.01, 95% CI 0.44 to 2.35, p=0.98; pooled OR 0.46, 95% CI 0.21 to 1.03, p=0.06). CONCLUSION: For reproductive-aged women with atypical endometrial hyperplasia or early endometrial cancer, progestin and metformin therapy compared with progestin therapy alone is associated with lower relapse rates, and similar remission, clinical pregnancy and live birth rates. PROSPERO REGISTRATION NUMBER: CRD42020179069.disease remission.

Fertility and Endocrine Preservation in the Management of Colorectal Cancer in Women.

CASE SUMMARY: A 28-year-old nulliparous woman presented with rectal bleeding. Colonoscopy revealed a 4-cm malignant-appearing mass in the proximal rectum, and biopsies confirmed invasive adenocarcinoma of the rectum. Computed tomography scan showed no evidence of metastatic disease. Staging MRI found transmural extension with minimal stranding in the adjacent fat, as well as no evidence of pathological pelvic adenopathy, consistent with a T3N0 lesion. The proposed treatment plan involved neoadjuvant chemotherapy and radiation therapy before primary surgical resection. The patient desired fertility preservation and was referred immediately to Reproductive Endocrinology and Infertility. She underwent assisted reproduction with oocyte and blastocyst cryopreservation followed by laparoscopic ovarian transposition. Nine months after surgical low anterior resection of the tumor and completion of her cancer treatment, her ovaries were repositioned to their normal pelvic position during an ileostomy takedown procedure. She underwent a frozen embryo transfer but did not conceive. She resumed menses and later conceived spontaneously. Her pregnancy was complicated by cervical incompetence, requiring cervical cerclage. She delivered a live male infant via cesarean delivery at 32 weeks gestation, approximately 2 years after completion of cancer therapy. Four years after diagnosis, the patient remains in remission with undetectable CEA levels.