Gallo, Alessandra (2023) Efficiency and safety of ovarian stimulation with levonorgestrel-intrauterine system and letrozole after combined fertility-sparing treatment of women with atypical endometrial lesions. [Tesi di dottorato]

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Abstract

Objective: The aim of this study was to demonstrate the safety and efficacy of ovarian stimulation (OS) with Levonorgestrel Intrauterine System (LNG-IUS) in situ and co-treatment with letrozole in young patients undergoing fertility-sparing combined treatment for atypical endometrial hyperplasia (AEH) or early endometrial cancer limited to the endometrium. Materials and Methods: a prospective case-control study was conducted at the Department of Gynecology and Obstetrics of Tertiary Care University Hospital, University of Naples “Federico II”, and involved the Hysteroscopy Unit and the Reproductive Endocrinology and Oncofertility Unit. Young women who underwent fertility-sparing “combined” treatment and subsequent OS with letrozole and LNG-IUS in situ were enrolled. Enrolled patients were treated by superficial endometrial resection preserving the basal layer of the endometrium, in case of diffuse atypical lesion, or by “three steps” hysteroscopic resection technique in case of focal development lesions. After achieving a complete response (CR), OS was started, oocytes retrieval was performed, and mature oocytes were cryopreserved. After removal of the LNG-IUS, embryo-transfer was performed. The comparative analysis of the outcomes of assisted reproductive technologies was performed considering two control groups: control group A) healthy infertile women undergoing OS for IVF/ICSI; control group B) patients diagnosed with breast cancer who underwent OS with letrozole. Results: Seventy-five patients were analysed, divided as follows: 15 patients undergoing oocyte cryopreservation after achieving a CR to fertility-sparing treatment (study group), 30 in control group A and 30 in control group B. No statistically significant differences were observed in oocyte and mature oocytes retrieved between the study group and the control groups. The clinical pregnancy rate was 55.6%, the cumulative live birth rate was 44.4%, the miscarriage rate was 20%. 3 patients with AEH had recurrence (20%), occurring 3, 6 and 16 months after removal of intrauterine system to attempt embryo transfer, respectively. Conclusion: This preliminary data demonstrated that fertility-sparing hysteroscopic “combined” treatment and subsequent OS with letrozole and LNG-IUS in situ could be suggested in women with AEH or early endometrial cancer who ask to preserve future fertility. Further studies are needed in order to investigate the effect of OS with letrozole and LNG-IUS in these women.

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