Assessing ovarian stimulation with letrozole and levonorgestrel intrauterine system after combined fertility-sparing approach for atypical endometrial lesions: a retrospective case-control study

Alessandra Gallo; Attilio Di Spiezio Sardo; Alessandro Conforti; Giuseppe Gabriele Iorio; Brunella Zizolfi; Cira Buonfantino; Maria Chiara De Angelis; Ida Strina; Vincenzo Marrone; Giuseppe Bifulco; Carlo Alviggi

doi:10.1016/j.rbmo.2023.103750

Assessing ovarian stimulation with letrozole and levonorgestrel intrauterine system after combined fertility-sparing approach for atypical endometrial lesions: a retrospective case-control study

Reprod Biomed Online. 2023 Nov 29;48(5):103750. doi: 10.1016/j.rbmo.2023.103750. Online ahead of print.

Affiliations

¹ University of Naples 'Federico II'. Department of Public Health. School of Medicine. Naples, Italy.
² University of Naples "Federico II". Department of Neuroscience, Reproductive Science and Odontostomatology, School of Medicine. Naples, Italy. Electronic address: alessandro.conforti@unina.it.
³ University of Naples "Federico II". Department of Neuroscience, Reproductive Science and Odontostomatology, School of Medicine. Naples, Italy.

PMID: 38430660
DOI: 10.1016/j.rbmo.2023.103750

Abstract

Research question: Is ovarian stimulation with levonorgestrel intrauterine system (LNG-IUS) in situ and co-treatment with letrozole safe and effective in patients undergoing fertility-sparing combined treatment for atypical endometrial hyperplasia (AEH) or early endometrial cancer limited to the endometrium?

Design: Retrospective case-control study recruiting women who had undergone fertility-sparing 'combined' treatment and ovarian stimulation with letrozole and LNG-IUS in situ. The 'three steps' hysteroscopic technique was used. Once complete response was achieved, the ovaries were stimulated, and mature oocytes cryopreserved. The LNG-IUS was removed, and embryos transferred. A comparative analysis was conducted between the two control groups of the initial outcomes of ART (number of oocytes and MII oocytes retrieved): healthy infertile women undergoing ovarian stimulation for IVF/ICSI (control group A); and patients diagnosed with breast cancer who underwent ovarian stimulation with letrozole (control group B).

Results: Of the 75 patients analysed, 15 underwent oocyte cryopreservation after achieving a complete response to fertility-sparing treatment (study group); 30 patients in control group A and B, respectively. No statistically significant differences were observed in retrieved oocytes and mature oocytes between the study and control groups. In the nine patients who underwent embryo transfer, clinical pregnancy (55.6%), cumulative live birth (44.4%) and miscarriage (20%) rates were reported. In three patients with AEH, recurrence occurred (12%) at 3, 6 and 16 months after removing the LNG-IUS to attempt embryo transfer, respectively.

Conclusion: Fertility-sparing hysteroscopic combined treatment and subsequent ovarian stimulation with letrozole and LNG-IUS in situ could be suggested to women with AEH or early endometrial cancer who ask for future fertility preservation.

Keywords: assisted reproductive technology; atypical endometrial hyperplasia; endometrial cancer; fertility-sparing; hysteroscopy; ovarian stimulation.