Innovative Protocol of ART in Women with LNG-Ius for Fertility-Sparing Treatment of Endometrial Intraepithelial Neoplasia

Abstract

<h3>Study Objective</h3> to evaluate the safety and efficacy of an Assisted Reproductive Technology (ART) program based on controlled ovarian stimulation with Levonorgestrel Intrauterine System (LNG-IUS) <i>in situ</i> in women affected by endometrial intraepithelial neoplasia<i>.</i> <h3>Design</h3> prospective observational study. <h3>Setting</h3> young women conservatively treated for FIGO IA G1 early endometrial cancer (EEC) and atypical endometrial hyperplasia (AEH) who underwent ART program with LNG-IUS <i>in situ</i>. <h3>Patients or Participants</h3> 6 patients undergoing conservative treatment for EEC (n=1) or AEH (n=5), from January 2019 to March 2021. <h3>Interventions</h3> patients with focal EEC were treated by hysteroscopic resection of the lesion according to Mazzon's technique; patients with AEH were treated by superficial endometrial resection preserving the basal layer of the endometrium. LNG-IUD was inserted in all patients after surgery. Patients were followed with histological evaluation at 3 months by endometrial biopsy, until two subsequent negative biopsies were obtained. At this time, controlled ovarian stimulation was started, oocytes retrieval was performed, and mature oocytes were cryopreserved. After removal of LNG-IUS, embryo transfer procedure was performed. Rates of oocytes retrieved, mature frozen oocytes and pregnancies were assessed. Rates of response and recurrence were also evaluated <h3>Measurements and Main Results</h3> out of 6 patients, 100% had a complete response and no subsequent relapse. Oocytes retrieved were 9.33±2.28 (mean±SD); mature oocytes were 7.5±1.89 (mean±SD). Embryo transfer was performed three months after the LNG-IUS removal. 4 pregnancies were obtained (66.67%),2(50%) of whom resulted in live birth, 1(25%) is still ongoing, 1(25%) resulted in a miscarriage in the first trimester. 2 patients (33.33%) experimented implantation failure and they are waiting for a further attempt <h3>Conclusion</h3> the presence of LNG-IUS during controlled ovarian stimulation has no detrimental effects on ovarian quality, while allowing to balance the potentially dangerous effect of hyperestrogenism on the endometrium of patients affected by AEH or EEC, with promising results about pregnancy outcomes.