A multi-centre randomised controlled trial comparing megestrol acetate to levonorgestrel-intrauterine system in fertility sparing treatment of atypical endometrial hyperplasia.

Goh, Charissa Shu Ying; Loh, Michelle Jia Min; Lim, Whui Whui; Ang, Joella Xiahong; Nadarajah, Ravichandran; Yong, Tze Tein; Tong, Pearl; Yeo, Yen Ching; Phoon, Jessie Wai Leng

Purpose: The objective of the trial was to compare the regression rate of atypical endometrial hyperplasia (AEH) in patients treated with megestrol acetate (MA) vs. levonorgestrel-intrauterine device (LNG-IUS). We also aimed to assess the fertility and pregnancy outcomes in these patients. Methods: The study was a phase II multi-centre randomised controlled trial on the use of MA compared to LNG-IUS in the treatment of AEH conducted from January 2020 to January 2024 in Singapore. Women who were diagnosed with AEH and between 21 and 40 years old were included. The patients were randomised to receive either MA (160 mg orally daily) or LNG-IUS. The primary outcomes assessed were the regression rates at 3 months, 6 months and 9 months of treatment. The secondary outcomes assessed were the side effects, patient acceptability and fertility outcomes. Results: Thirty-six patients completed the trial. The overall regression rate was 88.9% by 9 months. There was no statistically significant difference in the 9-month complete regression rate between MA vs. LNG-IUS. There was also no significant difference in side effects and weight change between both arms. Nineteen patients were actively pursuing fertility after complete regression. There were 8 pregnancies achieved, with resultant 4 live births and 4 miscarriages. Conclusion: Our study confirms a high regression rate of AH with medical treatment. LNG-IUS is a non-inferior treatment compared to megestrol acetate. Successful pregnancy outcomes can be achieved after regression of AEH. Long-term studies of sufficient sample-size are needed to assess for fertility and pregnancy outcomes, risk of recurrence and long-term risk of malignancy. Trial registration number: The study was registered with the Health Science Authority (HSA) (License No.: CTA1900087) on September 5, 2019: https://eservice.hsa.gov.sg/prism/ct%5fr/enquiry.do?action=loadSpecificDetail. The trial was registered retrospectively on ClinicalTrials.gov (ID: NCT05492487) on April 7, 2022: https://clinicaltrials.gov/study/NCT05492487.

ENDOMETRIAL hyperplasia; PREGNANCY outcomes; RANDOMIZED controlled trials; FERTILITY; HUMAN fertility

Journal of Assisted Reproduction & Genetics, 2024, Vol 41, Issue 9, p2485

1058-0468

Academic Journal

10.1007/s10815-024-03172-z