MATERIALS AND METHODS
Study design and patients
This single-center, open-label, randomized controlled phase II study (NCT03241888) was designed to investigate the efficacy of oral MA+LNG-IUS or LNG-IUS alone compared with oral MA alone as fertility-sparing treatment for AEH patients. This work was conducted from July 21th, 2017, to June 18th, 2020, in Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. This study was supported by the National Key Research and Development Program of China (Grant No 2019YFC1005200 and 2019YFC1005204), Shanghai Medical Centre of Key Programs for Female Reproductive Diseases (Grant No. 2017ZZ010616), Shanghai sailing program (Grant No.19YF1404200) and Shen Kang clinical project (SHDC22021219).
Eligible AEH patients met the following inclusion criteria were 18-45 years old; pathologically diagnosed with AEH for the first time by endometrial biopsy through dilation and curettage with or without hysteroscopy; with no signs of suspicious endometrial invasion or extrauterine metastasis by transvaginal ultrasonography; with the longest uterine diameter (from the fundus to endocervix) <7 cm by ultrasound (as larger uterine cavity might lead to LNG-IUS expulsion or reduce the treatment effect); with strong desire to preserve fertility; no contraindication for progestin treatment or pregnancy; not pregnant when participating in the trial; willing to follow the trial arrangement after being fully informed of all the risks and inconveniences caused by the trial.
Exclusion criteria were diagnosis of recurrent AEH, allergy history or contraindications for MA or LNG-IUS; during pregnancy, severe infection, severe chronic diseases (dysfunction of heart, liver, lung, or kidney), high risk of thrombosis, receiving hormone treatment for more than three months within six months before entering the trial, other malignancy history, concurrent malignancy in genital or other systems.
Pathologic diagnosis was confirmed by two experienced gynecological pathologists (Dr. Zhu Q and Dr. Zhou XR), according to the World Health Organization (WHO) pathological classification (2014)23. If their opinions differed, a seminar was held in the pathological department for the final diagnosis.
The trial was approved by the Institutional Review Board of the Obstetrics and Gynecology Hospital, Fudan University (Approval No.: 2017-30), and all patients were fully informed of the benefits and risks of this clinical trial and provided written informed consent.