Clinical study of a frameless indomethacin-containing copper intrauterine device combined with levonorgestrel-releasing intrauterine system in the treatment of adenomyosis

OBJECTIVE: To evaluate the safety and therapeutic efficacy of LNG-IUS alone versus LNG-IUS combined with frameless anchoring copper intrauterine device (IUD) (with or without indomethacin) in treating adenomyosis, and to explore the role of indomethacin in improving outcomes. STUDY DESIGN: A prospective study was conducted on 91 adenomyosis patients at Zhengzhou First People's Hospital (January 2022-January 2025), divided into three groups: Group A received LNG-IUS monotherapy alone (n = 29); Group B was treated with LNG-IUS combined with GyneFix® (GyneFix IN), a drug-free frameless copper IUD without indomethacin (n = 30); Group C received LNG-IUS paired with Jenefox (Jinizhimei), an indomethacin-loaded frameless copper IUD (n = 32).Baseline data, adverse events (complete expulsion, downward displacement and Removal), and efficacy indicators (uterine volume, hemoglobin [HGB], pictorial blood loss assessment chart [PBAC] score, visual analogue scale [VAS] score) were monitored during 12 months of follow-up. SETTING: Single tertiary hospital gynecology department affiliated to Xinxiang Medical College, Zhengzhou, China. PATIENTS: Women aged 30-52 years with ultrasonically confirmed symptomatic diffuse adenomyosis without fertility demands were enrolled. All subjects declined hysterectomy and long-term systemic hormonal medication, and agreed to complete all scheduled follow-up examinations. Patients with congenital uterine malformations, submucous fibroids, recent pelvic inflammatory disease, coagulation disorders, severe uncontrolled systemic diseases, or malignant gynecologic lesions were excluded. A total of 91 patients were allocated into three groups by treatment preference: Group A (LNG-IUS alone, n=29), Group B (LNG-IUS + GyneFix®, n=30), Group C (LNG-IUS + Jenefox, n=32). Baseline demographic and clinical parameters were balanced across the three groups (all P>0.05). INTERVENTIONS: Placement of standalone LNG-IUS, combined LNG-IUS with indomethacin-free frameless copper IUD, or combined LNG-IUS with indomethacin-containing frameless copper IUD under transabdominal ultrasound guidance. The LNG-IUS was ligated to the anchoring knot of frameless copper IUD to form a dual-device system, which was anchored into the uterine myometrium during insertion; diagnostic hysteroscopy was performed immediately after placement to inspect the uterine cavity in combined-device groups. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics were comparable among groups. Group A had a 17.24% complete expulsion rate, while no complete expulsion/ downward displacement occurred in Groups B and C. Group C showed significantly smaller uterine volume than Groups A and B from 3 months onward (P<0.05). PBAC scores in Groups B and C were significantly lower than in Group A, with Group C exhibiting better improvement (P<0.05). Group C had lower VAS scores than A and B within 6 months (P<0.05), and Group B outperformed A at 12 months. Adverse events were mild and self-limiting; Group C had a lower irregular bleeding rate (3.13%) than Group A (10.34%) and no abdominal/back pain (P<0.05). CONCLUSION: Within the 12-month follow-up of this single-center cohort, no complete IUD expulsion or severe uterine downward displacement occurred in Groups B and C, whereas the LNG-IUS monotherapy group had a complete expulsion rate of 17.24%. All three regimens improved uterine volume, hemoglobin, menstrual blood loss and dysmenorrhea, and Group C achieved the most pronounced reductions in uterine volume, PBAC and VAS scores, with the lowest rate of irregular bleeding. The dual-device regimens therefore represent promising uterus-sparing conservative options for adenomyosis patients at high risk of IUD expulsion.