GyneFix IUD Plus LNG-IUS for Adenomyosis (GYNEFIX-AM)

Clinical Efficacy and Safety of Indomethacin-GyneFix IUD Combined With a Levonorgestrel-Releasing Intrauterine System in Patients With Adenomyosis and Different Uterine Cavity Depths

Adenomyosis is a common gynecological condition that can cause menstrual pain, heavy menstrual bleeding, anemia, and reduced quality of life. The levonorgestrel-releasing intrauterine system is commonly used as a conservative treatment, but displacement or expulsion of the device may occur, especially in patients with an enlarged uterus or a deep uterine cavity.

This study evaluated whether combining an Indomethacin-GyneFix intrauterine device with a levonorgestrel-releasing intrauterine system could improve device stability in patients with adenomyosis. Eligible participants were randomly assigned to receive GyneFix IUD plus LNG-IUS, ring IUD plus LNG-IUS, or LNG-IUS alone. Participants were followed for 6 months after device placement. The main outcome was device displacement or expulsion at 6 months. Other outcomes included menstrual pain, menstrual blood loss, uterine volume, hemoglobin, CA125, adverse events, and treatment acceptance.

Study Overview

• Status: Completed
• Conditions: Adenomyosis
• Intervention / Treatment: Device: Indomethacin-GyneFix IUD Plus LNG-IUS; Device: Ring IUD Plus LNG-IUS; Device: LNG-IUS Alone

Detailed Description

This was a single-center, prospective, parallel-group, randomized controlled trial conducted at Wenzhou People's Hospital in patients with adenomyosis. The study was designed to compare three intrauterine treatment strategies for improving the stability of a levonorgestrel-releasing intrauterine system in patients with different uterine cavity depths.

Eligible patients were women diagnosed with adenomyosis who had no current desire for pregnancy, had no contraindications to intrauterine device placement, and were able to complete scheduled follow-up. After written informed consent was obtained, participants were randomly assigned in a 1:1:1 ratio to one of three groups: GyneFix IUD plus LNG-IUS, ring IUD plus LNG-IUS, or LNG-IUS alone.

In the GyneFix IUD plus LNG-IUS group, the Indomethacin-GyneFix IUD was used as an anchoring device to stabilize the LNG-IUS. The anchoring knot of the GyneFix IUD was placed in the uterine fundal myometrium under ultrasound guidance, allowing the LNG-IUS to remain suspended and stabilized within the uterine cavity. In the ring IUD plus LNG-IUS group, a ring IUD was placed together with the LNG-IUS to provide passive mechanical support. In the LNG-IUS-alone group, the LNG-IUS was inserted according to the standard procedure.

All procedures were performed under real-time ultrasound guidance by experienced gynecologists. Participants were followed at approximately 1 month, 3 months, and 6 months after device placement. Follow-up assessments included symptom evaluation, gynecological examination, ultrasound assessment of device position and uterine parameters, laboratory testing, adverse event monitoring, and treatment acceptance assessment.

The primary outcome was intrauterine device displacement or expulsion at 6 months. Secondary outcomes included changes in dysmenorrhea measured by visual analogue scale, menstrual blood loss measured by pictorial blood loss assessment chart, uterine volume, hemoglobin, serum CA125, adverse events, and patient acceptance. A subgroup analysis was planned according to uterine cavity depth.

• Study Type: Interventional
• Enrollment (Actual): 270
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Wenzhou, Zhejiang, China, 325000
      • Wenzhou People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Female patients aged 20 to 55 years.
• Diagnosed with adenomyosis by transvaginal ultrasound.
• No current desire for pregnancy and willing to receive conservative intrauterine treatment.
• No contraindications to intrauterine device placement.
• Able to understand the study procedures and voluntarily provide written informed consent.
• Able and willing to comply with scheduled follow-up visits and study assessments.

Exclusion Criteria:

• Pregnancy or suspected pregnancy.
• Concurrent malignant tumor of the reproductive system.
• Severe cervical lesions or uterine malformations.
• Severe coagulation disorder.
• Severe hepatic or renal insufficiency.
• Known hypersensitivity to levonorgestrel, copper, indomethacin, or related device components.
• Uncontrolled pelvic inflammatory disease or untreated vaginal infection.
• Uterine prolapse grade II or higher.
• Any condition judged by the investigator to make intrauterine device placement unsuitable.
• Inability to complete follow-up or incomplete key clinical data.
• Withdrawal of consent during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GyneFix IUD Plus LNG-IUS; Participants received Indomethacin-GyneFix IUD combined with a levonorgestrel-releasing intrauterine system. The GyneFix IUD was used as an anchoring device to stabilize the LNG-IUS. Under real-time ultrasound guidance, the anchoring knot of the GyneFix IUD was implanted into the uterine fundal myometrium, allowing the LNG-IUS to remain suspended and stabilized within the uterine cavity.	Device: Indomethacin-GyneFix IUD Plus LNG-IUS; The Indomethacin-GyneFix IUD was used as an anchoring device to stabilize the levonorgestrel-releasing intrauterine system. The LNG-IUS was connected to the upper portion of the GyneFix IUD with non-absorbable surgical suture. Under real-time ultrasound guidance, the anchoring knot of the GyneFix IUD was implanted into the uterine fundal myometrium, allowing the LNG-IUS to remain suspended and stabilized within the uterine cavity.; Other Names: GyneFix IUD Plus LNG-IUS; GyneFix IUD Combined With LNG-IUS; Mirena Plus GyneFix IUD
Active Comparator: Ring IUD Plus LNG-IUS; Participants received a ring IUD combined with a levonorgestrel-releasing intrauterine system. The ring IUD and LNG-IUS were sequentially inserted into the uterine cavity under ultrasound guidance. The ring IUD was positioned near the upper uterine cavity or fundal region to provide passive mechanical support for the LNG-IUS.	Device: Ring IUD Plus LNG-IUS; The ring IUD and the levonorgestrel-releasing intrauterine system were sequentially inserted into the uterine cavity under real-time ultrasound guidance. The ring IUD was positioned near the upper uterine cavity or fundal region to provide passive mechanical support for the LNG-IUS. The LNG-IUS was then released in the conventional manner with its transverse arms extended.; Other Names: Ring IUD Combined With LNG-IUS; LNG-IUS Plus Ring IUD; Support-Based IUD Fixation
Active Comparator: LNG-IUS Alone; Participants received LNG-IUS alone. The levonorgestrel-releasing intrauterine system was inserted according to the standard procedure under ultrasound guidance, with the transverse arms fully extended and the device positioned at the uterine fundus.	Device: LNG-IUS Alone; The levonorgestrel-releasing intrauterine system was inserted according to the standard procedure under real-time ultrasound guidance. Correct placement required full extension of the transverse arms and positioning of the device at the uterine fundus.; Other Names: Mirena; Levonorgestrel-Releasing Intrauterine System; LNG-IUS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device Displacement or Expulsion Rate at 6 Months	The proportion of participants with intrauterine device displacement or expulsion at 6 months after device placement. Device displacement or expulsion was assessed by gynecological examination and ultrasound evaluation according to predefined criteria for intrauterine device position.	6 months after device placement

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Dysmenorrhea VAS Score	Change in dysmenorrhea severity measured by the visual analogue scale. The VAS score ranges from 0 to 10, with higher scores indicating more severe pain.	Baseline, 1 month, 3 months, and 6 months after device placement
Change From Baseline in PBAC Score	Change in menstrual blood loss measured by the pictorial blood loss assessment chart. Higher PBAC scores indicate greater menstrual blood loss.	Baseline, 1 month, 3 months, and 6 months after device placement
Change From Baseline in Uterine Volume	Change in uterine volume measured by gynecological ultrasound. Uterine volume was calculated using three-dimensional uterine measurements.	Baseline, 3 months, and 6 months after device placement
Change From Baseline in Hemoglobin Level	Change in hemoglobin level measured from venous blood samples to evaluate improvement in anemia associated with heavy menstrual bleeding.	Baseline, 3 months, and 6 months after device placement
Change From Baseline in Serum CA125 Level	Change in serum cancer antigen 125 level measured by laboratory testing. CA125 was used as an indirect marker of adenomyosis disease activity.	Baseline, 3 months, and 6 months after device placement
Incidence of Adverse Events	Incidence of adverse events during follow-up, including irregular vaginal bleeding, low back pain, lower abdominal discomfort, increased vaginal discharge, pelvic inflammatory disease, ovarian cysts, breast tenderness, acne, weight gain, device removal for symptoms, uterine perforation, device displacement, and device expulsion.	Up to 6 months after device placement
Treatment Acceptance at 6 Months	Treatment acceptance assessed by questionnaire at 6 months, including willingness to choose the same treatment again and willingness to recommend the treatment to others with similar conditions.	6 months after device placement

Collaborators and Investigators

• Sponsor: Wenzhou People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2023
• Primary Completion (Actual): December 30, 2025
• Study Completion (Actual): December 31, 2025

Study Registration Dates

• First Submitted: June 26, 2026
• First Submitted That Met QC Criteria: June 26, 2026
• First Posted (Actual): July 2, 2026

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 26, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Dysmenorrhea; LNG-IUS; Heavy Menstrual Bleeding; Intrauterine Device Expulsion; GyneFix IUD; Indomethacin-GyneFix IUD; Levonorgestrel-Releasing Intrauterine System; Intrauterine Device Displacement; Uterine Cavity Depth
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pain; Neurologic Manifestations; Pathologic Processes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Hemorrhage; Pelvic Pain; Uterine Hemorrhage; Menstruation Disturbances; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Adenomyosis; Menorrhagia; Dysmenorrhea
• Other Study ID Numbers: WPH-KY-2023-200

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data underlying the results reported in this study may be made available from the corresponding author upon reasonable request, after publication and subject to approval by the study investigators and applicable institutional requirements.
• IPD Sharing Time Frame: Beginning after publication with no fixed end date.
• IPD Sharing Access Criteria: Researchers with a scientifically sound proposal may request access to de-identified data. Requests will be reviewed by the corresponding author and study investigators, and data sharing will be subject to ethics, privacy, and institutional requirements.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No