Improvement of Symptoms After Removal of the Essure® Contraceptive Implant (ABLES)

Prospective Multicenter Study of the Improvement of Symptoms After Removal of the Essure® Contraceptive Implant

ESSURE® is an implantable medical device for definitive and irreversible sterilization indicated for adult women of childbearing age. These implants are inserted into the fallopian tubes by hysteroscopy. Marketed in 2002, ESSURE® contraceptive implants were withdrawn from the French market in 2017 (and worldwide in 2017 and 2018) following the observation in certain patients of polymorphic and non-specific gynecological and extra-gynecological symptoms. Studies with small numbers and short-term follow-up have shown a significant improvement in these symptoms after implant explantation. This constitutes a real public health problem since according to the report of the EPI-PHARE Scientific Interest Group, 198,000 French women have these implants and only 30,000 of them, or 15%, have been explanted, knowing that explantation of ESSURE® implants is recommended only in symptomatic patients. A large number of these patients, presenting symptoms, have not yet been treated for an explant.

The physiopathological mechanism(s) is (are) not yet determined but several arguments are in favor of a dissemination of metallic elements contained in these implants whose accumulation could lead to inflammatory and/or allergic and/or autoimmune phenomena.

Carrying out a prospective study with long-term longitudinal follow-up appears essential to precisely assess the degree of improvement in the symptoms and quality of life of these patients, determine the most appropriate surgical techniques, and understand the pathophysiological mechanisms that may result in the implementation of specific treatments and relevant markers. From a surgical point of view, there is a real risk of fracture of implants whatever the type of intervention performed: study the biomechanical properties of implants with a view to characterizing their behavior to mechanical rupture but also their thermal resistance in an objective manner seems essential to limit the risk of fracture and help to inform the patient about the surgical technique proposed for explantation. From a biological point of view, the dosage of the metallic elements constituting ESSURE® implants and potentially toxic ones could make it possible to objectify the release of these metallic elements in the body. Analysis of pro-inflammatory cytokines, micro-RNAs (miRNA), quantitative analysis of inflammatory pathway messenger ribonucleic acid (mRNAs) (NanoString technology) and analysis of neuroinflammation by functional imaging should make it possible to explore potential pathophysiological mechanisms. This study responds to a significant request from patient associations.

Study Overview

• Status: Recruiting
• Conditions: Implant Complication; Contraceptive Device; Complications
• Intervention / Treatment: Device: Magnetic resonance imaging- Positron Emission Tomography (MRI-PET) examination; Biological: blood sample; Biological: urine collection; Biological: Collection of a lock of hair; Other: questionnaire

• Study Type: Interventional
• Enrollment (Estimated): 444
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gautier Chene, PU,PH; Phone Number: +33 0472355870; Email: gautier.chene@chu-lyon.fr
• Study Contact Backup: Name: Stéphanie MORET; Phone Number: +33 0472355878; Email: stephanie.moret@chu-lyon.fr

Study Locations

• France
  • Angers, France, 49933
    • Not yet recruiting
    • CHU de Angers
    • Contact: Guillaume Legendre, PU,PH; Phone Number: +33 0241354635; Email: guillaume.legendre@chu-angers.fr
    • Principal Investigator: Guillaume Legendre, PU,PH
  • Bron, France, 69677
    • Recruiting
    • Hôpital Femme Mère Enfant (Hospices Civils de Lyon)
    • Contact: Gautier Chene, PU,PH; Phone Number: +33 0472355870; Email: gautier.chene@chu-lyon.fr
    • Principal Investigator: Gautier Chene, PU,PH
  • Le Kremlin-Bicêtre, France, 94275
    • Not yet recruiting
    • Hôpital Bicêtre
    • Contact: Perrine CAPMAS, PU,PH; Phone Number: +33 0145217714; Email: perrine.capmas@aphp.fr
    • Principal Investigator: Perrine CAPMAS, PU,PH
  • Lille, France, 59037
    • Not yet recruiting
    • Hopital Jeanne de Flandres
    • Contact: Victoire Delporte, PU,PH; Phone Number: +33 0320446641; Email: victoire.delporte@chu-lille.fr
    • Principal Investigator: Victoire Delporte, PU,PH
  • Marseille, France, 13005
    • Not yet recruiting
    • Hôpital de La Conception
    • Contact: Aubert Agostini, PU,PH; Phone Number: +33 0491383702; Email: Aubert.AGOSTINI@ap-hm.fr
    • Principal Investigator: Aubert Agostini, PU,PH
  • Reims, France, 51092
    • Not yet recruiting
    • Institut Mère Enfant Alix de Champagne, CHU Reims
    • Contact: Olivier Graesslin, PU,PH; Phone Number: +33 0326783517; Email: ograesslin@chu-reims.fr
    • Principal Investigator: Olivier Graesslin, PU,PH
  • Rouen, France, 76000
    • Not yet recruiting
    • CHU de Rouen
    • Contact: Patrice Crochet, PU,PH; Phone Number: +33 0232881054; Email: patrice.crochet@chu-rouen.fr
    • Principal Investigator: Patrice Crochet, PU,PH
  • Strasbourg, France, 67200
    • Not yet recruiting
    • Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg
    • Contact: Thomas Boisrame, PU,PH; Phone Number: +33 0388127458; Email: thomas.boisrame@chru-strasbourg.fr
    • Principal Investigator: Thomas Boisrame, PU,PH
  • Toulouse, France, 31059
    • Not yet recruiting
    • Hôpital Paule de Viguier, CHU de Toulouse
    • Contact: Yann Tanguy Le Gac, PU,PH; Phone Number: +33 0567771105; Email: tanguylegac.y@chu-toulouse.fr
    • Principal Investigator: Yann Tanguy Le Gac, PU,PH
  • Versailles, France, 78157
    • Not yet recruiting
    • Hôpital André Mignot, Centre Hospitalier de Versailles
    • Contact: Pierre Panel, PU,PH; Phone Number: +33 0139638936; Email: ppanel@ch-versailles.fr
    • Principal Investigator: Pierre Panel, PU,PH

Participation Criteria

Eligibility Criteria

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

Description

• Inclusion Criteria * :

ESSURE Group:

• woman aged 35 to 75
• patient with at least one Essure® implant
• surgical intervention planned because the patient is symptomatic: removal of the Essure® implant(s)
• planned intervention via vaginal route, laparoscopy, robotic surgery, or Transvaginal natural orifice transluminal endoscopic surgery (VNotes)
• patient having given free, informed and signed consent

Selection for MRI-PET examination:

• if the answer is "poor" or "bad" to the first question of the SF-12 pre-operatively
• no hysterectomy
• no analgesic treatment, or treatment stopped 48 hours before the examination
• no psychotropic treatment (anxiolytics, hypnotics (sleeping pills), antidepressants, mood stabilizers, neuroleptics)
• patient having given free, informed and signed consent

Control group:

• woman aged 35 to 75
• planned surgical intervention: salpingectomy with or without hysterectomy for benign indication
• planned intervention via vaginal route, laparoscopy, robotic surgery, or VNotes
• patient having given free, informed and signed consent

Selection for MRI-PET examination:

• age matching (+/- 5 years) with Essure® patients who have had an MRI-PET
• matching on surgical technique with Essure® patients who have had an MRI-PET: salpingectomy with or without hysterectomy
• no analgesic treatment, or treatment stopped 48 hours before the examination
• no psychotropic treatment (anxiolytics, hypnotics (sleeping pills), antidepressants, mood stabilizers, neuroleptics)

• patient having given free, informed and signed consent

  • Exclusion Criteria * :

ESSURE Group:

• asymptomatic patient
• planned intervention by laparotomy
• patient potentially exposed to other heavy metals: wearer of metallic orthopedic equipment (hip or knee prosthesis, etc.), wearer of coronary stent, or tubal ligation clip
• inability to understand the information given
• persons deprived of liberty by a judicial or administrative decision
• people undergoing psychiatric care
• people admitted to a health or social establishment for purposes other than research
• adults subject to a legal protection measure (guardianship, curatorship)
• people not affiliated to a social security scheme or beneficiaries of a similar scheme
• person participating in another interventional research that may interfere with the research

Selection for MRI-PET examination:

• claustrophobia
• dosimetry of all radiological examinations over the past year not acceptable

Control Group :

• current pregnancy
• patient with cancer
• patient who has already had an Essure® implant removed
• patient potentially exposed to heavy metals: wearer of metallic orthopedic equipment (hip or knee prosthesis, etc.), wearer of coronary stent, or tubal ligation clip
• planned intervention by laparotomy
• inability to understand the information given
• persons deprived of liberty by a judicial or administrative decision
• people undergoing psychiatric care
• people admitted to a health or social establishment for purposes other than research
• adults subject to a legal protection measure (guardianship, curatorship)
• people not affiliated to a social security scheme or beneficiaries of a similar scheme
• person participating in another interventional research that may interfere with the research

Selection for MRI-PET examination:

• claustrophobia
• dosimetry of all radiological examinations over the past year not acceptable

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Essure Group; Patients requiring removal of the Essure® contraceptive implant	Device: Magnetic resonance imaging- Positron Emission Tomography (MRI-PET) examination; An MRI-PET examination will be carried out pre-operatively and at 6 months for the first 20 patients with Essure® and pre-operatively for the first 10 control patients presenting the selection criteria. The duration of each acquisition will be approximately 2 hours. Upon arrival, participants will be greeted by electroradiography technicians. A venous catheter will be placed in a vein in the right or left arm. Participants will be installed in the hybrid MRI-PET imager. The injection of [11C]PK11195 will take place in the MRI-PET acquisition room. Recording of functional neuroimaging data will begin immediately after intravenous injection of [11C]PK11195 and will last for 70 minutes in a resting state. At the end of the examination, the venous catheter will be removed and the visit will be over.; Biological: blood sample; Patients with Essure : Blood sample pre-operatively (20 mL) and at 2 months (10 mL) and 12 months (5 mL). Control patients : Blood sample pre-operatively (20 mL); Biological: urine collection; Patients with Essure : urine collection pre-operatively (10 mL) and at 2 months (10 mL) and 12 months (10 mL). Control patients : urine collection pre-operatively (10 mL); Biological: Collection of a lock of hair; Patients with Essure : Collection of a lock of hair pre-operatively and at 12 months Control patients : Collection of a lock of hair pre-operatively; Other: questionnaire; Questionnaires pre-operatively (except PGI-I) and at 2, 6, 12 months then twice a year up to 5 years for patients with Essure, and pre-operatively (except PGI-I) and at 2 months for control patients : PGI-I: symptom improvement score; SF-12: quality of life with physical and mental dimension.; FIQ: quality of life of women with fibromyalgia symptoms; HADS: anxiety and depressive dimension; MFI-20: fatigue according to 5 dimensions ); VAS : pain assessment; QDSA: assessment of sensory and emotional impact of pain; FSFI : quality of sexual life; Higham score
Active Comparator: Control Group; Control patients who should benefit from a salpingectomy with or without hysterectomy for a benign indication	Device: Magnetic resonance imaging- Positron Emission Tomography (MRI-PET) examination; An MRI-PET examination will be carried out pre-operatively and at 6 months for the first 20 patients with Essure® and pre-operatively for the first 10 control patients presenting the selection criteria. The duration of each acquisition will be approximately 2 hours. Upon arrival, participants will be greeted by electroradiography technicians. A venous catheter will be placed in a vein in the right or left arm. Participants will be installed in the hybrid MRI-PET imager. The injection of [11C]PK11195 will take place in the MRI-PET acquisition room. Recording of functional neuroimaging data will begin immediately after intravenous injection of [11C]PK11195 and will last for 70 minutes in a resting state. At the end of the examination, the venous catheter will be removed and the visit will be over.; Biological: blood sample; Patients with Essure : Blood sample pre-operatively (20 mL) and at 2 months (10 mL) and 12 months (5 mL). Control patients : Blood sample pre-operatively (20 mL); Biological: urine collection; Patients with Essure : urine collection pre-operatively (10 mL) and at 2 months (10 mL) and 12 months (10 mL). Control patients : urine collection pre-operatively (10 mL); Biological: Collection of a lock of hair; Patients with Essure : Collection of a lock of hair pre-operatively and at 12 months Control patients : Collection of a lock of hair pre-operatively; Other: questionnaire; Questionnaires pre-operatively (except PGI-I) and at 2, 6, 12 months then twice a year up to 5 years for patients with Essure, and pre-operatively (except PGI-I) and at 2 months for control patients : PGI-I: symptom improvement score; SF-12: quality of life with physical and mental dimension.; FIQ: quality of life of women with fibromyalgia symptoms; HADS: anxiety and depressive dimension; MFI-20: fatigue according to 5 dimensions ); VAS : pain assessment; QDSA: assessment of sensory and emotional impact of pain; FSFI : quality of sexual life; Higham score

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with improvement in symptoms Percentage of patients with improvement in symptoms	Percentage of patients with a score of 1, 2 or 3 (corresponding to improvement in symptoms) on the Patient Global Impression of Improvement (PGI-I) scale. The PGI-I is a transition scale that is a single question asking the patient to rate their symptoms now, as compared with how it was prior to before beginning treatment on a scale from 1 = Very much better to 7 = Very much worse.	At 2 months after surgical intervention (removal of the Essure® contraceptive implant)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with improvement in symptoms	Percentage of patients with a score of 1, 2 or 3 (corresponding to improvement in symptoms) on the PGI-I scale. The PGI-I is a transition scale that is a single question asking the patient to rate their symptoms now, as compared with how it was prior to before beginning treatment on a scale from 1 = Very much better to 7 = Very much worse.	up 5 years
Short Form 12 (SF-12) score	quality of life with assessment of the physical dimension (from 9.94738 to 70.02246) and the mental dimension (from 5.89058 to 71.96825). For each, the average in the general population is 50.	up 5 years
Fibromyalgia Impact Questionnaire (FIQ) score	quality of life of women with fibromyalgia symptoms (from 0 : no symptoms to 100 : important symptoms)	up 5 years
Hospital Anxiety and Depression scale (HADS) score	anxiety dimension and depressive dimension (for each dimension, from 0 : no symptom to 21 : certain symptomatology)	up 5 years
Multidimensional Fatigue Inventory (MFI)-20 score	Fatigue assessment according to 5 dimensions (General Fatigue, Physical and Mental Fatigue, Reduction in Motivation and Activities) (score from 20 : no fatigue to 100 : important fatigue)	up 5 years
Visual analog scale (VAS) score	pain assessment (from 0 : no pain to 100 : unbearable pain)	up 5 years
Questionnaire Douleur St-Antoine (QDSA) score	Assessment of sensory impact of pain (from 0: no pain to 36: important impact) and emotional impact of pain (from 0: no pain to 28 : important impact). The global score ranges from 0 to 64.	up 5 years
Female Sexual Function Index (FSFI) score	quality of sexual life (from 2 to 36). A low score indicates poorer sexual function.	up 5 years
Higham questionnaires	The Higham score is used to quantify blood loss during menstruation. A score ≥ 100 indicates a loss of 80 ml or more, which defines menorrhagia. A score ≥ 150 may indicate an indication for surgery for menometrorrhagia.	up 5 years
visual analog scale (VAS) score	Assessment by the surgeon of the difficulty of performing the ablation on a visual analog scale : from 0 (very easy) to 100 mm (very difficult)	During surgical intervention
Duration of the procedure	Duration of the procedure (calculated between incision and closure) in number of minutes	During surgical intervention
Complications	Number and types of per- and post-operative complications	Up to 2 months after the operation
characterization of the mechanical behavior of the implant	characterization of the mechanical behavior of the Essure® device implant will be assessed during tensile breakage and thermal breakage for its two parts (internal part and external part)	During surgical intervention
determination of the associated mechanical stress levels determination of the associated mechanical stress levels	determination of the associated mechanical stress levels of the Essure® device implant will be assessed during tensile breakage and thermal breakage for its two parts (internal part and external part)	During surgical intervention
quantification of the factors influencing these levels of mechanical stress	quantification of the factors influencing these levels of mechanical stress of the Essure® device implant will be assessed during tensile breakage and thermal breakage for its two parts (internal part and external part)	During surgical intervention
thermal resistance	The thermal resistance of the Essure® device implant during coagulations/electrical sections will be assessed.	During surgical intervention
risk of degradation	The risk of degradation depending on the temperature f the Essure® device implant used during coagulations/electrical sections will be assessed.	During surgical intervention
Concentrations of titanium constituting the Essure® implant	Concentrations of titanium constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).	up 12 months after surgical intervention
Concentrations of nickel constituting the Essure® implant	Concentrations of nickel constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).	up 12 months after surgical intervention
Concentrations of chromium constituting the Essure® implant	Concentrations of chromium constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).	up 12 months after surgical intervention
Concentrations of tin constituting the Essure® implant	Concentrations of tin constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).	up 12 months after surgical intervention
Concentrations of platinum constituting the Essure® implant	Concentrations of platinum constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).	up 12 months after surgical intervention
Concentrations of iridium constituting the Essure® implant	Concentrations of iridium constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).	up 12 months after surgical intervention
Concentrations of molybdenum constituting the Essure® implant	Concentrations of molybdenum constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).	up 12 months after surgical intervention
Concentrations of manganese constituting the Essure® implant	Concentrations of manganese constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).	up 12 months after surgical intervention
Concentrations of tungsten constituting the Essure® implant	Concentrations of tungsten constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).	up 12 months after surgical intervention
Concentrations of silver constituting the Essure® implant	Concentrations of silver constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).	up 12 months after surgical intervention
Concentrations of iron constituting the Essure® implant	Concentrations of iron constituting the Essure® implant in the peritoneal fluid, in the surgical piece, in the urine, in the blood, in the appendages (hair).	up 12 months after surgical intervention
concentration of pro-inflammatory cytokines	concentration of pro-inflammatory cytokines in the blood will be assessed	Up 2 months after surgical intervention
expression profile of miRNAs	Expression profile of miRNAs in the peritoneal fluid will be assessed.	Up 2 months after surgical intervention
activated T lymphocyte profile	activated T lymphocyte profile in blood will be assessed.	Up 2 months after surgical intervention
analysis of inflammatory pathway mRNAs	analysis of inflammatory pathway mRNAs (nanostring® technology) in a pathology sample from the surgical specimen will be assessed.	Up 2 months after surgical intervention
Percentage of detection of Human Leukocyte Antigen	Percentage of detection of Human Leukocyte Antigen (HLA)-DR53 (DRB4∗01) associated with nickel allergies in blood will be assessed.	Up 2 months after surgical intervention
Functional brain functions	MRI-PET (Magnetic resonance imaging- Positron Emission Tomography) examination : Mapping of brain inflammation: binding potential mapping of [11C]PK11195 characteristic of activated microglia; Brain anatomical imaging: clinical type anatomical MRI examination to assess the presence of cerebral anatomical abnormality; Brain mapping of functional connectivity at rest using Functional magnetic resonance imaging (fMRI); Brain mapping of structural connectivity by diffusion MRI; Perfusion imaging : perfusion MRI examination without contrast product to assess the presence of cerebral perfusion abnormality; Magnetic susceptibility imaging: to detect possible hemorrhages	up 6 months after Surgical intervention

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2025
• Primary Completion (Estimated): April 17, 2032
• Study Completion (Estimated): February 17, 2037

Study Registration Dates

• First Submitted: March 28, 2024
• First Submitted That Met QC Criteria: April 3, 2024
• First Posted (Actual): April 9, 2024

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Contraceptive implant; Symptoms; Essure implant
• Additional Relevant MeSH Terms: Health Care Quality, Access, and Evaluation; Investigative Techniques; Epidemiologic Methods; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Data Collection; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Surveys and Questionnaires; Blood Specimen Collection; Urine Specimen Collection; Physical Examination
• Other Study ID Numbers: 69HCL23_0899; 2023-A02010-45 (Other Identifier: ID-RCB)

Drug and device information, study documents

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