Evolution of Endometriosis Lesions Followed by Ultrasound and Quality of Life of Patients: Factors That Influence Disease Progression in a Prospective Cohort

Official title

Evolution of Endometriosis Lesions and Quality of Life of Patients

Overview

The goal of this prospective cohort study is to determine the factors that influence the progression of endometriosis and the quality of life of patients. The main questions it aims to answer are: 1. Is endometriosis a progressive disease? 2. Is the progression of lesions visualized by ultrasound dependent on the medical treatment received? 3. Does the clinical progression of patients correlate with the progression of lesions visualized on transvaginal ultrasound? 4. Is ultrasound follow-up necessary for patients? 5. Could clinical follow-up alone be safe for selected patients? Researchers will follow up a prospective cohort of 100 patients diagnosed with deep infiltrating endometriosis (DIE) +/- endometriomas during 2 years, collecting data regarding their ultrasound exam and their symptoms and quality of life at stablished controls at recruitment, 6 months, 12 months and 24 months.

Detailed description

This prospective observational cohort study aims to characterize the clinical and ultrasonographic progression of endometriosis and to identify the factors associated with disease evolution, ovarian reserve, symptom burden, and patient-reported quality of life. The protocol is designed to integrate longitudinal clinical assessments, structured transvaginal ultrasound evaluations, hormonal profiling, and digital monitoring through the validated mobile application "Endometric".

The study will follow a cohort of adult women with confirmed endometriosis for two years, using standardized evaluation intervals (baseline, 6 months, 1 year, and 2 years) to capture meaningful changes in lesion morphology, symptoms, and functional outcomes.

Ultrasound assessments will be performed according to the IDEA consensus (Guerriero S, et al. Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the International Deep Endometriosis Analysis (IDEA) group. Ultrasound Obstet Gynecol. 2016 Sep;48(3):318-32. doi: 10.1002/uog.15955) and lesions will be classified using the Enzian system (Keckstein J, et al. The #Enzian classification: A comprehensive non-invasive and surgical description system for endometriosis. Acta Obstet Gynecol Scand. 2021 Jul;100(7):1165-75. doi: 10.1111/aogs.14099), enabling precise measurement of endometriomas, deep infiltrating lesions, associated adhesions, and adnexal involvement.

Ovarian reserve will be estimated using antral follicle count and antimüllerian hormone (AMH) levels, analyzed in a single specialized laboratory to minimize inter-assay variability. Clinical progression will be assessed through standardized symptom scales and the Endometriosis Health Profile Questionnaire (EHP-30). Participants will be managed with expectant, medical, or combined approaches according to routine clinical practice; treatments will not be randomized, but exposure will be precisely documented to evaluate its relationship with disease evolution.

The study functions as a patient registry with predefined longitudinal data collection and structured quality-assurance procedures. Data will be stored in a dedicated Clinapsis database with controlled access and pseudonymization through unique patient codes. A detailed data dictionary will define each variable, its source, coding strategy (including standardized terminology for medications and symptoms), and reference ranges for biological parameters. Automated data-entry checks will detect inconsistencies, missing fields, and out-of-range values at the point of entry. Additional validation procedures will include periodic cross-checks between electronic case-report forms and source data (ultrasound measurements, laboratory results, medical records). Source data verification will be conducted by authorized investigators to ensure accuracy and completeness.

Standard Operating Procedures (SOPs) will govern all registry operations: patient identification and recruitment; informed-consent procedures; clinical and ultrasound assessments; biological-sample handling; data entry, monitoring, and auditing; management of adverse events; and change-control processes for any protocol modifications. The biobank procedures-collection and storage of serum, plasma, urine, and endometriotic tissue-adhere to institutional and regulatory standards, allowing future biomarker research on inflammation, interleukins, and miRNAs.

The planned sample size of 100 patients represents a pragmatic estimate based on available annual referrals and expected retention; although formal power calculations are limited by absent prior data, this cohort is considered sufficient to detect clinically meaningful trends and associations.

Missing data will be addressed through predefined rules distinguishing "missing," "not applicable," and "uninterpretable" entries, with sensitivity analyses planned to assess potential bias.

The statistical analysis plan includes descriptive analysis of all variables according to their scale, repeated-measures ANOVA to evaluate temporal changes across the four scheduled visits, and ANCOVA models to explore the impact of covariates such as age, baseline symptom severity, and treatment type. Comparisons between treatment groups will adjust for confounding when possible, acknowledging that therapeutic choice is not randomized. A significance threshold of 0.05 (two-sided) will be used. Data will be analyzed using IBM SPSS v29 or later.

Monitoring and audit procedures ensure compliance with regulatory and ethical standards. Investigators will maintain study documents for at least five years, and authorized monitors, auditors, ethical committees, or health authorities may access anonymized source documentation for verification.

The project is supported by the Fundació La Marató de TV· (Reg 55/173, project 20241910), which ensures adequate resources for data management, sample processing, and technological support for the clinical-monitoring application.

Primary outcome measures

• Ultrasound-assessed progression of endometriosic lesions at recruitment, 6, 12 and 24 months [Time frame: From enrollment to the end of follow-up at 24 months]
• Evolution of clinical presentation at recruitment, 6, 12 and 24 months [Time frame: From enrollment to the end of follow-up at 24 months]

Secondary outcome measures (2)

• Evolution of Ovarian Reserve at recruitment, 6, 12 and 24 months [Time frame: From enrollment to the end of follow-up at 24 months]
• Evolution of Quality of Life (QoL) at recruitment, 6, 12 and 24 monts [Time frame: From enrollment to the end of follow-up at 24 months]

Eligibility criteria

Inclusion criteria

• Women with a confirmed diagnosis of endometriosis, based on ultrasound criteria. Diagnosis must be confirmed by transvaginal ultrasound with evidence of visible and measurable endometriotic lesions.
• Patients over 18 years of age. This criterion ensures that participants can provide informed consent and are of reproductive age, when the effects of endometriosis and its treatments are relevant to the study.
• A transvaginal ultrasound performed prior to enrollment showing endometriotic lesions (either endometriomas or deep lesions) with sufficient dimensions and characteristics for evaluation and follow-up.
• Patients who do not have an indication for scheduled surgery within the next two years. This ensures that the effects of treatment and the progression of the disease can be evaluated throughout the study follow-up period.
• Signed informed consent from the patient, indicating that she has understood the purpose of the study, the procedures involved, and the potential risks.

Exclusion criteria

• Patients with an indication for scheduled surgical treatment within the next two years. This includes patients requiring surgery for the removal of endometriotic lesions or to address related complications.
• Patients who are unwilling to undergo follow-up transvaginal ultrasound at scheduled visits (6 months, 1 year, 2 years). Ultrasound is essential for assessing disease progression and the impact of treatment.
• Patients who are unwilling to participate in the study after receiving all the information and providing their informed consent. Voluntary participation is crucial for the ethics of the study.
• Patients with intellectual disabilities or conditions that impair their understanding of the study terms and procedures, which could affect their ability to provide valid informed consent.
• Patients who are pregnant or breastfeeding at the time of enrollment. These conditions can influence the course of endometriosis and the response to treatment, and could complicate disease monitoring.
• Patients with serious concurrent illnesses or medical conditions that may interfere with the assessment of endometriosis, its progression, or the impact of treatment (e.g., severe chronic inflammatory diseases or cancer).
• Patients receiving concurrent treatments not permitted by the study protocol (e.g., experimental treatments for endometriosis or related conditions) that may interfere with the interpretation of the results.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Spain · 1 center

• Hospital de la Santa Creu i Sant Pau — Barcelona

Publications

• Vannuccini S, Clemenza S, Rossi M, Petraglia F. Hormonal treatments for endometriosis: The endocrine background. Rev Endocr Metab Disord. 2022 Jun;23(3):333-355. doi: 10.1007/s11154-021-09666-w. Epub 2021 Aug 17. PMID 34405378
• Brown J, Crawford TJ, Datta S, Prentice A. Oral contraceptives for pain associated with endometriosis. Cochrane Database Syst Rev. 2018 May 22;5(5):CD001019. doi: 10.1002/14651858.CD001019.pub3. PMID 29786828
• Vercellini P, Crosignani P, Somigliana E, Vigano P, Frattaruolo MP, Fedele L. 'Waiting for Godot': a commonsense approach to the medical treatment of endometriosis. Hum Reprod. 2011 Jan;26(1):3-13. doi: 10.1093/humrep/deq302. Epub 2010 Nov 11. PMID 21071490
• Becker CM, Bokor A, Heikinheimo O, Horne A, Jansen F, Kiesel L, King K, Kvaskoff M, Nap A, Petersen K, Saridogan E, Tomassetti C, van Hanegem N, Vulliemoz N, Vermeulen N; ESHRE Endometriosis Guideline Group. ESHRE guideline: endometriosis. Hum Reprod Open. 2022 Feb 26;2022(2):hoac009. doi: 10.1093/hropen/hoac009. eCollection 2022. PMID 35350465
• National Guideline Alliance (UK). Endometriosis: diagnosis and management. London: National Institute for Health and Care Excellence (NICE); 2017 Sep. Available from http://www.ncbi.nlm.nih.gov/books/NBK453273/ PMID 29787038
• Koninckx PR, Fernandes R, Ussia A, Schindler L, Wattiez A, Al-Suwaidi S, Amro B, Al-Maamari B, Hakim Z, Tahlak M. Pathogenesis Based Diagnosis and Treatment of Endometriosis. Front Endocrinol (Lausanne). 2021 Nov 25;12:745548. doi: 10.3389/fendo.2021.745548. eCollection 2021. PMID 34899597
• de Ziegler D, Borghese B, Chapron C. Endometriosis and infertility: pathophysiology and management. Lancet. 2010 Aug 28;376(9742):730-8. doi: 10.1016/S0140-6736(10)60490-4. PMID 20801404
• Perello MF, Martinez-Zamora MA, Torres X, Munros J, Balasch Cortina J, Carmona F. Endometriotic Pain Is Associated with Adenomyosis but Not with the Compartments Affected by Deep Infiltrating Endometriosis. Gynecol Obstet Invest. 2017;82(3):240-246. doi: 10.1159/000447633. Epub 2016 Oct 7. PMID 27710968

Identifiers

NCT: NCT07282990 · IIBSP-ECE-2024-127

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗