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

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.

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.