Development and Validation of an Endometriosis Diagnostic Method Based on Serum Biomarkers and Clinical Variables

Abstract

Endometriosis affects more than 10% of women of reproductive age, significantly impacting their quality of life. Diagnosis typically takes 4 to 11 years from symptom onset. The gold standard for diagnosing this disease, laparoscopy, is invasive, contributing to this delay in diagnosis. Two studies were conducted to develop a diagnostic test based on the combination of serum biomarkers and clinical variables. Study 1, the development study, aimed to: (i) confirm the ability of CA125, BDNF and clinical variables to differentiate between cases and controls, and (ii) develop a diagnostic algorithm based on these results. Study 2 validated the clinical performance of the developed in vitro diagnostic (IVD) test in diagnosing endometriosis. Serum samples and clinical variables extracted from psychometric questionnaires were obtained from the Oxford Endometriosis CaRe Centre biobank (UK). Case/control classification was performed based on laparoscopy and histological verification of the excised lesions. Studies 1 and 2 included n = 204 and n = 79 patients, respectively. Study 1 found a statistically significant difference between cases and controls for levels of both biomarkers. Of the assessed clinical variables from the patients’ medical histories, six were found to be significantly different between endometriosis cases and controls. CA125, BDNF and these six clinical variables were combined into a multivariable prediction model. In Study 2, the IVD test demonstrated sensitivity and specificity values of 46.2% (25.5–66.8%) and 100% (86.7–100%), respectively. Due to its high specificity, this IVD test is a simple and accurate rule-in test for early disease identification, even in the presence of non-specific symptoms.

Validation of an in vitro diagnostic test for endometriosis: impact of confounding medical conditions and lesion location

“…The serum samples were then preserved in the biobank at temperatures as low as -80 ºC for a duration of up to 5 years, after which they were transferred to the designated laboratory for analysis. The ELISA utilized in this in vitro diagnostic test functions as a solid-phase sandwich enzyme-immunoassay for the precise determination of BDNF and CA125 levels within human serum [22].…”

“…Recently, we have developed a diagnostic treatment algorithm that combines CA125 and BDNF measurements with six pertinent clinical variables: patient’s surgical history related to endometriosis, the manifestation of painful periods as a leading symptom for endometriosis referral, the intensity of menstrual pain during the previous cycle, the age at the onset of intercourse-related pain, the age at the initiation of regular pain-killer usage, and the age at the initial diagnosis of an ovarian cyst. CA125, BDNF, and the six clinical factors were integrated into the final logistic regression model, achieving an AUC of 0.867, sensitivity of 51.5%, and specificity of 95.6% [22].…”

A Comprehensive Review of the Diagnostic Landscape of Endometriosis: Assessing Tools, Uncovering Strengths, and Acknowledging Limitations

“…While individual biomarkers like CA-125 have undergone extensive study, a panel of multiple markers will likely offer greater accuracy than any single biomarker in diagnosing endometriosis [ 13 ]. Further research and validation are imperative to establish clinically reliable, non-invasive tests for endometriosis detection and to enhance patient outcomes [ 31 ].…”

Direct analysis of very small amount of blood by a disposable monolithic column mass spectrometry kit

“…In vitro diagnostics (IVD) is an essential component of clinical care that performs a diagnostic test on biological samples taken from a living body, such as blood, urine, etc. [1][2][3][4][5] In 2018, the export value of IVD products in China was approximately 1 billion dollars, of which 760 million dollars was the value of instrument exports. [6] Whole blood analysis is a typical IVD task in clinical tests, which calls for analytical methods for rapid, sensitive, low-cost, and muti-component analysis.…”