Nisenblat · The Cochrane database of systematic reviews 2016 · systematic review of diagnostic test accuracy studies · n=11 studies (1,339 participants)

Combination of the non-invasive tests for the diagnosis of endometriosis.

Cited 224 times in the scientific literature.

Level 1 - systematic review of randomized trials

Systematic review of diagnostic test accuracy studies

PubMed 27405583 · doi:10.1002/14651858.CD012281 · record verified 2026-08-26

What was done

Authors conducted a Cochrane systematic review searching multiple electronic databases through mid-2015 for cross-sectional or randomised studies evaluating combinations of non-invasive tests (blood, urinary, or endometrial biomarkers; transvaginal ultrasound; clinical history; physical examination) compared to surgical diagnosis for pelvic, ovarian, or deep infiltrating endometriosis. Quality was evaluated using the QUADAS-2 tool. Target diagnostic thresholds were defined for replacement tests (sensitivity ≥0.94, specificity ≥0.79) and triage tests (≥0.95 sensitivity for rule-out SnOUT; ≥0.95 specificity and ≥0.50 sensitivity for rule-in SpIN).

What was found

Eleven studies (1,339 participants) evaluated 15 distinct diagnostic combinations; data could not be pooled due to heterogeneity of test combinations. Two individual combinations met replacement criteria: serum IL-6 plus endometrial PGP 9.5 for pelvic endometriosis (sensitivity 1.00, 95% CI 0.91 to 1.00; specificity 0.93, 95% CI 0.80 to 0.98) and vaginal examination plus transvaginal ultrasound (TVUS) for rectal endometriosis (sensitivity 0.96, 95% CI 0.86 to 0.99; specificity 0.98, 95% CI 0.94 to 1.00). Several combinations met SpIN triage criteria, such as urine vitamin-D-binding protein multiplied by serum CA-125 for pelvic endometriosis (sensitivity 0.74, specificity 0.97) and TVUS combined with CA-125 or CA 19.9 for endometrioma. However, all findings derived from single studies with wide confidence intervals.

Why it matters

Non-invasive diagnostic combinations currently lack sufficient evidence to replace or triage patients for diagnostic surgery, meaning laparoscopy remains the mandatory gold standard in clinical practice.

Limits

All 11 included studies exhibited poor methodological quality and high risk of bias. Heterogeneity precluded meta-analysis, and every reported combination was evaluated in only a single small study with wide confidence intervals and no independent validation.

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