Cho 2007.

Study characteristics
Patient sampling	Primary objective: To evaluate serum and urinary levels of VEGF, TNF‐a and sFlt‐1 in patients with endometriosis Study population: Women who underwent laparoscopy or laparotomy for different indications including pelvic masses, pelvic pain, suspicious endometriosis, infertility and diagnostic evaluation Selection criteria: Inclusion criteria: pre‐menopausal age Study design: Cross‐sectional, two‐gate design, prospective collection of samples
Patient characteristics and setting	Clinical presentation: Pelvic pain, infertility, pelvic mass, other not specified Age: Mean age 32.65 ± 6.82 years (endometriosis group), 30.96 ± 6.36 years (controls) Number of participants enrolled: 70 women Number of participants available for analysis: 70 women (in follicular or luteal cycle phase, numbers not specified) Setting: Department of O&G, Yongdong Severance Hospital, Yonsei University College of Medicine Place of study: Seoul, Korea Period of study: Not stated Language: English
Index tests	Index test: Urinary vascular endothelial growth factor (VEGF), tumour necrosis factor‐alpha (TNF‐a) and soluble fms like tyrosine kinase (sFlt‐1) Details of the index test procedure as stated: Urine concentrations of VEGF, sFlt‐1, and TNF‐a, were measured using specific commercial sandwich ELISA kit according to manufacturer protocols (Quantikine; R&D systems Inc, MN, USA); sample processing described Threshold for positive result: Not provided Examiners: No information provided; unclear if blinded to the result of reference standard Interobserver variability: Not reported
Target condition and reference standard(s)	Target condition: Endometriosis Prevalence of target condition in the sample: n = 46/70 (66%): stage I‐II 15, stage III‐IV 31; controls n = 24 Reference standard: Laparoscopy/Laparotomy and histology Description of positive case definition by reference standard as reported: Visual inspection, confirmed by histopathology; staging according to the rASRM classification Examiners: No information provided
Flow and timing	Time interval between index test and reference standard: Urine sample was collected after induction of anaesthesia Withdrawals: None
Comparative
Key conclusions by the authors	The pathogenesis of minimal‐to‐mild endometriosis and moderate‐to severe endometriosis seems to be different. Increased sFlt‐1 levels in serum and urine of minimal‐to‐mild disease indicate that sFlt‐1 may have an important role in inhibiting angiogenic process of the disease
Conflict of interest	Not reported
Notes	For VEGF and TNF‐a there was no statistically significant difference between the groups ‐ no data available for meta‐analysis Urinary levels for all biomarkers were corrected for creatinine Urinary VEGF and TNF‐a levels were unaffected by severity of endometriosis or menstrual cycle phase For sFlt‐1 there was statistically significant difference between the groups, but there was insufficient data to construct 2 x 2 tables ‐ not included in this review
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Did the study avoid inappropriate exclusions?	Yes
Was a 'two‐gate' design avoided?	No
		High	High
DOMAIN 2: Index Test All tests
Were the index test results interpreted without knowledge of the results of the reference standard?	Unclear
If a threshold was used, was it pre‐specified?	No
Was a cycle phase considered in interpretation of the result of index test	Yes
		High	Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
		Low	Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
		Low