Riley 2007.

Study characteristics
Patient sampling	Primary objective: to test local (PF) and systemic inflammatory markers in order to explore what parts of inflammation are activated in endometriosis, and test whether this was related to stage and symptoms of the disease Participants: patients with histologically confirmed endometriosis and controls undergoing surgery for benign gynaecological disorders Selection criteria: not specified Study design: cross‐sectional, two‐gate design, prospective collection of samples
Patient characteristics and setting	Clinical presentation: dyspareunia ‐ 12/32, dysmenorrhoea ‐ 21/32, other pelvic pain ‐ 19/32, infertility, fibroids Age: median age (95% CI): 33 (29‐36) years (endometriosis group), 37 (31‐43) years (controls) Number of participants enrolled: 32 women (14 in follicular, 14 in luteal cycle phase; 3 women were menopausal and 1 had undetermined cycle phase due to AUB) Number of participants available for analysis: 30 women Setting: Department of O&G, St. Olavs University Hospital Place of study: Trondheim, Norway Period of study: not provided Language: English
Index tests	Index test: CA‐125, CRP Details of the index test procedure as stated: serum concentrations of CA‐125 and CRP were measured by using the commercial kits (Elecsys, CA‐125II Roche/Roche/Hitachi Modular Analytics E170, Germany and Tina‐quant CRPLX, Roche/Hitachi Modular Analytics E170, Roche) on the day of collection; sample processing not described Threshold for positive result: CA‐125 > 35 kU/l, not pre‐specified Examiners: no information provided; unclear if blinded to the result of reference standard Interobserver variability: not provided
Target condition and reference standard(s)	Target condition: endometriosis Prevalence of target condition in the sample: n = 18: stage I ‐ 10, stage III‐IV ‐ 8; controls n = 14 Reference standard: laparoscopy n = 32 (100%) Description of positive case definition by reference standard as reported: staging according to the rAFS score Examiners: no information provided
Flow and timing	Time interval between index test and reference standard: blood samples were collected at surgery Withdrawals: 2 women were excluded (1 ‐ ovarian abscess diagnosed at surgery, 1 ‐ on NSAIDs for rheumatoid arthritis)
Comparative
Key conclusions by the authors	Neutrophil granulocytes in endometriosis patients may have a lowered ability to respond to weak activation signals, while in more extensive endometriosis stronger neutrophil activation may be related to a pro‐inflammatory effect of endometriotic tissue
Conflict of interest	Not reported
Notes	For CA‐125 and CRP there was no statistically significant difference between the groups ‐ no data available for meta‐analysis The data for markers measured in peritoneal fluid are not presented 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?	No
Did the study avoid inappropriate exclusions?	Unclear
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?	Unclear
		High	Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Unclear
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
		Unclear	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