Drosdzol‐Cop 2012a.

Study characteristics
Patient sampling	Primary objective: to determine the role of serum and peritoneal interleukin (IL)‐6, tumour necrosis factor (TNF)‐α and glycodelin A levels as diagnostic markers of endometriosis in adolescent girls Participants: adolescent girls after menarche undergoing laparoscopy for chronic pelvic pain Selection criteria: inclusion criteria: chronic pelvic pain, defined as non‐cyclic lower abdominal pain, not connected with the menstrual cycle, lasting at least 3 months or cyclic pain ongoing for 6 months, severe enough to cause functional disability or require medical or surgical treatment; exclusion criteria: general, chronic, autoimmune or endocrinological diseases, history of pregnancy or hormonal medications for at least 6 months prior to the study Study design: cross‐sectional, single‐gate design, prospective collection of samples
Patient characteristics and setting	Clinical presentation: Chronic pelvic pain; age of menarche (12.2 ± 1.4 and 12.8 ± 1.3 years) and percentage of ovulatory menstrual cycles (n = 15, 45.5% and n = 8, 47.1%) were comparable in both groups Age: mean age 17.4 ± 1.1 years (endometriosis group) and 16.4 ± 2.0 years (controls) Number of participants enrolled: 50 participants Number of participants available for analysis: 50 participants (all in follicular cycle phase, day 3‐7) Setting: University Hospital: Woman's Health Institute, the Medical University of Silesia Place of study: Katowice, Poland Period of study: not stated Language: English
Index tests	Index test: IL‐6, TNF‐α and glycodelin A Details of the index test procedure as stated: Serum levels of IL‐6, TNF‐α and glycodelin A were measured by using commercial ELISA kits according to the manufacturers instructions; the detection limit of IL‐6 was 2 pg/ml, of TNF‐α was 0.7 pg/ml and of glycodelin A was 6 ng/ml; sample handling described Threshold for positive result: not reported Examiners: no information provided; unclear if were blinded to the results of reference standard Interobserver variability: Intra‐ and interassay CVs were: for IL‐6 4.3% and 4.9%, for TNF‐α 6.5% and 3.9%, for glycodelin A 8.3% and 4.6%
Target condition and reference standard(s)	Target condition: endometriosis Prevalence of target condition in the sample: n = 33/50 (66%): stage I‐II 19, stage III‐IV 14; controls n = 17 Reference standard: laparoscopy N = 50 (100%) + histology Description of positive case definition by reference standard test as reported: visualisation at surgery with subsequent histological confirmation; staging according to the rAFS classification Examiners: no information provided
Flow and timing	Time interval between index test and reference standard: blood samples were collected at surgery Withdrawals: none reported
Comparative	Studies on sHLA‐I and sICAM‐1 may help to clarify the pathogenic mechanisms of endometriosis, and their serum concentrations may serve as additional markers for the early detection of recurrence of the disease during the monitoring of treatment outcome
Key conclusions by the authors	At the cut‐off value of 3.00 pg/ml, peritoneal TNF‐α can be a reliable screening marker for the prediction of endometriosis in adolescents, giving a 14.6‐fold higher probability of endometriosis detection in girls with chronic pelvic pain
Conflict of interest	The authors declared no conflict of interests
Notes	For IL‐6, TNF‐α and glycodelin A there was no 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?	Unclear
Did the study avoid inappropriate exclusions?	Yes
Was a 'two‐gate' design avoided?	Yes
		Unclear	Low
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