Tuten 2014a.

Study characteristics
Patient sampling	Primary objective: to determine whether serum copeptin levels were altered in women with endometriosis and played a role in the pathophysiology of the disease Participants: women who had undergone laparoscopy or laparotomy due to suspected ovarian endometriosis, infertility and pelvic pain Selection criteria: inclusion criteria: reproductive age, regular menstrual cycle; exclusion criteria: postmenopausal FSH levels, pregnancy, suspicion of a malignant ovarian disease, history of any hormone therapy in past 3/12 months, presence of any non‐endometriotic ovarian cyst/mass Study design: cross‐sectional single‐gate, prospective sample collection
Patient characteristics and setting	Clinical presentation: adnexal mass, infertility, pelvic pain; none had a history of a previous ovarian surgery and any other endocrine or autoimmune disease Age: mean age 31.9 ± 8.2 years (endometrioma group), 30.7 ± 7.8 years (controls) Number of participants enrolled: 92 women Number of participants available for analysis: 86 women (menstrual cycle phase not reported) Setting: Department of O&G, Istanbul University Cerrahpasa School of Medicine Place of study: Istanbul, Turkey Period of study: May 2012 ‐ July 2013 Language: English
Index tests	Index test: Copeptin, CRP, WBC, CA‐125, CA‐19.9, CA‐15.3 Details of the index test procedure as stated: serum CA‐125, CA‐19.9, CA‐15.3 were measured using an IMMULITE 2000 (DPC, Los Angeles, CA): chemiluminescent immunometric assay for CA‐125 and CA‐15‐3 and immunometric assay for CA‐19.9; serum copeptin was measured by using Human Vasopressin‐neurophysin 2‐copeptin ELISA kit (EIAab Wuhan EIAab Science Co. Ltd, China); with minimum detectable dose of Human Vasopressin‐neurophysin 2‐copeptin was < 10 pg/ml, detection rate of 15.6–1000.0 pg/ml; CRP was measured using an automated CRPLX Tina‐quant C‐Reactive Protein (Latex) assay (Roche, Belgium) with lower detection limit of 0.425 mg/L and the functional sensitivity of 0.88 mg/L; sample handling described Threshold for positive result: CA‐125 > 26.29 IU/ml, CA‐19.9 >10.67 IU/ml, CA‐15‐5 >15.04 IU/ml; copeptin >251.18 pg/ml ‐ not pre‐specified Examiners: no information provided; unclear if were 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 = 50/86 (58%): stage I‐II ‐ 27, stage III‐IV ‐ 23; controls n = 36 Reference standard: laparoscopy/laparotomy n = 88 (100%) + histology Description of positive case definition by reference standard test as reported: thorough examination of the abdominopelvic cavity with histological confirmation; staging according to the ASRM classification Examiners: no information provided
Flow and timing	Time interval between index test and reference standard: blood samples were collected immediately before surgery Withdrawals: 5 patients were excluded (met exclusion criteria)
Comparative
Key conclusions by the authors	Serum copeptin levels were significantly higher in patients with endometriosis as compared to healthy controls and severity of the disease was correlated with serum copeptin levels
Conflict of interest	The authors disclosed no conflict of interests
Notes	For CRP and WBC there was no statistically significant difference between the groups ‐ no data available for meta‐analysis
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?	Unclear
		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