Guerriero 1996b.

Study characteristics
Patient sampling	Primary objectives To assess the role of transvaginal ultrasonography in combination with CA‐125 plasma levels in diagnosis of endometrioma Study population Women who were submitted to laparoscopy or laparotomy because of the presence of a persistent adnexal mass Selection criteria Inclusion criteria: premenopausal, non‐pregnant women Study Design Cross‐sectional, single‐gate design, prospective recruitment and collection of samples, consecutive series
Patient characteristics and setting	Clinical presentation Adnexal mass Age: Age range 20‐49 years, mean age not provided Number of enrolled 101 women Number of available for analysis 101 women (only moderate‐severe endometriosis included; all in follicular cycle phase) Setting University Hospital, University of Cagliari Place of study Cagliari, Italy Period of study November 1993 ‐ October 1994 Language English
Index tests	Index test CA‐125 in serum + Transvaginal Ultrasonography (TVUS) Details of the index test procedure as stated Serum CA‐125 levels assessed by immunoradiometric assay (CIS Bio International, Gif sur Yvette, France), limit of detection 0.5 U/ml; TVUS performed with a 5 MHz endovaginal probe (Acuson XP/10 OB ultrasound system), procedure described in details Threshold for positive result CA‐125: ≥20 IU/ml ≥25 IU/ml, ≥35 IU/ml pre‐specified; TVUS ‐ presence of round, homogenous, hypoechoic "tissue," within the ovary ‐ referenced to the primary source, pre‐specified Examiners For blood assays ‐ no information provided; unclear if were blinded to the results of reference standard; for TVUS ‐ same physician blinded to reference standard Interobserver variability Intra‐ and inter‐assay CV for CA‐125 3.9% and 4.2%
Target condition and reference standard(s)	Target condition Ovarian endometriosis Prevalence of target condition in the sample n = 29/101 (29%): all stage III‐IV; controls n = 72 Reference standard Laparoscopy/ Laparotomy (number for each group not reported) + histopathology Description of positive case definition by reference test as reported: Visual inspection confirmed on histopathology; histological criteria reported; surgical procedure described; surgical staging according to the rAFS classification Examiners No information provided
Flow and timing	Time interval between index test and reference standard Blood was collected on the day of surgery, TVUS was performed several days prior Withdrawals None
Comparative
Key conclusions by the authors	Transvaginal ultrasonography used alone has a better predictive capacity in differentiating endometrioma from other adnexal masses than combined methods.
Conflict of interest	Not reported
Notes	The reported diagnostic estimates for blood biomarker or TVUS alone are presented in other reviews from this series
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Did the study avoid inappropriate exclusions?	Yes
Was a 'two‐gate' design avoided?	Yes
		Low	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?	Yes
Was a cycle phase considered in interpretation of the result of index test?	Yes
Did the study provide a clear pre‐specified definition of what was considered to be a positive result of index test?	Yes
Was the index test performed by a single operator or interpreted by consensus in a joint session?	Yes
Were the same clinical data available when the index test results were interpreted as would be available when the test is used in practice?	Unclear
		Unclear	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