Koninckx 1996.

Study characteristics
Patient sampling	Primary objective: to evaluate clinical examination during menstruation and plasma CA‐125 concentration to diagnose endometriosis Participants: women scheduled for laparoscopy for suspected endometriosis Selection criteria: exclusion criteria: hormonal treatment or medical treatment for endometriosis in the 3 months preceding laparoscopy, refusal a clinical examination during menstruation (only DIE considered) Study design: cross‐sectional single‐gate, prospective recruitment and collection of samples, consecutive series
Patient characteristics and setting	Clinical presentation: infertility (n = 33), pain (n = 13), infertility + pain (n = 6), hydrosalpinx (n = 1), ovarian cyst (n= 2) Age: range 20‐45 years (personal communication with the author) Number of participants enrolled: 61 women Number of participants available for analysis: 55 women (only DIE, endometrioma and severe pelvic adhesions included; all in menstrual, follicular and early luteal phase of menstrual cycle) Setting: division of endoscopic surgery, University Hospital Gasthiusberg, University of Leuven Place of study: Leuven, Belgium Period of study: not stated Language: English
Index tests	Index test: CA‐125 in mid‐follicular phase Details of the index test procedure as stated: CA‐125 assay by second generation IRMA kit (CA‐125 II, Centocor, Malvern, Pa); all the samples assayed in duplicate using kits from the same production batch Threshold for positive result: > 35 U/ml, not pre‐specified Examiners: no information provided; unclear if were blinded to the result of reference standard Interobserver variability: intra‐ and interassay variation < 5% and < 8%
Target condition and reference standard(s)	Target condition: deep infiltrating endometriosis and ovarian endometrioma Prevalence of target condition in the sample: n = 38/55 (69%): stage I‐II 29, stage III‐IV 9; deep endometriosis 13, endometrioma 9, deep endometriosis + severe cul‐de‐sac adhesions + endometrioma 24; controls n = 17 Reference standard: laparoscopy N = 55 (100%) Description of positive case definition by reference standard test as reported: visual inspection, deep endometriosis classified as type I and type II, reference to the source with diagnostic criteria and described; staging according to the rAFS classification . Examiners: not stated
Flow and timing	Time interval between index test and reference standard: the samples were collected up to 4 months before surgery (personal communication with the author) Withdrawals: in 6 women (11%) the surgery was cancelled for various reasons
Comparative
Key conclusions by the authors	Clinical examination during menstruation can reliably diagnose deep infiltrating endometriosis, cystic ovarian endometriosis or cul‐de‐sac adhesions. This test, preferentially combined with a follicular phase CA‐125 assay, should be used to decide whether a preparation for bowel surgery should be given
Conflict of interest	Not reported
Notes	The reported diagnostic estimates for clinical examination or for a combination of clinical examination with blood test are not presented in this review The presented diagnostic estimates are for DIE, ovarian endometrioma and severe cul‐de‐sac adhesions; the authors also report separate diagnostic estimates for each of these conditions ‐ 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?	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?	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?	Unclear
		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?	No
		High