Koninckx 1996.

Study characteristics
Patient sampling	Primary objectives To evaluate clinical examination during menstruation and plasma CA‐125 concentration to diagnose endometriosis Study population Women scheduled for laparoscopy for suspected endometriosis Selection criteria Exclusion criteria: hormonal treatment or medical treatment for endometriosis in the three months preceding laparoscopy, refusal for 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 or endometrioma or 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 Clinical examination in menstrual phase (menstrual nodularities) + CA‐125 in mid follicular phase Details of the index test procedure as stated Clinical examination included pelvic bimanual examination with careful assessment of pelvic nodularities and their tenderness; CA‐125 assay using a second generation IRMA kit (CA‐125 II, Centocor, Malvern, Pa; all kits from the same production batch) Threshold for positive result Clinical examination ‐ presence of induration (with one or more small nodules) or painful nodularities (larger spherical nodule), pre‐specified and described in details; CA‐125 >35 U/ml, not pre‐specified Examiners Clinical examination: one of the two authors, always preoperatively and hence blinded to the results of reference standard; CA‐125 ‐ no information provided; unclear if were blinded to reference standard Interobserver variability CA‐125: intra‐and inter‐assay variation < 5% and < 8%
Target condition and reference standard(s)	Target condition DIE, ovarian endometrioma or severe pelvic adhesions Prevalence of target condition in the sample n = 38/55 (69%): stage I‐II 29, stage III‐IV 9; DIE 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 ‐ III, reference to the source with diagnostic criteria and described; staging according to the rAFS classification . Examiners Not stated; unclear if were blinded to the result of pelvic examination
Flow and timing	Time interval between index test and reference standard The tests were performed within four months before surgery (personal communication with the author) Withdrawals In six women (11%) the surgery was cancelled for various reasons
Comparative
Key conclusions by the authors	Clinical examination during menstruation can diagnose reliably deep 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 blood biomarker alone are presented in other reviews from this series The presented diagnostic estimates are for DIE or ovarian endometrioma or severe cul de sac adhesions
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
Did the study provide a clear pre‐specified definition of what was considered to be a positive result of index test?
Was the index test performed by a single operator or interpreted by consensus in a joint session?
Were the same clinical data available when the index test results were interpreted as would be available when the test is used in practice?
		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