Bourlev 2006.

Study characteristics
Patient sampling	Primary objective: to examine the relationship between microvessel density, mitotic activity in blood vessels and expression of VEGF‐A and its receptors VEGFR‐1 and VEGFR‐2 in eutopic endometrium from women with and without endometriosis and in peritoneal endometriotic lesions Participants: women with laparoscopically confirmed endometriosis and women who underwent laparoscopic sterilisation with confirmed normal pelvis Selection criteria: exclusion criteria: patients with irregular menstrual cycles or gynaecological disorders other than endometriosis and those who had received hormonal treatment within the last 3 months Study design: observational two‐gate design, prospective sample collection, retrospective selection of cases
Patient characteristics and setting	Clinical presentation: not specified Age: mean age 32.7 years (range 22‐44), endometriosis; 29.0 years (range 20–37); controls Number enrolled: 39 women (retrospective selection) Number available for analysis: 39 women (19 in proliferative and 20 in secretory phase of menstrual cycle) Setting: Research Centre of Obstetrics, Gynaecology and Perinatology, Russian Academy of the Medical Sciences Place of study: Moscow, Russia Period of study: not provided Language: English
Index tests	Index test: MVD, Ki‐67, VEGF‐A, VEGFR‐1, VEGFR‐2 Description of positive case definition by index test as reported: MVD was determined by IHC staining as number of microvessels per mm2, calculated as mean value of 5 randomly chosen fields, 0.109 mm2 each; proliferative index (PI) was calculated as the percentage of cells that were Ki‐67 positive (IHC method); VEGF‐A, VEGFR‐1 and VEGFR‐2 levels defined by IC staining intensity and classified 0 when comparable to the negative control, 1 when weak (clearly visible but no more), 2 when between weak and strong, 3 when strong; laboratory technique described in details Examiners: examination by 2 independent observers, unclear if were blinded to diagnosis Interobserver variability: not provided
Target condition and reference standard(s)	Target condition: endometriosis Prevalence of target condition in the sample: n/N = 25/39 (64%), all stage II‐III Reference standard: laparoscopy + histology Description of positive case definition by reference test as reported: laparoscopically and histologically confirmed endometriosis, staged according to rASRM Examiners: none mentioned
Flow and timing	TIme interval between index test and reference standard: prior to laparoscopy Withdrawals: none reported
Comparative
Notes	Conclusion: There seems to be a dysregulation of angiogenic activity in the eutopic endometrium of women with endometriosis, and endometriotic lesions with high proliferative activity were accompanied by higher local angiogenic activity and higher levels of VEGF in serum and peritoneal fluid. Comments: For Ki‐67 there was no statistically significant difference between the groups ‐ no data available for meta‐analysis (Appendix 7) For MVD, VEGF‐A, VEGFR‐1 and VEGFR‐2 there was a statistically significant difference between the groups, but there were insufficient data to construct 2 × 2 tables ‐ not included 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?	No
Did the study avoid inappropriate exclusions?	Yes
Was a 'two‐gate' design avoided?	No
		High	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 menstrual cycle phase considered in interpreting the 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