Cetin 2013.

Study characteristics
Patient sampling	Primary objective: to determine whether the number of macrophage cells in the endometrium, the detection of nerve fibres or both can be used in the diagnosis of endometriosis Participants: patients undergoing and having undergone laparoscopy/laparotomy Selection criteria: exclusion criteria: adenomyosis, malignancy, use of hormonal treatment for 3/12 months before surgery Study design: cross‐sectional two‐gate, prospective collection of samples (prospective recruitment, n = 31 and retrospective random selection, n = 34)
Patient characteristics and setting	Clinical presentation: indications for surgery: ovarian cysts, pelvic pain, infertility, tubal ligation, endometrial hyperplasia, AUB, myoma uteri Age: mean age 38.29 ± 6.24 years, endometriosis group; 37.24 ± 5.40 years, controls Number enrolled: 65 women Number available for analysis: 60 women (any stage of menstrual cycle) Setting: university hospital: Istanbul University Istanbul School of Medicine Hospital Place of study: Istanbul, Turkey Period of study: 2006‐2011 Language: English
Index tests	Index test: endometrial nerve fibres ‐ PGP 9.5 and NF; macrophages ‐ CD68 + Description of positive case definition by index test as reported: neural marker results were noted as present or absent via IHC staining (evaluation by using Olympus BX‐51 microscope); macrophages markers reported as sum of IHC stained macrophage cells (evaluation under 400 × magnification in 10 fields); threshold was not reported Examiners: All samples were evaluated by a single pathologist who was blinded to patient data and who is highly experienced in gynaeco‐pathology Interobserver variability: NA
Target condition and reference standard(s)	Target condition: endometriosis Prevalence of target condition in the sample: n/N = 31/60 (52%): stage I‐II 6, stage III‐IV 25; controls 29 Reference standard: laparoscopy/laparotomy + histology Description of positive case definition by reference test as reported: visual inspection confirmed by biopsy; staging according to the rAFS Examiners: no information provided
Flow and timing	TIme interval between index test and reference standard: samples were taken preoperatively Withdrawals: 5 women were excluded due to insufficient tissue sample
Comparative
Notes	Conclusions: The detection of nerve fibres in the eutopic endometrium with the markers of PGP 9.5 and NF is not found to be helpful in the diagnosis of endometriosis. Macrophage cells may be helpful in the diagnosis only in the proliferative phase Comments: Nerve fibres markers were not detected in either group For macrophages there was no statistically significant difference between the groups; no data available for meta‐analysis (Appendix 7); subanalysis revealed differential expression only in proliferative phase of the cycle, but there was no data for construction of 2 × 2 tables
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?	Yes
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?	No
		High