Elgafor el Sharkwy 2013.

Study characteristics
Patient sampling	Primary objective: to evaluate the diagnostic value of serum measurement of IL‐6 combined with the presence of nerve fibres in the functional layer of endometrium for diagnosis of minimal‐mild endometriosis Participants: women undergoing laparoscopy for infertility, pelvic pain or both Selection criteria: inclusion criteria: reproductive age, follicular phase of the cycle and regular menstrual cycle; exclusion criteria: any current infection, any medication within 1 month prior to laparoscopy, previous surgery for endometriosis and smoking or drinking alcohol Study design: observational, single‐gate, prospective recruitment and sample collection
Patient characteristics and setting	Clinical presentation (n/N): infertility ‐ 91/114; dysmenorrhoea ‐ 64/114; dyspareunia ‐ 17/114; dyschezia ‐ 6/114; other pelvic pain ‐ 35/114 Age: mean age 29 ± 0.6 years, controls; 31 ± 1.1 years, endometriosis Number enrolled: 114 women Number available for analysis: 78 women (all in follicular cycle phase; only control and endometriosis stage I‐II were analysed) Setting: University hospital ‐ Zagazig University Hospital Place of study: Zagazig, Egypt Period of study: December 2010 to April 2012 Language: English
Index tests	Index test: endometrial nerve fibres ‐ PGP 9.5 Description of positive case definition by index test as reported: presence of nerve fibres in the functional layer of endometrium, assessed by IHC staining for PGP 9.5 (an average of 4–5 sections per specimen were examined by using an Olympus microscope) Examiners: 2 pathologists, both of whom have good experience in nerve fibre identification Interobserver variability: close (96%) correlation between the 2 pathologists
Target condition and reference standard(s)	Target condition: endometriosis Prevalence of target condition in the sample: n/N = 74/114 (65%): stage I‐II 38, stage III‐IV 36; controls 40 Reference standard: laparoscopy Description of positive case definition by reference test as reported: visualisation of the endometriotic lesions with surgical staging according to rASRM classification Examiners: 3 experienced gynaecologists in endometriosis
Flow and timing	Time interval between index test and reference standard: endometrial biopsy was obtained prior to laparoscopy Withdrawals: data were not available for all women with advanced endometriosis (stage III‐IV), n = 36
Comparative
Notes	Conclusion: Serum IL‐6 and nerve fibres in the functional layer of endometrium will both allow more accurate detection of women who are at risk of having early stages of endometriosis. Comment: The reported data on the serum marker or combination of serum‐endometrial marker are 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?	No
Did the study avoid inappropriate exclusions?	Yes
Was a 'two‐gate' design avoided?	Yes
		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?	Yes
Was a menstrual cycle phase considered in interpreting the index test	Yes
		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?	No
		High