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Hum. Reprod. Advance Access published online on August 18, 2009

Human Reproduction, doi:10.1093/humrep/dep275
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© The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Diagnosis of endometriosis by detection of nerve fibres in an endometrial biopsy: a double blind study

M. Al-Jefout1,2,3,4, G. Dezarnaulds2, M. Cooper2, N. Tokushige1, G.M. Luscombe1, R. Markham1 and I.S. Fraser1,2

1 Department of Obstetrics and Gynaecology, Queen Elizabeth II Research Institute for Mothers and Infants, University of Sydney, Sydney, NSW 2006, Australia 2 Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050, Australia 3 The Department of Obstetrics & Gynaecology, Mutah Medical Faculty, Mutah University, Karak, Jordan

4 Correspondence address. Tel: +61-962-797377790; Fax: +61-2-9351-4560; E-mail: drmoamar{at}yahoo.co.uk

BACKGROUND: Diagnosis of endometriosis currently requires a laparoscopy and this need probably contributes to the considerable average delay in diagnosis. We have reported the presence of nerve fibres in the functional layer of endometrium in women with endometriosis, which could be used as a diagnostic test. Our aim was to assess efficacy of nerve fibre detection in endometrial biopsy for making a diagnosis of endometriosis in a double-blind comparison with expert diagnostic laparoscopy.

METHODS: Endometrial biopsies, with immunohistochemical nerve fibre detection using protein gene product 9.5 as marker, taken from 99 consecutive women presenting with pelvic pain and/or infertility undergoing diagnostic laparoscopy by experienced gynaecologic laparoscopists, were compared with surgical diagnosis.

RESULTS: In women with laparoscopic diagnosis of endometriosis (n = 64) the mean nerve fibre density in the functional layer of the endometrial biopsy was 2.7 nerve fibres per mm2 (±3.5 SD). Only one woman with endometriosis had no detectable nerve fibres. Six women had endometrial nerve fibres but no active endometriosis seen at laparoscopy. The specificity and sensitivity were 83 and 98%, respectively, positive predictive value was 91% and negative predictive value was 96%. Nerve fibre density did not differ between different menstrual cycle phases. Women with endometriosis and pain symptoms had significantly higher nerve fibre density in comparison with women with infertility but no pain (2.3 and 0.8 nerve fibre per mm2, respectively, P = 0.005).

CONCLUSIONS: Endometrial biopsy, with detection of nerve fibres, provided a reliability of diagnosis of endometriosis which is close to the accuracy of laparoscopic assessment by experienced gynaecological laparoscopists.

This study was registered with the Australian Clinical Trials Registry (ACTR) 00082242 (registered: 12/12/2007). The study was approved by the Ethics Review Committee (RPAH Zone) of the Sydney South West Area Health Service (Protocol number X05-0345) and The University of Sydney Human Research Ethics Committee (Ref. No. 10761) and all women gave their informed consent for participation.

Key words: endometriosis diagnosis/laparoscopy/immunohistochemistry/endometrial biopsy/nerve fibres

Submitted on March 17, 2009; resubmitted on June 29, 2009; accepted on July 2, 2009.


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