Hum. Reprod. Advance Access published online on August 18, 2009
Human Reproduction, doi:10.1093/humrep/dep283
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Density of small diameter sensory nerve fibres in endometrium: a semi-invasive diagnostic test for minimal to mild endometriosis
1 Experimental Laboratory for Gynaecology, Department of Obstetrics and Gynaecology, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium 2 Department of Electrical Engineering (ESAT-SCD), University of Leuven, Kasteelpark Arenberg 10, B-3001 Leuven, Belgium 3 Department of Obstetrics and Gynaecology, National Health Centre, Róbert Károly körút 44, 1134 Budapest, Hungary 4 Leuven University Fertility Center, Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium
5 Correspondence address. Leuven University Fertility Center, Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. Fax: +32 16 343607; E-mail: thomas.dhooghe{at}uz.kuleuven.ac.be
BACKGROUND: The aim of our study was to test the hypothesis that multiple-sensory small-diameter nerve fibres are present in a higher density in endometrium from patients with endometriosis when compared with women with a normal pelvis, enabling the development of a semi-invasive diagnostic test for minimal–mild endometriosis.
METHODS: Secretory phase endometrium samples (n = 40), obtained from women with laparoscopically/histologically confirmed minimal–mild endometriosis (n = 20) and from women with a normal pelvis (n = 20) were selected from the biobank at the Leuven University Fertility Centre. Immunohistochemistry was performed to localize neural markers for sensory C, A
, adrenergic and cholinergic nerve fibres in the functional layer of the endometrium. Sections were immunostained with anti-human protein gene product 9.5 (PGP9.5), anti-neurofilament protein, anti-substance P (SP), anti-vasoactive intestinal peptide (VIP), anti-neuropeptide Y and anti-calcitonine gene-related polypeptide. Statistical analysis was done using the Mann–Whitney U-test, receiver operator characteristic analysis, stepwise logistic regression and least-squares support vector machines.
RESULTS: The density of small nerve fibres was 
14 times higher in endometrium from patients with minimal–mild endometriosis (1.96 ± 2.73) when compared with women with a normal pelvis (0.14 ± 0.46, P < 0.0001).
CONCLUSIONS: The combined analysis of neural markers PGP9.5, VIP and SP could predict the presence of minimal–mild endometriosis with 95% sensitivity, 100% specificity and 97.5% accuracy. To confirm our findings, prospective studies are required.
Key words: endometriosis/semi-invasive diagnosis/nerve fibres
Submitted on February 18, 2009; resubmitted on May 26, 2009; accepted on June 3, 2009.
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