Density of small diameter sensory nerve fibres in endometrium: A semi-invasive diagnostic test for minimal to mild endometriosis

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, Aδ, 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.