Diagnosis of endometriosis by detection of nerve fibres in an endometrial biopsy: a double blind study
Abstract
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 mm(2) (+/-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 mm(2), 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.
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In Al-Jefout's study, it cannot be determined how many women had pain or how endometriosis was diagnosed.
“It is impossible to determine how many women had pain or how the diagnosis of endometriosis was made (biopsy or visualization)”
From Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications (2011) · cites this paper as Al-Jefout et al., 2009
The Results (Table I; page not provided) give counts for pain alone (52), pain with infertility (20), and no pain symptoms (22), so the number of women with pain is reported. Surgical procedures and sampling technique (page not provided) identifies laparoscopy with visualization of lesions as the diagnostic reference standard and says biopsy confirmation was available in almost all cases. The paper does not specify which individual cases had biopsy confirmation, but it does state how diagnosis was made. (LLM, conf=0.94)
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Experimental — accuracy not yet measuredTwo groups found that nerve fibers in the endometrium are a marker for endometriosis with high specificity and sensitivity.
“two groups, who both found that the presence of nerve fibers in endometrium serves as a marker for endometriosis with high specificity and sensitivity”
From Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications (2011) · cites this paper as Al-Jefout et al., 2009
The two studies together may indicate that nerve fibers in eutopic endometrium diagnose endometriosis regardless of whether the patient has pain.
“Together, the two studies may indicate that nerve fibers in eutopic endometrium are diagnostic of endometriosis regardless of whether the patient suffers pain.”
From Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications (2011) · cites this paper as Al-Jefout et al., 2009
Al-Jefout's study examined many factors in relation to nerve fiber density but did not perform multivariate comparisons controlling for how those factors interrelate.
“In Al-Jefout's study (2009), many factors were examined for their relation to nerve fiber density without performing multivariate comparisons controlling for how these factors might interrelate.”
From Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications (2011) · cites this paper as Al-Jefout et al., 2009
Nerve fibers were not observed in other benign gynecologic conditions to include endometritis, leiomyomata, or endometrial polyps.
“Importantly, nerve fibers were not observed in other benign gynecologic conditions to include endometritis, leiomyomata, or endometrial polyps.”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [140]
In a double blind study of endometrial pipelle samples from 99 consecutive women undergoing laparoscopy for pelvic pain and/or infertility, immunohistochemical detection of PGP9.5 demonstrated 98% sensitivity and 83% specificity for the finding of endometriosis at surgery.
“In a double blind study of endometrial pipelle samples from 99 consecutive women undergoing laparoscopy for pelvic pain and/or infertility, immunohistochemical detection of PGP9.5 demonstrated 98% sensitivity and 83% specificity for the finding of endometriosis at surgery [140].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [140]
A first step toward validation of biomarkers has been made.
“A first step toward validation of biomarkers has been made [24, 140]; however, further studies are needed to develop a clinically useful test.”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [140]
Endometrial biopsy, with detection of nerve fibres, provides a reliability of diagnosis of endometriosis close to the accuracy of laparoscopic assessment by experienced gynecological laparoscopists.
“It has been reported that endometrial biopsy, with detection of nerve fibres, provides a reliability of diagnosis of endometriosis which is close to the accuracy of laparoscopic assessment by experienced gynecological laparoscopists.86”
From Defining Future Directions for Endometriosis Research: Workshop Report From the 2011 World Congress of Endometriosis in Montpellier, France (2013) · cites this paper as [86]
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References 19 · Cited by 151
- Authors
- Al-Jefout, M., Dezarnaulds, G., Cooper, M., Tokushige, N., Luscombe, G. M., Markham, R., & Fraser, I. S.
- Affiliations
- Royal Prince Alfred Hospital (AU)
- The University of Sydney (AU)
- Venue
- Human Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-08-18
- Volume
- 24
- Issue
- 12
- Pages
- 3019-3024
- ISSN
- 0268-1161 (ISSN-L)
- 1460-2350
- OpenAlex
- W2096141938
- Cited by
- 151
- References
- 19
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 7 · 2018: 11 · 2017: 3 · 2016: 8 · 2015: 14 · 2014: 15 · 2013: 21 · 2012: 17
- FWCI
- 20.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Reproduction (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Obstetrics and Gynecology › Gynecological conditions and treatments
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ectopic Pregnancy Diagnosis and Management
- Keywords
- endometriosis, nerve fibers, endometrial biopsy, protein gene product 9.5, diagnostic accuracy, diagnostic laparoscopy, pelvic pain, infertility, delayed diagnosis
- MeSH terms
- Adult, Biopsy, Diagnostic Techniques, Obstetrical and Gynecological, Double-Blind Method, Endometriosis, Endometrium, Female, Humans, Immunohistochemistry, Middle Aged, Sensitivity and Specificity, Nerve Fibers, Unmyelinated, Early Diagnosis, Ubiquitin Thiolesterase, Young Adult
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