PGP 9.5 Positive Neural Fibers in Eutopic Endometrium of Women with Endometriosis: A Prospective Case-Control Study

In: Türk Üreme Tıbbı ve Cerrahisi Dergisi · 2025 · vol. 9(3) , pp. 91–96 · doi:10.24074/tjrms.2025-116346 · W7122766776
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This prospective case-control study found that PGP 9.5-positive neural fibers in the eutopic endometrium were uncommon and did not significantly differ between women with sonographically confirmed endometrioma and asymptomatic controls.

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This prospective case-control study investigated the presence and density of PGP 9.5-positive neural fibers in the eutopic endometrium of women with sonographically confirmed endometriomas compared to asymptomatic controls. The research included 59 participants, utilizing Pipelle biopsies and automated immunohistochemistry to detect nerve fibers while controlling for age and parity. Results indicated that neural fibers were uncommon in both groups, with no statistically significant difference in detection rates between patients with pain symptoms and those without. The authors concluded that these markers do not discriminate endometriosis-associated pain from asymptomatic states in this cohort, noting limitations regarding sample size and lack of laparoscopic validation. This paper is centrally about endometriosis — specifically examining neural innervation patterns in the eutopic endometrium as a potential biomarker for pain phenotypes.

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Abstract

Objective: TTo investigate the presence and number of PGP 9.5-positive endometrial neural fibers in women with sonographically confirmed endometrioma and pain symptoms, and to compare these findings with an asymptomatic control population.Material and Methods: In this prospective case-control study, 59 women aged 18-49 years were divided into 2 groups (31 endometriosis, 28 controls).The endometriosis group consisted of women with ultrasoundconfirmed endometrioma.Controls had normal ultrasonography and underwent endometrial biopsy for abnormal uterine bleeding without pelvic pain, dysmenorrhea, dyspareunia, infertility, or clinical suspicion of endometriosis.Pain severity was graded using the Biberoglu-Behrman scale.Pipelle was used to sample the eutopic endometrium.Specimens were stained for PGP 9.5 using an automated immunohistochemical platform.A single blinded gynecologic pathologist evaluated neural fibers.Appropriate parametric and non-parametric tests were applied, and p<0.05 was considered significant.Results: Mean age, age at menarche, and parity distributions were comparable, whereas median gravidity was lower in the endometriosis group (p=0.005).Dysmenorrhea, dyspareunia, and chronic pelvic pain were substantially more frequent and severe among endometriosis patients (all p<0.001).PGP 9.5 positive neural fibers were detected in 2/31 (6.5%) cases and 1/28 (3.6%) controls, with no significant difference in detection rates (p=0.599).Conclusion: In hormone-naive women sampled in the mid-proliferative phase, PGP 9.5 positive endometrial neural fibers were uncommon and did not discriminate endometriosis-associated pain from asymptomatic controls.Larger laparoscopically validated studies using standardized quantification are needed to clarify eutopic innervation and any biomarker role in pain phenotypes.
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Abstract

Objective TTo investigate the presence and number of PGP 9.5-positive endometrial neural fibers in women with sonographically confirmed endometrioma and pain symptoms, and to compare these findings with an asymptomatic control population.

Material and methods

In this prospective case–control study, 59 women aged 18-49 years were divided into 2 groups (31 endometriosis, 28 controls). The endometriosis group consisted of women with ultrasoundconfirmed endometrioma. Controls had normal ultrasonography and underwent endometrial biopsy for abnormal uterine bleeding without pelvic pain, dysmenorrhea, dyspareunia, infertility, or clinical suspicion of endometriosis. Pain severity was graded using the Biberoglu–Behrman scale. Pipelle was used to sample the eutopic endometrium. Specimens were stained for PGP 9.5 using an automated immunohistochemical platform. A single blinded gynecologic pathologist evaluated neural fibers. Appropriate parametric and non-parametric tests were applied, and p<0.05 was considered significant.

Results

Mean age, age at menarche, and parity distributions were comparable, whereas median gravidity was lower in the endometriosis group (p=0.005). Dysmenorrhea, dyspareunia, and chronic pelvic pain were substantially more frequent and severe among endometriosis patients (all p<0.001). PGP 9.5 positive neural fibers were detected in 2/31 (6.5%) cases and 1/28 (3.6%) controls, with no significant difference in detection rates (p=0.599).

Conclusion

In hormone-naive women sampled in the mid-proliferative phase, PGP 9.5 positive endometrial neural fibers were uncommon and did not discriminate endometriosis- associated pain from asymptomatic controls. Larger laparoscopically validated studies using standardized quantification are needed to clarify eutopic innervation and any biomarker role in pain phenotypes.

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Outcome instruments

Biberoglu-Behrman

Condition tags

endometriosisendometriomachronic_pelvic_paindysmenorrheadyspareuniainfertility

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