Correlation Between Levels of Interleukin-6 in Peritoneal Fluid With Degree of Pain, Adhesion, and Endometriosis Fertility Index Score in Endometriosis
DOI:
https://doi.org/10.25077/aoj.5.2.193-205.2021Abstract
Introduction : Endometriosis is a benign gynecological disorder characterized by the presence of endometrial tissue and stroma outside the uterine cavity. Several theories have been proposed to explain the occurrence of endometriosis, one of which is the theory of inflammation. Endometriosis lesions can produce inflammatory cytokines, resulting in their increased levels in the peritoneal fluid. This process causes disruption in pelvic anatomy, ovarian function, prostaglandin production and growth factor production that causes pain, adhesions and infertility. Interleukin-6 (IL-6) is an important and potential inflammatory cytokine in assisting the diagnosis of endometriosis. These cytokines act as activating macrophages that can stimulate endometrial cell proliferation and modulate the secretion of other cytokines such as IL-10, IL-13 and TNF-α which augments the inflammatory process. High levels of IL-6 in the peritoneum are relatedto advanced endometriosis associated with pain, severe pelvic adhesions and embryotoxic effects leading to infertility. The effect of IL-6, both local and systemic, on the growth of endometriosis lesions and its associated symptoms is great that this cytokine is considered an important marker.
Objective : This study aims to determine the relationship between local inflammatory factors (IL-6 in peritoneal fluid) obtained during laparoscopy with the degree of pain, the degree of adhesions and the correlation with the Endometriosis Fertility Index (EFI) score in endometriosis patients.
Material and methods : This is a quantitative analytic research with a cross sectional study design which was conducted on 22 patients with endometriosis. Prior to the laparoscopy, historical factor (EFI score) was recorded and an assessment of the pain scale was performed by filling out a questionnaire. Intraoperatively, the peritoneal fluid was obtained. If the peritoneal fluid was found, it was taken directly with a volume of 3-5 cc using 10 cc syringe. If no fluid was found, peritoneal rinsing was performed using 0.9% NaCl fluid, then 3-5 cc fluid was aspirated using a 10 cc syringe. Subsequently, an examination was carried out using the RayBio Human IL-6 ELISA Kit. During the laparoscopy procedure, the degree of adhesion of the pelvic organs was assessed by looking at the shape and how the adhesions can be separated. Surgical factor (EFI score) was assessed intraoperatively to obtain data for the least function score, AFS endometriosis score and AFS total score. Statistical analysis was performed using paired t test and correlation test.
Results : The mean age of the respondents was 34.86 ± 6.11 years, 81.8% were nulliparous, 100% were married, 100% experienced both primary and secondary infertility and 81.8% had no prior pregnancy history. In the study, it was found that IL-6 levels of peritoneal fluid were higher in patients with the degree of severe pain (P <0.05) compared to moderate with the results of 32.58 ± 7.31 pg/ml and 25.39 ± 2.70 pg/ml. IL-6 levels were found to be higher in grade three adhesions than grade two (P <0.05) with results of 32.78 ± 6.65 pg/ml and 23.86 ± 2.18 pg/ml. The mean peritoneal fluid IL-6 levels were 30.75 ± 7.01 pg/ml and the mean EFI score was 4.09 ± 2.09. The correlation of IL-6 levels in peritoneal fluid with EFI score showed a value of r = -0.448 which had moderate strength and a negative pattern, indicating that the higher the IL-6 level of peritoneal fluid, the lower the EFI score (P <0.05).
Conclusion : There is a relationship between IL-6 levels of peritoneal fluid in endometriosis with the degree of pain and the degree of adhesion, where IL-6 levels were found to be higher in the degree of severe than moderate pain (P <0.05), higher in third degree adhesions than second degree ( P <0.05). There was a correlation between IL-6 levels of peritoneal fluid with EFI score (P <0.05) with a negative pattern of moderate strength analysis results (r = -0.448).
Keywords: Endometriosis, Interleukin-6, Degree of Pain, Degree of Adhesion, Endometriosis Fertility Index ScoreReferences
Himpunan Endokrinologi Reproduksi dan Fertilitas – Persatuan Obstetri dan Ginekologi Indonesia. Konsensus Tatalaksana Nyeri Haid pada Endometriosis. 2013.
Harada, T, Taniguchi F, Onishi,K et al. Obstetrical Complications in Women with Endometriosis: A Cohort Study in Japan. Research articcle. 2016.
Brosens, I, Puttemans, P, Benagiano, G. Reproductive Endocrinology and Infertility Endometriosis: A Life Cycle Approach?. American Journal Obstetrics and Gynecology. 2013.
Petraglia, S, Arcuri, F, Zigler, D.D, Chapron, C. Inflammation : A Link between Endometriosis and Preterm Birth. France. 2012.
Ahn, S.H, Singh, V, Tayade, C. Biomarkers in Endometriosis : Challenges and Opportunities. Department of Biomedical and Molecular Science Queen’s University Canada. 2017.
Miller, J.E, Ahn, S.H, Monsanto, S.P, Khalaj, K, Koti, M. Tayede, C. Implications of Immune Dysfunction on Endometriosis Associated Infertility. Department of Biomedical and Molecular Science Queen’s University Canada. 2016. Oncotarget 8 (4) : 7138 – 7147.
Elnouri, A. Endometriosis at Invited speaker abstracts from the 24th EBCOG European Congress of Obstetrics and Gynaecology held in Torino Italy. Cairo University : 251-263. 2016.
Morassutto, C, Monasta, L, Ricci, G, Barbonr, F, Ronfani, L. Incidence and Estimated Prevalence of Endometriosis and Adenomyosis in Northeast
Italy: A Data Linkage Study. 2016.
Wu, I.B, Tendean, H.M, Mewengkang, M.E. Gambaran Karakteristik Penderita Endometriosis di RSUP Prof. Dr. R. D. Kandou Manado. Bagian Obstetri dan Ginekologi Fakultas Kedokteran Unsrat. 2017.
Suparman, E. Penatalaksanaan Endometriosis. Bagian/SMF Obsteri dan Ginekologi Fakultas Kedokteran Universitas Samratulangi. 2012.
Sakti, I.R, Hardianto, G. Dismenore pada Pasien Endometriosis yang
Menjalani Laparoskopi. Program Studi Pendidikan Bidan Fakultas Kedokteran Universitas Airlangga. 2013.
Hendry, D, Hidayat, A. Karakteristik Penderita Endometriosis dan Adenomiosis di RSUP DR M Djamil Padang Periode Januari 2017-Oktober 2018. Andalas Obstetrics dan Gynecology Journal. 2019.
Wu, M.H, Hsiao, K.Y, Tsai, S.J. Endometriosis and Possible Inflammation Markers on Gynecology and minimally Invasive Therapy. 2015.
Tanbo, T. Endometriosis-associated Infertility: Aspects of Pathophysiological Mechanisms and Treatment Options. Acta Obstet Gynecol Scand. 96: 659-667. 2016.
Triolo, O, Legana, A.S, Sturlese, E. Chronic Pelvic Pain in Endometriosis : An Overview. J Clin Med Res.2013;5(3):153-165.
Ashraf A, Ibrahim A. Role of some biomarkers in chronic pelvic pain for early detection of endometriosis in infertile women. Fertility and Sterility. 2012.
Rapkin A, Morgan M, Bonpane C, Maza OM. Peritoneal fluid interleukin-6 in women with chronic pelvic pain. Fertility and Sterility. 2000;74(2):325-8.
Andrade VTD, Nacul AP, Santos BRD, Lecke SB, Spritzer PM. Circulating and peritoneal fluid interleukin-6 levels and gene expression in pelvic endometriosis. Experimental and Therapeutic Medicine. 2017;14:2317-22.
Cheong YC, Shelton JB, Laird SM, Richmond, Kudesia G, Li TC, et al. IL-1, IL-6, and TNF-a concentrations in the peritoneal fluid of women with pelvic adhesions. Human Reproduction. 2002;17(1):69-75.
Buyalos RP, Funari VA, Azziz R, Watson JM, Martinez-Maza O. Elevated interleukin-6 levels in peritoneal fluid of patients with pelvic pathology. Fertil Steril 1992;58:302–6
El Kader, A.I, Gonied, A.S, Mohamed, M.L. Impact of Endometriosis Related Adhesions on Quality of Life among Infertile Women. Royan Institute International Journal of Fertility and Sterility. 2019.
Barcz E, Milewski L, Dziunycz P, Kaminski P, P 1oski R, Malejczyk J. Peritoneal cytokines and adhesion formation in endometriosis: an inverse association with VEGF concentration. Fertil Steril 2012. doi: 10.1016/j.fertnstert. 2012.03.057.
Wang, X.M, Ma, Z.Y, Song, N. Inflammatory cytokines IL-6, IL-10, IL-13, TNF-α and peritoneal fluid flora were associated with infertility in patients
with endometriosis. European Review for Medical and Pharmacological Sciences. 2018.
Iwabe T, Harada T, Terakawa N. Role of Cytokines in Endometriosis-Associated Infertility. Gynecol Obstet Invest. 2002;53(1):19-25.
Hadisaputra W. Clinical signs, symptoms and serum level of interleukin-6 and tumor necrosis factor in women with or without endometriosis. Asian Pasific Journal of Reproduction. 2013;2(2):142-5.
Lin, Y.H, Chen, Y.H, Chang, H.Y, et al. Chronic Niche Inflammation in
Endometriosis-Associated Infertility: Current Understanding and Future Therapeutic Strategies. International Journal of Molecular Sciences. 2018.
Wahyuni, A. Endometriosis dan Infertilitas. Bagian Ilmu Obstetri dan Ginekologi Program Studi Pendidikan Dokter Universitas Muhammadiyah Yogyakarta. 2008.
Li, X, Zheng, C, Zhao, YF et al. Endometriosis Fertility Index for Predicting Pregnancy After Endometriosis Surgery. Chinese Medical Journal. 2017;130(16).
Downloads
Published
Issue
Section
License
Copyright (c) 2021 Andalas Obstetrics And Gynecology Journal
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright
Authors who publish with this journal agree to the following terms:
- Authors retain the copyright of published articles and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
License:
Andalas Obstetrics and Gynecology Journal (AOJ) is published under the terms of the Creative Commons Attribution 4.0 International License. This license permits anyone to copy and redistribute this material in any form or format, compose, modify, and make derivatives of this material for any purpose, including commercial purposes, as long as they credit the author for the original work.
