{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:19:55Z","timestamp":1787822395149,"version":"build-2784847793"},"reference-count":31,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Oradea"},{"id":[{"id":"https:\/\/ror.org\/00wzhv093","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Endometriosis is a chronic inflammatory disease associated with impaired fertility, but the extent to which its systemic inflammatory profile differs from that observed in infertile women without endometriosis remains incompletely understood. This study aimed to characterize and compare the systemic inflammatory profiles of women with endometriosis, infertile women without endometriosis, and healthy controls by evaluating serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-\u03b1), and high-sensitivity C-reactive protein (hs-CRP). In addition, the study explored the IL-6\/TNF-\u03b1 ratio as an indicator of inflammatory balance and evaluated its relationship with ovarian reserve. Materials and Methods: This observational comparative study included 87 women divided into three groups: healthy controls (n = 29), women with endometriosis (n = 29), and infertile women without endometriosis (n = 29). Serum IL-6, TNF-\u03b1, and hs-CRP concentrations were determined specifically for the present study, whereas the corresponding clinical and embryological data were retrieved from medical records. Group comparisons were performed using the Kruskal\u2013Wallis test followed by Dunn\u2019s post hoc test with Holm correction. The IL-6\/TNF-\u03b1 ratio was calculated as an exploratory indicator of inflammatory balance. Associations between inflammatory biomarkers and anti-M\u00fcllerian hormone (AMH) concentrations were assessed using Spearman\u2019s correlation analysis. Results: Significant differences in serum inflammatory biomarkers were observed among the three groups. IL-6 concentrations were significantly increased in both women with endometriosis and infertile women without endometriosis compared with healthy controls, whereas TNF-\u03b1 concentrations were significantly elevated only in infertile women without endometriosis compared with both healthy controls and women with endometriosis (adjusted p &lt; 0.001 for both comparisons). Differences in hs-CRP were more modest but remained significant overall. Women with endometriosis exhibited a significantly higher IL-6\/TNF-\u03b1 ratio than infertile women without endometriosis, suggesting distinct inflammatory patterns between these conditions. No significant correlations were identified between circulating inflammatory biomarkers and AMH concentrations. Conclusions: Women with endometriosis and infertile women without endometriosis exhibit distinct systemic inflammatory profiles rather than simply different levels of inflammation. The IL-6\/TNF-\u03b1 ratio may provide additional information regarding the balance of inflammatory pathways beyond the isolated evaluation of individual cytokines. Larger prospective studies integrating systemic and local inflammatory biomarkers with assisted reproductive outcomes are warranted to validate these findings and further explore their clinical relevance.<\/jats:p>","DOI":"10.3390\/medicina62091641","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T08:02:27Z","timestamp":1787817747000},"page":"1641","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct Systemic Inflammatory Signatures in Women with Endometriosis and Infertility Without Endometriosis: Implications for Assisted Reproduction"],"prefix":"10.3390","volume":"62","author":[{"given":"Luana","family":"Ghilea (Sele\u0219)","sequence":"first","affiliation":[{"name":"Department of Surgical Sciences, Obstetrics and Gynecology, Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania"},{"name":"Doctoral School of Biological and Biomedical Sciences, University of Oradea, 1 University Street, 410087 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8901-8271","authenticated-orcid":false,"given":"Laura","family":"Maghiar","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, Obstetrics and Gynecology, Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania"},{"name":"Doctoral School of Biological and Biomedical Sciences, University of Oradea, 1 University Street, 410087 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viorela Romina","family":"Murvai","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Calla\u2014Infertility Diagnostic and Treatment Center, Constantin A. Rosetti Street, 410103 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goman","family":"Marius","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Calla\u2014Infertility Diagnostic and Treatment Center, Constantin A. Rosetti Street, 410103 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alin","family":"Bodog","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, Obstetrics and Gynecology, Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania"},{"name":"Doctoral School of Biological and Biomedical Sciences, University of Oradea, 1 University Street, 410087 Oradea, Romania"},{"name":"Department of Embryology, Calla\u2014Infertility Diagnostic and Treatment Center, Constantin A. Rosetti Street, 410103 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen Anca","family":"Huniadi","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, Obstetrics and Gynecology, Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania"},{"name":"Doctoral School of Biological and Biomedical Sciences, University of Oradea, 1 University Street, 410087 Oradea, Romania"},{"name":"Department of Obstetrics and Gynecology, Calla\u2014Infertility Diagnostic and Treatment Center, Constantin A. Rosetti Street, 410103 Oradea, Romania"},{"name":"Department of Embryology, Calla\u2014Infertility Diagnostic and Treatment Center, Constantin A. Rosetti Street, 410103 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"ref_1","first-page":"2513","article-title":"Inflammatory cytokines IL-6, IL-10, IL-13, TNF-\u03b1 and peritoneal fluid flora were associated with infertility in patients with endometriosis","volume":"22","author":"Wang","year":"2018","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1093\/aje\/kwx272","article-title":"A prospective study of inflammatory markers and risk of endometriosis","volume":"187","author":"Mu","year":"2018","journal-title":"Am. J. Epidemiol."},{"key":"ref_3","first-page":"793","article-title":"The value of CA-125, CA 19-9, interleukin-6, interleukin-8 and hsCRP in the diagnosis of endometriosis","volume":"31","author":"Akpak","year":"2015","journal-title":"Acta Med. Mediterr."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zhang, H., Li, X., Zhang, F., Li, F., Jin, H., Su, Y., and Li, G. (2023). Serum C-reactive protein levels are associated with clinical pregnancy rate after in vitro fertilization among normal-weight women. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.934766"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"W\u00f3jtowicz, M., Zdun, D., Owczarek, A.J., Skrzypulec-Plinta, V., and Olszanecka-Glinianowicz, M. (2025). Evaluation of proinflammatory cytokines concentrations in plasma, peritoneal, and endometrioma fluids in women operated on for ovarian endometriosis\u2014A pilot study. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26115117"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kokot, I., Piwowar, A., J\u0119dryka, M., So\u0142kiewicz, K., and Kratz, E.M. (2021). Diagnostic significance of selected serum inflammatory markers in women with advanced endometriosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052295"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/s44294-025-00110-x","article-title":"Circulating inflammatory biomarkers and endometriosis lesion characteristics in the WisE consortium","volume":"3","author":"Terry","year":"2025","journal-title":"npj Women\u2019s Health"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Krygere, L., Jukna, P., Jariene, K., and Drejeriene, E. (2024). Diagnostic potential of cytokine biomarkers in endometriosis: Challenges and insights. Biomedicines, 12.","DOI":"10.3390\/biomedicines12122867"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ou, Y., Wang, H., Zhou, C., Chen, Y., Lyu, J., Feng, M., and Huang, X. (2025). Endometriosis-associated infertility: Multi-omics insights into pathogenesis and precision therapeutics. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1613334"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e070750","DOI":"10.1136\/bmj-2022-070750","article-title":"Pathophysiology, diagnosis, and management of endometriosis","volume":"379","author":"Horne","year":"2022","journal-title":"BMJ"},{"key":"ref_11","first-page":"100363","article-title":"Global, regional, and national prevalence and disability-adjusted life-years for endometriosis in 204 countries and territories, 1990\u20132019: Findings from a Global Burden of Disease study","volume":"25","author":"Shen","year":"2025","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol. X"},{"key":"ref_12","first-page":"173","article-title":"Oocyte quality in women with endometriosis","volume":"90","author":"Trinchant","year":"2025","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e23130","DOI":"10.1096\/fj.202300907","article-title":"Endometriosis in the era of precision medicine and impact on sexual and reproductive health across the lifespan and in diverse populations","volume":"37","author":"Giudice","year":"2023","journal-title":"FASEB J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"eadk8230","DOI":"10.1126\/scitranslmed.adk8230","article-title":"Nociceptor-to-macrophage communication through CGRP\/RAMP1 signaling drives endometriosis-associated pain and lesion growth in mice","volume":"16","author":"Fattori","year":"2024","journal-title":"Sci. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chen, L., Lo, W., Huang, H., and Wu, H. (2023). A lifelong impact on endometriosis: Pathophysiology and pharmacological treatment. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24087503"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wang, Y., Dragovic, R., Greaves, E., Becker, C., and Southcombe, J. (2023). Macrophages and small extracellular vesicle-mediated intercellular communication in the peritoneal microenvironment: Impact on endometriosis development. Front. Reprod. Health, 5.","DOI":"10.3389\/frph.2023.1130849"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Li, W., Lin, A., Qi, L., Lv, X., Yan, S., Xue, J., and Mu, N. (2023). Immunotherapy: A promising novel endometriosis therapy. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1128301"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"104415","DOI":"10.1016\/j.jri.2024.104415","article-title":"Peri-implantation treatment with TNF-\u03b1 inhibitor for endometriosis and\/or adenomyosis women undergoing frozen-thawed embryo transfer: A retrospective cohort study","volume":"167","author":"Liu","year":"2025","journal-title":"J. Reprod. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.2147\/IJGM.S417430","article-title":"Autoimmune disease-related hub genes are potential biomarkers and associated with immune microenvironment in endometriosis","volume":"16","author":"Yang","year":"2023","journal-title":"Int. J. Gen. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Radu, A., and Bungau, S. (2021). Management of rheumatoid arthritis: An overview. Cells, 10.","DOI":"10.3390\/cells10112857"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1186\/s13048-024-01508-y","article-title":"Research progress of ferroptosis in female infertility","volume":"17","author":"Peiyin","year":"2024","journal-title":"J. Ovarian Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3649","DOI":"10.1111\/jcmm.17921","article-title":"Digestive system deep infiltrating endometriosis: What do we know?","volume":"27","author":"Yin","year":"2023","journal-title":"J. Cell. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"122370","DOI":"10.1016\/j.lfs.2023.122370","article-title":"Spotlight on iron overload and ferroptosis: Research progress in female infertility","volume":"340","author":"Zhang","year":"2024","journal-title":"Life Sci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Didziokaite, G., Biliute, G., Gudaite, J., and Kvedariene, V. (2023). Oxidative stress as a potential underlying cause of minimal and mild endometriosis-related infertility. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043809"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e21209","DOI":"10.1096\/fj.202002178R","article-title":"Endometrial epithelial ARID1A is critical for uterine gland function in early pregnancy establishment","volume":"35","author":"Marquardt","year":"2021","journal-title":"FASEB J."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Xie, Z., He, Y., Feng, Y., and Wang, X. (2024). Identification of programmed cell death-related genes and diagnostic biomarkers in endometriosis using a machine learning and Mendelian randomization approach. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1372221"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1210\/endrev\/bnad020","article-title":"Epigenetic dysregulation in endometriosis: Implications for pathophysiology and therapeutics","volume":"44","author":"Marquardt","year":"2023","journal-title":"Endocr. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1007\/s10815-021-02247-5","article-title":"The impact of the female genital tract microbiome in women\u2019s health and reproduction: A review","volume":"38","author":"Labarta","year":"2021","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kobayashi, H., Yoshimoto, C., Matsubara, S., Shigetomi, H., and Imanaka, S. (2023). Current understanding of and future directions for endometriosis-related infertility research with a focus on ferroptosis. Diagnostics, 13.","DOI":"10.3390\/diagnostics13111926"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Latif, S., Khanjani, S., and Saridogan, E. (2024). Endometriosis and in vitro fertilization. Medicina, 60.","DOI":"10.3390\/medicina60081358"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1007\/s10815-022-02460-w","article-title":"Association of embryo transfer type with infertility in endometriosis: A systematic review and meta-analysis","volume":"39","author":"Chang","year":"2022","journal-title":"J. Assist. Reprod. Genet."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/9\/1641\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T08:39:10Z","timestamp":1787819950000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/9\/1641"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,27]]},"references-count":31,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["medicina62091641"],"URL":"https:\/\/doi.org\/10.3390\/medicina62091641","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,27]]}}}