{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:15:21Z","timestamp":1792167321595,"version":"4.4.0"},"reference-count":45,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Endometriosis is a chronic, estrogen-dependent disorder characterized by the presence of functional endometrial tissue, comprising both glandular and stromal components, located outside the uterine cavity, affecting approximately 6\u201310% of women of reproductive age and up to 30\u201350% of those with infertility. Increasing evidence indicates that endometriosis is not solely a localized gynecological condition but rather a systemic inflammatory and immune-mediated disease. Chronic inflammation and immune dysregulation contribute to disease progression and may impair reproductive function. This review aims to analyze the current evidence regarding the inflammatory and immunological mechanisms underlying endometriosis and to evaluate their impact on reproductive dysfunction and assisted reproductive technology (ART) outcomes. Materials and Methods: A comprehensive narrative review was conducted using major scientific databases, including PubMed, Scopus, and Web of Science. Relevant articles published in the last decade were selected using keywords such as \u201cendometriosis\u201d, \u201cinflammation\u201d, \u201cimmune response\u201d, \u201ccytokines\u201d, and \u201cART outcomes\u201d. Both clinical and experimental studies were included to assess the relationship between inflammatory markers, immune alterations, and reproductive performance. Results: Endometriosis is associated with elevated levels of pro-inflammatory cytokines, including interleukin (IL)-1\u03b2, IL-6, and tumor necrosis factor-alpha (TNF-\u03b1), as well as increased oxidative stress and altered peritoneal microenvironment. Immune dysfunction is characterized by activated macrophages, decreased natural killer (NK) cell cytotoxicity, and an imbalance in T-cell populations. These alterations negatively affect oocyte quality, fertilization, embryo development, and endometrial receptivity. Emerging biomarkers such as IL-6, TNF-\u03b1, and CA-125 show potential in predicting disease severity and ART outcomes, although their clinical utility remains under investigation. Conclusions: Endometriosis should be regarded as a systemic immuno-inflammatory disorder with significant implications for reproductive health. The interaction between chronic inflammation and immune dysregulation plays a central role in infertility and suboptimal ART outcomes. Further research is required to validate reliable biomarkers and develop targeted therapeutic strategies to improve reproductive success in affected patients.<\/jats:p>","DOI":"10.3390\/medicina62050885","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T10:01:30Z","timestamp":1777975290000},"page":"885","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Endometriosis Uncovered: From Chronic Inflammation to Reproductive Dysfunction and Impaired ART Outcomes"],"prefix":"10.3390","volume":"62","author":[{"given":"Luana","family":"Ghilea Sele\u0219","sequence":"first","affiliation":[{"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":"Calla-Infertility Diagnostic and Treatment Center, Constantin A. Rosetti Street, 410103 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 Psychoneurosciences and Rehabilitation, University of Oradea, 1 University Street, 410087 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alin","family":"Bodog","sequence":"additional","affiliation":[{"name":"Department of Surgical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 10 Piata 1 Decembrie Street, 410073 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca","family":"Huniadi","sequence":"additional","affiliation":[{"name":"Department of Surgical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 10 Piata 1 Decembrie Street, 410073 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Czubak, P., Herda, K., Niewiadomska, I., Putowski, L., \u0141a\u0144cut, M., and Mas\u0142yk, M. (2025). Understanding Endometriosis: A Broad Review of Its Causes, Management, and Impact. Int. J. Mol. Sci., 26.","DOI":"10.20944\/preprints202505.0315.v1"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Simancas-Racines, D., Jim\u00e9nez-Flores, E., Montalvan, M., Horowitz, R., Araujo, V., and Reytor-Gonz\u00e1lez, C. (2026). Endometriosis as a Systemic and Complex Disease: Toward Phenotype-Based Classification and Personalized Therapy. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27020908"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Gerede, A., Oikonomou, E., Gkaitatzi, F., Danavasi, M., Papasozomenou, P., Potiris, A., Stavros, S., Kourti, V., Domali, A., and Koutlaki, N. (2026). Endometriosis at the Single-Cell Level: Molecular Insights and Implications for Assisted Reproduction Success. Biomolecules, 16.","DOI":"10.3390\/biom16030402"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Mariadas, H., Chen, J.-H., and Chen, K.-H. (2025). The Molecular and Cellular Mechanisms of Endometriosis: From Basic Pathophysiology to Clinical Implications. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26062458"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Cano-Herrera, G., Salmun Nehmad, S., Ruiz de Ch\u00e1vez Gasc\u00f3n, J., M\u00e9ndez Vionet, A., van Tienhoven, X.A., Osorio Mart\u00ednez, M.F., Muleiro Alvarez, M., Vasco Rivero, M.X., L\u00f3pez Torres, M.F., and Barroso Valverde, M.J. (2024). Endometriosis: A Comprehensive Analysis of the Pathophysiology, Treatment, and Nutritional Aspects, and Its Repercussions on the Quality of Life of Patients. Biomedicines, 12.","DOI":"10.3390\/biomedicines12071476"},{"key":"ref_6","first-page":"e66128","article-title":"Endometriosis: A Comprehensive Exploration of Inflammatory Mechanisms and Fertility Implications","volume":"16","author":"Rathod","year":"2024","journal-title":"Cureus"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Smolarz, B., Szy\u0142\u0142o, K., and Romanowicz, H. (2021). Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment, and Genetics (Review of Literature). Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910554"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lamceva, J., Uljanovs, R., and Strumfa, I. (2023). The Main Theories on the Pathogenesis of Endometriosis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054254"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.ogc.2012.10.002","article-title":"Endometriosis and Infertility: A Review of the Pathogenesis and Treatment of Endometriosis-Associated Infertility","volume":"39","author":"Macer","year":"2012","journal-title":"Obstet. Gynecol. Clin. N. Am."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s10815-010-9436-1","article-title":"Endometriosis and Infertility","volume":"27","author":"Bulletti","year":"2010","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Fran\u00e7a, P.R., Lontra, A.C., and Fernandes, P.D. (2022). Endometriosis: A Disease with Few Direct Treatment Options. Molecules, 27.","DOI":"10.3390\/molecules27134034"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e2300907","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_13","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-G\u00f3mez, E., V\u00e1zquez-Mart\u00ednez, E.R., Reyes-Mayoral, C., Cruz-Orozco, O.P., Camacho-Arroyo, I., and Cerb\u00f3n, M. (2019). Regulation of Inflammation Pathways and Inflammasome by Sex Steroid Hormones in Endometriosis. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00935"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Chen, S., Liu, Y., Zhong, Z., Wei, C., Liu, Y., and Zhu, X. (2023). Peritoneal Immune Microenvironment of Endometriosis: Role and Therapeutic Perspectives. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1134663"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Giacomini, E., Minetto, S., Li Piani, L., Pagliardini, L., Somigliana, E., and Vigan\u00f2, P. (2021). Genetics and Inflammation in Endometriosis: Improving Knowledge for Development of New Pharmacological Strategies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22169033"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"114909","DOI":"10.1016\/j.biopha.2023.114909","article-title":"Research Advances in Endometriosis-Related Signaling Pathways: A Review","volume":"164","author":"Zhang","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.7150\/ijbs.35128","article-title":"Cyclooxygenase-2 in Endometriosis","volume":"15","author":"Lai","year":"2019","journal-title":"Int. J. Biol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s11154-021-09666-w","article-title":"Hormonal Treatments for Endometriosis: The Endocrine Background","volume":"23","author":"Vannuccini","year":"2022","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Fan, W., Yuan, Z., Li, M., Zhang, Y., and Nan, F. (2023). Decreased Oocyte Quality in Patients with Endometriosis Is Closely Related to Abnormal Granulosa Cells. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1226687"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Filip, L., Duic\u0103, F., Pr\u0103datu, A., Cre\u021boiu, D., Suciu, N., Cre\u021boiu, S.M., Predescu, D.-V., Varlas, V.N., and Voinea, S.-C. (2020). Endometriosis-Associated Infertility: A Critical Review and Analysis on Etiopathogenesis and Therapeutic Approaches. Medicina, 56.","DOI":"10.3390\/medicina56090460"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"153","DOI":"10.2147\/IJWH.S151845","article-title":"Chronic Pain during Pregnancy: A Review of the Literature","volume":"10","author":"Wendel","year":"2018","journal-title":"Int. J. Women\u2019s Health"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/s41386-019-0439-z","article-title":"Sleep Deficiency and Chronic Pain: Potential Underlying Mechanisms and Clinical Implications","volume":"45","author":"Haack","year":"2020","journal-title":"Neuropsychopharmacology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.2147\/IJGM.S261139","article-title":"Impact of Endometriosis on Life-Course Potential: A Narrative Review","volume":"14","author":"Missmer","year":"2021","journal-title":"Int. J. Gen. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1002\/ejp.2006","article-title":"Psychosocial Factors Associated with Pain and Health-Related Quality of Life in Endometriosis: A Systematic Review","volume":"26","author":"Kalfas","year":"2022","journal-title":"Eur. J. Pain"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Arana, M.L., Pereira S\u00e1nchez, A., Vaquero Arg\u00fcello, G., Tejerina Gonz\u00e1lez, E., Alonso-Iniesta, M., and P\u00e9rez Medina, T. (2026). The Role of Chronic Endometritis in Endometriosis: A Personalized Diagnostic Tool?. J. Pers. Med., 16.","DOI":"10.3390\/jpm16020073"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Mappa, I., Page, Z.P., Di Mascio, D., Patelli, C., D\u2019Antonio, F., Giancotti, A., Gebbia, F., Mariani, G., Cozzolino, M., and Muzii, L. (2024). The Effect of Endometriosis on In Vitro Fertilization Outcomes: A Systematic Review and Meta-Analysis. Healthcare, 12.","DOI":"10.3390\/healthcare12232435"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s10815-017-0919-1","article-title":"A Higher Prevalence of Endometriosis among Asian Women Does Not Contribute to Poorer IVF Outcomes","volume":"34","author":"Yamamoto","year":"2017","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_28","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_29","doi-asserted-by":"crossref","unstructured":"Practice Committee of the American Society for Reproductive Medicine (2012). Endometriosis and Infertility: A Committee Opinion. Fertil. Steril., 98, 591\u2013598.","DOI":"10.1016\/j.fertnstert.2012.05.031"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1016\/S0015-0282(02)03112-6","article-title":"Effect of Endometriosis on In Vitro Fertilization","volume":"77","author":"Barnhart","year":"2002","journal-title":"Fertil. Steril."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1111\/1471-0528.12366","article-title":"The Effect of Endometriosis on In Vitro Fertilisation Outcome: A Systematic Review and Meta-Analysis","volume":"120","author":"Harb","year":"2013","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1093\/humupd\/dmv035","article-title":"The Impact of Endometrioma on IVF\/ICSI Outcomes: A Systematic Review and Meta-Analysis","volume":"21","author":"Hamdan","year":"2015","journal-title":"Hum. Reprod. Update"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1007\/s10815-018-1214-5","article-title":"Endometriosis Does Not Affect Live Birth Rates of Patients Submitted to Assisted Reproduction Techniques","volume":"35","author":"Murta","year":"2018","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.rbmo.2015.03.005","article-title":"Impact of Ovarian Endometrioma on Ovarian Responsiveness and IVF: A Systematic Review and Meta-Analysis","volume":"31","author":"Yang","year":"2015","journal-title":"Reprod. Biomed. Online"},{"key":"ref_35","first-page":"803","article-title":"The Impact of Endometrioma on IVF\/ICSI Outcomes: A Systematic Review and Meta-Analysis","volume":"303","author":"Alshehre","year":"2020","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/uog.13366","article-title":"Impact of Endometriosis and Its Staging on Assisted Reproduction Outcome: A Systematic Review and Meta-Analysis","volume":"44","author":"Barbosa","year":"2014","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"102446","DOI":"10.1016\/j.jogoh.2022.102446","article-title":"The Effect of Endometriosis on IVF\/ICSI and Perinatal Outcome: A Systematic Review and Meta-Analysis","volume":"51","author":"Qu","year":"2022","journal-title":"J. Gynecol. Obstet. Hum. Reprod."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1097\/AOG.0000000000002675","article-title":"Long-Term Outcomes of Elagolix in Women with Endometriosis: Results from Two Extension Studies","volume":"132","author":"Surrey","year":"2018","journal-title":"Obstet. Gynecol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e052043","DOI":"10.1136\/bmjopen-2021-052043","article-title":"Pre-IVF Treatment with a GnRH Antagonist in Women with Endometriosis (PREGNANT): Study Protocol for a Prospective, Double-Blind, Placebo-Controlled Trial","volume":"12","author":"Taylor","year":"2022","journal-title":"BMJ Open"},{"key":"ref_40","first-page":"hoz001","article-title":"Continuous Oral Contraceptives versus Long-Term Pituitary Desensitization prior to IVF\/ICSI in Moderate to Severe Endometriosis: Study Protocol of a Non-Inferiority Randomized Controlled Trial","volume":"2019","author":"Lier","year":"2019","journal-title":"Hum. Reprod. Open"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"ESHRE Guideline Group on Ovarian Stimulation, Bosch, E., Broer, S., Griesinger, G., Grynberg, M., Humaidan, P., Kolibianakis, E., Kunicki, M., La Marca, A., and Lainas, G. (2020). ESHRE Guideline: Ovarian Stimulation for IVF\/ICSI. Hum. Reprod. Open, 2020, hoaa009.","DOI":"10.1093\/hropen\/hoaa009"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.rbmo.2018.11.021","article-title":"Ovarian Stimulation and Endometriosis Progression or Recurrence: A Systematic Review","volume":"38","author":"Somigliana","year":"2019","journal-title":"Reprod. Biomed. Online"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1093\/humrep\/dead262","article-title":"Towards Comprehensive Management of Symptomatic Endometriosis: Beyond the Dichotomy of Medical versus Surgical Treatment","volume":"39","author":"Mijatovic","year":"2024","journal-title":"Hum. Reprod."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1007\/s43032-023-01421-7","article-title":"Impact of Endometriosis Surgery on In Vitro Fertilization\/Intracytoplasmic Sperm Injection Outcomes: A Systematic Review and Meta-analysis","volume":"31","author":"Bourdon","year":"2024","journal-title":"Reprod. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1016\/j.jmig.2021.02.007","article-title":"Impact of Surgery for Deep Infiltrative Endometriosis before In Vitro Fertilization: A Systematic Review and Meta-analysis","volume":"28","author":"Casals","year":"2021","journal-title":"J. Minim. Invasive Gynecol."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/5\/885\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T10:47:21Z","timestamp":1777978041000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/5\/885"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,5]]},"references-count":45,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["medicina62050885"],"URL":"https:\/\/doi.org\/10.3390\/medicina62050885","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,5]]}}}