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Open research questions in Endometriosis Research and Treatment

328 unresolved questions extracted from the limitations and future-work sections of 1,323 Endometriosis Research and Treatment papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Limited understanding of prognostic factors for synchronous endometrial and ovarian cancers. Need for a systematic review and meta-analysis to identify these factors.

    Prognostic factors of synchronous endometrial and ovarian cancers: a systematic review and meta-analysis of cohort studies · 2026 · DOI

  • The role of Keratin 17 remains unclear in EC. Limited treatment options are available for advanced or recurrent EC cases.

    Keratin 17 drives endometrial cancer aggressiveness via epithelial-mesenchymal transition: a single-cell transcriptomic and integrative bioinformatics study · 2026 · DOI

  • No Hippo pathway-targeting strategy has been clinically validated for endometriosis - The physiological roles of YAP/TAZ in tissue homeostasis and regeneration require careful consideration - Further subtype-resolved mechanistic studies, robust preclinical validation, and clinical safety assessment are required

    Hippo pathway in endometriosis pathogenesis: from cellular dysregulation to therapeutic opportunities · 2026 · DOI

  • Robust preclinical evaluation of Hippo pathway-directed strategies is needed - Assessment of experimental YAP-TEAD-disrupting approaches in well-characterised cell, organoid and animal models - Investigation of combination approaches, including experimental YAP modulation with progestins

    Hippo pathway in endometriosis pathogenesis: from cellular dysregulation to therapeutic opportunities · 2026 · DOI

  • The study faced challenges due to incomplete documentation and missing data. The retrospective nature of the study limited the availability of certain data. Technical factors such as rectal gas, fecal material, probe angle, and patient tolerance may have affected TRS evaluations.

    Ultrasound Sliding Sign Assessed by Transvaginal or Transrectal Route for Predicting Complete Pouch of Douglas Obliteration in Patients with Ovarian Endometriomas: An Exploratory Retrospective Study · 2026 · DOI

  • direct measurement of image quality, rectal contents, probe pressure, or operator confidence, - investigation of the effects of standardized bowel preparation protocol on TRS

    Ultrasound Sliding Sign Assessed by Transvaginal or Transrectal Route for Predicting Complete Pouch of Douglas Obliteration in Patients with Ovarian Endometriomas: An Exploratory Retrospective Study · 2026 · DOI

  • Current approaches do not fully address persistent pain and variable treatment response in endometriosis and adenomyosis. There is a need for new strategies that target the underlying immune and fibrotic mechanisms. Non-hormonal therapies are needed to complement or replace hormonal suppression.

    Macrophage-centered immune-fibrotic persistence in endometriosis and adenomyosis: non-hormonal immunopharmacological targets · 2026 · DOI

  • Lack of a reliable and consistent model for endometriosis research. Limited understanding of the disease mechanisms and cellular behavior. Need for a model that can be used to study the disease and develop new treatments.

    Establishment of pathology‑validated immortalized patient‑derived ovarian endometriosis epithelial cell line · 2026 · DOI

  • The etiology of endometriosis is still unclear. A deep understanding of the molecular-level mechanisms of endometriosis is lacking. The occurrence of endometriosis pain is related to various factors, making it challenging to identify the specific mechanisms.

    Unveiling the Mechanisms of Pain in Endometriosis: Comprehensive Analysis of Inflammatory Sensitization and Therapeutic Potential · 2025 · DOI

  • There is a dearth of direct data on the precise mechanisms and involvement of stem cells in the pathophysiology of endogamy - There is insufficient direct evidence about the precise role and process of epithelial-mesenchymal transition - There is a lack of concrete evidence demonstrating how endometrial cells metastasize through the lymphatic or vascular system

    Unveiling the Mechanisms of Pain in Endometriosis: Comprehensive Analysis of Inflammatory Sensitization and Therapeutic Potential · 2025 · DOI

  • The heterogeneity of the available data on antioxidant therapy. The lack of standardized evidence to substantiate the routine application of antioxidants in clinical practice. The potential adverse effects of antioxidant supplementation, such as gastrointestinal side effects and malodorous effects.

    Antioxidant therapy for infertile couples: a comprehensive review of the current status and consideration of future prospects · 2025 · DOI

  • More robust, high-quality, and standardized evidence is needed to substantiate the routine application of AOXs in clinical practice, - Research on the optimal dosage and combination of AOXs, - Studies on the specific patient populations most likely to benefit from AOX therapy

    Antioxidant therapy for infertile couples: a comprehensive review of the current status and consideration of future prospects · 2025 · DOI

  • The causes and progression of endometriosis are not fully understood. There is a need to investigate the dietary impact on endometriosis incidence. The study identifies a gap in the understanding of the relationship between dietary selenium intake and endometriosis risk.

    Association between dietary selenium intake and endometriosis risk: a cross-sectional analysis · 2025 · DOI

  • Endometriosis is difficult to diagnose because symptoms can vary considerably among affected individuals. The condition is characterized by the presence of endometrial tissue outside the uterus, which can cause chronic pelvic pain and infertility. There is a lack of efficient or permanent treatment solutions for endometriosis.

    Pathogenesis of Endometriosis and Endometriosis-Associated Cancers · 2024 · DOI

  • The paper identifies the challenge of understanding the complex interactions between the microbiome, inflammation, and oxidative stress in endometriosis. Another challenge is the need to develop effective dietary and nutritional interventions that can influence the composition and function of the microbiome, reduce inflammation and oxidative stress, alleviate pain, and potentially affect EM-associated psychological disorders. The paper also highlights the challenge of addressing the heterogeneous symptoms associated with endometriosis, including chronic pelvic pain.

    Endometriosis, Pain, and Related Psychological Disorders: Unveiling the Interplay among the Microbiome, Inflammation, and Oxidative Stress as a Common Thread · 2024 · DOI

  • The paper identifies a gap in the understanding of the interplay among the microbiome, inflammation, and oxidative stress in endometriosis. There is a need to explore the emerging roles of the microbiome, inflammation, and oxidative stress as common links among EM, pain, and psychological comorbidities. The potential of dietary and nutritional interventions in managing EM symptoms is an area that requires further research.

    Endometriosis, Pain, and Related Psychological Disorders: Unveiling the Interplay among the Microbiome, Inflammation, and Oxidative Stress as a Common Thread · 2024 · DOI

  • One of the challenges identified is the unclear origin of endometriosis. Another challenge is the need to understand the association between hormonal dysregulation and the disease. The paper also identifies the challenge of developing effective treatments for endometriosis.

    The Known, the Unknown and the Future of the Pathophysiology of Endometriosis · 2024 · DOI

  • Investigate the impact of NK cells on the production of proangiogenic cytokines, - Examine the regulatory role of NK cells in ESC invasion in endometriosis, - Study the effect of estrogen on the cytotoxic activity of NK cells, - Explore the relationship between estrogen, NK cells, and endometrial receptivity

    An Estrogen–NK Cells Regulatory Axis in Endometriosis, Related Infertility, and Miscarriage · 2024 · DOI

  • The mechanisms contributing to endometriosis-associated infertility are still not well comprehended. The impact of NK cells on the production of proangiogenic cytokines remains limited.

    An Estrogen–NK Cells Regulatory Axis in Endometriosis, Related Infertility, and Miscarriage · 2024 · DOI

  • the study does not establish cause and effect relationships, - the impact of hormonal contraception on EM remains unclear, - the study only considered female patients

    The Role of NK and T Cells in Endometriosis · 2024 · DOI

  • further investigation of the relationship between immune parameters and clinical features of EM, - examination of the effects of EM on both systemic and local immune profiles, - characterization of patterns of aberrant NK and T cell profiles according to disease severity and symptomatology

    The Role of NK and T Cells in Endometriosis · 2024 · DOI

  • The diagnostic delay of 7-10 years could impair the clinical outcome and determine the progression of the disease. The onset of pathogenetic changes in adolescents with the initial forms of the disease remains poorly elucidated. The study had to analyze complex cellular and endosomal profiles of markers.

    Altered Glycolysis, Mitochondrial Biogenesis, Autophagy and Apoptosis in Peritoneal Endometriosis in Adolescents · 2024 · DOI

  • Small sample size (60 girls), - Limited to post-menarchal girls aged 15-17 years, - No long-term follow-up

    Altered Glycolysis, Mitochondrial Biogenesis, Autophagy and Apoptosis in Peritoneal Endometriosis in Adolescents · 2024 · DOI

  • Biomarker-informed patient selection - Compartment-specific endpoints - Fertility-compatible translational design

    Macrophage-centered immune-fibrotic persistence in endometriosis and adenomyosis: non-hormonal immunopharmacological targets · 2026 · DOI

  • endometriosis is difficult to diagnose because symptoms can vary considerably among affected individuals, - the relationship between coffee or alcohol intake and endometriosis risk remains unclear, - cigarette smoking is negatively associated with the risk of endometrial cancer but its relationship with endometriosis risk is inconsistent, - systematic gene sequencing of risk loci failed to causally link single-risk gene variants to endometriosis

    Pathogenesis of Endometriosis and Endometriosis-Associated Cancers · 2024 · DOI

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328 open questions have been extracted from the limitations and future-work passages of 1,323 Endometriosis Research and Treatment papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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