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Open research questions in Endometriosis Research and Treatment

702 gap statements mined from Endometriosis Research and Treatment papers in our 7.9M-paper local library, which holds 2,963 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • One of the challenges is the complex etiology of obesity. Another challenge is the unclear relationship between obesity and endometriosis. The paper also identifies the challenge of understanding the mechanisms responsible for the detrimental effects of obesity on female fertility.

    The Molecular Link between Obesity and the Endometrial Environment: A Starting Point for Female Infertility · 2024 · DOI

  • The specific role of adenomyosis in infertility is not easy to understand due to the frequent coexistence of endometriosis and adenomyosis. The mechanisms of adenomyosis-associated infertility are not fully understood. There is a need for patient-specific treatment options for adenomyosis-associated infertility.

    The Current Understanding of Molecular Mechanisms in Adenomyosis-Associated Infertility and the Treatment Strategy for Assisted Reproductive Technology · 2024 · DOI

  • The incidence and prevalence of endometriosis are difficult to quantify due to asymptomatic patients and the need for laparoscopic diagnosis. The complex nature of co-stimulatory or co-inhibitory immune checkpoints and the signalling between effector cells and APCs requires further investigation.

    Immune Checkpoints in Endometriosis—A New Insight in the Pathogenesis · 2024 · DOI

  • The exact cause of endometriosis is not fully understood. Pancreatic endometriosis is exceedingly rare and poses a significant diagnostic challenge.

    Pancreatic Endometriosis Coexisting with a Splenic Mesothelial Cyst: A Rare Case Report and Review of the Literature · 2025 · DOI

  • The precise aetiology of endometriosis remains unclear. There is a lack of understanding of the relationship between early life trauma and endometriosis.

    Early life trauma and endometriosis: A case-control study on type and timing of adverse experiences · 2026 · DOI

  • Sphingosine-1-phosphate (S1P) signaling regulates immune-cell trafficking, vascular remodeling, and tissue invasion, but its contribution to adenomyosis remains poorly defined.

    Stage-dependent sphingosine-1-phosphate pathway modulation as a therapeutic strategy in a murine model of adenomyosis · 2026 · DOI

  • However, how hypoxia regulates autophagy to drive lesion development remains unclear.

    Hypoxia-induced miR-21-5p promotes autophagy by downregulating CDC25A in endometriosis · 2026 · DOI

  • This gap in knowledge is partly due to the lack of suitable in vitro models for studying their effects on endometrial epithelial function.

    Somatic mutations in endometrial epithelium: biological insights and emerging in vitro models · 2026 · DOI

  • However, whether EVs promote type I collagen deposition in the eutopic endometrium through glycolytic reprogramming and subsequent non-histone lactylation remains unclear.

    Glycolytic reprogramming and MYH10 K1520 lactylation mediate eutopic endometrial collagen I deposition driven by PKM2-packaged ectopic endometrial extracellular vesicles · 2026 · DOI

  • Although its pathogenesis remains incompletely understood, accumulating evidence indicates that the tumor suppressor p53 and aberrant epigenetic modifications play critical roles in EMs initiation and progression.

    p53-mediated epigenetic regulation in the pathogenesis of endometriosis · 2026 · DOI

  • Future research should address long term safety beyond 48 months, direct comparisons with first line hormonal therapies, and cost effectiveness in non US healthcare settings.

    A Systematic Review of Elagolix for the Management of Endometriosis-associated Pain · 2026 · DOI

  • Further research into the potential use of DNase-based medicine for endometriosis patients involving more participants is warranted.

    Effect of deoxyribonuclease I therapy on free circulating DNA level and gene methylation profile changes in patients with endometriosis: Proof of concept and preliminary data · 2026 · DOI

  • These findings support further investigation of trace-element and oxidative-stress profiles as potential biomarkers of disease-related biological alterations, while larger multicenter and longitudinal studies are needed to establish their clinical relevance and causal relationships.

    Trace element imbalance and oxidative-inflammatory dysregulation in women with endometriosis · 2026 · DOI

  • While myofibroblast activation is central to fibrogenesis, the cellular origins and regulatory mechanisms remain incompletely understood.

    TGFB1/SMAD3-driven macrophage–myofibroblast transition promotes fibrosis progression in endometriosis · 2025 · DOI

  • Ovarian tumor domain-containing protein 1 (OTUD1) deubiquitinase binds to the MADH7 protein, although its specific role in endometriosis needs to be investigated.

    OTUD1 inhibits endometriosis fibrosis by deubiquitinating MADH7 · 2025 · DOI

  • Adenomyosis-the ectopic presence of endometrial glands and stroma within the myometrium-affects reproductive-age women and is associated with pain, bleeding, and subfertility, yet the immune events that precede pregnancy remain poorly defined.

    Temporal dynamics of uterine immune microenvironment remodeling in a murine model of adenomyosis · 2025 · DOI

  • The intrauterine period may be a susceptible window for subsequent development of adenomyosis and warrants further investigation.

    Early‐Life Exposures and Odds of Adenomyosis: A Population‐Based Case–Control Study · 2025 · DOI

  • Two previous Scandinavian cohort studies found limited evidence for associations between early-life risk factors, including birthweight, and risks of adenomyosis.

    Are There Indicators of Risk for Adenomyosis Already in Early Life? · 2025 · DOI

  • Unfortunately, this disease is understudied compared with many other benign gynaecological reproductive conditions.

    Are There Indicators of Risk for Adenomyosis Already in Early Life? · 2025 · DOI

  • However, conclusive data regarding the appropriateness of menopausal hormone therapy in women with endometriosis or a history of the disease are lacking.

    Menopause and endometriosis · 2024 · DOI

  • The diagnosis of endometriosis remains challenging due to the heterogeneity of symptoms and their overlap with conditions such as irritable bowel syndrome and inflammatory bowel disease. Women often face a diagnostic delay of 4-11 years, with an average of approximately seven years before a definitive diagnosis is established.

    Assessment of the Impact of Chronic Pain on the Prevalence of Depressive Disorders in Patients with Endometriosis · 2025 · DOI

  • The human endometrium is a complex, dynamic, and poorly understood tissue involving monthly cyclical regeneration likely from adult stem/progenitor cells.

    Somatic mutations in endometrial epithelium: biological insights and emerging in vitro models · 2026 · DOI

  • Endometriosis (EMs) is a chronic gynecological disease with poorly understood pathogenesis.

    Integrated lipidomics and transcriptomics reveal the key role of ceramides in the development of endometriosis · 2026 · DOI

  • Numerous in vivo rodent models of endometriosis have been developed to explore multiple aspects of this poorly understood disease.

    WERF Endometriosis Phenome and Biobanking Harmonisation Project for Experimental Models in Endometriosis Research (EPHect-EM-Heterologous): heterologous rodent models · 2025 · DOI

  • Further studies are needed to confirm the findings and explore the long-term outcomes of laparoscopy-assisted abdominal wall reconstruction - Research on the cost-effectiveness of the laparoscopy-assisted approach compared to the open approach is needed - Studies on the application of the laparoscopy-assisted approach in other types of abdominal wall defects…

    Laparoscopy-assisted versus open surgery for reconstruction of abdominal wall defects following endometriosis resection: a retrospective cohort study · 2026 · DOI

Most-cited papers in Endometriosis Research and Treatment

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Open questions raised by papers listed on this page include: (1) There is a lack of understanding of the relationship between early life trauma and endometriosis (“Early life trauma and endometriosis: A case-control study on type and timing of…”, 2026); (2) How hypoxia regulates autophagy to drive lesion development remains unclear (“Hypoxia-induced miR-21-5p promotes autophagy by downregulating CDC25A in…”, 2026); (3) This gap in knowledge is partly due to the lack of suitable in vitro models for studying their effects on endometrial epithelial function (“Somatic mutations in endometrial epithelium: biological insights and emerging…”, 2026); (4) Whether EVs promote type I collagen deposition in the eutopic endometrium through glycolytic reprogramming and subsequent non-histone lactylation remains unclear (“Glycolytic reprogramming and MYH10 K1520 lactylation mediate eutopic…”, 2026); (5) Although its pathogenesis remains incompletely understood, accumulating evidence indicates that the tumor suppressor p53 and aberrant epigenetic modifications play critical roles in EMs initiation and progression (“p53-mediated epigenetic regulation in the pathogenesis of endometriosis”, 2026). 702 gap statements have been mined from Endometriosis Research and Treatment papers in our 7.9M-paper local library, which holds 2,963 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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