Endometriosis

DOI: 10.1055/s-0045-1813025 Endometriosis Authors Endometriosis is a chronic condition known for its complexity and pervasive impact on women's health. Worldwide, it affects over 200 million women and imposes a substantial burden on physical health in the form of severe pelvic pain, infertility, and menstrual irregularities. It also deeply affects emotional well-being, social relationships, and daily functioning. Pathologically, it is characterized by the growth of endometrial-like tissue outside the uterus. Endometriosis is challenging to both diagnose and manage, and this is often compounded by socioeconomic and healthcare disparities that leave many women without adequate treatment. Endometriosis also imposes substantial financial costs. After adjusting a 2012 study for inflation and population growth, a reasonable estimate of the current economic costs of endometriosis exceeds $100 billion/year in the United States alone.[1] Indeed, Tewhaiti-Smith et al recently estimated that endometriosis imposes a lifetime cost of $2 million on affected individuals in New Zealand.[2] Shockingly, public investment in the disease is woefully small, amounting to only $3/year for each woman living with the disease.[3] Notwithstanding this obstacle, researchers have made steady (if too slow) progress in better understanding the disease. This issue of Seminars in Reproductive Medicine is dedicated to exploring the latest advancements and ongoing challenges in understanding and managing endometriosis. Here, experts offer insights into diagnostic advancements, pathophysiological mechanisms, and management strategies. In “Current Understanding of Endometriosis Pathophysiology and Future Perspectives,” Falsetta and Chrysilla synthesize current research on the multifactorial pathophysiology of endometriosis, emphasizing emerging molecular, cellular, and immunological mechanisms. The authors critically examine foundational theories—including retrograde menstruation, coelomic metaplasia, and stem cell involvement—highlighting persistent gaps in understanding disease origin. They explore key pathological drivers such as inflammation, oxidative stress, central sensitization, and hormonal dysregulation in depth. They also detail the roles of immune cells (macrophages, mast cells, dendritic cells, T cells), noncoding RNAs, mitochondrial dysfunction, and microbiota alterations in lesion development and pain signaling. They present promising avenues for elucidating disease mechanisms, such as transcriptomics, organoid models, and epigenetic profiling, and conclude with an overview of investigational therapies targeting inflammation, angiogenesis, oxidative stress, and neuroimmune interactions, as well as efforts to identify novel biomarkers for earlier, noninvasive diagnosis. In “Breaking Down Barriers: Improving Access to Quality Endometriosis Care,” Nieto, Lopez, Quintero Montaño, Sanabria, and Villegas-Echeverri explore the significant barriers hindering timely and effective treatment of endometriosis. They highlight the contribution of societal normalization of menstrual pain, stigma, and socioeconomic disparities to delayed diagnosis and limited access to care. They stress the need for multi-faceted strategies that enhance education, destigmatize the condition, and ensure equitable healthcare access. By advocating for education initiatives and healthcare reforms, the authors aim to promote early symptom recognition and provide improved management options for affected girls and women. In “Noninvasive Diagnostics for Endometriosis,” Lauar, Barbisan, Leite, Andres, and Abrao critically evaluate advancements in the diagnostic landscape for endometriosis. By focusing on noninvasive imaging modalities, this work challenges the traditional dependence on invasive procedures, emphasizing the importance of early and accurate disease assessment for both medical and potential surgical management of disease. The authors highlight how cutting-edge imaging techniques can improve surgical outcomes and patient education, and may enable more effective, patient-friendly approaches that can reduce diagnosis delays and improve quality of life. In “More than the Lesion: Unraveling the Complexities of Endometriosis-associated Pain,” Schmatz and Gubbels examine the complex nature of endometriosis-associated pain, emphasizing its multifaceted pathophysiology. They identify peripheral and central sensitization, inflammation, and neuroplastic changes as critical pain mechanisms, alongside comorbid pain syndromes that contribute to the overall disease burden. Despite the application of current treatments such as hormonal and surgical interventions, pain management remains inadequate. The authors advocate a multimodal approach emphasizing neuroinflammatory pathways and pelvic floor dysfunction to improve therapeutic outcomes, highlighting the critical need for innovative strategies in managing endometriosis-associated pain. In “Endometriosis and Fertility: Where Do We Draw the Line?” Rivera and Behbehani provide a timely and clinically relevant synthesis of current evidence regarding the complex relationship between endometriosis and infertility. They critically assess current classification systems and their limitations in predicting reproductive outcomes. Then they explore the multifaceted mechanisms by which endometriosis impairs fertility, including anatomical distortion, inflammation, and diminished ovarian reserve. After considering the effect of the disease on natural conception, they turn to evidence regarding assisted reproductive technologies (ART), with particular attention to IVF outcomes. They highlight conflicting data on the efficacy of medical pretreatment, especially GnRH agonists, and evaluate surgical approaches—ablation versus excision—and their influence on spontaneous pregnancy and ART success. Special consideration is given to endometriomas and deep infiltrating endometriosis, with emerging data supporting surgical intervention in select cases to improve fertility outcomes. The authors also discuss novel techniques such as ultrasound-guided sclerotherapy and the role of hemostatic methods in preserving ovarian reserve. In “Endometrioma: Contemporary Approach to Diagnosis and Management,” Sridhar, Mintz, and Billow describe the clinical challenges associated with diagnosing and managing endometriomas, a common form of ovarian endometriosis. They underscore the balance clinicians must achieve between symptom alleviation and fertility preservation, focusing on what is known about best practices in surgical and medical interventions. They also provide a strong practical dissection of advanced diagnostic imaging techniques and treatment strategies ranging from surveillance and medical therapy to laparoscopic cystectomy. The authors advocate for tailored management plans that minimize ovarian damage while providing effective relief. They emphasize the risks associated with surgical interventions, particularly regarding ovarian reserve, and discuss innovative approaches in management aimed at improving patient care outcomes through individualized care protocols. In “Role of Hysterectomy in Endometriosis Management,” Nicole Afuape delves into the complexities of managing the condition, emphasizing a holistic and longitudinal approach that integrates lifestyle changes, hormone therapy, and, when necessary, surgical intervention, including hysterectomy. While advancements in surgical techniques have improved outcomes, the lack of a definitive approach necessitates tailored management strategies that consider each patient's clinical presentation and fertility goals. This synthesis calls for balanced treatment modalities that address both symptom relief and quality of life enhancements. By bringing together these perspectives, this issue aims to advance our understanding of what is and isn't known about endometriosis. While our reviewers have done a masterful job summarizing the available literature, there are important gaps in our understanding. As a consequence of chronic underfunding, randomized, blinded studies remain rare in the disease. Most clinical studies are retrospective, meaning that confidence in the conclusions that can be drawn remains limited. From a basic science perspective, the interplay between genetic predisposition and environmental factors in disease onset and progression remains largely unexplored. We also don't really understand how the disease results in pain and infertility. While these gaps can be frustrating for patients and clinicians alike, they also represent important opportunities for young researchers to make highly impactful discoveries in both the clinical and basic science realms. We envision a future where such discoveries dramatically improve the lives of everyone affected by this challenging condition, and thank our authors for their valuable contribution to this future. Publication History Article published online: 20 January 2026 © 2025. Thieme. All rights reserved. Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA - References - 1 Simoens S, Dunselman G, Dirksen C. et al. The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres. Hum Reprod 2012; 27 (05) 1292-1299 - 2 Tewhaiti-Smith JMK, Gannott M, Semprini A. et al. The cost of endometriosis and chronic pelvic pain burden in New Zealand (Aotearoa): results from a nationwide survey. Preprints with the Lancet 2025 - 3 Wadman M. Probing the pain. Science 2025; 389 (6762): 771-777