Pathophysiology, diagnosis, and management of endometriosis

BMJ, Journal Year: 2022, Volume and Issue: unknown, P. e070750 - e070750

Published: Nov. 14, 2022

Endometriosis affects approximately 190 million women and people assigned female at birth worldwide. It is a chronic, inflammatory, gynecologic disease marked by the presence of endometrial-like tissue outside uterus, which in many patients associated with debilitating painful symptoms. Patients endometriosis are also greater risk infertility, emergence fatigue, multisite pain, other comorbidities. Thus, best understood as condition variable presentation effects multiple life stages. A long diagnostic delay after symptom onset common, persistence recurrence symptoms despite treatment common. This review discusses potential genetic, hormonal, immunologic factors that lead to endometriosis, focus on current management strategies for gynecologists, general practitioners, clinicians specializing conditions higher risk. examines evidence supporting different surgical, pharmacologic, non-pharmacologic approaches treating presents an easy adopt step-by-step strategy. As multisystem disease, should ideally be offered personalized, multimodal, interdisciplinary approach. priority future discovery determining clinically informative sub-classifications predict prognosis enhance prioritization.

Language: Английский

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Endometriosis Is Undervalued: A Call to Action

Frontiers in Global Women s Health, Journal Year: 2022, Volume and Issue: 3

Published: May 10, 2022

Endometriosis is an inflammatory chronic pain condition caused by uterine tissue growing outside of the uterus that afflicts at least 11% women (and people assigned female birth) worldwide. This results in a substantial burden to these women, and society large. Although endometriosis was first identified over 160 years ago, knowledge gaps remain, including confirmation disease's etiology. Research funding for limited, with from bodies like National Institutes Health (NIH) constituting only 0.038% 2022 health budget—for affects 6.5 million US alone 190 A major issue diagnosis frequently delayed because surgery required histologically confirm diagnosis. delay increases symptom intensity, risk central peripheral sensitization costs disease patient their nation. Current conservative treatments presumed are management birth control. Both methods flawed can be entirely ineffective reduction suffering or improving ability work, neither addresses severe infertility issues higher certain cancers. research deserves attention befits its prevalence, effects, economic costs. could improve outcomes introducing less invasive more timely treatment, options such as novel biomarkers, nanomedicine, microbiome alterations.

Language: Английский

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Targeting Oxidative Stress Involved in Endometriosis and Its Pain

Biomolecules, Journal Year: 2022, Volume and Issue: 12(8), P. 1055 - 1055

Published: July 29, 2022

Endometriosis is a common gynecological disorder seen in women and characterized by chronic pelvic pain infertility. This becoming more prevalent with increased morbidity. The etiology of endometriosis remains to be fully elucidated, which will lead improved therapeutic options. In this review, we evaluate the biochemical mechanisms leading oxidative stress their implication pathophysiology endometriosis, as well potential treatments that target these processes. A comprehensive exploration previous research revealed associated elevated reactive oxygen species oxidation products, decreased antioxidants detoxification enzymes, dysregulated iron metabolism. High levels contributed inflammation, extracellular matrix degradation, angiogenesis, cell proliferation, may explain its role endometriosis. Endometriosis-associated was attributed neurogenic inflammation feed-forward mechanism involving macrophages, pro-inflammatory cytokines, pain-inducing prostaglandins. N-acetylcysteine, curcumin, melatonin, combined vitamin C E supplementation displayed promising results for treatment but further needed use population.

Language: Английский

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Recurrent implantation failure: reality or a statistical mirage?

Fertility and Sterility, Journal Year: 2023, Volume and Issue: 120(1), P. 45 - 59

Published: Feb. 22, 2023

ImportanceTo date, recurrent implantation failure (RIF) has no clear definition and clearly identified impaired function. Hence, the term RIF is currently used somewhat haphazardly, on basis of clinicians’ judgment.ObjectiveInternational experts in reproductive medicine met July 1, 2022, Lugano, Switzerland, to review different facets define diagnosis its appropriate management.Evidence ReviewA systematic without meta-analysis studies published English from January 2015 May 2022.FindingsData indicated that been largely overevaluated, overdiagnosed, overtreated sufficient critical assessment true nature. Our analyses show extremely uncommon—occurring <5% couples with infertility—and reassurance continued conventional therapies are warranted most cases assisted technology (ART) failure. Although biologic determinants may exist a small subset people infertility, they elude available tools for assessment. Without identification underlying etiology(ies), it reasonable not assign this patient until she failed at least 3 euploid blastocyst transfers (or equivalent number unscreened embryo transfers, adjusted patient’s age corresponding euploidy rate). In addition, other factors should be ruled out contribute her reduced odds sustained implantation. such cases, only issue considered case ART because result multiple necessarily repetitive or persistent. reality, impacting probability further success very rare occurrence.ConclusionTrue uncommon, occurring infertility. Reassurance cases. It would seem embryos, age).RelevanceGiven internationally recognized field present Lugano meeting our publication constitutes consensus statement. To judgment. International management. A 2022. Data occurrence. True age).

Language: Английский

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

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6473 - 6473

Published: June 12, 2024

Endometriosis (EM), a chronic condition in endometrial tissue outside the uterus, affects around 10% of reproductive-age women, significantly affecting fertility. Its prevalence remains elusive due to surgical confirmation needed for diagnosis. Manifesting with range symptoms, including dysmenorrhea, dyschezia, dysuria, dyspareunia, fatigue, and gastrointestinal discomfort, EM impairs quality life severe pelvic pain (CPP). Psychological manifestations, notably depression anxiety, frequently accompany physical CPP serving as key mediator. Pain stems from lesions, involving oxidative stress, neuroinflammation, angiogenesis, sensitization processes. Microbial dysbiosis appears be crucial inflammatory mechanisms underlying associated CPP, well psychological symptoms. In this scenario, dietary interventions nutritional supplements could help manage symptoms by targeting inflammation, microbiome. Our manuscript starts delving into complex relationship between comorbidities. It subsequently addresses emerging roles microbiome, stress common links among these abovementioned conditions. Furthermore, review explores how may influence composition function reduce inflammation alleviate pain, potentially affect EM-associated disorders.

Language: Английский

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The female reproductive tract microbiotas, inflammation, and gynecological conditions

Frontiers in Reproductive Health, Journal Year: 2022, Volume and Issue: 4

Published: Aug. 9, 2022

The intricate interactions between the host cells, bacteria, and immune components that reside in female reproductive tract (FRT) are essential maintaining homeostasis. Much of our current knowledge surrounding FRT microbiota relates to vaginal microbiota, where ‘health’ has long been associated with low bacterial diversity Lactobacillus dominance. This concept recently challenged as women can have a diverse microbial composition absence symptomatic disease. structures upper (the endocervix, uterus, Fallopian tubes, ovaries) distinct, lower biomass microbiotas than vagina; however, existence permanent at these sites is disputed. During homeostasis, balance exists bacteria system maintains quiescence. Alterations system, or local environment may result perturbances defined dysbiosis. inflammatory signature perturbed “dysbiotic” characterized by elevated concentrations pro-inflammatory cytokines cervical fluid. It appears homeostasis be disrupted two different mechanisms: first, shift toward increased trigger inflammation, second, immunity altered some manner, which disrupts response an environmental change. dysbiosis negative effects on health. review will examine increasing evidence for involvement inflammation gynecologic conditions such endometriosis, infertility, endometrial ovarian cancer; precise mechanisms involved remains speculative present. While only their infancy, use antibiotics probiotics therapeutically alter being studied discussed herein. Our understanding intimate relationship its early days, more research needed deepen mechanistic this assess how present harnessed assist diagnosis treatment conditions.

Language: Английский

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Personalized Nutrition in the Management of Female Infertility: New Insights on Chronic Low-Grade Inflammation

Nutrients, Journal Year: 2022, Volume and Issue: 14(9), P. 1918 - 1918

Published: May 3, 2022

Increasing evidence on the significance of nutrition in reproduction is emerging from both animal and human studies, suggesting a mutual association between female fertility. Different “fertile” dietary patterns have been studied; however, humans, conflicting results or weak correlations are often reported, probably because individual variations genome, proteome, metabolome, microbiome extent exposure to different environmental conditions. In this scenario, “precision nutrition”, namely personalized based deep phenotyping metabolomics, microbiome, nutrigenetics each case, might be more efficient for infertile patients than applying generic nutritional approach. review, we report new insights into management patients, discussing main nutrigenetic, nutrigenomic, microbiomic aspects that should investigated achieve effective interventions. Specifically, will focus low-grade chronic inflammation, which associated with several infertility-related diseases.

Language: Английский

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The bidirectional relationship between endometriosis and microbiome

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: March 7, 2023

Endometriosis has been described by many different theories of pathogenesis over the years. It is now also appreciated to be a state chronic inflammation, and role immune dysfunction in its development proven. There increasing evidence support microbiome formation progression endometriosis via inflammatory pathways. The dysbiosis seen thought both causative consequence pathogenesis. Gut, peritoneal fluid female reproductive tract microbiota studied understand if there are any signatures specific endometriosis. New research on how manipulate for better detection treatment emerging.

Language: Английский

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The pathophysiological role of estrogens in the initial stages of pregnancy: molecular mechanisms and clinical implications for pregnancy outcome from the periconceptional period to end of the first trimester

Human Reproduction Update, Journal Year: 2023, Volume and Issue: 29(6), P. 699 - 720

Published: June 23, 2023

Abstract BACKGROUND Estrogens regulate disparate female physiological processes, thus ensuring reproduction. Altered estrogen levels and signaling have been associated with increased risks of pregnancy failure complications, including hypertensive disorders low birthweight babies. However, the role estrogens in periconceptional period early is still understudied. OBJECTIVE AND RATIONALE This review aims to summarize current evidence on maternal during first trimester pregnancies conceived naturally following ART. Detailed molecular mechanisms related clinical impacts are extensively described. SEARCH METHODS Data for this narrative were independently identified by seven researchers Pubmed Embase databases. The keywords selected: ‘estrogens’ OR ‘estrogen level(s)’ ‘serum estradiol’ ‘estradiol/estrogen concentration’, ‘early pregnancy’ ‘first ‘preconceptional period’ ‘ART’ ‘In Vitro Fertilization (IVF)’ ‘Embryo Transfer’ ‘Frozen Embryo ‘oocyte donation’ ‘egg ‘miscarriage’ ‘pregnancy outcome’ ‘endometrium’. OUTCOMES During (defined here as critical time window starting 1 month before conception), play a crucial endometrial receptivity, through activation paracrine/autocrine signaling. A derailed estrogenic milieu within seems be detrimental both natural ART-conceived pregnancies. Low non-conception cycles On other hand, excessive supraphysiologic concentrations at LH peak correlate lower live birth rates higher complications. In pregnancy, plays massive placentation mainly modulating angiogenic factor expression—and development an immune-tolerant uterine micro-environment remodeling function killer T-helper cells. Lower thought trigger abnormal pregnancies, whereas excess worsen outcomes. WIDER IMPLICATIONS Most available endorses relation between outcomes, further depicting optimal concentration range optimize success. how co-operate factors order maintain fine balance local tolerance towards developing fetus immune responses pathogens remains elusive. Further studies highly warranted, also aiming identify determinants response biomarkers personalized administration regimens

Language: Английский

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New concepts on the etiology of endometriosis

Journal of Obstetrics and Gynaecology Research, Journal Year: 2023, Volume and Issue: 49(4), P. 1090 - 1105

Published: Feb. 6, 2023

Abstract Endometriosis is a serious, chronic disorder where endometrial tissue grows outside the uterus, causing severe pelvic pain and infertility. It affects 11% of women. multifactorial unclear etiology, although retrograde menstruation plays major role. has genetic component with over 40 risk factors mapped, their mechanism action still emerging. New evidence suggests role for stem/progenitor cells, now that identifying markers these cells are available. Recent lineage tracing clearing microscopy 3D reconstruction provided new understanding glandular structure, particularly horizontal orientation interconnection basalis glands. sequencing technologies, whole genome DNA revealing somatic mutations, including in cancer driver genes, normal eutopic endometrium patients endometriosis, as well ectopic endometriotic lesions. Methylome offering insight into regulation genes environmental factors. Single cell RNA reveals transcriptome individual shedding light on diversity range cellular subpopulations types present epithelial organoid cultures replicating epithelium providing tractable models studying endometriosis. Organoids derived from menstrual fluid offer non‐invasive source avenue testing drugs developing personalized medicine treating These approaches rapidly advancing our endometriosis etiology.

Language: Английский

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