Medicine › Reproductive Medicine

Endometriosis Research and Treatment

Works Count: 71061

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This cluster of papers focuses on the diagnosis, pathophysiology, management, and impact of endometriosis. It covers topics such as the association between endometriosis and infertility, quality of life, epidemiology, immunobiology, stem cells, and the surgical treatment of endometriosis. The papers also explore the impact of endometriosis on women's lives and the challenges in reaching a diagnosis.

Keywords

Diagnosis; Management; Pathophysiology; Infertility; Quality of Life; Epidemiology; Immunobiology; Stem Cells; Pain Symptoms; Surgical Treatment

Dating the Endometrial Biopsy

1950-01-01

R. W. Noyes , Arthur T. Hertig , John A. Rock

Retrograde menstruation in healthy women and in patients with endometriosis.

1984-08-01

Jouko Halme , Mary Hammond , J.F. Hulka +2 more

Blood was found in the peritoneal fluid in 90% of women with patent tubes at laparoscopy during perimenstrual time. If the fallopian tubes were occluded, then only 15% of patients … Blood was found in the peritoneal fluid in 90% of women with patent tubes at laparoscopy during perimenstrual time. If the fallopian tubes were occluded, then only 15% of patients had evidence of blood in the pelvis. Also, 90% of patients with endometriosis and eight of nine women on oral contraceptives had bloody fluid during the menstrual period. The present observations indicate that retrograde menstruation through the fallopian tubes into the peritoneal cavity is a very common physiologic event in all menstruating women with patent tubes.

Endometriosis

2010-06-23

Linda C. Giudice

A healthy 25-year-old woman presents with worsening dysmenorrhea, new-onset left lower quadrant pain, and dyspareunia. She has regular menstrual cycles, and her last menstrual period was 3 weeks before presentation. … A healthy 25-year-old woman presents with worsening dysmenorrhea, new-onset left lower quadrant pain, and dyspareunia. She has regular menstrual cycles, and her last menstrual period was 3 weeks before presentation. How should this patient be evaluated and treated?

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Endometriosis and Infertility

2012-11-24

Matthew Macer , Hugh S. Taylor

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Complications of abdominal and vaginal hysterectomy among women of reproductive age in the United States

1982-12-01

Richard C. Dicker , Joel Greenspan , Lilo T. Strauss +6 more

Chronic Pelvic Pain: Prevalence, Health-Related Quality of Life, and Economic Correlates

1996-03-01

Susan D. Mathias

To determine the prevalence of chronic pelvic pain in U.S. women aged 18–50 years, and to examine its association with health-related quality of life, work productivity, and health care utilization. … To determine the prevalence of chronic pelvic pain in U.S. women aged 18–50 years, and to examine its association with health-related quality of life, work productivity, and health care utilization. In April and May 1994, the Gallup Organization telephoned 17,927 U.S. households to identify women aged 18–50 years who experienced chronic pelvic pain, ie, of at least 6 months' duration. Those who reported chronic pelvic pain were surveyed on severity, frequency, and diagnosis; quality of life; work loss and productivity; and health care utilization. Among 5263 eligible women who agreed to participate, 773 (14.7%) reported chronic pelvic pain within the past 3 months. Those who reported chronic pelvic pain had significantly lower mean scores for general health than those who did not (70.5 versus 78.8, P < .05), and 61% of those with chronic pelvic pain reported that the etiology was unknown. Women diagnosed with endometriosis reported the most health distress, pain during or after intercourse, and interference with activities because of pain. Estimated direct medical costs for outpatient visits for chronic pelvic pain for the U.S. population of women aged 18–50 years are $881.5 million per year. Among 548 employed respondents, 15% reported time lost from paid work and 45% reported reduced work productivity. Frequently, the cause of chronic pelvic pain is undiagnosed, although it affects approximately one in seven U.S. women. Increased awareness of its cost and impact on quality of life should promote increased medical attention to this problem.

Ovarian Conservation at the Time of Hysterectomy and Long-Term Health Outcomes in the Nurses’ Health Study

2009-05-01

William H. Parker , Michael S. Broder , Eunice Chang +7 more

In Brief OBJECTIVE: To report long-term health outcomes and mortality after oophorectomy or ovarian conservation. METHODS: We conducted a prospective, observational study of 29,380 women participants of the Nurses' Health … In Brief OBJECTIVE: To report long-term health outcomes and mortality after oophorectomy or ovarian conservation. METHODS: We conducted a prospective, observational study of 29,380 women participants of the Nurses' Health Study who had a hysterectomy for benign disease; 16,345 (55.6%) had hysterectomy with bilateral oophorectomy, and 13,035 (44.4%) had hysterectomy with ovarian conservation. We evaluated incident events or death due to coronary heart disease (CHD), stroke, breast cancer, ovarian cancer, lung cancer, colorectal cancer, total cancers, hip fracture, pulmonary embolus, and death from all causes. RESULTS: Over 24 years of follow-up, for women with hysterectomy and bilateral oophorectomy compared with ovarian conservation, the multivariable hazard ratios (HRs) were 1.12 (95% confidence interval [CI] 1.03–1.21) for total mortality, 1.17 (95% CI 1.02–1.35) for fatal plus nonfatal CHD, and 1.14 (95% CI 0.98–1.33) for stroke. Although the risks of breast (HR 0.75, 95% CI 0.68–0.84), ovarian (HR 0.04, 95% CI 0.01–0.09, number needed to treat=220), and total cancers (HR 0.90, 95% CI 0.84–0.96) decreased after oophorectomy, lung cancer incidence (HR=1.26, 95% CI 1.02–1.56, number needed to harm=190), and total cancer mortality (HR=1.17, 95% CI 1.04–1.32) increased. For those never having used estrogen therapy, bilateral oophorectomy before age 50 years was associated with an increased risk of all-cause mortality, CHD, and stroke. With an approximate 35-year life span after surgery, one additional death would be expected for every nine oophorectomies performed. CONCLUSION: Compared with ovarian conservation, bilateral oophorectomy at the time of hysterectomy for benign disease is associated with a decreased risk of breast and ovarian cancer but an increased risk of all-cause mortality, fatal and nonfatal coronary heart disease, and lung cancer. In no analysis or age group was oophorectomy associated with increased survival. LEVEL OF EVIDENCE: II Oophorectomy is associated with an increased risk of all-cause mortality, fatal and nonfatal coronary heart disease, and lung cancer.

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Endometriosis: pathogenesis and treatment

2013-12-24

Paolo Vercellini , Paola Viganò , Edgardo Somigliana +1 more

Immunobiology of endometriosis

2001-01-01

Dan I. Lebovic , Michael D. Mueller , Robert N. Taylor

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Ovarian steroid regulation of vascular endothelial growth factor in the human endometrium: implications for angiogenesis during the menstrual cycle and in the pathogenesis of endometriosis.

1996-08-01

Jan L. Shifren , Jennifer F. Tseng , Charles Zaloudek +5 more

The human endometrium undergoes a complex process of vascular and glandular proliferation, differentiation, and regeneration with each menstrual cycle in preparation for implantation. Vascular endothelial growth factor (VEGF) is an … The human endometrium undergoes a complex process of vascular and glandular proliferation, differentiation, and regeneration with each menstrual cycle in preparation for implantation. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific angiogenic protein that appears to play an important role in both physiological and pathological neovascularization. To investigate whether VEGF may regulate human endometrial angiogenesis, we examined VEGF messenger ribonucleic acid (mRNA) and protein throughout the menstrual cycle and studied the regulation of VEGF by reproductive steroids in isolated human endometrial cells. By ribonuclease protection analysis, VEGF mRNA increased relative to early proliferative phase expression by 1.6-,2.0-, and 3.6-fold in midproliferative, late proliferative, and secretory endometrium, respectively. In histological sections, VEGF mRNA and protein were localized focally in glandular epithelial cells and more diffusely in surrounding stroma, with greatest VEGF expression in secretory endometrium. Consistent with these in vivo results, the treatment of isolated human endometrial cells with estradiol (E2), medroxyprogesterone acetate (MPA), or E2 plus MPA significantly increased VEGF mRNA expression over the control value by 3.1-, 2.8-, and 4.7-fold, respectively. The VEGF response to E2 was rapid, with steady state levels of VEGF mRNA reaching 85% maximum 1 h after the addition of steroid. E2 also caused a 46% increase in secreted VEGF protein, and the combination of E2 and MPA caused an 18% increase. VEGF expression in endometriosis, an angiogenesis-dependent, estrogen-sensitive disease was similar to that seen in eutopic endometrium. Peritoneal fluid concentrations of VEGF were significantly higher in women with moderate to severe endometriosis than in women with minimal to mild endometriosis or no disease. VEGF, therefore, may be important in both physiological and pathological angiogenesis of human endometrium, as it is an estrogen-responsive angiogenic factor that varies throughout the menstrual cycle and is elevated in women with endometriosis.

EPIDEMIOLOGY OF ENDOMETRIOSIS

1997-06-01

Brenda Eskenazi , Marcella Warner

Effect of endometriosis on in vitro fertilization

2002-06-01

Kurt T. Barnhart , Rebecca Dunsmoor-Su , Christos Coutifaris

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Gene Expression Analysis of Endometrium Reveals Progesterone Resistance and Candidate Susceptibility Genes in Women with Endometriosis

2007-05-18

Richard O. Burney , Saïd Talbi , Amy E. Hamilton +5 more

The identification of molecular differences in the endometrium of women with endometriosis is an important step toward understanding the pathogenesis of this condition and toward developing novel strategies for the … The identification of molecular differences in the endometrium of women with endometriosis is an important step toward understanding the pathogenesis of this condition and toward developing novel strategies for the treatment of associated infertility and pain. In this study, we conducted global gene expression analysis of endometrium from women with and without moderate/severe stage endometriosis and compared the gene expression signatures across various phases of the menstrual cycle. The transcriptome analysis revealed molecular dysregulation of the proliferative-to-secretory transition in endometrium of women with endometriosis. Paralleled gene expression analysis of endometrial specimens obtained during the early secretory phase demonstrated a signature of enhanced cellular survival and persistent expression of genes involved in DNA synthesis and cellular mitosis in the setting of endometriosis. Comparative gene expression analysis of progesterone-regulated genes in secretory phase endometrium confirmed the observation of attenuated progesterone response. Additionally, interesting candidate susceptibility genes were identified that may be associated with this disorder, including FOXO1A, MIG6, and CYP26A1. Collectively these findings provide a framework for further investigations on causality and mechanisms underlying attenuated progesterone response in endometrium of women with endometriosis.

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Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer

2004-12-26

Daniela M. Dinulescu , Tan A. Ince , Bradley J. Quade +3 more

ENDOMETRIAL CARCINOMA OF THE OVARY, ARISING IN ENDOMETRIAL TISSUE IN THAT ORGAN

1925-01-01

John A. Sampson

Many interesting and important problems have presented themselves to clinicians and pathologists, who have appreciated the frequency of ectopic endometrium-like tissue in the pelvis and have had an opportunity to … Many interesting and important problems have presented themselves to clinicians and pathologists, who have appreciated the frequency of ectopic endometrium-like tissue in the pelvis and have had an opportunity to observe the various lesions in the ovaries and other pelvic structures resulting from this tissue. One of the most interesting problems is the source of these implantation-like lesions occurring on the surface of the various pelvic structures. Are they true implantations derived primarily from uterine or tubal epithelium escaping through the tubes into the peritoneal cavity, as the study of many of these lesions in human beings indicates1and as Jacobson,2in the autotransplantation of endometrial tissue in rabbits, has experimentally proved possible, or are they derived from scattered localized metaplasias of the serosal mesothelium or from developmental inclusions of portions of the Wolffian body or Müllerian duct? This problem has not yet been definitely solved to the

Pathogenesis and pathophysiology of endometriosis

2012-07-20

Richard O. Burney , Linda C. Giudice

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Pelvic Inflammatory Disease and Fertility

1992-07-01

L Weström , Riduan M. Joesoef , Gladys H. Reynolds +2 more

From 1960 10 1984, 2,501 women underwent diagnostic laparoscopy (index laparoscopy) because of a clinical suspicion of acute pelvic inflammatory disease (PID). Of these women, 1,844 had abnormal laparoscopic findings … From 1960 10 1984, 2,501 women underwent diagnostic laparoscopy (index laparoscopy) because of a clinical suspicion of acute pelvic inflammatory disease (PID). Of these women, 1,844 had abnormal laparoscopic findings (patients) and 657 had normal findings (control subjects). The reproductive events after index laparoscopy of 1,732 patients and 601 control subjects were followed. The patients and control subjects were followed for a total of 13,400 and 3,958 woman-years, respectively. During the follow-up period, 1,309 (75.6%) of the patients and 451 (75.0%) of the control subjects attempted to conceive. Of these women, 209 (16.0%) of the patients and 12 (2.7%) of the control subjects failed to conceive. A total of 141 (10.8%) of the patients and 0 (0%) of the control subjects had confirmed tubal factor infertility, 21 (1.6%) of the patients and 3 (0.7%) control subjects had other causes of infertility, and 47 (3.6%) patients and 9 (2.0%) control subjects did not have a complete infertility evaluation. Additional information on tubal morphology (hysterosalpingography, laparoscopy, or laparotomy) in women from couples for whom evaluation was incomplete indicated that 165 (12.2%) patients and 4 (0.9%) of the control subjects had abnormal tubal function or morphology after index laparoscopy. Tubal factor infertility after PID was associated with number and severity of PID episodes. The ectopic pregnancy rate for first pregnancy after index laparoscopy was 9.1% among the patients and 1.4% among control subjects.

Endometriosis and infertility

2010-06-24

Carlo Bulletti , Maria Elisabetta Coccia , Silvia Battistoni +1 more

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Endometriosis and infertility: pathophysiology and management

2010-08-01

Dominique de Ziegler , Bruno Borghese , Charles Chapron

Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities

1997-10-01

Michelle Nisolle , Jacques Donnez

Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case–control studies

2012-02-22

Celeste Leigh Pearce , Claire Templeman , Mary Anne Rossing +7 more

Endometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative … Endometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes of ovarian cancer.

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Clonogenicity of Human Endometrial Epithelial and Stromal Cells1

2004-06-01

Rachel Chan , Kjiana E. Schwab , Caroline E. Gargett

The human endometrium regenerates from the lower basalis layer, a germinal compartment that persists after menstruation to give rise to the new upper functionalis layer. Because adult stem cells are … The human endometrium regenerates from the lower basalis layer, a germinal compartment that persists after menstruation to give rise to the new upper functionalis layer. Because adult stem cells are present in tissues that undergo regeneration, we hypothesized that human endometrium contains small populations of epithelial and stromal stem cells responsible for cyclical regeneration of endometrial glands and stroma and that these cells would exhibit clonogenicity, a stem-cell property. The aims of this study were to determine 1) the clonogenic activity of human endometrial epithelial and stromal cells, 2) which growth factors support this clonogenic activity, and 3) determine the cellular phenotypes of the clones. Endometrial tissue was obtained from women undergoing hysterectomy. Purified single- cell suspensions of epithelial and stromal cells were cultured at cloning density (300–500/cm2) in serum medium or in serum- free medium supplemented with one of eight growth factors. Small numbers of epithelial (0.22%) and stromal cells (1.25%) initiated colonies in serum-containing medium. The majority of colonies were small, containing large, loosely arranged cells, and 37% of epithelial and 1 in 60 of stromal colonies were classified as large, comprising small, densely packed cells. In serum-free medium, transforming growth factor-α (TGFα), epidermal growth factor (EGF), platelet-derived growth factor-BB (PDGF-BB) strongly supported clonogenicity of epithelial cells, while leukemia-inhibitory factor (LIF), hepatocyte growth factor (HGF), stem-cell factor (SCF), insulin-like growth factor-I (IGF- I) were weakly supportive, and basic fibroblast growth factor (bFGF) was without effect. TGFα, EGF, PDGF-BB, and bFGF supported stromal cell clonogenicity, while HGF, SCF, LIF, and IGF- I were without effect. Small epithelial colonies expressed three epithelial markers but not stromal markers; however, large epithelial colonies showed little reactivity for all markers except α6-integrin. All stromal colonies contained fibroblasts, expressing stromal markers, and in some colonies, myofibroblasts were also identified. This analysis of human endometrium has demonstrated the presence of rare clonogenic epithelial and stromal cells with high proliferative potential, providing the first evidence for the existence of putative endometrial epithelial and stromal stem cells.

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Recurrence of endometriosis and its control

2009-03-11

Sun‐Wei Guo

BACKGROUNDAlthough surgery is currently the treatment of choice for managing endometriosis, recurrence poses a formidable challenge. To delay or to eliminate the recurrence is presently an unmet medical need in … BACKGROUNDAlthough surgery is currently the treatment of choice for managing endometriosis, recurrence poses a formidable challenge. To delay or to eliminate the recurrence is presently an unmet medical need in the management of endometriosis. To this end, proposals to investigate patterns of recurrence, to develop biomarkers for recurrence and to carry out biomarker-based intervention have been made.

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Expression Profiling of Endometrium from Women with Endometriosis Reveals Candidate Genes for Disease-Based Implantation Failure and Infertility

2003-04-15

L.C. Kao , Ariane Germeyer , Suzana Tulač +6 more

Endometriosis is clinically associated with pelvic pain and infertility, with implantation failure strongly suggested as an underlying cause for the observed infertility. Eutopic endometrium of women with endometriosis provides a … Endometriosis is clinically associated with pelvic pain and infertility, with implantation failure strongly suggested as an underlying cause for the observed infertility. Eutopic endometrium of women with endometriosis provides a unique experimental paradigm for investigation into molecular mechanisms of reproductive dysfunction and an opportunity to identify specific markers for this disease. We applied paralleled gene expression profiling using high-density oligonucleotide microarrays to investigate differentially regulated genes in endometrium from women with vs. without endometriosis. Fifteen endometrial biopsy samples (obtained during the window of implantation from eight subjects with and seven subjects without endometriosis) were processed for expression profiling on Affymetrix Hu95A microarrays. Data analysis was conducted with GeneChip Analysis Suite, version 4.01, and GeneSpring version 4.0.4. Nonparametric testing was applied, using a P value of 0.05, to assess statistical significance. Of the 12,686 genes analyzed, 91 genes were significantly increased more than 2-fold in their expression, and 115 genes were decreased more than 2-fold. Unsupervised clustering demonstrated down-regulation of several known cell adhesion molecules, endometrial epithelial secreted proteins, and proteins not previously known to be involved in the pathogenesis of endometriosis, as well as up-regulated genes. Selected dysregulated genes were randomly chosen and validated with RT-PCR and/or Northern/dot-blot analyses, and confirmed up-regulation of collagen alpha2 type I, 2.6-fold; bile salt export pump, 2.0-fold; and down-regulation of N-acetylglucosamine-6-O-sulfotransferase (important in synthesis of L-selectin ligands), 1.7-fold; glycodelin, 51.5-fold; integrin alpha2, 1.8-fold; and B61 (Ephrin A1), 4.5-fold. Two-way overlapping layer analysis used to compare endometrial genes in the window of implantation from women with and without endometriosis further identified three unique groups of target genes, which differ with respect to the implantation window and the presence of disease. Group 1 target genes are up-regulated during the normal window of implantation but significantly decreased in women with endometriosis: IL-15, proline-rich protein, B61, Dickkopf-1, glycodelin, N-acetylglucosamine-6-O-sulfotransferase, G0S2 protein, and purine nucleoside phosphorylase. Group 2 genes are normally down-regulated during the window of implantation but are significantly increased with endometriosis: semaphorin E, neuronal olfactomedin-related endoplasmic reticulum localized protein mRNA and Sam68-like phosphotyrosine protein alpha. Group 3 consists of a single gene, neuronal pentraxin II, normally down-regulated during the window of implantation and further decreased in endometrium from women with endometriosis. The data support dysregulation of select genes leading to an inhospitable environment for implantation, including genes involved in embryonic attachment, embryo toxicity, immune dysfunction, and apoptotic responses, as well as genes likely contributing to the pathogenesis of endometriosis, including aromatase, progesterone receptor, angiogenic factors, and others. Identification and validation of selected genes and their functions will contribute to uncovering previously unknown mechanism(s) underlying implantation failure in women with endometriosis and infertility, mechanisms underlying the pathogenesis of endometriosis and providing potential new targets for diagnostic screening and intervention.

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The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres

2012-03-14

Steven Simoens , G.A.J. Dunselman , Carmen D. Dirksen +7 more

This study aimed to calculate costs and health-related quality of life of women with endometriosis-associated symptoms treated in referral centres. A prospective, multi-centre, questionnaire-based survey measured costs and quality of … This study aimed to calculate costs and health-related quality of life of women with endometriosis-associated symptoms treated in referral centres. A prospective, multi-centre, questionnaire-based survey measured costs and quality of life in ambulatory care and in 12 tertiary care centres in 10 countries. The study enrolled women with a diagnosis of endometriosis and with at least one centre-specific contact related to endometriosis-associated symptoms in 2008. The main outcome measures were health care costs, costs of productivity loss, total costs and quality-adjusted life years. Predictors of costs were identified using regression analysis. Data analysis of 909 women demonstrated that the average annual total cost per woman was €9579 (95% confidence interval €8559–€10 599). Costs of productivity loss of €6298 per woman were double the health care costs of €3113 per woman. Health care costs were mainly due to surgery (29%), monitoring tests (19%) and hospitalization (18%) and physician visits (16%). Endometriosis-associated symptoms generated 0.809 quality-adjusted life years per woman. Decreased quality of life was the most important predictor of direct health care and total costs. Costs were greater with increasing severity of endometriosis, presence of pelvic pain, presence of infertility and a higher number of years since diagnosis. Our study invited women to report resource use based on endometriosis-associated symptoms only, rather than drawing on a control population of women without endometriosis. Our study showed that the economic burden associated with endometriosis treated in referral centres is high and is similar to other chronic diseases (diabetes, Crohn's disease, rheumatoid arthritis). It arises predominantly from productivity loss, and is predicted by decreased quality of life.

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Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries

2011-07-25

Kelechi Nnoaham , Lone Hummelshøj , Premila Webster +6 more

To assess the impact of endometriosis on health-related quality of life (HRQoL) and work productivity. To assess the impact of endometriosis on health-related quality of life (HRQoL) and work productivity.

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ESHRE guideline for the diagnosis and treatment of endometriosis

2005-06-24

Stephen Kennedy , Agneta Bergqvist , Charles Chapron +6 more

The objective was to develop recommendations for the diagnosis and treatment of endometriosis and its associated symptoms. A working group was convened comprised of practising gynaecologists and experts in evidence-based … The objective was to develop recommendations for the diagnosis and treatment of endometriosis and its associated symptoms. A working group was convened comprised of practising gynaecologists and experts in evidence-based medicine from Europe, as well as an endometriosis self-help group representative. After reviewing existing evidence-based guidelines and systematic reviews, the expert panel met on three occasions for a day during which the guideline was developed and refined. Recommendations based solely on the clinical experience of the panel were avoided as much as possible. The entire ESHRE Special Interest Group for Endometriosis and Endometrium was given the opportunity to comment on the draft guideline, after which it was available for comment on the ESHRE website for 3 months. The working group then ratified the guideline by unanimous or near-unanimous voting; finally, it was approved by the ESHRE Executive Committee. The guideline will be updated regularly, and will be made available at http://www.endometriosis.org/guidelines.html with hyperlinks to the supporting evidence, and the relevant references and abstracts. For women presenting with symptoms suggestive of endometriosis, a definitive diagnosis of most forms of endometriosis requires visual inspection of the pelvis at laparoscopy as the ‘gold standard’ investigation. However, pain symptoms suggestive of the disease can be treated without a definitive diagnosis using a therapeutic trial of a hormonal drug to reduce menstrual flow. In women with laparoscopically confirmed disease, suppression of ovarian function for 6 months reduces endometriosis-associated pain; all hormonal drugs studied are equally effective although their side-effects and cost profiles differ. Ablation of endometriotic lesions reduces endometriosis-associated pain and the smallest effect is seen in patients with minimal disease; there is no evidence that also performing laparoscopic uterine nerve ablation (LUNA) is necessary. In minimal–mild endometriosis, suppression of ovarian function to improve fertility is not effective, but ablation of endometriotic lesions plus adhesiolysis is effective compared to diagnostic laparoscopy alone. There is insufficient evidence available to determine whether surgical excision of moderate–severe endometriosis enhances pregnancy rates. IVF is appropriate treatment especially if there are coexisting causes of infertility and/or other treatments have failed, but IVF pregnancy rates are lower in women with endometriosis than in those with tubal infertility. The management of severe/deeply infiltrating endometriosis is complex and referral to a centre with the necessary expertise is strongly recommended. Patient self-help groups can provide invaluable counselling, support and advice.

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ESHRE guideline: management of women with endometriosis

2014-01-15

G.A.J. Dunselman , Nathalie Vermeulen , Christian M. Becker +7 more

What is the optimal management of women with endometriosis based on the best available evidence in the literature? What is the optimal management of women with endometriosis based on the best available evidence in the literature?

Endometriosis: epidemiology and aetiological factors

2004-04-01

Paola Viganò , Fabio Parazzini , Edgardo Somigliana +1 more

Estimates of the frequency of endometriosis vary widely. Based on the few reliable data, the prevalence of the condition can reasonably be assumed to be around 10%. Although no consistent … Estimates of the frequency of endometriosis vary widely. Based on the few reliable data, the prevalence of the condition can reasonably be assumed to be around 10%. Although no consistent information is available on the incidence of the disease, temporal trends suggest an increase among women of reproductive age. This could be explained—at least in part—by changing reproductive habits. Numerous epidemiological studies have indicated that nulliparous women and women reporting short and heavy menstrual cycles are at increased risk of developing endometriosis; data on other risk factors are less consistent. These epidemiological findings strongly support the menstrual reflux hypothesis. Additional evidence in favour of this theory includes the demonstration of viable endometrial cells in the menstrual effluent and peritoneal fluid, experimental implantation and growth of endometrium within the peritoneal cavity, observation of some degree of retrograde menstruation in most women undergoing laparoscopy during menses, and an association between obstructed menstrual outflow and endometriosis.

Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity

1927-01-01

John A. Sampson

Suggestive evidence that pelvic endometriosis is a progressive disease, whereas deeply infiltrating endometriosis is associated with pelvic pain

1991-04-01

Philippe R. Koninckx , Christel Meuleman , Stephan Demeyere +2 more

ESHRE Guideline: management of women with premature ovarian insufficiency

2016-03-22

Lisa Webber , Melanie Davies , Richard A. Anderson +7 more

LW chaired the guideline development group and hence fulfilled a leading role in collecting the evidence, writing the manuscript and dealing with reviewer comments.NV, as methodological expert, performed all literature … LW chaired the guideline development group and hence fulfilled a leading role in collecting the evidence, writing the manuscript and dealing with reviewer comments.NV, as methodological expert, performed all literature searches for the guideline, provided methodological support and was overall coordinator of the guideline production.MD was co-

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Laparoscopic Surgery in Infertile Women with Minimal or Mild Endometriosis

1997-07-24

Sylvie Marcoux , Rodolphe Maheux , Sylvie Bérubé

Minimal or mild endometriosis is frequently diagnosed in infertile women. It is often treated by resection or ablation of the lesions, but whether this improves fertility has not been established. … Minimal or mild endometriosis is frequently diagnosed in infertile women. It is often treated by resection or ablation of the lesions, but whether this improves fertility has not been established. We carried out a randomized, controlled trial to determine whether laparoscopic surgery enhanced fecundity in infertile women with minimal or mild endometriosis.We studied 341 infertile women 20 to 39 years of age with minimal or mild endometriosis. During diagnostic laparoscopy the women were randomly assigned to undergo resection or ablation of visible endometriosis or diagnostic laparoscopy only. They were followed for 36 weeks after the laparoscopy or, for those who became pregnant during that interval, for up to 20 weeks of pregnancy.Among the 172 women who had resection or ablation of endometriosis, 50 became pregnant and had pregnancies that continued for 20 weeks or longer, as compared with 29 of the 169 women in the diagnostic-laparoscopy group (cumulative probabilities, 30.7 percent and 17.7 percent, respectively; P=0.006 by the log-rank test). The corresponding rates of fecundity were 4.7 and 2.4 per 100 person-months (rate ratio, 1.9; 95 percent confidence interval, 1.2 to 3.1). Fetal losses occurred in 20.6 percent of all the recognized pregnancies in the laparoscopic-surgery group and in 21.6 percent of all those in the diagnostic-laparoscopy group (P=0.91). Four minor operative complications (intestinal contusion, slight tear of the tubal serosa, difficult pneumoperitoneum, and vascular trauma) were reported (three in the surgery group and one in the control group).Laparoscopic resection or ablation of minimal and mild endometriosis enhances fecundity in infertile women.

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Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the International Deep Endometriosis Analysis (IDEA) group

2016-06-28

S. Guerriero , G. Condous , T. Van den Bosch +7 more

The IDEA (International Deep Endometriosis Analysis group) statement is a consensus opinion on terms, definitions and measurements that may be used to describe the sonographic features of the different phenotypes … The IDEA (International Deep Endometriosis Analysis group) statement is a consensus opinion on terms, definitions and measurements that may be used to describe the sonographic features of the different phenotypes of endometriosis. Currently, it is difficult to compare results between published studies because authors use different terms when describing the same structures and anatomical locations. We hope that the terms and definitions suggested herein will be adopted in centers around the world. This would result in consistent use of nomenclature when describing the ultrasound location and extent of endometriosis. We believe that the standardization of terminology will allow meaningful comparisons between future studies in women with an ultrasound diagnosis of endometriosis and should facilitate multicenter research. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Enfoque sistemático para la evaluación ecográfica de la pelvis en mujeres con posible endometriosis, incluyendo términos, definiciones y mediciones: una opinión consensuada del Grupo Internacional de Análisis de la Endometriosis Profunda La declaración del Grupo Internacional de Análisis de la Endometriosis Profunda (IDEA, por sus siglas en inglés) es una opinión basada en un consenso sobre los términos, definiciones y medidas que se pueden utilizar para describir las características ecográficas de los distintos fenotipos de la endometriosis. Actualmente es difícil comparar los resultados entre los estudios publicados porque los autores utilizan términos diferentes para describir las mismas estructuras y localizaciones anatómicas. Esperamos que los términos y definiciones propuestas en este documento se adopten en centros de investigación de todo el mundo. Esto resultaría en un uso uniforme de la nomenclatura para describir la ubicación y el alcance de la endometriosis en la evaluación ecográfica. Creemos que la normalización de la terminología permitirá realizar comparaciones significativas entre futuros estudios de mujeres con diagnóstico de endometriosis mediante ecografía y debería facilitar la investigación entre múltiples centros de investigación. Endometriosis is a common gynecological problem, affecting approximately 5% of women1. The disease can be found in many sites throughout the pelvis, in particular the ovaries, pelvic peritoneum, pouch of Douglas (POD), rectum, rectosigmoid, rectovaginal septum (RVS), uterosacral ligaments (USLs), vagina and urinary bladder. Correct site-specific diagnosis is fundamental in defining the optimal treatment strategy for endometriosis. Non-invasive imaging methods are required to map accurately the location and extent of endometriotic lesions. The recent consensus statement produced by the World Endometriosis Society recommended the establishment of centers of expertise for the management of higher-stage disease2. This recommendation requires a reliable preoperative system of triage which enables immediate understanding of the location and severity of disease. Increasingly, endometriosis is being managed medically and surgery can be avoided or delayed in a growing proportion of cases. Transvaginal sonography (TVS) is the first-line imaging technique in the diagnosis of pelvic endometriosis and in particular for deep infiltrating endometriosis (DIE)3. It is important to note, however, that there is substantial heterogeneity in the reported sensitivity and specificity of TVS with regard to detection of DIE, irrespective of its location4, 5. Adding ultrasound examination by an experienced operator to history and pelvic examination improves the accuracy of diagnosis of pelvic endometriosis6, 7. In their meta-analysis, Hudelist et al.8 concluded that TVS with or without the use of prior bowel preparation is an accurate test for non-invasive, presurgical detection of DIE of the rectosigmoid. Although the diagnostic performance of ultrasound for detecting DIE reported by individual units is excellent for certain anatomical locations9-11, the lack of standardized definitions in the sonographic classification and diagnosis of DIE is a general cause for concern. This lack of uniformity when classifying anatomical location and extent of disease contributes to the considerable variation in the reported diagnostic accuracy of TVS in the diagnosis of endometriosis. The aim of this consensus opinion is to ensure that the ultrasound examination of a woman with potentially underlying endometriosis is performed in a standardized manner, that the measurement of endometriotic lesions is standardized and that the terminology used when describing the location of DIE and the sonographic features of DIE and other manifestations of endometriosis (endometriomas, adenomyosis, pelvic adhesions) is uniform. This consensus opinion should be useful in clinical practice as well as in research. We believe that careful definition of ultrasound-detected DIE will facilitate interpretation of research and lead to improved clinical care. This work is based on the opinion of a panel of clinicians, gynecological sonologists, advanced laparoscopic surgeons and radiologists (International Deep Endometriosis Analysis (IDEA) group) with expertise in diagnosis and management of endometriosis. Criteria used to invite the experts to participate in this consensus process included their having significant peer-reviewed publications in the field of diagnosis and management of endometriosis. An initial statement was presented in 2011 at the ISUOG congress in Copenhagen12, incorporating several suggestions from all participants. A first draft was written in December 2014 by a joint effort of the two first authors (S.G. and G.C.) and sent to all coauthors. All coauthors had the opportunity to comment within a fixed time limit. Reply was mandatory for coauthorship. Taking all comments into account, a revised draft was then sent to all coauthors. In case of conflicting opinions, a consensus was proposed after discussion between the two first authors and the last author (D.T.). This pathway was repeated until a consensus between all authors was reached. The consensus also included ultrasound images/videos and schematic drawings to illustrate the text. After 13 revisions, the manuscript was deemed ready for submission. In addition to terms, definitions and measurements to describe the sonographic features of DIE, adhesions, adenomyosis and endometriomas, this consensus opinion includes recommendations regarding how to take a history, how to perform a clinical examination, how to perform an ultrasound examination and which ultrasound modality to use when examining patients with suspected or known endometriosis. DIE anatomical locations in this consensus were modified from Chapron's anatomical distribution of pelvic DIE13. A detailed clinical history should be taken for all women with suspected endometriosis, with particular emphasis on symptoms which could be attributed to endometriosis14, 15. The following should be noted specifically: age; height; weight; ethnic origin; parity; bleeding pattern (regular, irregular or absent); last menstrual period; previous surgery for endometriosis (type, effect); previous myomectomy or Cesarean delivery (these entail increased risk of DIE in the bladder); family history of endometriosis; previous non-surgical treatment for endometriosis (type, duration, effect); subfertility including duration of subfertility; treatment for infertility and outcome of fertility treatment; pain (dysmenorrhea, dyspareunia, dysuria, dyschezia, chronic pelvic pain); hematochezia and/or hematuria. The onset and duration of symptoms should be noted and, if possible, the intensity of the pain recorded by letting the patient use a visual analog scale or investigating it with a 0–10 narrative numeric rating scale. A pelvic examination should be performed either before or after the pelvic ultrasound scan, with the aim of defining the presence or absence of vaginal and/or low rectal endometriosis7. The pelvic examination should include speculum examination (direct visualization of vaginal or cervical DIE) and vaginal palpation. Mobility, fixation and/or tenderness of the uterus should be evaluated carefully. Site-specific tenderness in the pelvis should also be evaluated. The purpose of performing an ultrasound examination in a woman with suspected endometriosis is to try to explain underlying symptoms, map the disease location and assess the severity of disease prior to medical therapy or surgical intervention. Various ultrasound approaches have been published, but to date none has been externally validated16, 17. We propose four basic sonographic steps when examining women with suspected or known endometriosis, as shown in Figure 1. Note that these steps can be adopted in this or any order as long as ALL four steps are performed to confirm/exclude the different forms of endometriosis. Using TVS as the first-line imaging tool, the operator should examine the uterus and the adnexa. The mobility of the uterus should be evaluated: normal, reduced or fixed ('question mark sign')18. Sonographic signs of adenomyosis should be searched for and described using the terms and definitions published in the Morphological Uterus Sonographic Assessment consensus opinion19. The presence or absence of endometriomas (Figure S1a), their size, measured systematically in three orthogonal planes (see 'Measurement of lesions', below), the number of endometriomas and their ultrasound appearance should be noted20. The sonographic characteristics of any endometrioma should be described using the International Ovarian Tumor Analysis terminology21. An atypical endometrioma (Figure S1b) is defined as a unilocular-solid mass with ground glass echogenicity with a papillary projection, a color score of 1 or 2 and no flow inside the papillary projection20. Ovarian endometriomas are associated frequently with other endometriotic lesions, such as adhesions and DIE22, 23. The 'kissing' ovaries sign (Figure S2) suggests that there are severe pelvic adhesions; bowel and Fallopian tube endometriosis are significantly more frequent in women with kissing ovaries vs those without kissing ovaries: 18.5% vs 2.5% and 92.6% vs 33%, respectively24. Endometriomas may undergo decidualization in pregnancy, in which case they can be confused with an ovarian malignancy on ultrasound examination (Figure S3)25. Simultaneous presence of other endometriotic lesions may facilitate a correct diagnosis of endometrioma in pregnancy and minimize the risk of unnecessary surgery. The second step is to search for sonographic 'soft markers', i.e. site-specific tenderness (SST) and fixed ovaries. The presence of soft markers increases the likelihood of superficial endometriosis and adhesions26, 27. By applying pressure between the uterus and ovary, one can assess if the ovary is fixed to the uterus medially, to the pelvic side wall laterally or to the USLs. The presence of adhesions can also be suspected if, on palpation with the probe and/or abdominal palpation with the free hand, the ovaries or the uterus appear to be fixed to adjacent structures (broad ligament, POD, bladder, rectum and/or parietal peritoneum). If there is pelvic fluid, fine strands of tissue (adhesions) may be seen between the ovary (with or without endometrioma) and the uterus or the peritoneum of the POD27-30. If there are endometriomas or pelvic endometriosis, the Fallopian tubes are frequently involved in the disease process. Adhesions may distort the normal Fallopian tubal course and occlusion of the Fallopian tube(s) by endometriotic foci or distal tubular adhesions may also occur. As a consequence, a sactosalpinx may develop. For these reasons, hydrosalpinx/hematosalpinx and peritoneal cysts should be searched for and reported. The third step is to assess the status of the POD using the real-time TVS-based 'sliding sign'. In order to assess the sliding sign when the uterus is anteverted (Figure 2a), gentle pressure is placed against the cervix using the transvaginal probe, to establish whether the anterior rectum glides freely across the posterior aspect of the cervix (retrocervical region) and posterior vaginal wall. If the anterior rectal wall does so, the 'sliding sign' is considered positive for this location (Videoclip S1a). The examiner then places one hand over the woman's lower anterior abdominal wall in order to ballot the uterus between the palpating hand and the transvaginal probe (which is held in the other hand), to assess whether the anterior bowel glides freely over the posterior aspect of the upper uterus/fundus. If it does so, the sliding sign is also considered positive in this region (Videoclip S1b). When the sliding sign is found to be positive in both of these anatomical regions (retrocervix and posterior uterine fundus), the POD is recorded as being not obliterated. If on TVS it is demonstrated that either the anterior rectal wall or the anterior sigmoid wall does not glide smoothly over the retrocervix or the posterior uterine fundus, respectively, i.e. at least one of the locations has a negative sliding sign, then the POD is recorded as obliterated31, 32. Demonstrating and describing the real-time ultrasound-based sliding sign in a retroverted uterus is different (Figure 2b). Gentle pressure is placed against the posterior upper uterine fundus with the transvaginal probe, to establish whether the anterior rectum glides freely across the posterior upper uterine fundus. If the anterior rectum does so, the sliding sign is considered to be positive for this location (Videoclip S2a). The examiner then places one hand over the woman's lower anterior abdominal wall in order to ballot the uterus between the palpating hand and transvaginal probe (which is held in the other hand), to assess whether the anterior sigmoid glides freely over the anterior lower uterine segment. If it does so, the sliding sign is also considered to be positive in this region (Videoclip S2b). As long as the sliding sign is found to be positive in both of these anatomical regions (i.e. the posterior uterine fundus and the anterior lower uterine segment), the POD is recorded as non-obliterated33. The fourth step is to search for DIE nodules in the anterior and posterior compartments. To assess the anterior compartment, the transducer is positioned in the anterior fornix of the vagina. If bladder endometriosis is suspected on the basis of symptoms, patients should be asked not to empty their bladder completely before the ultrasound examination. A slightly filled bladder facilitates evaluation of the walls of the bladder and detection and description of endometriotic nodules. Finally, the transducer is positioned in the posterior fornix of the vagina and slowly withdrawn through the vagina to allow visualization of the posterior compartment. Some authors advocate the use of bowel preparation on the evening before the pelvic scan and the use of a rectal enema within an hour before the ultrasound examination to eliminate fecal residue and gas in the rectosigmoid34-37. However, this is not mandatory, and there are no published prospective studies comparing TVS with and without bowel preparation for the diagnosis of bowel DIE. In a recent meta-analysis, TVS, either with or without bowel preparation, was found to be an accurate predictor of rectosigmoid DIE8. The anterior compartment includes the following anatomical locations: urinary bladder, uterovesical region and ureters. Bladder DIE occurs more frequently in the bladder base and bladder dome than in the extra-abdominal bladder (Videoclip S3)38. The bladder is best scanned if it contains a small amount of urine because this reduces false-negative findings. Although Savelli et al.38 described two zones (bladder base and dome), we propose dividing the bladder ultrasound assessment into four zones (Figure 3): (i) the trigonal zone, which lies within 3 cm of the urethral opening, is a smooth triangular region delimited by the two ureteral orifices and the internal urethral orifice (Figure S4a); (ii) the bladder base, which faces backward and downward and lies adjacent to both the vagina and the supravaginal cervix (Figure S4b); (iii) the bladder dome, which lies superior to the base and is intra-abdominal (Figure S4c); and (iv) the extra-abdominal bladder (Figure S4d). Figure S5 and Videoclip S3 demonstrate the most frequent location of endometriotic bladder nodules, i.e. the bladder base. On two-dimensional (2D) ultrasound the appearance of DIE in the anterior compartment can be varied, including hypoechoic linear or spherical lesions, with or without regular contours involving the muscularis (most common) or (sub)mucosa of the bladder6, 38-43. The dimensions of the bladder nodule should be measured in three orthogonal planes. Bladder DIE is diagnosed only if the muscularis of the bladder wall is affected; lesions involving only the serosa represent superficial disease. Obliteration of the uterovesical region can be evaluated using the sliding sign, i.e. the transvaginal probe is placed in the anterior fornix and the uterus is balloted between the probe and one hand of the operator placed over the suprapubic region. If the posterior bladder slides freely over the anterior uterine wall, then the sliding sign is positive and the uterovesical region is classified as non-obliterated (Videoclip S4). If the bladder does not slide freely over the anterior uterine wall, then the sliding sign is negative and the uterovesical region is classified as obliterated44 (Figure S6). Adhesions in the anterior pelvic compartment are present in nearly one third of women with a previous Cesarean section and are not necessarily a sign of pelvic endometriosis44. The distal ureters should be examined routinely using the transvaginal probe. The ureters can be found by identifying the urethra in the sagittal plane and moving the probe towards the lateral pelvic wall. The intravesical segment of the ureter is identified and its course followed to where it leaves the bladder and then further, to the pelvic side wall and up to the level of the bifurcation of the common iliac vessels. It is helpful to wait for peristalsis to occur as this confirms ureteric patency. Ureters typically appear as long tubular hypoechoic structures, with a thick hyperechoic mantle, extending from the lateral aspect of the bladder base towards the common iliac vessels. Dilatation of the ureter due to endometriosis is caused by stricture (from either extrinsic compression or intrinsic infiltration) and the distance from the distal ureteric orifice to the stricture should be measured (Figure S7)35, 45, 46. Thorough evaluation of the ureter at the time of surgery is important in all cases in which ureteral involvement is suspected. In all women with DIE, a transabdominal scan of the kidney to search for ureteral stenosis is necessary, because the prevalence of endometriotic lesions in the urinary tract may be underestimated and women with DIE involving the ureter may be asymptomatic47-51. The degree of hydronephrosis should be assessed and graded using generally accepted ultrasound criteria52. Women with evidence of hydronephrosis should be referred for urgent stenting of a stenosed ureter to prevent further loss of renal function. According to Chapron et al.53, the most common sites of DIE in the posterior compartment are: USLs, posterior vaginal fornix, anterior rectum/anterior rectosigmoid junction and sigmoid colon. Sonographic assessment of the posterior compartment should aim at identifying the number, size and anatomical location of DIE nodules affecting these structures. On TVS, posterior compartment DIE lesions appear as hypoechoic thickening of the wall of the bowel or vagina, or as hypoechoic solid nodules which may vary in size and have smooth or irregular contours54. Some studies have defined the TVS diagnosis of DIE in the RVS as absence of the normal appearance of the hyperechoic layer between the vagina and rectum due to the presence of a DIE nodule55. Other researchers have used the terms 'RVS DIE' and 'rectovaginal DIE (RV DIE)' interchangeably to describe DIE in the RVS55, 56. The RVS is an individual anatomical structure with a specific location, whereas RV DIE describes DIE located in the rectovaginal area. The rectovaginal area includes the vagina, the rectum and the RVS. Furthermore, there is inconsistency in the definition of RV DIE in the literature. RV DIE has been described as endometriotic lesions which infiltrate both the rectum and the posterior vaginal fornix with possible extension into the RVS55. Others have used the term 'rectovaginal endometriosis' to describe nodules which primarily infiltrate the RVS with possible extension into the vagina and/or rectum. Isolated RVS endometriosis is uncommon. We propose that involvement of the RVS should be suspected when a DIE nodule is seen on TVS in the rectovaginal space below the line passing along the lower border of the posterior lip of the cervix (under the peritoneum)39 (Figure 4). Isolated RVS DIE is rare (Figure 5); RVS DIE is usually an extension of posterior vaginal wall (Figure 6), anterior rectal wall (Figure 7) or both posterior vaginal wall and anterior rectal wall involvement57 (Figure 8). The use of sonovaginography improves the detection of posterior vaginal and RVS DIE54, 58. The dimensions of the RVS DIE nodule should be recorded in three orthogonal planes and the distance between the lower margin of the lesion and the anal verge should be measured. This should be done whether the DIE is only in the vagina or only in the rectum, or involves the vagina, RVS and rectum. Low RVS lesions, when managed surgically, are associated with severe complications, including fistulae56, 59-61. We propose that involvement of the posterior vaginal fornix and/or lateral vaginal fornix should be suspected when a DIE nodule is seen on TVS in the rectovaginal space below the line passing along the caudal end of the peritoneum of the lower margin of the rectouterine peritoneal pouch (cul-de-sac of Douglas) and above the line passing along the lower border of the posterior lip of the cervix (under the peritoneum) (seen in Figure 4). Posterior vaginal fornix or forniceal endometriosis is suspected if the posterior vaginal fornix is thickened or if a discrete nodule is found in the hypoechoic layer of the vaginal wall (Figure S8a). The hypoechoic nodule may be homogeneous or inhomogeneous with or without large cystic areas (Figure S8a) and there may or may not be cystic areas surrounding the nodule6, 39, 41, 42. Figure S8b is an ultrasound image demonstrating posterior vaginal fornix DIE. The dimensions of the vaginal wall DIE nodule should be measured in three orthogonal planes. Hourglass-shaped or 'diabolo'-like nodules occur when DIE lesions in the posterior vaginal fornix extend into the anterior rectal wall62 (Figure S9a). On ultrasound, the part of the DIE lesion situated in the anterior rectal wall is the same size as the part situated in the posterior vaginal fornix (Figure S9b). There is a small but easily visualized continuum between these two parts of the lesion. These lesions are located below the peritoneum of the POD and are usually large (3 cm on average)63. Normal USLs are usually not visible on ultrasound (Figure S10a). USL DIE lesions can be seen in the mid-sagittal view of the uterus (Figure S10b). However, these are best seen by placing the transvaginal probe in the posterior vaginal fornix in the midline in the sagittal plane and then sweeping the probe inferolaterally to the cervix. USLs are considered to be affected by DIE when a hypoechoic thickening with regular or irregular margins is seen within the peritoneal fat surrounding the USLs. The lesion may be isolated or may be part of a larger nodule extending into the vagina or into other surrounding structures. The thickness of a 'thickened' USL can be measured in the transverse plane at the insertion of the ligament on the cervix provided that the ligament can be distinguished clearly from adjacent structures (Figure S10c). In some cases the DIE lesion involving the USL is located at the torus uterinus (Figure S10d). If so, it is seen as a central thickening of the retrocervical area64. The dimensions of the USL DIE nodule should be recorded in three orthogonal planes. Bowel DIE classically involves the anterior rectum, rectosigmoid junction and/or sigmoid colon, all of which can be visualized using TVS. Figure S11a demonstrates a schematic drawing of a DIE lesion within the upper anterior rectum. Bowel DIE can take the form of an isolated lesion or can be multifocal (multiple lesions affecting the same segment) and/or multicentric (multiple lesions affecting several bowel segments, i.e. small bowel, large bowel, cecum, ileocecal junction and/or appendix)65. Although TVS can be used to visualize multifocal rectal DIE (Figure S11b), there are no published data assessing its performance. Computed tomographic colonography and magnetic resonance imaging (MRI) can be used to diagnose both multifocal and multicentric bowel endometriosis65. Histologically, bowel endometriosis is defined as the presence of endometrial glands and stroma in the bowel wall, reaching at least the muscularis propria66, where this invariably induces smooth-muscle hyperplasia and fibrosis. This results in thickening of the bowel wall and some narrowing of the bowel lumen. Normal rectal wall layers can be visualized on TVS: the anterior rectal serosa is seen as a thin hyperechoic line; the muscularis propria is hypoechoic, with the longitudinal smooth muscle (outer) and circular smooth muscle (inner) separated by a faint thin hyperechoic line; the submucosa is hyperechogenic; and the mucosa is hypoechoic37, 67 (Figure S12a). Bowel DIE usually appears on TVS as a thickening of the hypoechoic muscularis propria or as hypoechoic nodules, with or without hyperechoic foci (Figure S12b) with blurred margins. The morphological type of bowel lesion should be described according to Figure 9. Sonographically, bowel lesions are hypoechoic and in some cases a thinner section or a 'tail' is noted at one end, resembling a 'comet'68 (Figure 9b). The normal appearance of the muscularis propria of the rectum or rectosigmoid is replaced by a nodule of abnormal tissue with possible retraction and adhesions, resulting in the so-called 'Indian headdress' or 'moose antler' sign (Figure 9c,e,f)42; the size of these lesions can vary. We propose that bowel DIE lesions noted on TVS be described according to the segment of the rectum or sigmoid colon in which they occur, with DIE lesions located below the level of the insertion of the USLs on the cervix being denoted as lower (retroperitoneal) anterior rectal DIE lesions, those above this level being denoted as upper (visible at laparoscopy) anterior rectal DIE lesions, those at the level of the uterine fundus being denoted as rectosigmoid junction DIE lesions and those above the level of the uterine fundus being denoted as anterior sigmoid DIE lesions (Figure 10). The dimensions of the rectal and/or rectosigmoid DIE nodules should be recorded in three orthogonal planes and the distance between the lower margin of the most caudal lesion and the anal verge should be measured using TVS. Because bowel DIE may affect the bowel simultaneously at different sites, other bowel lesions should be looked for carefully when there is a DIE lesion affecting the rectum (Figure S12b) or rectosigmoid. Preliminary data showed that rectal DIE lesions may be associated with a second intestinal lesion in 54.6% of cases34. Ultrasound diagnosis of POD obliteration31, 32 has been explained extensively earlier in this article. The obliteration can be graded as partial or complete depending on whether one side (left or right) or both sides, respectively, demonstrate a negative sliding sign. Furthermore, an experienced operator can identify the level of POD obliteration, i.e. specifying, in an anteverted uterus, whether it is at the retrocervical level (lower third of the uterus), mid-posterior uterus (middle third) and/or posterior uterine fundus (upper third)69 and, in a retroverted uterus, whether it is at the posterior uterine fundus, mid-anterior uterus and/or lower anterior uterine wall33(Figure S13). We propose that each endometrioma and DIE lesion should be measured systematically in three orthogonal planes, to obtain the length (mid-sagittal measurement), thickness (anteroposterior measurement) and transverse diameter (Figure 11). This approach of measuring in three planes applies to DIE lesions located in the bladder, RVS, vagina, USLs, anterior rectum and rectosigmoid. Additionally, in cases of endometriosis in the ureters, it is important to measure the distance between the distal ureteric orifice and a DIE lesion which causes a ureteric stricture; the stricture can be caused by either extrinsic compression or intrinsic infiltration. Once the stricture is identified along the longitudinal course of the ureter, one caliper should be placed at this level and the other at the distal ureteric orifice for measurement (Figure S7). In cases of multifocal bowel DIE lesions the total mid-sagittal length of the bowel segment involved, from caudal to cephalic aspect, should be measured (Figure 12). It is important to be aware that the retraction within rectosigmoid DIE lesions can result in an overestimation of the true thickness of the lesion and an underestimation of the true length of the lesion (Figure S14). This has been described as the 'mushroom cap' sign on MRI and can also be noted on TVS70. In cases of DIE lesions in the bowel or RVS, it is important to measure the distance between the anal verge and the lesion (Figure S15). It is possible to measure the distance from the anus to the bowel lesion using transrectal so

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Endometriosis: Epidemiology, Diagnosis and Clinical Management

2017-01-27

Parveen Parasar , Pınar Özcan , Kathryn L. Terry

Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium

2017-04-10

Margherita Y. Turco , Lucy Gardner , Jasmine Hughes +7 more

Revised American Society for Reproductive Medicine classification of endometriosis: 1996

1997-05-01

American Society for Reproductive Medicine

Risk for and consequences of endometriosis: A critical epidemiologic review

2018-07-03

Amy L. Shafrir , Leslie V. Farland , D.K. Shah +4 more

Endometriosis affects approximately 10% of women of reproductive age. Characteristics robustly associated with a greater risk for endometriosis include early age at menarche, short menstrual cycle length, and lean body … Endometriosis affects approximately 10% of women of reproductive age. Characteristics robustly associated with a greater risk for endometriosis include early age at menarche, short menstrual cycle length, and lean body size, whereas greater parity has been associated with a lower risk. Relationships with other potential characteristics including physical activity, dietary factors, and lactation have been less consistent, partially because of the need for rigorous data collection and a longitudinal study design. Critical methodologic complexities include the need for a clear case definition; valid selection of comparison/control groups; and consideration of diagnostic bias and reverse causation when exploring demographic characteristics, medical history, and lifestyle factors. Reviewers and editors must demand a detailed description of rigorous methods to facilitate comparison and replication to advance our understanding of endometriosis.

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Clinical diagnosis of endometriosis: a call to action

2019-01-06

Sanjay K. Agarwal , Charles Chapron , Linda C. Giudice +5 more

Endometriosis can have a profound impact on women's lives, including associated pain, infertility, decreased quality of life, and interference with daily life, relationships, and livelihood. The first step in alleviating … Endometriosis can have a profound impact on women's lives, including associated pain, infertility, decreased quality of life, and interference with daily life, relationships, and livelihood. The first step in alleviating these adverse sequelae is to diagnose the underlying condition. For many women, the journey to endometriosis diagnosis is long and fraught with barriers and misdiagnoses. Inherent challenges include a gold standard based on an invasive surgical procedure (laparoscopy) and diverse symptomatology, contributing to the well-established delay of 4–11 years from first symptom onset to surgical diagnosis. We believe that remedying the diagnostic delay requires increased patient education and timely referral to a women's healthcare provider and a shift in physician approach to the disorder. Endometriosis should be approached as a chronic, systemic, inflammatory, and heterogeneous disease that presents with symptoms of pelvic pain and/or infertility, rather than focusing primarily on surgical findings and pelvic lesions. Using this approach, symptoms, signs, and clinical findings of endometriosis are anticipated to become the main drivers of clinical diagnosis and earlier intervention. Combining these factors into a practical algorithm is expected to simplify endometriosis diagnosis and make the process accessible to more clinicians and patients, culminating in earlier effective management. The time has come to bridge disparities and to minimize delays in endometriosis diagnosis and treatment for the benefit of women worldwide. Endometriosis can have a profound impact on women's lives, including associated pain, infertility, decreased quality of life, and interference with daily life, relationships, and livelihood. The first step in alleviating these adverse sequelae is to diagnose the underlying condition. For many women, the journey to endometriosis diagnosis is long and fraught with barriers and misdiagnoses. Inherent challenges include a gold standard based on an invasive surgical procedure (laparoscopy) and diverse symptomatology, contributing to the well-established delay of 4–11 years from first symptom onset to surgical diagnosis. We believe that remedying the diagnostic delay requires increased patient education and timely referral to a women's healthcare provider and a shift in physician approach to the disorder. Endometriosis should be approached as a chronic, systemic, inflammatory, and heterogeneous disease that presents with symptoms of pelvic pain and/or infertility, rather than focusing primarily on surgical findings and pelvic lesions. Using this approach, symptoms, signs, and clinical findings of endometriosis are anticipated to become the main drivers of clinical diagnosis and earlier intervention. Combining these factors into a practical algorithm is expected to simplify endometriosis diagnosis and make the process accessible to more clinicians and patients, culminating in earlier effective management. The time has come to bridge disparities and to minimize delays in endometriosis diagnosis and treatment for the benefit of women worldwide. THE PROBLEM: Endometriosis is undiagnosed in a large proportion of affected women, resulting in ongoing and progressive symptoms with associated negative impacts on health and well-being. Current practice standards, which rely primarily on laparoscopy for a definitive diagnosis before beginning therapy, frequently result in prolonged delay between symptom onset, diagnosis, and subsequent treatment.A SOLUTION: Enhanced use of clinical diagnostic techniques may reduce the delay in time to diagnosis and hence bring more rapid relief to affected patients, limit disease progression, and prevent sequelae. THE PROBLEM: Endometriosis is undiagnosed in a large proportion of affected women, resulting in ongoing and progressive symptoms with associated negative impacts on health and well-being. Current practice standards, which rely primarily on laparoscopy for a definitive diagnosis before beginning therapy, frequently result in prolonged delay between symptom onset, diagnosis, and subsequent treatment. A SOLUTION: Enhanced use of clinical diagnostic techniques may reduce the delay in time to diagnosis and hence bring more rapid relief to affected patients, limit disease progression, and prevent sequelae. Endometriosis has such wide-ranging and pervasive sequelae that it has been described as "nothing short of a public health emergency" requiring immediate action.1Hatch O. This is nothing short of a public health emergency. CNN.March 28, 2018https://www.cnn.com/2018/03/27/opinions/endometriosis-start-a-conversation-hatch-opinion/index.htmlDate accessed: April 14, 2018Google Scholar Population-based data suggest that more than 4 million reproductive-age women have diagnosed endometriosis in the United States.2Fuldeore M.J. Soliman A.M. Prevalence and symptomatic burden of diagnosed endometriosis in the United States: national estimates from a cross-sectional survey of 59,411 women.Gynecol Obstet Invest. 2017; 82: 453-461Crossref PubMed Scopus (142) Google Scholar As daunting as this number is, it only tells part of the story, as an estimated 6 of 10 endometriosis cases are undiagnosed.3Morassutto C. Monasta L. Ricci G. Barbone F. Ronfani L. Incidence and estimated prevalence of endometriosis and adenomyosis in northeast Italy: a data linkage study.PLoS One. 2016; 11: e0154227Crossref PubMed Scopus (91) Google Scholar Thus more than 6 million American women may experience repercussions of endometriosis without the benefit of understanding the cause of their symptoms or appropriate management. When discussing the patient's experience with endometriosis, pain and infertility are usually of greatest concern, as they are 2 of the disease's more common symptoms. However, the real toll is even greater: women with endometriosis experience diminished quality of life, increased incidence of depression, adverse effects on intimate relationships, limitations on participation in daily activities, reduced social activity, loss of productivity and associated income, increased risk of chronic disease, and significant direct and indirect healthcare costs.4Culley L. Law C. Hudson N. et al.The social and psychological impact of endometriosis on women's lives: a critical narrative review.Hum Reprod Update. 2013; 19: 625-639Crossref PubMed Scopus (336) Google Scholar, 5Moradi M. Parker M. Sneddon A. Lopez V. Ellwood D. Impact of endometriosis on women's lives: a qualitative study.BMC Womens Health. 2014; 14: 123Crossref PubMed Scopus (209) Google Scholar, 6Kvaskoff M. Mu F. Terry K.L. et al.Endometriosis: a high-risk population for major chronic diseases?.Hum Reprod Update. 2015; 21: 500-516Crossref PubMed Scopus (217) Google Scholar, 7Soliman A.M. Coyne K.S. Gries K.S. Castelli-Haley J. Snabes M.C. Surrey E.S. The effect of endometriosis symptoms on absenteeism and presenteeism in the workplace and at home.J Manag Care Spec Pharm. 2017; 23: 745-754Crossref PubMed Scopus (80) Google Scholar, 8Soliman A.M. Surrey E. Bonafede M. Nelson J.K. Castelli-Haley J. Real-world evaluation of direct and indirect economic burden among endometriosis patients in the United States.Adv Ther. 2018; 35: 408-423Crossref PubMed Scopus (64) Google Scholar Moreover, emerging data indicate that endometriosis is associated with greater risk of obstetric and neonatal complications.9Harada T. Taniguchi F. Onishi K. et al.Obstetrical complications in women with endometriosis: a cohort study in Japan.PLoS One. 2016; 11: e0168476Crossref PubMed Scopus (48) Google Scholar, 10Berlac J.F. Hartwell D. Skovlund C.W. Langhoff-Roos J. Lidegaard O. Endometriosis increases the risk of obstetrical and neonatal complications.Acta Obstet Gynecol Scand. 2017; 96: 751-760Crossref PubMed Scopus (64) Google Scholar, 11Zullo F. Spagnolo E. Saccone G. et al.Endometriosis and obstetrics complications: a systematic review and meta-analysis.Fertil Steril. 2017; 108: 667-672Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar, 12Chen I. Lalani S. Xie R.H. Shen M. Singh S.S. Wen S.W. Association between surgically diagnosed endometriosis and adverse pregnancy outcomes.Fertil Steril. 2018; 109: 142-147Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar There are no pathognomonic features or biomarkers necessary and sufficient to define endometriosis. Rather, key symptoms that currently prompt surgical evaluation, such as pain and infertility, can have multiple causes. Endometriosis is typically defined by its histology: extrauterine lesions consisting of endometrial glands, endometrial stroma, and/or hemosiderin-laden macrophages. Based on location and depth, lesions are further described as superficial peritoneal lesions, ovarian endometrioma, or deep endometriosis. However, the presence of lesions does not preclude other etiologies for the patient's symptoms, and the lack of obvious lesions does not eliminate the possibility of endometriosis. Furthermore, there is poor correlation between symptoms and severity or extent of disease, as quantified by current staging systems.13Johnson N.P. Hummelshoj L. Adamson G.D. et al.World Endometriosis Society consensus on the classification of endometriosis.Hum Reprod. 2017; 32: 315-324Crossref PubMed Scopus (309) Google Scholar From a clinical perspective, endometriosis may be better defined as a menstrual cycle−dependent, chronic, inflammatory, systemic disease that commonly presents as pelvic pain. Moving from a histological to a clinical definition opens the door to a different approach to diagnosis, one that emphasizes symptoms and their origins over lesion presence or absence, and that may, in the future, be validated by specific, noninvasive disease biomarkers. Among those who ultimately receive a successful definitive diagnosis, contemporary literature describes delays from symptom onset to diagnosis ranging from 4 to 11 years.5Moradi M. Parker M. Sneddon A. Lopez V. Ellwood D. Impact of endometriosis on women's lives: a qualitative study.BMC Womens Health. 2014; 14: 123Crossref PubMed Scopus (209) Google Scholar, 14Nnoaham K.E. Hummelshoj L. Webster P. et al.Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries.Fertil Steril. 2011; 96: 366-373Abstract Full Text Full Text PDF PubMed Scopus (779) Google Scholar, 15Hudelist G. Fritzer N. Thomas A. et al.Diagnostic delay for endometriosis in Austria and Germany: causes and possible consequences.Hum Reprod. 2012; 27: 3412-3416Crossref PubMed Scopus (242) Google Scholar, 16Fourquet J. Sinaii N. Stratton P. et al.Characteristics of women with endometriosis from the USA and Puerto Rico.J Endometr Pelvic Pain Disord. 2015; 7: 129-135Crossref PubMed Scopus (12) Google Scholar, 17Staal A.H. Van Der Zanden M. Nap A.W. Diagnostic delay of endometriosis in the Netherlands.Gynecol Obstet Invest. 2016; 81: 321-324Crossref PubMed Scopus (70) Google Scholar, 18Soliman A.M. Fuldeore M. Snabes M.C. Factors associated with time to endometriosis diagnosis in the United States.J Womens Health (Larchmt). 2017; 26: 788-797Crossref PubMed Scopus (54) Google Scholar Several factors exacerbate this delay,14Nnoaham K.E. Hummelshoj L. Webster P. et al.Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries.Fertil Steril. 2011; 96: 366-373Abstract Full Text Full Text PDF PubMed Scopus (779) Google Scholar, 15Hudelist G. Fritzer N. Thomas A. et al.Diagnostic delay for endometriosis in Austria and Germany: causes and possible consequences.Hum Reprod. 2012; 27: 3412-3416Crossref PubMed Scopus (242) Google Scholar, 17Staal A.H. Van Der Zanden M. Nap A.W. Diagnostic delay of endometriosis in the Netherlands.Gynecol Obstet Invest. 2016; 81: 321-324Crossref PubMed Scopus (70) Google Scholar, 18Soliman A.M. Fuldeore M. Snabes M.C. Factors associated with time to endometriosis diagnosis in the United States.J Womens Health (Larchmt). 2017; 26: 788-797Crossref PubMed Scopus (54) Google Scholar including "normalization" of symptoms and misdiagnosis.15Hudelist G. Fritzer N. Thomas A. et al.Diagnostic delay for endometriosis in Austria and Germany: causes and possible consequences.Hum Reprod. 2012; 27: 3412-3416Crossref PubMed Scopus (242) Google Scholar The presence of diagnostic delays is a worldwide phenomenon, occurring even in countries with universal healthcare.15Hudelist G. Fritzer N. Thomas A. et al.Diagnostic delay for endometriosis in Austria and Germany: causes and possible consequences.Hum Reprod. 2012; 27: 3412-3416Crossref PubMed Scopus (242) Google Scholar, 17Staal A.H. Van Der Zanden M. Nap A.W. Diagnostic delay of endometriosis in the Netherlands.Gynecol Obstet Invest. 2016; 81: 321-324Crossref PubMed Scopus (70) Google Scholar Consequences of the delay in diagnosis are experienced by patients in multiple ways, including persistent symptoms and a commensurate detrimental impact on quality of life,14Nnoaham K.E. Hummelshoj L. Webster P. et al.Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries.Fertil Steril. 2011; 96: 366-373Abstract Full Text Full Text PDF PubMed Scopus (779) Google Scholar erosion of the patient−physician relationship,4Culley L. Law C. Hudson N. et al.The social and psychological impact of endometriosis on women's lives: a critical narrative review.Hum Reprod Update. 2013; 19: 625-639Crossref PubMed Scopus (336) Google Scholar, 5Moradi M. Parker M. Sneddon A. Lopez V. Ellwood D. Impact of endometriosis on women's lives: a qualitative study.BMC Womens Health. 2014; 14: 123Crossref PubMed Scopus (209) Google Scholar and development of central sensitization—a mechanism whereby persistent endometriosis-associated pain increases pain awareness, even at sites unconnected anatomically with the lesion(s).14Nnoaham K.E. Hummelshoj L. Webster P. et al.Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries.Fertil Steril. 2011; 96: 366-373Abstract Full Text Full Text PDF PubMed Scopus (779) Google Scholar, 19Issa B. Onon T.S. Agrawal A. et al.Visceral hypersensitivity in endometriosis: a new target for treatment?.Gut. 2012; 61: 367-372Crossref PubMed Scopus (59) Google Scholar, 20As-Sanie S. Harris R.E. Harte S.E. Tu F.F. Neshewat G. Clauw D.J. Increased pressure pain sensitivity in women with chronic pelvic pain.Obstet Gynecol. 2013; 122: 1047-1055Crossref PubMed Scopus (87) Google Scholar, 21Li T. Mamillapalli R. Ding S. et al.Endometriosis alters brain electro-physiology, gene expression and increased pain sensitization, anxiety, and depression in female mice.Biol Reprod. 2018; 99: 349-359Crossref PubMed Scopus (44) Google Scholar Moreover, although the evidence is limited, failure of timely diagnosis and adequate endometriosis management may foster disease progression and adhesion formation that may compromise fertility and increase the risk of central sensitization and chronic pelvic pain.22Unger C.A. Laufer M.R. Progression of endometriosis in non-medically managed adolescents: a case series.J Pediatr Adolesc Gynecol. 2011; 24: e21-e23Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 23Brosens I. Gordts S. Benagiano G. Endometriosis in adolescents is a hidden, progressive and severe disease that deserves attention, not just compassion.Hum Reprod. 2013; 28: 2026-2031Crossref PubMed Scopus (101) Google Scholar, 24Coxon L. Horne A.W. Vincent K. Pathophysiology of endometriosis-associated pain: a review of pelvic and central nervous system mechanisms.Best Pract Res Clin Obstet Gynaecol. 2018; 51: 53-67Crossref PubMed Scopus (65) Google Scholar The current diagnostic paradigm, endorsed by professional societies, requires laparoscopy with or without histologic verification as the gold standard, although many societies endorse the treatment of symptoms before obtaining a definitive surgical diagnosis.25Practice bulletin no. 114: management of endometriosis.Obstet Gynecol. 2010; 116: 223-236Crossref PubMed Scopus (226) Google Scholar, 26Leyland N. Casper R. Laberge P. Singh S.S. Society of Obstetricians and Gynaecologists of Canada Endometriosis: diagnosis and management.J Obstet Gynaecol Can. 2010; 32: S1-S32Abstract Full Text PDF PubMed Scopus (244) Google Scholar, 27Johnson N.P. Hummelshoj L. World Endometriosis Society Montpellier ConsortiumConsensus on current management of endometriosis.Hum Reprod. 2013; 28: 1552-1568Crossref PubMed Scopus (371) Google Scholar, 28Practice Committee of the American Society for Reproductive Medicine Treatment of pelvic pain associated with endometriosis: a committee opinion.Fertil Steril. 2014; 101: 927-935Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar, 29Dunselman G.A. Vermeulen N. Becker C. et al.ESHRE guideline: management of women with endometriosis.Hum Reprod. 2014; 29: 400-412Crossref PubMed Scopus (1417) Google Scholar Notably, the 2017 National Institute for Health and Care Excellence guidelines reflect a philosophical shift, presenting empiric therapy prior to laparoscopy in the diagnostic and treatment algorithm unless fertility is a priority.30National Institute for Health and Care ExcellenceEndometriosis: diagnosis and management (NG73). London, United Kingdom; 2017.http://nice.org.uk/guidance/ng73Date accessed: May 18, 2018Google Scholar Although the merits of laparoscopy and its role in disease management should not be minimized, its accuracy, risks, and cost-effectiveness warrant reevaluation. The poor correlation between reported symptoms and extent of disease found at laparoscopy further illustrates the limitations of surgical disease assessment.31Vercellini P. Fedele L. Aimi G. Pietropaolo G. Consonni D. Crosignani P.G. Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients.Hum Reprod. 2007; 22: 266-271Crossref PubMed Scopus (327) Google Scholar Detecting endometriosis via laparoscopy relies on the visual identification of lesions, a practice that is challenged by heterogeneous lesion appearance,32Albee Jr., R.B. Sinervo K. Fisher D.T. Laparoscopic excision of lesions suggestive of endometriosis or otherwise atypical in appearance: relationship between visual findings and final histologic diagnosis.J Minim Invasive Gynecol. 2008; 15: 32-37Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar inaccessible lesion location (particularly for deep lesions),33Singh S.S. Suen M.W. Surgery for endometriosis: beyond medical therapies.Fertil Steril. 2017; 107: 549-554Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar and interobserver variability.34Schliep K.C. Chen Z. Stanford J.B. et al.Endometriosis diagnosis and staging by operating surgeon and expert review using multiple diagnostic tools: an inter-rater agreement study.Br J Obstet Gynecol. 2017; 124: 220-229Crossref Scopus (20) Google Scholar Surgical risks associated with laparoscopy are generally low,33Singh S.S. Suen M.W. Surgery for endometriosis: beyond medical therapies.Fertil Steril. 2017; 107: 549-554Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar, 35Surrey E.S. Soliman A.M. Yang H. Du E.X. Su B. Treatment patterns, complications, and health care utilization among endometriosis patients undergoing a laparoscopy or a hysterectomy: a retrospective claims analysis.Adv Ther. 2017; 34: 2436-2451Crossref PubMed Scopus (18) Google Scholar although they merit consideration, given the potential for major (albeit rare) complications36Chapron C. Fauconnier A. Goffinet F. Breart G. Dubuisson J.B. Laparoscopic surgery is not inherently dangerous for patients presenting with benign gynaecologic pathology. Results of a meta-analysis.Hum Reprod. 2002; 17: 1334-1342Crossref PubMed Scopus (168) Google Scholar and the need for re-treatment after initial laparoscopy because there is no surgical cure for endometriosis.37Soliman A.M. Du E.X. Yang H. Wu E.Q. Haley J.C. Retreatment rates among endometriosis patients undergoing hysterectomy or laparoscopy.J Womens Health (Larchmt). 2017; 26: 644-654Crossref PubMed Scopus (15) Google Scholar From a pragmatic perspective, evaluation of laparoscopy for endometriosis diagnosis and management must include a discussion of costs, which are substantially higher compared with nonsurgical approaches.38Soliman A.M. Taylor H.S. Bonafede M. Nelson J.K. Castelli-Haley J. Incremental direct and indirect cost burden attributed to endometriosis surgeries in the United States.Fertil Steril. 2017; 107: 1181-1190Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar Reliance on laparoscopy for endometriosis diagnosis supports the viewpoint that the presence of identifiable lesions in the pelvis is the central tenet of endometriosis, rather than approaching endometriosis as a menstrual cycle−dependent, chronic, inflammatory, systemic disease that often presents as pelvic pain. By shifting the paradigm to the patient rather than the lesion, the path to clinical diagnosis has the potential to be more inclusive with reduced diagnostic delay. Indeed, Soliman et al18Soliman A.M. Fuldeore M. Snabes M.C. Factors associated with time to endometriosis diagnosis in the United States.J Womens Health (Larchmt). 2017; 26: 788-797Crossref PubMed Scopus (54) Google Scholar reported diagnosing endometriosis by nonsurgical methods shortened the mean time from first consultation to diagnosis compared with surgical diagnosis. This shift, however, requires clinical diagnostic methodologies that accurately identify endometriosis. To that end, we have compiled data on the accuracy of clinical assessments for diagnosing endometriosis (Table 1). Notably, these studies were highly heterogeneous, which precluded performance of a meaningful meta-analysis.Table 1Predictive value of signs, symptoms, and clinical findings for diagnosing endometriosisStudy design and populationMethod of diagnosisAssessment or parameterResultsEndometriosis (general)Saha 201747Saha R. Marions L. Tornvall P. Validity of self-reported endometriosis and endometriosis-related questions in a Swedish female twin cohort.Fertil Steril. 2017; 107: 174-178Abstract Full Text Full Text PDF PubMed Scopus (19) Google ScholaraReported are the agreement between self-reported symptoms of endometriosis and diagnosis of endometriosis recorded in medical recordsCross-sectional survey of a Swedish twin cohort (N = 26,898)Endometriosis diagnosis listed in electronic medical recordSevere dysmenorrheaSensitivity, 58%; specificity, 70%Chronic pelvic painSensitivity, 25%; specificity, 89%DyspareuniaSensitivity, 16%; specificity, 96%InfertilitySensitivity, 28%; specificity, 93%Oral pill as contraceptiveSensitivity, 16%; specificity, 80%Fuldeore 20172Fuldeore M.J. Soliman A.M. Prevalence and symptomatic burden of diagnosed endometriosis in the United States: national estimates from a cross-sectional survey of 59,411 women.Gynecol Obstet Invest. 2017; 82: 453-461Crossref PubMed Scopus (142) Google ScholarRespondents to an online, cross-sectional survey (N = 48,020)Self-report (replying in the affirmative that a doctor had previously told the subject that she has or is suspected of having endometriosis)Menstrual pelvic pain/crampingOR, 1.6 (95% CI, 1.4–1.8)Nonmenstrual pelvic pain/crampingOR, 4.1 (95% CI, 3.6–4.6)DyspareuniaOR, 3.1 (95% CI, 2.8–3.5)Heavy menstrual bleedingOR, 1.5 (95% CI, 1.3–1.7)Excessive or irregular bleedingOR, 2.1 (95% CI, 1.8–2.4)Passage of clotsOR, 1.8 (95% CI, 1.6–2.0)Irregular menstrual periods (timing/duration)OR, 1.5 (95% CI, 1.3–1.7)Constipation/bloating/diarrheaOR, 1.9 (95% CI, 1.7–2.2)Fatigue/weariness/anemiaOR, 2.2 (95% CI, 2.0–2.5)InfertilityOR, 3.6 (95% CI, 3.0–4.4)Ashrafi 201650Ashrafi M. Sadatmahalleh S.J. Akhoond M.R. Talebi M. Evaluation of risk factors associated with endometriosis in infertile women.Int J Fertil Steril. 2016; 10: 11-21PubMed Google ScholarRetrospective case-control study involving women who underwent laparoscopy for infertility evaluation (341 with endometriosis; 332 with a normal pelvis)Laparoscopically visualized endometriosisFamily history of endometriosisOR, 2.7 (95% CI, 1.06–7.1)History of galactorrheaOR, 1.8 (95% CI, 1.1–3.05)History of pelvic surgeryOR, 14.5 (95% CI, 6.1–34.2)DysmenorrheaOR, 1.8 (95% CI, 1.1–2.8)Pelvic painOR, 4.1 (95% CI, 2.4–6.8)DyspareuniaOR, 1.6 (95% CI, 1.09–2.4)Premenstrual spottingOR, 2.2 (95% CI, 1.3–3.6)FatigueOR, 2.6 (95% CI, 1.3–5.1)Apostolopoulos 201664Apostolopoulos N.V. Alexandraki K.I. Gorry A. Coker A. Association between chronic pelvic pain symptoms and the presence of endometriosis.Arch Gynecol Obstet. 2016; 293: 439-445Crossref PubMed Scopus (32) Google ScholarProspective, observational study of women who underwent laparoscopy for chronic pelvic pain (N = 144)Laparoscopically visualized endometriosisNoncyclical painEndometriosis, 62.5%; no endometriosis, 70.8%; p = 0.48DysmenorrheaEndometriosis, 79.1%; no endometriosis, 87.5%; p = 0.37DyspareuniaEndometriosis, 25.0%; no endometriosis, 33.3%; p = 0.46DyscheziaEndometriosis, 25.0%; no endometriosis, 20.8%; p = 0.69Schliep 201540Schliep K.C. Mumford S.L. Peterson C.M. et al.Pain typology and incident endometriosis.Hum Reprod. 2015; 30: 2427-2438Crossref PubMed Scopus (82) Google ScholarOperative cohort from the ENDO study—women without a history of surgically confirmed endometriosis who underwent laparoscopy or laparotomy (N = 473)Surgically visualized endometriosisChronic pelvic painEndometriosis, 44.2%; other, 39.0%; normal pelvis, 30.2%; p = 0.04Cyclic pelvic painEndometriosis, 49.5%; other, 31.0%; normal pelvis, 33.1%; p < 0.001Vaginal pain with intercourseEndometriosis, 54.7%; other, 41.5%; normal pelvis, 32.4%; p < 0.001Deep pain with intercourseEndometriosis, 53.2%; other, 38.1%; normal pelvis, 30.9%; p < 0.001Burning vaginal pain after intercourseEndometriosis, 33.2%; other, 22.5%; normal pelvis, 22.1%; p = 0.03Pain just before menstrual periodEndometriosis, 75.3%; other, 61.9%; normal pelvis, 66.2%; p = 0.03Level of cramps with periodEndometriosis, 91.1%; other, 85.0%; normal pelvis, 79.4%; p = 0.01Pain after period is overEndometriosis, 38.4%; other, 26.5%; normal pelvis, 38.2%; p = 0.04Pain at ovulation (mid-cycle)Endometriosis, 67.4%; other, 49.0%; normal pelvis, 52.2%; p = 0.001DysuriaEndometriosis, 22.6%; other, 19.1%; normal pelvis, 11.0%; p = 0.03DyscheziaEndometriosis, 44.2%; other, 32.7%; normal pelvis, 25.7%; p = 0.002Heitman 201448Heitmann R.J. Langan K.L. Huang R.R. Chow G.E. Burney R.O. Premenstrual spotting of ≥2 days is strongly associated with histologically confirmed endometriosis in women with infertility.Am J Obstet Gynecol. 2014; 211: 358Abstract Full Text Full Text PDF PubMed Scopus (13) Google ScholarRetrospective cohort of consecutive women with or without pelvic pain who were evaluated for infertility (N = 80)Histologically verified endometriosisPremenstrual spotting for ≥2 daysSensitivity, 76%; specificity, 90%; PPV, 96%; NPV, 74%; accuracy, 81%DysmenorrheaSensitivity, 87%; specificity, 63%; PPV, 75%; NPV, 79%; accuracy, 76%DyspareuniaSensitivity, 38%; specificity, 83%; PPV, 74%; NPV, 51%; accuracy, 58%Peterson 201341Peterson C.M. Johnstone E.B. Hammoud A.O. et al.Risk factors associated with endometriosis: importance of study population for characterizing disease in the ENDO Study.Am J Obstet Gynecol. 2013; 208: 451Abstract Full Text Full Text PDF PubMed Scopus (77) Google ScholarbData are adjusted odds ratiosENDO Study—Prospective, matched-exposure cohort study comprising women undergoing pelvic surgery (n = 495) and a matched cohort (n = 131)Surgically visualized endometriosis (operative cohort)Pelvic MRI-diagnosed endometriosis (matched cohort)History of infertilityOR, 2.43 (95% CI, 1.57–3.76) [operative]; 7.91 (1.69–37.2) [matched]DysmenorrheaOR, 2.46 (95% CI, 1.28–4.72) [operative]; 1.41 (0.28–7.14) [matched]Pelvic painOR, 1.39 (95% CI, 0.95–2.04) [operative]; 0.76 (0.09–6.54) [matched]Pelvic pain (surgical indication)OR, 3.67 (95% CI, 2.44–5.50) [operative]Nnoaham 201243Nnoaham K.E. Hummelshoj L. Kennedy S.H. Jenkinson C. Zondervan K.T. World Endometriosis Research Foundation Women's Health Symptom Survey ConsortiumDeveloping symptom-based predictive models of endometriosis as a clinical screening tool: results from a multicenter study.Fertil Steril. 2012; 98: 692-701Abstract Full Text Full Text PDF PubMed Scopus (74) Google ScholarProspective, observational study of symptomatic women with scheduled laparoscopy (N = 1396)Laparoscopically visualized endometriosisModel comprising multiple factors (eg, dysmenorrhea, dyschezia, nonmenstrual pelvic pain, ovarian cyst, family history, race, etc)Sensitivity, 85%; specificity, 44%Model and ultrasoundSensitivity, 58%; specificity, 89%Paulson 201154Paulson J.D. Paulson J.N. Anterior vaginal wall tenderness (AVWT) as a physical symptom in chronic pelvic pain.JSLS. 2011; 15: 6-9Crossref PubMed Scopus (8) Google ScholarProspective cohort of women with chronic pelvic pain (N = 284)Laparoscopically or histologically confirmed endometriosisAnterior vaginal wall tenderness (endometriosis and other pathology)Sensitivity, 93%Anterior vaginal wall tenderness (endometriosis only)Sensitivity, 17%Droz 201165Droz J. Howard F.M. Use of the Short-Form McGill Pain Questionnaire as a diagnostic tool in women with chronic pelvic pain.J Minim Invasive Gynecol. 2011; 18: 211-217Abstract Full Text Full Text PDF PubMed Scopus (24) Google ScholarRetrospective cohort of women evaluated for chronic pelvic pain (N = 331)Histologically verified endometriosisShort-form MPQ pain descriptor:CrampingSensitivity, 92%; specificity, 33%; PPV, 40%, NPV, 89%SickeningSensitivity, 73%; specificity, 46%; PPV, 40%; NPV, 78%Tiring/exhaustingSensitivity, 77%; specificity, 38%; PPV

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Rethinking mechanisms, diagnosis and management of endometriosis

2019-09-05

Charles Chapron , Louis Marcellin , Bruno Borghese +1 more

Endometriosis is a chronic systemic disease: clinical challenges and novel innovations

2021-02-01

Hugh S. Taylor , Alexander Kotlyar , Valerie A. Flores

Endometriosis: Etiology, pathobiology, and therapeutic prospects

2021-05-01

Philippa T. K. Saunders , Andrew W. Horne

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Endometriosis

2019-04-17

Serdar E. Bulun , Bahar D. Yilmaz , Christia Sison +7 more

Abstract Pelvic endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects primarily pelvic tissues, including the ovaries. It is caused when shed endometrial tissue travels … Abstract Pelvic endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects primarily pelvic tissues, including the ovaries. It is caused when shed endometrial tissue travels retrograde into the lower abdominal cavity. Endometriosis is the most common cause of chronic pelvic pain in women and is associated with infertility. The underlying pathologic mechanisms in the intracavitary endometrium and extrauterine endometriotic tissue involve defectively programmed endometrial mesenchymal progenitor/stem cells. Although endometriotic stromal cells, which compose the bulk of endometriotic lesions, do not carry somatic mutations, they demonstrate specific epigenetic abnormalities that alter expression of key transcription factors. For example, GATA-binding factor-6 overexpression transforms an endometrial stromal cell to an endometriotic phenotype, and steroidogenic factor-1 overexpression causes excessive production of estrogen, which drives inflammation via pathologically high levels of estrogen receptor-β. Progesterone receptor deficiency causes progesterone resistance. Populations of endometrial and endometriotic epithelial cells also harbor multiple cancer driver mutations, such as KRAS, which may be associated with the establishment of pelvic endometriosis or ovarian cancer. It is not known how interactions between epigenomically defective stromal cells and the mutated genes in epithelial cells contribute to the pathogenesis of endometriosis. Endometriosis-associated pelvic pain is managed by suppression of ovulatory menses and estrogen production, cyclooxygenase inhibitors, and surgical removal of pelvic lesions, and in vitro fertilization is frequently used to overcome infertility. Although novel targeted treatments are becoming available, as endometriosis pathophysiology is better understood, preventive approaches such as long-term ovulation suppression may play a critical role in the future.

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Endometriosis

2004-11-01

Linda C. Giudice , L.C. Kao

Endometriosis

2018-07-19

Krina T. Zondervan , Christian M. Becker , Kaori Koga +3 more

ESHRE guideline: endometriosis

2022-01-01

Christian M. Becker , Attila Bokor , Oskari Heikinheimo +7 more

How should endometriosis be diagnosed and managed based on the best available evidence from published literature?The current guideline provides 109 recommendations on diagnosis, treatments for pain and infertility, management of … How should endometriosis be diagnosed and managed based on the best available evidence from published literature?The current guideline provides 109 recommendations on diagnosis, treatments for pain and infertility, management of disease recurrence, asymptomatic or extrapelvic disease, endometriosis in adolescents and postmenopausal women, prevention and the association with cancer.Endometriosis is a chronic condition with a plethora of presentations in terms of not only the occurrence of lesions, but also the presence of signs and symptoms. The most important symptoms include pain and infertility.The guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 1 December 2020 and written in English were included in the literature review.Based on the collected evidence, recommendations were formulated and discussed within specialist subgroups and then presented to the core guideline development group (GDG) until consensus was reached. A stakeholder review was organized after finalization of the draft. The final version was approved by the GDG and the ESHRE Executive Committee.This guideline aims to help clinicians to apply best care for women with endometriosis. Although studies mostly focus on women of reproductive age, the guideline also addresses endometriosis in adolescents and postmenopausal women. The guideline outlines the diagnostic process for endometriosis, which challenges laparoscopy and histology as gold standard diagnostic tests. The options for treatment of endometriosis-associated pain symptoms include analgesics, medical treatments and surgery. Non-pharmacological treatments are also discussed. For management of endometriosis-associated infertility, surgical treatment and/or medically assisted reproduction are feasible. While most of the more recent studies confirm previous ESHRE recommendations, there are five topics in which significant changes to recommendations were required and changes in clinical practice are to be expected.The guideline describes different management options but, based on existing evidence, no firm recommendations could be formulated on the most appropriate treatments. Also, for specific clinical issues, such as asymptomatic endometriosis or extrapelvic endometriosis, the evidence is too scarce to make evidence-based recommendations.The guideline provides clinicians with clear advice on best practice in endometriosis care, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in endometriosis.The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payments. C.M.B. reports grants from Bayer Healthcare and the European Commission; Participation on a Data Safety Monitoring Board or Advisory Board with ObsEva (Data Safety Monitoring Group) and Myovant (Scientific Advisory Group). A.B. reports grants from FEMaLE executive board member and European Commission Horizon 2020 grant; consulting fees from Ethicon Endo Surgery, Medtronic; honoraria for lectures from Ethicon; and support for meeting attendance from Gedeon Richter; A.H. reports grants from MRC, NIHR, CSO, Roche Diagnostics, Astra Zeneca, Ferring; Consulting fees from Roche Diagnostics, Nordic Pharma, Chugai and Benevolent Al Bio Limited all paid to the institution; a pending patent on Serum endometriosis biomarker; he is also Chair of TSC for STOP-OHSS and CERM trials. O.H. reports consulting fees and speaker's fees from Gedeon Richter and Bayer AG; support for attending meetings from Gedeon-Richter, and leadership roles at the Finnish Society for Obstetrics and Gynecology and the Nordic federation of the societies of obstetrics and gynecology. L.K. reports consulting fees from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; honoraria for lectures from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; support for attending meetings from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; he also has a leadership role in the German Society of Gynecological Endocrinology (DGGEF). M.K. reports grants from French Foundation for Medical Research (FRM), Australian Ministry of Health, Medical Research Future Fund and French National Cancer Institute; support for meeting attendance from European Society for Gynaecological Endoscopy (ESGE), European Congress on Endometriosis (EEC) and ESHRE; She is an advisory Board Member, FEMaLe Project (Finding Endometriosis Using Machine Learning), Scientific Committee Chair for the French Foundation for Research on Endometriosis and Scientific Committee Chair for the ComPaRe-Endometriosis cohort. A.N. reports grants from Merck SA and Ferring; speaker fees from Merck SA and Ferring; support for meeting attendance from Merck SA; Participation on a Data Safety Monitoring Board or Advisory Board with Nordic Pharma and Merck SA; she also is a board member of medical advisory board, Endometriosis Society, the Netherlands (patients advocacy group) and an executive board member of the World Endometriosis Society. E.S. reports grants from National Institute for Health Research UK, Rosetrees Trust, Barts and the London Charity; Royalties from De Gruyter (book editor); consulting fees from Hologic; speakers fees from Hologic, Johnson & Johnson, Medtronic, Intuitive, Olympus and Karl Storz; Participation in the Medicines for Women's Health Expert Advisory Group with Medicines and Healthcare Products Regulatory Agency (MHRA); he is also Ambassador for the World Endometriosis Society. C.T. reports grants from Merck SA; Consulting fees from Gedeon Richter, Nordic Pharma and Merck SA; speaker fees from Merck SA, all paid to the institution; and support for meeting attendance from Ferring, Gedeon Richter and Merck SA. The other authors have no conflicts of interest to declare.This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose (Full disclaimer available at www.eshre.eu/guidelines.).

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Endometriosis

2009-01-14

Serdar E. Bulun

This review emphasizes the participation of estrogen and inflammation in the development of endometriosis. A feedback cycle in which prostaglandins and aromatase activity are prominent allows for the persistence of … This review emphasizes the participation of estrogen and inflammation in the development of endometriosis. A feedback cycle in which prostaglandins and aromatase activity are prominent allows for the persistence of endometriotic tissue. Knowledge of this cycle has important implications for the treatment of endometriosis.

Endometriosis

2020-03-25

Krina T. Zondervan , Christian M. Becker , Stacey A. Missmer

About 10% of reproductive-age women have endometriosis. Symptoms can include severe pain, dysmenorrhea, dyspareunia, dysuria, infertility, and fatigue. The pathogenesis is unclear. Hormonal therapy controls symptoms in some women; others … About 10% of reproductive-age women have endometriosis. Symptoms can include severe pain, dysmenorrhea, dyspareunia, dysuria, infertility, and fatigue. The pathogenesis is unclear. Hormonal therapy controls symptoms in some women; others require surgery, which may not be effective.

Endometriosis

1993-06-17

David L. Olive , Lisa Barrie Schwartz

Endometriosis is a common disorder, yet it is among the most enigmatic of gynecologic diseases. The literature on endometriosis is extensive, though often contradictory or inadequate, and reflects our frequent … Endometriosis is a common disorder, yet it is among the most enigmatic of gynecologic diseases. The literature on endometriosis is extensive, though often contradictory or inadequate, and reflects our frequent inability to decipher even the most fundamental aspects of common diseases. Recent studies have produced new insights into this complex disorder, however.In this review we shall critically evaluate what we know -- and do not know -- about endometriosis. Established facts will be separated from unsupported impressions, and areas of controversy will be highlighted.DefinitionEndometriosis is classically defined as the presence of endometrial glands and stroma outside the . . .

Deeply infiltrating pelvic endometriosis: histology and clinical significance

1990-06-01

Freddy Cornillie , Didier J. Oosterlynck , J. M. Lauweryns +1 more

Electroacupuncture Ameliorates Endometriosis-Associated Ovarian Dysfunction by Activating Nrf2 Pathway to Upregulate GPX4 Function and Inhibiting Ferroptosis

2025-06-25

Yan Zan , Xiaoquan Huang , Yu Zhuang +5 more

<title>Abstract</title> Background Endometriosis (EMs) often leads to ovarian dysfunction and infertility. Its mechanism is closely associated with oxidative stress and ferroptosis induced by pelvic iron overload. Electroacupuncture (EA) has potential … <title>Abstract</title> Background Endometriosis (EMs) often leads to ovarian dysfunction and infertility. Its mechanism is closely associated with oxidative stress and ferroptosis induced by pelvic iron overload. Electroacupuncture (EA) has potential in treating reproductive disorders, but its mechanism of action on ovarian ferroptosis in EMs remains unclear. This study aimed to investigate the protective effect of EA on ovarian function in an EMs mouse model and its underlying molecular mechanisms. Methods A mouse model simulating chronic hemorrhage in EMs was used. Mice were randomly divided into a Normal group, Sham group, EMs group, and EA group. Ovarian function (estrous cycle, ovarian weight/index, serum sex hormones, ovarian histopathology), iron metabolism levels (peritoneal fluid/ovarian Fe2⁺, ferritin, Prussian blue staining), oxidative stress levels (ovarian ROS, GSH content, T-SOD activity, Nrf2 and its downstream HO-1/SOD2/NQO1 mRNA), and ferroptosis levels (ferroptosis markers GPX4, SLC7A11, FTH1, ACSL4, COX-2 protein and mRNA, and MDA levels) were assessed using qRT-PCR, Western blot, IHC, colorimetric methods, and histochemistry. Results EA intervention significantly improved ovarian function in EMs mice. This was reflected in the normalization of the estrous cycle, increased ovarian weight/index, restored serum sex hormone levels, increased number of primordial follicles, and reduced atretic follicles. EA effectively alleviated ovarian iron overload (reduced Fe2⁺, ferritin, iron deposition) and oxidative stress (inhibited ROS, increased GSH, enhanced T-SOD activity). Mechanistically, EA activated the Nrf2 pathway (upregulated Nrf2, HO-1, SOD2, NQO1), upregulated key anti-ferroptosis molecules (GPX4, SLC7A11) and ferritin (FTH1). Furthermore, EA downregulated pro-ferroptosis factors (ACSL4, COX-2) and reduced lipid peroxidation (MDA). The results demonstrated that EA effectively blocked the ferroptosis process in ovarian granulosa cells by activating the Nrf2 pathway to upregulate GPX4 activity and suppressing ACSL4-mediated lipid peroxidation. Conclusions This study confirms that iron overload–oxidative stress–granulosa cell ferroptosis is a key pathological mechanism of EMs-induced ovarian damage. EA effectively inhibits ovarian granulosa cell ferroptosis by activating the Nrf2 pathway to upregulate GPX4 activity and suppress ACSL4-mediated lipid peroxidation, thereby ameliorating EMs-associated ovarian dysfunction. This provides important experimental evidence supporting EA as a complementary therapy for EMs-related infertility.

Homeobox C6 is Up-Regulated and Affects the Pathogenesis of Endometriosis

2025-06-25

Jianfa Jiang , Luyao Zhang , Lijie Li | Reproductive Sciences

EZH2 promotes endometriosis progression through estrogen receptor and TNFα expression

2025-06-24

Xiaohan Liu , Liqin Cheng , Liuxuan Huang +7 more | Frontiers in Endocrinology

Endometriosis is a chronic inflammatory gynecological condition marked by the presence of tissue similar to the endometrium grows outside the uterus, often leading pelvic pain and infertility. This study explores … Endometriosis is a chronic inflammatory gynecological condition marked by the presence of tissue similar to the endometrium grows outside the uterus, often leading pelvic pain and infertility. This study explores how enhancer of zeste homolog 2 (EZH2) influences endometriosis, particularly through its interaction with estrogen receptors (ERs). We found that EZH2 reduces ERα expression, allowing ERβ to bind to the tumor necrosis factor α (TNFα) promoter and increase TNFα levels, fueling inflammation. In mice, the EZH2 inhibitor GSK343 reduced TNFα levels and endometriosis progression, similar to gene knockdown of ERβ or EZH2. In human samples, endometriotic tissue showed higher levels of EZH2 and ERβ and lower levels of ERα than in controls. Thus, EZH2 promotes TNFα-driven inflammation, contributing to endometriosis. Targeting EZH2, as with GSK343, could be a promising therapeutic strategy for endometriosis treatment.

The Swiss Endometriosis Database: a retrospective multicentre cohort study on pain levels and multimodal treatment needs of endometriosis patients

2025-06-24

Sara Imboden , Sylvie Lang , A Martino +7 more | Schweizerische medizinische Wochenschrift

STUDY AIMS: This study aimed to deepen the understanding of endometriosis symptoms, types, and therapy recommendations for Swiss endometriosis patients in Swiss-certified endometriosis centres in 2022. METHODS:In this exploratory retrospective … STUDY AIMS: This study aimed to deepen the understanding of endometriosis symptoms, types, and therapy recommendations for Swiss endometriosis patients in Swiss-certified endometriosis centres in 2022. METHODS:In this exploratory retrospective multicentre cohort study, data from 3538 women who had their first consultation at a certified endometriosis centre in Switzerland in 2022 were analysed retrospectively. Data were collected by using questionnaires that were filled out by the patient and the physician at the first consultation, to evaluate parameters that included the main reason for consultation, visual analogue scale (VAS) scores for pain, clinical findings and therapy recommendations. RESULTS: This study analysed all patients who had provided consent and were diagnosed with endometriosis (n = 3403, 96.2%) during their first consultation at a Swiss-certified endometriosis centre in 2022. The median age was 33.0 years (11–66 years). Of 812 documented VAS scores, 71.6% of the patients felt general pain, resulting in a median VAS score for dysmenorrhoea of 8 (0–10). After the first examination, peritoneal endometriosis (n = 1453, 54.8%) was diagnosed most often, followed by adenomyosis (n = 1366, 51.5%), deep infiltrating endometriosis (n = 857, 32.3%) and cystic/ovarian endometriosis (n = 643, 24.2%). In 46.2% of the patients, more than one working hypothesis, with regard to their condition, was identified – in most cases, a combination of peritoneal endometriosis and adenomyosis (15.6%). Endocrine therapy was the most frequent treatment recommended (60.6%), followed by recommendations for medical pain therapy (57%), surgery (34.4%), complementary procedures (23.5%), reproductive therapy (5.7%) and multimodal pain therapy (5.6%). Analysis of correlations between symptoms, diagnosis and treatment recommendations showed only a few notable findings such as correlations between peritoneal endometriosis and hormonal-/medical treatment as well as correlations between deep infiltrating endometriosis and treatment recommendation for surgery. CONCLUSION: The high VAS scores in dysmenorrhoea underline the degree of suffering of patients with endometriosis seeking consultation at a certified endometriosis centre. Most patients presented multiple phenotypes with uncorrelated symptoms and diverse as well as multimodal treatment options were indicated, underlining the complexity and individuality of the disease.

Beyond pain: employment status affects endometriosis-associated quality of life – a cross-sectional study

2025-06-24

Jonas Jean Mathieu Vibert , Inès Ben Jazia , Milena Alec +2 more | Gynecological Endocrinology

Background: Endometriosis is a chronic condition affecting physical health, emotional well-being, and socioeconomic stability. While pain is a well-recognized determinant of health-related quality of life (HR-QoL), the role of pain … Background: Endometriosis is a chronic condition affecting physical health, emotional well-being, and socioeconomic stability. While pain is a well-recognized determinant of health-related quality of life (HR-QoL), the role of pain experience over employment status remains underexplored. Objective: To determine among women with endometriosis whether employment status independently contributes to HR-QoL, beyond clinical symptoms. Methods: This cross-sectional study was conducted at the University Hospital of Geneva. Women with a confirmed diagnosis of endometriosis were included. Employment status was categorized as full-time employment (>80%), part-time employment (≤80%), voluntary unemployment, and involuntary unemployment. HR-QoL was measured using the Endometriosis Health Profile-30 (EHP-30). Results: A total of 324 patients were included (mean age 32 ± 7.2 years); 78.2% had deep infiltrating endometriosis, and 34.5% reported prior surgery. Regarding employment, 63.2% were employed (51.5% full-time, 11.7% part-time), while 36.7% were unemployed, including 26.2% by choice. Full-time and part-time employment were linked to lower EHP-30 pain scores, with part-time employment showing a stronger association (β = -34.48, 95% CI: -58.00 to -10.88, p = 0.006) than full-time employment (β = -20.57, 95% CI: -40.70 to -0.43, p = 0.046). Unemployed women actively seeking work exhibited worse HR-QoL, particularly in social support (β = 34.95, 95% CI: 1.89 to 70.80, p = 0.048) and overall HR-QoL burden (β = 168.27, 95% CI: 30.60 to 205.91, p = 0.019). Conclusion: Employment status is an independent predictor of HR-QoL in women with endometriosis. Beyond pain, professional identity and social integration play key roles in endometriosis burden.

Diagnostic Accuracy of MRI Using the #Enzian Classification in Endometriosis: A Single-Center Retrospective Cohort Study

2025-06-24

Ala Aiob , Dina Gumin , Amirit Luder Stinski +2 more | Gynecologic and Obstetric Investigation

To evaluate the diagnostic accuracy of pelvic magnetic resonance imaging (MRI) interpreted using the #Enzian classification system by comparing MRI findings with laparoscopic outcomes in women suspected of having endometriosis. … To evaluate the diagnostic accuracy of pelvic magnetic resonance imaging (MRI) interpreted using the #Enzian classification system by comparing MRI findings with laparoscopic outcomes in women suspected of having endometriosis. Retrospective observational study. Twenty-four women aged 19 to 49 who underwent laparoscopic surgery for endometriosis at Galilee Medical Center from 2016 to 2023 had preoperative pelvic MRI available. MRI and laparoscopic findings were classified using the #Enzian classification across 64 anatomical compartments. Diagnostic accuracy was evaluated for lesion location and size. Associations between MRI accuracy and patient characteristics were analyzed using appropriate statistical tests. MRI accurately identified the lesion location in 31.3% of compartments and lesion size in 20.3%. The highest accuracy was found in the tubo-ovarian region (60%), rectovaginal septum (42.9%), and ovaries (41.7%), while the lowest accuracy was observed in the parametrium (7.1%) and compartments C, F, FA, and FB (0%). Higher age, parity, and gastrointestinal symptoms were significantly associated with improved MRI accuracy (p < 0.05). The small sample size, retrospective design, and MRI scans from various centers with differing imaging quality and radiologist expertise may restrict generalizability. MRI utilizing the #Enzian classification offers a structured method for evaluating deep infiltrating endometriosis, but it demonstrates limited accuracy for superficial or parametrial disease. While it is useful for surgical planning, MRI cannot substitute for laparoscopy, which remains crucial for a thorough evaluation and treatment of endometriosis.

Douleurs pelviennes chroniques de la femme

2025-06-24

Marine Osada , Eamonn Faller | EMC - Gynécologie

Upregulation of miR-183 inhibits the invasion and migration of endometrial stromal cells in endometriosis patients by downregulating Ezrin

2025-06-24

Jinmei Shi , Junbo Cai , Lin Kong +4 more | Frontiers in Oncology

Purpose The present study investigated the expression and role of miR-183 in the proliferation, invasion, migration, and apoptosis of endometrial stromal cells in endometriosis patients and the potential involvement of … Purpose The present study investigated the expression and role of miR-183 in the proliferation, invasion, migration, and apoptosis of endometrial stromal cells in endometriosis patients and the potential involvement of targeting Ezrin. Methods Normal, non-ectopic, and ectopic endometrial stromal cells (ESCs) were extracted from endometrial samples. RT-qPCR was used to evaluate miR-183 expression levels in endometrial tissue samples. Flow cytometry, cell proliferation assay, adhesion assay and Transwell assays and cell scratch assay were performed to assess cell apoptosis, viability, migration, and invasion of cells transfected with miR-183 inhibitor, miR-183 mimics, or controls. Western blotting was used to determine the expression of the migration-and invasion-related proteins. The expression status of RhoA/ROCK/Ezrin in endometriosis was verified by animal models. Results miR-183 expression levels were markedly downregulated and RhoA and Ezrin expression levels were upregulated in ectopic endometrial samples. Upregulation of miR-183 expression inhibited cell apoptosis, migration and invasion and promoted cell adhesion in ESCs, but had no significant impact on cell proliferation. miR-183 mimics decreased the expressions of Ezrin, RhoA, RhoC, and Rock. Conclusion Upregulated expression of miR-183 promoted cell adhesion and suppressed the apoptosis, invasion, and migration of ESCs by downregulating Ezrin. miR-183 may play a suppressor role in endometriosis by downregulating Ezrin to inactivate the Rho/ROCK pathway.

Global landscape of clinical trials for endometriosis: dynamic trends and future directions

2025-06-24

Sijie He , Huiqi Li , Li Wan +1 more | International Journal of Surgery

Chronic pain across clinical settings: the changing understanding of pain and its treatment in endometriosis

2025-06-24

Maria Temmes , Elina Helosvuori , Venla Oikkonen | BioSocieties

Abstract An ongoing shift toward multidisciplinary pain care and growing emphasis on non-pharmaceutical treatment are reshaping the parameters of how chronic pain is assessed and treated. The article explores these … Abstract An ongoing shift toward multidisciplinary pain care and growing emphasis on non-pharmaceutical treatment are reshaping the parameters of how chronic pain is assessed and treated. The article explores these ongoing changes through a chronic gynecological illness, endometriosis. Drawing on interviews with clinicians, people with endometriosis and endometriosis activists in Finland, we ask how pain is understood and its treatment envisioned in cases where the standard course of endometriosis treatment does not alleviate pain. The analysis shows that difficult-to-treat endometriosis pain is conceptualized differently at different clinical sites including endometriosis clinics, pain clinics, emergency care, and primary care settings. We demonstrate that pain treatment in endometriosis is not fixed but constitutes an object of ongoing negotiations between the patient and clinician. In particular, tensions arise when patients move between the siloed clinical sites, and their pain is re-evaluated and approached through different epistemic framings of pain and pain care.

Matrix Tropism Influences Endometriotic Cell Attachment Patterns

2025-06-23

Hannah S. Theriault , Hannah Kimmel , Alison C. Nunes +5 more | Advanced Functional Materials

Abstract The initiation of endometriotic lesions is not well understood or characterized because endometriosis is typically diagnosed at an advanced stage. Endometriotic lesions are most often found on pelvic tissues … Abstract The initiation of endometriotic lesions is not well understood or characterized because endometriosis is typically diagnosed at an advanced stage. Endometriotic lesions are most often found on pelvic tissues and organs, especially the ovaries. To investigate the role of tissue tropism on ovarian endometrioma initiation, a well‐characterized polyacrylamide microarray system is adapted to investigate the role of tissue‐specific extracellular matrix and adhesion motifs on endometriotic cell attachment, morphology, and size. The influence of cell origin (endometriotic vs non‐endometriotic) is reported, substrate stiffness mimicking aging and fibrosis, and the role of multicellular (epithelial‐stromal) cohorts on cell attachment patterns. Multiple ovarian‐specific attachment motifs are identified that significantly increase endometriotic (vs non‐endometriotic) cell cohort attachment that can be implicated in early disease etiology.

Endometriosis and Ovarian Cancer: Insights from NHANES and Mendelian Randomization Analysis

2025-06-23

Dong Liu , Yuke Wu , Kunyan Zhou | Reproductive Sciences

Endometriosis describes the growth of extra-uterine endometrium, causing pain and inflammation, and the condition has been estimated to affect 10% of women of reproductive age. It remains under-diagnosed and has … Endometriosis describes the growth of extra-uterine endometrium, causing pain and inflammation, and the condition has been estimated to affect 10% of women of reproductive age. It remains under-diagnosed and has been linked to increased cancer risk. This study evaluated the correlation between endometriosis and cancer. The significance of specific loci to cancer was analyzed via Mendelian randomization (MR). Of the 4092 samples included, cancer diagnoses were self-reported by 326 women with endometriosis and 3766 women without endometriosis. Correlations between individual cancer types and endometriosis were analyzed by multivariable logistic regression models and odds ratios (OR) adjusted for confounders. Mortality was evaluated by Kaplan-Meier survival analysis. Genetic variants associated with endometriosis were linked to ovarian cancer by MR analysis. Women with endometriosis had a higher association of overall cancer (OR = 1.80, 95% CI: 1.19-2.72) and this was especially the case for ovarian cancer (OR = 11.40, 95% CI: 3.00-43.34). Subgroup and sensitivity analyses confirmed the robustness of these results. Kaplan-Meier analysis indicated lower survival from all causes in women with endometriosis (p = 0.022) but no significant difference in cancer survival. MR analysis supported a positive relationship between endometriosis and ovarian cancer (OR = 1.203, 95% CI: 1.011-1.433). The history of endometriosis was positively associated with the history of overall and ovarian cancer. Women with a history of endometriosis should have access to enhanced cancer surveillance and proactive management. Further research is needed to confirm these associations and to give mechanistic insights.

Psychological Factors Contributing to Health-Related Quality of Life Following Endometriosis Surgery: Results of a Cross-Sectional Study

2025-06-23

Zoë Boersen , Joukje M. Oosterman , C. I. M. Aalders +3 more | Reproductive Sciences

Endometriosis causes severe and chronic pain leading to impaired Health-Related Quality of Life (HRQoL). While endometriosis surgery does improve pain intensity, psychological factors have an important role in pain perception. … Endometriosis causes severe and chronic pain leading to impaired Health-Related Quality of Life (HRQoL). While endometriosis surgery does improve pain intensity, psychological factors have an important role in pain perception. The current study aims to evaluate the independent contribution of pain catastrophizing and anxiety and depression to HRQoL between six months and nine years following endometriosis surgery. This is a cross-sectional questionnaire study including women with endometriosis who were surgically treated for endometriosis-related pain. Hierarchical multiple linear regression analysis was used to evaluate the relationship of pain catastrophizing and a total score for anxiety and depression to HRQoL, in addition to the contributions of pain intensity, fatigue and sleep quality. In a sub-analysis, we evaluated this relationship in patients with a shorter and with a longer time since surgery (TSS). The study included 195 participants, revealing significant correlations between HRQoL, pain catastrophizing and anxiety and depression. Subgroup analysis demonstrated that both pain catastrophizing and a combined anxiety and depression score significantly predicted HRQoL in both the shorter and longer TSS groups. These associations were found in addition to the contribution of pain intensity, fatigue and sleep quality to HRQoL. The current study demonstrates that pain catastrophizing and a combination of anxiety and depression contribute to HRQoL in patients six months to nine years after surgical treatment of endometriosis. Extended post-surgical care could be warranted to address these factors accordingly, for example with psychological care, in addition to surgery alone.

Awareness of Physical Therapy in Managing Endometriosis among Obstetrician and Gynecologists

2025-06-23

Zarnab Asif , Mehwish Khalid , Hassan Bin Akram | Journal of Riphah College of Rehabilitation Sciences

Stachydrine Protects Against Cyclophosphamide‐Induced Premature Ovarian Insufficiency in Wistar Rats by Inhibiting Oxidative Stress and Apoptosis via the Activation of the Nrf2/<scp>HO</scp>‐1 Signalling Pathway

2025-06-22

Feng Cong , Jiang Yue , Yuehui Zhang +2 more | Clinical and Experimental Pharmacology and Physiology

ABSTRACT Excessive oxidative stress and apoptosis of ovarian granulosa cells lead to severe ovarian dysfunctions and even premature ovarian insufficiency (POI). Stachydrine (STA), the main active component of Leonurus japonicas … ABSTRACT Excessive oxidative stress and apoptosis of ovarian granulosa cells lead to severe ovarian dysfunctions and even premature ovarian insufficiency (POI). Stachydrine (STA), the main active component of Leonurus japonicas , possesses antioxidant and anti‐apoptotic actions. However, the effects of STA on POI remain unknown. This work aimed to investigate STA's role in cyclophosphamide (CP)‐induced POI. CP was intraperitoneally injected into rats for 14 days (200 mg/kg for day 1, 8 mg/kg for day 2–14) to establish a POI model, and STA (20 or 40 mg/kg/d) was orally given to rats for three weeks after CP treatment. We found that STA treatment (40 mg/kg) alleviated the estrous cycle disorder and the imbalance of serum sex hormone levels in CP‐treated rats. Further, STA administration (40 mg/kg) inhibited oxidative stress and apoptosis of ovarian granulosa cells. Subsequently, human granulosa‐like cells (KGN) were treated with CP (250 μM) for 48 h, followed by STA administration (1 μM) for 24 h to investigate the in vitro effects of STA. Consistently, STA treatment prevented KGN cells from CP‐induced cell damage. In detail, STA treatment activated the Nrf2/HO‐1 signalling pathway, thereby inhibiting the oxidative stress and cell apoptosis of CP‐injured KGN cells. In conclusion, STA exerted a protective role in CP‐induced POI by alleviating oxidative stress and apoptosis through activating the Nrf2/HO‐1 signalling pathway, providing a new insight into POI treatment.

Pathophysiology of Endometriosis: Insights from Immunohistochemical Analysis of Ectopic and Eutopic Tissues

2025-06-22

Fahad T. Alotaibi | International Journal of Molecular Sciences

Endometriosis is a complex gynecological disorder characterized by the presence of endometrial-like tissue outside the uterus, leading to chronic pain and infertility. Immunohistochemistry (IHC) serves as a vital technique for … Endometriosis is a complex gynecological disorder characterized by the presence of endometrial-like tissue outside the uterus, leading to chronic pain and infertility. Immunohistochemistry (IHC) serves as a vital technique for elucidating the molecular and cellular differences between ectopic endometriotic tissues and eutopic endometrium. IHC reveals significant variations in the expression of inflammatory markers, adhesion molecules, and cell cycle regulators. This literature review compiles findings from various studies that assess the role of key proteins, such as leukemia inhibitory factor (LIF), cyclooxygenase-2 (COX-2), and b-cell lymphoma 2 (BCL-2), across different menstrual phases and lesion types. Notably, elevated LIF levels and increased mast cell activity in ectopic tissues underscore the inflammatory landscape of endometriosis. Additionally, altered expression of adhesion molecules like integrins and cluster of differentiation 44 (CD44) suggests modified cellular interactions, while apoptotic markers reveal a survival advantage for ectopic cells. These insights enhance our understanding of endometriosis pathophysiology.

Epigallocatechin Gallate as a Potential Therapeutic Agent in Endometriosis: A Narrative Review

2025-06-21

Anna Markowska , Zbigniew Kojs , Michał Antoszczak +2 more | Nutrients

Endometriosis is a chronic, hormone-dependent disease that affects women of reproductive age. It leads to numerous adverse clinical symptoms, which significantly impact women’s quality of life. The chronic nature of … Endometriosis is a chronic, hormone-dependent disease that affects women of reproductive age. It leads to numerous adverse clinical symptoms, which significantly impact women’s quality of life. The chronic nature of the disease and its recurrence are the main reasons for the search for new, non-hormonal drugs and drug candidates, either as adjunct treatment options or alternative therapies. The catechin found in green tea, epigallocatechin gallate (EGCG), has been shown to exhibit a wide array of biological activities, which may also contribute to its potential effectiveness in treating endometriosis. The poor physicochemical stability and relatively low bioavailability of EGCG have stimulated the development of a peracetylated prodrug (pro-EGCG) and other solutions, based on nanotechnology, that would eliminate the problems with EGCG. In this review article, we summarize the studies on the effects of EGCG, pro-EGCG, and EGCG-based nanoparticles on the course of endometriosis published in the GoogleScholar and PubMed databases. Of note is the fact that the results of in vitro and animal model studies have suggested that EGCG and pro-EGCG can reduce the number of endometriosis foci and their size and volume, and they can prevent fibrosis by affecting multiple molecular factors and signaling pathways. The promising results provide a basis for using green herbal extracts for endometriosis treatment in a clinical trial. Nevertheless, it should be emphasized that the number of studies on the topic is currently very limited; further expansion in the coming years is necessary. Broad, well-designed clinical trials are also essential to validate the true potential of EGCG and related compounds in the fight against endometriosis.

Bladder endometriosis mimicking bladder neoplasm: A case report

2025-06-21

Ahmad S. Kreishan , Hasan N. Al-Haidari , Omar Tamimi +4 more | Radiology Case Reports

Inverse association between dietary antioxidant intake and endometriosis among US women: A cross-sectional NHANES study

2025-06-20

Huoling Luo , Xinya Li , Terence T. Lao +5 more | European Journal of Obstetrics & Gynecology and Reproductive Biology

Improved surgical outcomes in adenomyosis: a novel insight into the superiority of secretory phase adenomyomectomy

2025-06-20

Wen He , Manzhu He , Jinhong Li +5 more | Archives of Gynecology and Obstetrics

To evaluate whether the timing of adenomyomectomy within the menstrual cycle influences outcomes in patients with adenomyosis, and to assess whether surgery performed during the secretory phase offers clinical advantages … To evaluate whether the timing of adenomyomectomy within the menstrual cycle influences outcomes in patients with adenomyosis, and to assess whether surgery performed during the secretory phase offers clinical advantages over the proliferative phase. We conducted a retrospective cohort study of patients with histologically confirmed adenomyosis who underwent uterus-sparing adenomyomectomy at our institution between January 2021 and April 2024. Patients were categorized according to the menstrual phase at the time of surgery: secretory phase and proliferative phase. The primary outcomes were postoperative recurrence rate and time to recurrence. Comparative analysis was conducted between the two groups. Of 163 patients initially enrolled, 143 were included in the final analysis after excluding 20 lost to follow-up (secretory phase: n = 80; proliferative phase: n = 63). The secretory phase group exhibited a significantly lower recurrence rate (14.3% vs. 38.8%, P < 0.001) and a longer median recurrence-free survival [median RFS: 45.19 (41.69-48.70) vs. 34.40 (29.89-38.91) months, log-rank P = 0.001], as demonstrated by Kaplan-Meier analysis. No significant differences were observed in intraoperative blood loss or postoperative complication rates. In multivariate Cox regression analysis, surgery during the secretory phase remained an independent protective factor against recurrence. Compared to the proliferative phase, surgery in the secretory phase was associated with a significantly reduced risk of recurrence (HR = 0.277, 95% CI 0.114-0.673, P = 0.005), corresponding to a 72.3% risk reduction after adjusting for potential confounders. Adenomyomectomy performed during the secretory phase is associated with significantly lower recurrence rates and improved long-term outcomes. These findings provide novel evidence supporting the secretory phase as a potentially optimal surgical window for the treatment of adenomyosis, which may contribute to optimizing surgical timing in clinical practice.

Global, regional, and national burden of endometriosis among women of childbearing age from 1990 to 2021: a cross-sectional analysis from the 2021 global burden of disease study

2025-06-20

Shuangfei Xu , Yi Zhang , Ye Peng +5 more | International Journal of Surgery

Background: Endometriosis is a major contributor to infertility and pelvic pain, which brings a significant burden on family and society. Although the data of endometriosis in Global Burden of Disease … Background: Endometriosis is a major contributor to infertility and pelvic pain, which brings a significant burden on family and society. Although the data of endometriosis in Global Burden of Disease (GBD) 2019 was reviewed, no updated analysis has been conducted using GBD 2021, and the disease burden across different age groups has not been analyzed. The aim of this cross-sectional analysis was to provide an up-to-date assessment of the prevalence, incidence, and disability-adjusted life-years (DALYs) of endometriosis from 1990 to 2021 at the global, national, and regional levels. Material and methods: We obtained data on the prevalence, incidence, and DALYs of endometriosis from GBD 2021. These data were analyzed to provide an overview of the epidemiological trends and disease burden of endometriosis in 204 countries and regions worldwide from 1990 to 2021, and we projected trends through 2040. Health inequality analysis, joinpoint regression analysis, and decomposition analysis were applied to data assessment. Results: In 2021, the global burden of endometriosis remained substantial, with a total of 22.28 million cases (95% UI: 13.67, 33.69), corresponding to an age-standardized prevalence rate (ASPR) of 1023.8 per 100 000 (95% UI: 627.36, 1549.77). The age-standardized incidence rates (ASIR) was 162.71 (95% UI: 85.21, 265.35) per 100 000, while the age-standardized DALY rate (ASDR) was 94.25 (95% UI: 50.82, 157.73) per 100 000. Regionally, areas with low sociodemographic index (SDI) experienced the highest ASPR, ASIR, and ASDR, while high SDI regions exhibited the lowest rates. Geospatially, Oceania and Eastern Europe displayed the highest ASPR, ASIR, and ASDR. Among countries, Niger had both the highest ASPR and ASDR, and Solomon Islands had the highest ASIR. Women aged 25–29 years emerged as the most affected group, suggesting that this cohort should be a key focus for interventions. By 2040, the global ASPR of endometriosis is projected decline to 887.89 per 100 000 (95% CI: 530.79, 1245), representing a decrease of 13.28% from 2021. Decomposition analysis showed population growth was the major contributing factor, followed by epidemiologic change. Conclusion: While the burden of endometriosis has decreased globally from 1990 to 2021, significant disparities remain, especially in low SDI regions. It is necessary to develop better policies and preventive measures to effectively address the range of problems associated with endometriosis.

Standardizing the histopathological diagnosis of adenomyosis: an international Delphi consensus

2025-06-20

Tristan McCaughey , Marsali Newman , Leonie Constable +6 more | Histopathology

Aims To use the Delphi consensus methodology to establish standardized criteria for the histopathological diagnosis of adenomyosis. Methods and results Between April and September 2024, a modified three‐round Delphi consensus … Aims To use the Delphi consensus methodology to establish standardized criteria for the histopathological diagnosis of adenomyosis. Methods and results Between April and September 2024, a modified three‐round Delphi consensus study was conducted. Thirty‐one gynaecological pathologists from 18 countries participated in surveys to evaluate and refine a diagnostic framework for adenomyosis in hysterectomy specimens. Key areas achieving the highest level of agreement included: 4–6 blocks for routine histopathological examination of hysterectomy specimens with benign indications; defining adenomyosis as endometrial glands and/or stroma greater than 2 mm into the myometrium or more than one‐third of myometrial thickness; that the absolute number of glands or stromal tissue does not contribute to the diagnosis of adenomyosis; a single gland or stromal focus can be diagnostic; and definitions of focal, extensive, superficial and deep adenomyosis. In total, 93% of respondents were in favour of standardizing the diagnosis to reduce inter‐pathologist variability. Conclusion This study proposes the first consensus‐based guideline for the histopathological diagnosis of adenomyosis. Supported by the responses of 31 international experts through a modified Delphi method, this framework provides pathologists with clear diagnostic criteria. Further research should correlate these criteria with clinical symptoms and outcomes.

What's new in guidance? Evidence‐based management of patients with endometriosis undergoing assisted conception

2025-06-20

Madeleine Hardy , Karolina Skorupskaite , Harish Bhandari +3 more | The Obstetrician & Gynaecologist

Evaluation of inflammatory serum parameters as a diagnostic tool in patients with endometriosis: a case-control study

2025-06-20

Mariz Kasoha , P Sklavounos , István Molnár +4 more | Scientific Reports

Abstract Even though non-invasive prediction of endometriosis may seem technically feasible using sophisticated machine learning algorithms, a standard clinical use case for non-surgical diagnosis of endometriosis has not yet been … Abstract Even though non-invasive prediction of endometriosis may seem technically feasible using sophisticated machine learning algorithms, a standard clinical use case for non-surgical diagnosis of endometriosis has not yet been established. In the present paper, we assess the potential of the inflammatory serum markers hepcidin, soluble urokinase-type plasminogen activator receptor (suPar), and interleukin-6 (IL-6) in a cohort of 87 patients. Hereby, 59 patients were histologically diagnosed with endometriosis, whereas other 28 patients served as our non-endometriosis control group. An initial exploratory univariate statistical analysis (Mann-Whitney test) revealed the diagnostic potential of different serum levels of suPar ( p = 0.024) and IL-6 ( p < 0.001) between both groups; the formation of a distinct training data set ( n = 77) subsequently allowed to train a supervised machine learning analysis (tree classifier) employing serum levels of suPar, hepcidin, and IL-6 as predictor variables. Based on an internal 5-fold cross validation, the classifier performance was initially assessed using standard metrics such as sensitivity, positive predictive value, and AUROC curve. Additionally, the algorithm was tested on an external validation (holdout) data set ( n = 10), showing sufficient overall accuracy of 80% without tendencies of overfitting. In conclusion, our data demonstrates the diagnostic potential of IL-6 and suPar as pro-inflammatory serum biomarkers in endometriosis. Using a decision tree-based supervised learning approach, we additionally present a straight-forward way of a potential clinical employment, aiming at less invasive (non-surgical) diagnosis.

Head to toe: expand your diagnosis on routine imaging to include endometriosis

2025-06-20

Anuradha S. Shenoy-Bhangle , Carlos Carnelli , Angela Tong +7 more | Abdominal Radiology

PREVALÊNCIA DA ENDOMETRIOSE EM ADOLESCENTES BRASILEIRAS (2014 A 2024)

2025-06-19

Thais Emanuelly Vidal Bezerra Angelim | Brazilian Journal of Implantology and Health Sciences

A endometriose é uma doença ginecológica caracterizada pela existência de tecido endometrial ectópico que causa diferentes sintomas como dismenorreia, dor pélvica crônica, dispareunia, infertilidade e queixas intestinais e urinárias cíclicas. … A endometriose é uma doença ginecológica caracterizada pela existência de tecido endometrial ectópico que causa diferentes sintomas como dismenorreia, dor pélvica crônica, dispareunia, infertilidade e queixas intestinais e urinárias cíclicas. No Brasil, estima-se que cerca de sete milhões de brasileiras sofrem com a endometriose. Apesar da maioria dos sintomas iniciais aparecerem durante a adolescência, o diagnóstico definitivo, frequentemente, acontece de forma tardia, em estágios mais avançados da doença. O Brasil registrou 137.002 casos de endometriose no período em estudo. A maior prevalência foi na região sudeste com 58.403 internações, seguida da região nordeste com 35.383 diagnósticos. O último biênio (2023/2024) apresentou o maior número de internamentos para endometriose desde 2014, tendo o ano de 2023 registrado 15.961 ocorrências e o ano de 2024, 16.014 casos, respectivamente. A presente pesquisa tem o objetivo de analisar a prevalência da endometriose em adolescentes brasileiras, no período de 2014 a 2024. Foi realizado um estudo ecológico, quantitativo e retrospectivo, mediante coleta de dados no SIH/SUS (Sistema de Informações Hospitalares do SUS), vinculado ao DATASUS, referente à prevalência da endometriose em adolescentes brasileiras, de janeiro de 2014 a novembro de 2024. Constatou-se um aumento no número de casos de endometriose nos últimos dois anos no Brasil, sendo que em 2024, foi registrado o maior pico de internações da década. O atual cenário epidemiológico mostra a importância de campanhas de saúde pública que conscientizem a população, sobre a necessidade do diagnóstico e tratamento precoces. Observa-se também, um elevado número de internamentos de adolescentes com endometriose no país, reforçando a relevância do regular acompanhamento ginecológico, desde o início da idade fértil.

Life‐threatening spontaneous uterine rupture in a non‐gravid, unscarred uterus of a nulliparous woman: A case report

2025-06-19

Wan‐Ling Hsieh , Tsun‐Wen Hsiao , Chang‐Yao Chu +1 more | International Journal of Gynecology & Obstetrics

Caesarean Scar Endometriosis - A Rare Case Report

2025-06-19

K. V. N. Sunitha , Achal Madhulika | International Journal of Contemporary Medicine

Background *Endometriosis is the presence of ectopic functioning endometrial tissue outside the uterine cavity. Scar endometriosis is a rare condition that typically follows obstetrical and gynaecological surgeries. The diagnosis of … Background *Endometriosis is the presence of ectopic functioning endometrial tissue outside the uterine cavity. Scar endometriosis is a rare condition that typically follows obstetrical and gynaecological surgeries. The diagnosis of scar endometriosis remains challenging and requires a comprehensive approach, including clinical presentation and histological and radiological findings. We are reporting a case of 28 yr old parous woman with 2 prior LSCS admitted to our hospital presented with a chief complaint of pain at the scar site persisting for the past 4 months, with a gradual increase in intensity over the last 2 months. on clinical and radiological examination, it was found to be a left sided mass noted in the lower abdomen. on laparotomy 4*4 cm size scar endometriotic tissue. On HPE, suggestive of scar endometrioses with inter-spread endometrial glands. Results *Ultrasonography reported a hypoechoic lesion measuring 2.5x1.5cm with irregular borders noted in left iliac fossa region in subcutaneous region indenting rectus muscle with no internal vascularity. An MRI abdomen was taken and shows round nodular lesion with spiculated margins noted in left lower abdomen in deep subcutaneous flat planes abutting rectus abdominus. Minimal fat stranding noted adjacent to the lesion and it concluded that it is likely to represent a scar endometriosis, correlating with clinical history after which she underwent laparotomy for the same. Conclusion *Scar endometriosis is a rare and elusive diagnosis often mimicking with a variety of clinical conditions, and presenting as a diagnostic dilemma. Physicians’ ought to maintain a high degree of suspicion in a reproductive age group women presenting with pain and localized symptoms at the site of incision following gynaecological/obstetric surgery.

The effects of music therapy on pain and anxiety in young nulliparous patients undergoing laparoscopic cystectomy for endometriosis: a randomized controlled trial

2025-06-19

Wenwei Li , Huiyan Feng , Xiaohui Yang +3 more | Journal of Psychosomatic Obstetrics & Gynecology

Endometriosis (EMS) is associated with a markedly increased incidence of depression and anxiety, primarily due to cyclic pain, concerns about infertility from impaired ovarian function, and fear of disease recurrence. … Endometriosis (EMS) is associated with a markedly increased incidence of depression and anxiety, primarily due to cyclic pain, concerns about infertility from impaired ovarian function, and fear of disease recurrence. Surgery and its associated pain may trigger both emotional and physiological stress responses. Young, nulliparous patients with fertility intentions often experience additional psychological burdens related to surgical safety, postoperative recovery, and the potential impact on future fertility. Music has been shown to promote relaxation, reduce tension and anxiety, and alleviate pain. However, no studies have evaluated the postoperative effects of music therapy in this specific patient population. To investigate whether music therapy can effectively reduce postoperative pain and alleviate perioperative anxiety in young patients with fertility desires undergoing laparoscopic cystectomy for endometriotic ovarian cysts, and to explore its potential as a simple, non-pharmacological intervention. A single-center, two-arm, single-masked randomized controlled trial (RCT). The Third Affiliated Hospital of Sun Yat-sen University (a teaching hospital). A total of 149 patients were included for analysis, with 75 assigned to the music group and 74 to the control group. Perioperative music therapy administered to young, nulliparous patients with fertility intentions undergoing laparoscopic cystectomy for EMS. One participant withdrew during follow-up, and 149 patients were included in the final analysis. Baseline characteristics-including age, BMI, marital status, preoperative VAS scores, and GAD-7 scores and anxiety levels-showed no significant differences between groups. Postoperative VAS scores at 6 h (p = 0.20), Day 1 (p = 0.438), Day 3 (p = 0.714), and Day 7 (p = 0.899) revealed no significant differences. Similarly, GAD-7 scores and anxiety severity levels on postoperative Day 1 (p = 0.541; p = 0.984), Day 3 (p = 0.287; p = 0.436), and Day 7 (p = 0.468; p = 0.703) showed no statistical significance between groups. Music therapy may serve as an adjunctive intervention for young, nulliparous patients with fertility intentions undergoing laparoscopic cystectomy for endometriosis; however, no significant effects were observed in reducing perioperative anxiety or postoperative pain in this population.

The Role of miRNA in Endometriosis-Related Infertility—An Update

2025-06-19

Hanna Surmann , Ludwig Kiesel | International Journal of Molecular Sciences

Endometriosis, affecting up to 10% of women in their reproductive years, is a chronic and multifactorial disease characterized by the presence of endometrial tissue outside the uterus. Traditionally associated with … Endometriosis, affecting up to 10% of women in their reproductive years, is a chronic and multifactorial disease characterized by the presence of endometrial tissue outside the uterus. Traditionally associated with pain and infertility, recent studies highlight its systemic nature, implicating inflammatory, immunological, and hormonal dysregulation in its pathogenesis. This paper explores the emerging role of microRNAs (miRNAs) in the pathophysiology of endometriosis and its related infertility. Evidence suggests that dysregulation of specific miRNAs influences cellular proliferation, migration, and progesterone resistance, thereby contributing to the development and progression of endometriotic lesions. Additionally, altered miRNA expression profiles hold promise as non-invasive biomarkers for improving diagnostic accuracy and as potential targets for novel therapeutic interventions. Although current diagnostic methods, such as laparoscopy, remain the gold standard, the integration of miRNA-based approaches could reduce reliance on invasive procedures and enhance treatment outcomes. Ultimately, further research-particularly regarding the interplay between endometriosis and infertility-is crucial to fully elucidate these complex mechanisms and foster the development of more effective diagnostic and therapeutic strategies.

Bladder endometriosis in a patient with undirected manifestations: a case report

2025-06-19

Kenana Tawashi , Ahmad Alhamid , Hadi Alabdullah +3 more | Journal of Medical Case Reports

Endometriosis is defined as the presence of functional glands and stroma of the uterus outside its cavity. It affects 10-20% of women of reproductive age. It can form in different … Endometriosis is defined as the presence of functional glands and stroma of the uterus outside its cavity. It affects 10-20% of women of reproductive age. It can form in different parts of the body; the involvement of the urinary tract is rare (1% of all cases). We report here a case of a 37-year-old Syrian woman who presented to the clinic with urinary hesitancy, dysuria, suprapubic pain, and intermittent hematuria for a year. The patient experienced dysmenorrhea, irregular menstruation, dyspareunia, and pelvic pain for 3 years until now. According to the patient, these symptoms did not follow a specific pattern related to menstruation. The laboratory findings included hematuria and an international normalized ratio of 2.5. The radiological investigations revealed a 3 cm mass on the posterior bladder wall extending toward the uterus. The surgical procedure was conducted through a lower abdominal approach employing a Pfannenstiel incision. Upon gaining access to the pelvic cavity, the bladder was carefully exposed and opened. Examination revealed a solid mass located on the posterior bladder wall, which was meticulously dissected and excised to ensure the preservation of adjacent anatomical structures. The bladder was subsequently repaired without complications. The postoperative period was uneventful, and the patient was discharged without any immediate complications. Histopathological analysis of the excised lesion confirmed a diagnosis of benign bladder endometriosis. The patient underwent regular postoperative surveillance for 2 years, during which no evidence of recurrence was observed. The case highlights the importance of considering bladder endometriosis in the differential diagnosis of patients presenting with unexplained urinary symptoms and pelvic pain. Early recognition and surgical management can lead to favorable outcomes.

Association between depressive symptoms and dienogest in patients treated for endometriosis: Using the Center for Epidemiological Studies Depression (CES-D) and the State-Trait Anxiety Inventory (STAI)

2025-06-19

Yunjeong Park , Na-Young Bae , Sung Pil Choo +6 more | European Journal of Obstetrics & Gynecology and Reproductive Biology

WISP2/CCN5 revealed as a potential diagnostic biomarker for endometriosis based on machine learning and single-cell transcriptomic analysis

2025-06-19

Sheng Dou , Shaohua Ling , Weihua Nong +5 more | Functional & Integrative Genomics

Perspectives in transvaginal sonography for the diagnosis of adenomyosis

2025-06-19

Xin An , Jun Zhang , Xu Yun +4 more | Frontiers in Medicine

Adenomyosis is a common gynecological condition affecting women of reproductive age, posing significant diagnostic challenges due to its diverse clinical presentations. This extended opinion study critically reviews the diagnostic methods … Adenomyosis is a common gynecological condition affecting women of reproductive age, posing significant diagnostic challenges due to its diverse clinical presentations. This extended opinion study critically reviews the diagnostic methods for adenomyosis, with a focus on transvaginal sonography (TVS), a widely used non-invasive imaging technique. The study evaluates the effectiveness, limitations, and clinical applicability of TVS, while exploring the role of histopathological confirmation when non-invasive methods are insufficient. Advancements in TVS, including three-dimensional ultrasound and color Doppler, have enhanced diagnostic precision, particularly in assessing uterine morphology and blood flow. Additionally, artificial intelligence integration offers potential to further optimize diagnostic accuracy and efficiency. While histopathological examination remains the gold standard, its use is often impractical in patients who do not undergo hysterectomy. This study provides a comprehensive overview of the current status of TVS in diagnosing adenomyosis, analyzing its accuracy, strengths, and limitations across diverse patient populations. Results suggest that TVS is a reliable diagnostic tool, though its accuracy improves when combined with magnetic resonance imaging, especially in complex cases. Ongoing research is needed to refine TVS capabilities and identify non-invasive alternatives to histopathological confirmation, improving accessibility and diagnostic efficiency.

First birth and total fertility rate in women with surgically verified endometriosis – A nationwide register study of 18 320 women across reproductive life course

2025-06-19

Anni Tuominen , Liisu Saavalainen , Juuso Saavalainen +4 more | Acta Obstetricia Et Gynecologica Scandinavica

Abstract Introduction Endometriosis is associated with pain and infertility. However, little is known about birth rate among women with endometriosis on population level. We studied whether women with endometriosis have … Abstract Introduction Endometriosis is associated with pain and infertility. However, little is known about birth rate among women with endometriosis on population level. We studied whether women with endometriosis have lower birth rate than women in the general population. Material and Methods This historical population‐based cohort study used data from 18 320 fertile‐aged women with first surgical verification of endometriosis in 1998–2012. Women with endometriosis were further divided into sub‐cohorts: women with solely peritoneal ( n = 5786), ovarian ( n = 6519) and deep endometriosis ( n = 1267). Women with combined types and rare forms of endometriosis formed a sub‐cohort of combined/other endometriosis ( n = 4748). The reference cohort comprised 35 788 women. The follow‐up started at the age of 15 years and ended at first birth, sterilization/bilateral oophorectomy/hysterectomy, emigration, death, age of 50 years, or December 31, 2019. From Kaplan–Meier survival curves of not giving birth, that is, until the first birth, we assessed the statistical difference of first births with crude and adjusted restricted mean survival time (RMST). In addition, we studied the fertility rate of women until the end of follow‐up. Results Altogether 12 491 (68.2%) women with endometriosis compared with 28 871 (80.7%) reference women gave birth during follow‐up. Women with peritoneal and deep endometriosis had higher first birth rate (73.1% and 71.3%) compared with women with ovarian and combined/other forms of endometriosis (65.2% and 65.5%) ( p < 0.001). The RMST of not giving birth was longer in women with endometriosis 18.9 (18.8–19.0) years compared with the reference cohort 15.5 (15.4–15.6) with both crude and adjusted RMST difference ( p < 0.001). Moreover, each sub‐cohort showed a longer RMST of not giving birth than reference cohort ( p < 0.001) . Total fertility rate of women was 1.33 (SD 1.16) in the endometriosis and 1.89 (1.46) in the reference cohort ( p < 0.001) with smaller differences among endometriosis sub‐cohorts. Conclusions Findings suggest that fertility outcome is compromised depending on the endometriosis subtype. Thus, timely diagnosis and appropriate treatment might be beneficial for fertility.

Pelvic nerve endometriosis: MRI features and key findings for surgical decision

2025-06-19

Justine Bourg , Édouard Ruaux , Pierre‐Adrien Bolze +5 more | Insights into Imaging

Differences in the proteomic profiles of the eutopic endometrium in patients with internal and external adenomyosis

2025-06-18

Marta Valdés‐Bango , Mikel Azkargorta , Meritxell Gràcia +7 more | PLOS Global Public Health

Two separate phenotypes of adenomyosis have been recognized, determined by the anatomical position of the adenomyotic lesions within the myometrium. This suggests that adenomyosis impacting the inner myometrium and that … Two separate phenotypes of adenomyosis have been recognized, determined by the anatomical position of the adenomyotic lesions within the myometrium. This suggests that adenomyosis impacting the inner myometrium and that affecting the outer myometrial layer may have distinct origins and display different clinical and radiological characteristics. We aimed to investigate the endometrial proteomic profiles of patients with both adenomyosis phenotypes to identify differentially expressed proteins and molecular pathways, shedding light on their distinct pathogenic mechanisms. We conducted a cross-sectional study that included thirty-six participants (nine with internal adenomyosis, nine with external adenomyosis, and eighteen healthy controls based on sonographic criteria) from September 2021 to September 2022. Endometrial samples were collected and processed for proteomic analysis. Mass spectrometry and a Data Independent Acquisition strategy were used to identify differentially expressed proteins. Gene Ontology and Ingenuity Pathway Analysis were employed for further functional analysis and network generation. The proteomic profiles of the eutopic endometrium differed significantly among women with internal adenomyosis, external adenomyosis, and controls. Biological functions related to the innate immune response were affected by differentially expressed proteins in patients with both phenotypes of adenomyosis compared to controls. The proteomic profiles of the endometrium of women with external versus internal adenomyosis exhibited significant differences, with external adenomyosis showing a heightened immune response and inflammatory activity, while internal adenomyosis was associated with altered signaling pathways related to cell migration and apoptosis. Upstream regulator analysis predicted the activation of inflammatory mediators like LPS, TGF-β1, IL-4, and IFN-γ in external adenomyosis, and MAPK1 and IRF2BP2 along with multiple microRNAs in internal adenomyosis. Overall, our findings support distinct pathogenic mechanisms for the two adenomyosis phenotypes, highlighting the need for further research to explore their implications for diagnosis, correlation with symptoms, and new potential therapeutic strategies.

Mass spectrometry imaging reveals alterations in protein and N-glycan molecular signatures in endometriosis tissues

2025-06-18

Monica Lin , Erin H. Seeley , Suzanne Ledet +3 more | Analytical and Bioanalytical Chemistry

The Effect of Surgery on Endometriomas on Fertility (2025 Second Edition)

2025-06-18

Prasanna Raj Supramaniam , Meenakshi Mittal , Christian M. Becker +1 more | BJOG An International Journal of Obstetrics & Gynaecology

Plain Language Summary Endometriosis is a condition where the lining of the uterus (womb) is found in other locations in the body such as, but not limited to, the ovaries, … Plain Language Summary Endometriosis is a condition where the lining of the uterus (womb) is found in other locations in the body such as, but not limited to, the ovaries, bowel and bladder. It is a common condition that can affect up to one in 10 women and can be found in between three to five in 10 women who have been diagnosed with subfertility. Women with endometriosis often present with painful periods, heavy periods, pain while opening their bowels or passing urine, pain during sexual intercourse and difficulty in conceiving. A proportion of those with endometriosis remain asymptomatic of the disease. Care should be tailored to each individual. The significant improvement in diagnostic technology has increased the detection rate of endometriosis. People with ovarian endometriosis, also known as an ovarian endometrioma, can be diagnosed using a transvaginal (internal) or transabdominal (via the tummy) ultrasound scan. Detection rates of up to 90% have been reported for routine ultrasound scans. Ovarian endometriomas can impact fertility outcomes, and for these people a multidisciplinary approach to care is required. The presence of an ovarian endometrioma and endometriosis is known to have a negative impact on the ovarian reserve (egg count and quality) and overall, chance of successful conception. Women with known endometriosis should therefore be counselled about the various options available for fertility preservation. The treatment for ovarian endometrioma(s) in those wanting to conceive can be broadly divided into two categories, expectant (watch‐and‐wait approach), and surgical which most commonly involves‐keyhole surgery. Expectant management avoids the risks of surgery, along with no further surgically related reduction in ovarian reserve. It also reduces the delay from diagnosis to starting fertility treatment. The disadvantages of this approach, however, would be the persistence of pain symptoms, and ongoing difficulty with accessing the ovaries during assisted fertility treatment such as in vitro fertilisation. Surgical treatment for ovarian endometrioma(s) in the context of women trying to conceive is often approached with caution. Surgery has been shown to reduce the ovarian reserve further, and clinicians would attempt to limit the degree of impact by reducing the amount of surgical stress to an ovary. The benefits of this approach, however, would be an improvement in symptoms and access to the ovaries for fertility treatment.

IL-24 producing regulatory T and B lymphocytes in endometriosis

2025-06-18

A Kedzierska , Daria Lorek , Anna Sławek +6 more | Frontiers in Immunology

Problem Unbalanced production of pro- and anti-inflammatory cytokines by immune cells is a hallmark of endometriosis. IL-24, a member of the IL-10 family, is a pleiotropic cytokine produced by both … Problem Unbalanced production of pro- and anti-inflammatory cytokines by immune cells is a hallmark of endometriosis. IL-24, a member of the IL-10 family, is a pleiotropic cytokine produced by both non-immune cells like astrocytes, keratinocytes, pancreatic myofibroblasts, and endothelial cells and immune cells such as monocytes, macrophages, dendritic cells, NK cells, T cells (including Th2 and Th17), and B cells. However, its expression in regulatory T (Tregs) and B lymphocytes (Bregs) has not been explored. In this study, we determined the expression of IL-24 in Tregs and selected Breg subpopulations in women with endometriosis compared with healthy women. Methods Percentages of Tregs, B10 cells, immature B cells, and plasmablasts that produce IL-24 were measured in the peripheral blood of women with endometriosis (n=24) and healthy women (n=24) using flow cytometry. Results We observed an increased percentage of IL-24–producing Tregs in the total pool of women with endometriosis and in women with stages III and IV of endometriosis compared to controls. Within the Breg subpopulations, the percentages of IL-24–producing plasmablasts were higher in the overall endometriosis cohort as well as in women with stage IV endometriosis compared with healthy women. In contrast, the percentages of IL-24–producing immature B cells were lower in the endometriosis group than that in the control group. Conclusions We have shown, for the first time, that Tregs and Bregs secrete IL-24 and that their percentages are altered in endometriosis. The significance of this cytokine secretion by regulatory cells is unclear, but we speculated that IL-24 may enhance the improper immunosuppressive activity of Tregs and plasmablasts in endometriosis, which enables the implantation and growth of endometrial lesions outside the uterus.

S1PR4 promotes cell viability, invasion and glycolysis via the mTOR signaling pathway in endometriosis

2025-06-18

H Yuan , Zhiqin Xie , Minqing Feng +5 more | Gynecologic and Obstetric Investigation

Objective: Endometriosis is a chronic gynecological disorder that can cause infertility in women of reproductive age, and its clinical treatment still faces significant challenges. However, the pathogenesis of endometriosis remains … Objective: Endometriosis is a chronic gynecological disorder that can cause infertility in women of reproductive age, and its clinical treatment still faces significant challenges. However, the pathogenesis of endometriosis remains unclear. Methods: S1PR4 knockdown and overexpression were constructed in primary ectopic endometrial stromal cells (EESCs) with or without the glycolysis inhibitor 2-deoxy-D-glucose (2-DG) and normal endometrial stromal cells (ESCs) with or without the mTOR signaling pathway inhibitor AZD8055, respectively. CCK-8 and Transwell assays were used to evaluate the viability and invasive capabilities. The cellular glycolytic capacity was assessed by measuring the extracellular acidification rate and lactate levels in the cell culture supernatant. An endometriosis mouse model was established in vivo, and histopathological changes in the endometrium were analyzed by hematoxylin-eosin staining. The expression of S1PR4, LDHA, and p-mTOR in endometrium and ESCs was assessed using qRT-PCR, Western blotting or immunofluorescence. Results: Glycolytic levels were increased in EESCs, and inhibiting glycolysis in vitro reduced the viability and invasive capabilities of EESCs, as well as suppressed the growth of ectopic lesions in vivo. S1PR4 was abnormally overexpressed in endometriosis, and knocking down S1PR4 inhibited the viability, invasion, and glycolysis of EESCs, along with downregulation of p-mTOR expression. Conversely, overexpression of S1PR4 promoted the viability, invasion, and glycolysis of ESCs via the mTOR signaling pathway. Conclusions: In endometriosis, S1PR4 enhances cellular glycolysis by activating the mTOR signaling pathway, thereby promoting the viability and invasion of EESCs.

AI In Personalized Treatment Plans For Endometriosis A Data-Driven Approach To Therapy Selection

2025-06-18

Nayar Latif , Rubina Babe , Kainat Raz +3 more | Frontiers in Health Informatics

Background: Endometriosis is a chronic inflammatory disease that affects around 10% of women of reproductive age. It is a cause of pelvic pain, infertility and reduced quality of life. Varying … Background: Endometriosis is a chronic inflammatory disease that affects around 10% of women of reproductive age. It is a cause of pelvic pain, infertility and reduced quality of life. Varying efficacy and patient dissatisfaction is a result of current treatment strategies being empirical and not patient-oriented. Data Integration and Predictive Modelling: AI-based solutions may aid precise therapy selection through data integration and predictive modeling. Objectives:To assess the accuracy of AI algorithms to discover personalized therapeutic approaches for endometriosis from clinical, genetic and imaging data. Study design: A Retrospective Study. Place and duration of study: Department of Gynae Gomal Medical College Dera Ismail Khan Pakistan from January to dec 2023 Methods:100 endometriosis patients from Department of Gynae Gomal Medical College Dera Ismail Khan Pakistan from January to dec 2023. The machine learning models (random forest, logistic regression, Boost) were trained using patient features including the hormonal receptor status, the imaging findings, the genetic polymorphisms, and the prior treatment outcomes. The data was split into training (70%) and validation (30%) sets. We evaluated the performance of the model using AUC-ROC, F1-score, precision and recall metrics for the 10%, 20%, 30% and baseline data set. Results:100 patients were analyzed, with a mean age of 32.7 ± 6.4 years. AUC-ROC with 0.91 proved Boost algorithm to be the runaway winner. Patients chosen for AI-guided therapy also showed a 27 percent greater rate of symptom resolution over those in usual care (p = 0.002). There was also an 18% decrease in treatment switching (p = 0.01), suggesting better compatibility of initial therapy. Predictive features were ESR1 and CYP2C19 polymorphisms, location of lesions, and treatment history. Conclusion:AI-based models predicted the best treatment for endometriosis with high accuracy, ensuring better clinical outcomes and fewer failed trial-and-error approaches. Together, these findings bolster the use of AI as part of personalized care pathways. Additional prospective studies are needed for clinical application. Warning: The above citation should be considered while referencing this article.

Psychiatric symptoms on the ovarian hormone roller-coaster

2025-06-18

Erika Comasco , C. Neill Epperson , Jayashri Kulkarni | The British Journal of Psychiatry

Summary This themed issue examines the impact of ovarian hormone fluctuations on women’s mental health across the lifespan, including puberty, the menstrual cycle, pregnancy, postpartum and menopause. It highlights critical … Summary This themed issue examines the impact of ovarian hormone fluctuations on women’s mental health across the lifespan, including puberty, the menstrual cycle, pregnancy, postpartum and menopause. It highlights critical gaps and calls for sex-specific approaches in reproductive psychiatry and hormone-informed mental care.

Age-Related Dynamics in Endometrial Vascularity: A Comprehensive Three-Dimensional Ultrasound Evaluation During Follicular and Luteal Phases

2025-06-18

Badreldeen Ahmed , Justin C. Konje | Journal of Clinical Medicine

Objective: Transvaginal ultrasonography plays a crucial role in contemporary fertility management, offering insights into uterine and endometrial blood flow. Three-dimensional ultrasonography utilizing power Doppler angiography (3D-CPA) allows precise measurement of … Objective: Transvaginal ultrasonography plays a crucial role in contemporary fertility management, offering insights into uterine and endometrial blood flow. Three-dimensional ultrasonography utilizing power Doppler angiography (3D-CPA) allows precise measurement of endometrial volume and vascular parameters, such as the vascularization index (VI), blood flow index (FI), and vascularization flow index (VFI); variables that indirectly assess endometrial receptivity and integrity. Doppler technology allows for the capture of changes in the uterus induced by hormonal-related fluctuations during the menstrual cycle, revealing a significant correlation between endometrial receptivity and vascularity. Age-related changes in endometrial function are implicated in declining fertility, with limited research exploring this aspect. The aim of this study was to investigate the impact of aging on various ultrasound parameters of the uterus, including endometrial vascularity. Methods: A retrospective cross-sectional study of women who attended the Feto-Maternal Centre from January 2022 to December 2023. Each woman whose menstrual cycle was regular underwent 3D ultrasound with power Doppler as part of the routine assessment of the pelvis. Parameters assessed include the VI, FI, and VFI as well as uterine volume, endometrial volume, and endometrial thickness. The women were grouped based on age, and the variables measured in the follicular and luteal phases were compared between the age groups using SPSS version 30 September 2024. Results: A total of 907 women (427 follicular and 480 luteal phase) were studied: 297 (131 follicular and 166 luteal) were 20-29 years old; 471 (240 follicular and 231 luteal) were aged 30-39; and 139 (56 follicular and 83 luteal) were aged 40-49. Uterine volume, endometrial volume, and thickness increased significantly and steadily with age. VI, VFI, and FI decreased significantly with age in the follicular phase, but in the luteal phase there was no statistically significant difference in any of these indices with age. Conclusions: Uterine volume, endometrial thickness, and endometrial volume increased with age, but the vascular indices decreased with age in the follicular but not in the luteal phase. These age-related changes in endometrial vascularity may partly explain the decrease in age-related fertility. Further research is needed to comprehensively explore the complexities of uterine aging and its implications for female fertility.

“Activism Was a Survival Strategy”: Chronic Illness and the Power of Endometriosis Activism as Work

2025-06-18

Anika König , Caroline Meier zu Biesen | Anthropology of Work Review

ABSTRACT This article is part of the special issue “Laboring from Ex‐Centric Sites: Disability, Chronicity and Work”, Anthropology of Work Review 46(1), July 2025, edited by Giorgio Brocco and Stefanie … ABSTRACT This article is part of the special issue “Laboring from Ex‐Centric Sites: Disability, Chronicity and Work”, Anthropology of Work Review 46(1), July 2025, edited by Giorgio Brocco and Stefanie Mauksch. In this article, we take the example of endometriosis activism to explore the interrelationship between chronic illness, activism, and work. Endometriosis is a life‐limiting condition affecting at least one in ten girls and women, and unmeasured numbers of transgender and gender‐diverse people. While most studies emphasize the disease's negative effects on people's paid work, we extend the concept of work to include the unpaid labor of activism. Moreover, building on critical analyses of care work and activism, we also illuminate the complex link between endometriosis and activism, highlighting both activism's empowering potential and its connection to paid employment. The framing of activism as work also reveals the condition's susceptibility to capitalist performance pressures which may negatively impact health and well‐being, highlighting the broader interplay between activism, political structures, and labor. This article thus makes two key contributions: first, it theorizes activism as an invisible and unpaid form of labor that plays a vital role in shaping the lived experiences, narratives, and public understanding of endometriosis and chronic illness more broadly. Second, it deepens our understanding of the multifaceted implications of endometriosis in relation to labor—both paid and unpaid—thereby situating the condition within broader sociopolitical and economic structures.

Endometriosis and autoimmunity: a large-scale case-control study of endometriosis and 10 distinct autoimmune diseases

2025-06-18

Md. Abdul Aziz , Maura Beaton , Jessica Opoku‐Anane +1 more | npj Women s Health

In this study, we assessed if women with endometriosis have greater odds than matched controls of receiving an autoimmune diagnosis within two-years of their endometriosis diagnosis. We conducted a retrospective … In this study, we assessed if women with endometriosis have greater odds than matched controls of receiving an autoimmune diagnosis within two-years of their endometriosis diagnosis. We conducted a retrospective cohort study using two large-scale administrative claims databases (2010-2017), identifying 332,409 patients with endometriosis and 1,220,932 matched controls. Compared to matched controls, patients with endometriosis had an increased risk of being diagnosed with rheumatoid arthritis, Hashimoto's disease, systemic lupus erythematosus, multiple sclerosis, pernicious anemia, Sjogren's syndrome or myositis within two-years of their endometriosis diagnosis. The odds of receiving a diagnosis of at least one of the autoimmune conditions among patients with endometriosis were approximately two times greater than matched controls. Our study is the first to show a significant association between endometriosis and autoimmune conditions within a two-year diagnosis window, adding to growing evidence suggesting a potential link between endometriosis and autoimmunity, warranting investigation into shared mechanisms.

Validation of self-reported endometriosis

2025-06-18

Dereje G. Gete , Annette J. Dobson , Sally Mortlock +4 more | Maturitas

To assess the validity and reliability of self-reported diagnoses of endometriosis. The study included 8572 women from two Australian birth cohorts (1989-95 and 1973-78), using data from the Genetic variants, … To assess the validity and reliability of self-reported diagnoses of endometriosis. The study included 8572 women from two Australian birth cohorts (1989-95 and 1973-78), using data from the Genetic variants, Early Life exposures, and Longitudinal Endometriosis Symptoms Study (GELLES), a sub-study of the Australian Longitudinal Study on Women's Health. Validity was assessed using predictive values, and reliability was evaluated with kappa statistics. Self-reported endometriosis diagnoses from the GELLES question "Has a doctor or healthcare provider ever diagnosed you with endometriosis?" were validated using a longitudinal survey and linked administrative records as the gold standard. The findings from the 1989-95 and 1973-78 cohorts showed good agreement for overall self-reported endometriosis diagnosis, with uncorrected kappa values of 0.67 and 0.70 (or 0.86 and 0.83 after correction for bias and prevalence effects), and positive predictive values of 0.75 and 0.84, respectively. The agreement was notably stronger for self-reported surgical diagnoses, with uncorrected kappa values of 0.87 and 0.79, and positive predictive values of 0.84 and 0.85, respectively. However, the validity of clinically suspected diagnoses was lower due to the higher occurrence of discrepancies in case assignments. The findings indicate that self-reported endometriosis obtained from two questions about diagnoses made by doctors and specified methods (surgical or clinical) are valid and reliable, particularly for surgical diagnoses. Women's responses to these questions can be reliable for identifying endometriosis cases in epidemiological research. Self-reported data of clinically suspected diagnoses (i.e. without surgical confirmation) should be interpreted cautiously.

Rise and Rise of Endometriosis—An Enigma

2025-06-01

Sujata Dalvi | The Journal of Obstetrics and Gynecology of India