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1.
PLoS One ; 19(6): e0304591, 2024.
Article En | MEDLINE | ID: mdl-38843259

OBJECTIVE: The systemic immuno-inflammatory index (SII), a novel immune marker of inflammation, has not been previously associated with endometriosis. The objective of this research is to explore the link between SII and the occurrence of endometriosis. METHODS: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2001 to 2006, we screened and extracted relevant information from the population. Participants missing data on either SII or endometriosis were excluded. We divided the remaining cohort into quartiles based on SII levels: Q1 (SII < 249, n = 848), Q2 (249 ≤ SII < 604.55, n = 847), Q3 (604.55 ≤ SII < 825.35, n = 847), and Q4 (SII ≥ 852.35, n = 848). Multiple linear regression and smooth curve fitting techniques, were to evaluate the non-linear association between SII and endometriosis. RESULTS: The study included 3,390 adults aged 20 to 55. Multiple linear regression analysis revealed a significant positive correlation between SII and endometriosis [3.14, 95% CI (2.22, 4.45), P < 0.01]. This correlation was consistent across subgroups defined by marital status, poverty income ratio, BMI, alcohol consumption, and age at first menstrual period. However, the relationship between SII and endometriosis was significantly modified by age, education, and history of pregnancy in the stratified analyses. The curve fitting indicated an S-shaped curve, with an inflection point at SII = 1105.76. CONCLUSION: The SII may serve as a predictive marker for endometriosis risk among women in the United States, offering a potentially simple and cost-effective approach. However, given the cross-sectional design of this investigation, further validation in prospective studies is necessary.


Biomarkers , Endometriosis , Inflammation , Nutrition Surveys , Humans , Endometriosis/immunology , Endometriosis/epidemiology , Female , Adult , Cross-Sectional Studies , Middle Aged , Young Adult , United States/epidemiology
2.
J Ovarian Res ; 17(1): 122, 2024 Jun 06.
Article En | MEDLINE | ID: mdl-38844959

INTRODUCTION: Endometriosis is a heritable, complex chronic inflammatory disease, for which much of the causal pathogenic mechanism remain unknown.Despite the high prevalence of ovarian chocolate cyst, its origin is still under debate. METHODS: Prevailing retrograde menstruation model predicts that ectopic endometrial cells migrate and develop into ovarian chocolate cyst. However, other models were also proposed. Genome-wide association studies (GWASs) have proved successful in identifying common genetic variants of moderate effects for various complex diseases. RESULTS: A growing body of evidence shows that the remodeling of retrograde endometrial tissues to the ectopic endometriotic lesions involves multiple epigenetic alterations, such as DNA methylation, histone modification, and microRNA expression.Because DNA methylation states exhibit a tissue specific pattern, we profiled the DNA methylation for ovarian cysts and paired eutopic endometrial and ovarian tissues from four patients. Surprisingly, DNA methylation profiles showed the ovarian cysts were closely grouped with normal ovarian but not endometrial tissues. CONCLUSIONS: These results suggested alterative origin of ovarian cysts or strong epigenetic reprogramming of infiltrating endometrial cells after seeding the ovarian tissue. The data provide contributing to the pathogenesis and pathophysiology of endometriosis.


DNA Methylation , Endometrium , Ovarian Cysts , Ovary , Female , Humans , Ovarian Cysts/genetics , Ovarian Cysts/pathology , Ovarian Cysts/metabolism , Endometrium/metabolism , Endometrium/pathology , Adult , Ovary/metabolism , Ovary/pathology , Endometriosis/genetics , Endometriosis/pathology , Endometriosis/metabolism , Epigenesis, Genetic
3.
PLoS One ; 19(6): e0304766, 2024.
Article En | MEDLINE | ID: mdl-38833439

BACKGROUND: Xenoestrogens are synthetic or naturally occurring chemicals capable of altering the endocrine system of humans and animals owing to their molecular similarity to endogenous hormones. There is limited data regarding their effects on women´s health. Chronic exposure to xenoestrogens can promote the development of estrogen-related diseases. OBJECTIVES: To examine xenoestrogen concentration (TEXB-α) differences between women with leiomyomas or endometriosis and control women, and to study the relationship between the clinical and sociodemographic characteristics of these patients and their xenoestrogen levels. METHODS: Prospective case-control study. We selected 221 women who underwent surgery at Quironsalud Madrid University Hospital between 2017 and 2021. The cases included 117 patients: 74 women who underwent surgery for uterine leiomyomas, 21 with endometriosis, and 22 with both pathologies. The control group comprised 104 healthy women who underwent surgical procedures for other reasons. TEXB-α was determined in the omental fat of all patients. Using a questionnaire and reviewing the patients' medical records, we collected sociodemographic data and other relevant variables. RESULTS: A significant majority of study participants (68.8%) had detectable levels of xenoestrogens. We found no association between TEXB-α levels in omental fat and the presence of myomas or endometriosis. In the case group, women living or working in Madrid Community exhibited, on average, 3.12 Eeq pM/g higher levels of TEXB-α compared to those working in other areas (p = 0.030). Women who referred to the use of estrogen-containing hormonal contraceptives had, on average, 3.02 Eeq pM/g higher levels of TEXB-α than those who had never used them (p = 0.022). CONCLUSIONS: This study found no association between omental xenoestrogen levels and leiomyomas or endometriosis. However, their presence in most participants and their association with highly polluted areas emphasizes the importance of limiting environmental exposure to these substances. We also identified an association between hormonal contraceptive use and xenoestrogen concentration.


Endometriosis , Leiomyoma , Humans , Female , Leiomyoma/surgery , Adult , Case-Control Studies , Middle Aged , Prospective Studies , Uterine Neoplasms , Estrogens/analysis
4.
PLoS One ; 19(5): e0300186, 2024.
Article En | MEDLINE | ID: mdl-38722932

INTRODUCTION: Endometriosis is a chronic disease that affects up to 190 million women and those assigned female at birth and remains unresolved mainly in terms of etiology and optimal therapy. It is defined by the presence of endometrium-like tissue outside the uterine cavity and is commonly associated with chronic pelvic pain, infertility, and decreased quality of life. Despite the availability of various screening methods (e.g., biomarkers, genomic analysis, imaging techniques) intended to replace the need for invasive surgery, the time to diagnosis remains in the range of 4 to 11 years. AIMS: This study aims to create a large prospective data bank using the Lucy mobile health application (Lucy app) and analyze patient profiles and structured clinical data. In addition, we will investigate the association of removed or restricted dietary components with quality of life, pain, and central pain sensitization. METHODS: A baseline and a longitudinal questionnaire in the Lucy app collects real-world, self-reported information on symptoms of endometriosis, socio-demographics, mental and physical health, economic factors, nutritional, and other lifestyle factors. 5,000 women with confirmed endometriosis and 5,000 women without diagnosed endometriosis in a control group will be enrolled and followed up for one year. With this information, any connections between recorded symptoms and endometriosis will be analyzed using machine learning. CONCLUSIONS: We aim to develop a phenotypic description of women with endometriosis by linking the collected data with existing registry-based information on endometriosis diagnosis, healthcare utilization, and big data approach. This may help to achieve earlier detection of endometriosis with pelvic pain and significantly reduce the current diagnostic delay. Additionally, we may identify dietary components that worsen the quality of life and pain in women with endometriosis, upon which we can create real-world data-based nutritional recommendations.


Early Diagnosis , Endometriosis , Machine Learning , Quality of Life , Self Report , Humans , Endometriosis/diagnosis , Female , Adult , Pelvic Pain/diagnosis , Prospective Studies , Mobile Applications
5.
PLoS One ; 19(5): e0292978, 2024.
Article En | MEDLINE | ID: mdl-38728307

Endosalpingiosis (ES) and endometriosis (EM) refer to the growth of tubal and endometrial epithelium respectively, outside of their site of origin. We hypothesize that uterine secretome factors drive ectopic growth. To test this, we developed a mouse model of ES and EM using tdTomato (tdT) transgenic fluorescent mice as donors. To block implantation factors, progesterone knockout (PKO) tdT mice were created. Fluorescent lesions were present after oviduct implantation with and without WT endometrium. Implantation was increased (p<0.05) when tdt oviductal tissue was implanted with endometrium compared to oviductal tissue alone. Implantation was reduced (p<0.0005) in animals implanted with minced tdT oviductal tissue with PKO tdT endometrium compared to WT endometrium. Finally, oviductal tissues was incubated with and without a known implantation factor, leukemia inhibitory factor (LIF) prior to and during implantation. LIF promoted lesion implantation. In conclusion, endometrial derived implantation factors, such as LIF, are necessary to initiate ectopic tissue growth. We have developed an animal model of ectopic growth of gynecologic tissues in a WT mouse which will potentially allow for development of new prevention and treatment modalities.


Endometriosis , Endometrium , Uterus , Animals , Female , Mice , Endometriosis/metabolism , Endometriosis/pathology , Endometriosis/genetics , Uterus/metabolism , Endometrium/metabolism , Leukemia Inhibitory Factor/metabolism , Leukemia Inhibitory Factor/genetics , Secretome/metabolism , Mice, Transgenic , Disease Models, Animal , Fallopian Tubes/metabolism , Progesterone/metabolism , Mice, Knockout , Embryo Implantation/physiology
6.
PLoS One ; 19(5): e0302108, 2024.
Article En | MEDLINE | ID: mdl-38696383

OBJECTIVE: To assess the reporting quality of published RCT abstracts regarding patients with endometriosis pelvic pain and investigate the prevalence and characteristics of spin in these abstracts. METHODS: PubMed and Scopus were searched for RCT abstracts addressing endometriosis pelvic pain published from January 1st, 2010 to December 1st, 2023.The reporting quality of RCT abstracts was assessed using the CONSORT statement for abstracts. Additionally, spin was evaluated in the results and conclusions section of the abstracts, defined as the misleading reporting of study findings to emphasize the perceived benefits of an intervention or to confound readers from statistically non-significant results. Assessing factors affecting the reporting quality and spin existence, linear and logistic regression was used, respectively. RESULTS: A total of 47 RCT abstracts were included. Out of 16 checklist items, only three items including objective, intervention and conclusions were sufficiently reported in the most abstracts (more than 95%), and none of the abstracts presented precise data as required by the CONSORT-A guidelines. In the reporting quality of material and method section, trial design, type of randomization, the generation of random allocation sequences, the allocation concealment and blinding were most items identified that were suboptimal. The total score for the quality varied between 5 and 15 (mean: 9.59, SD: 3.03, median: 9, IQR: 5). Word count (beta = 0.015, p-value = 0.005) and publishing in open-accessed journals (beta = 2.023, p-value = 0.023) were the significant factors that affecting the reporting quality. Evaluating spin within each included paper, we found that 18 (51.43%) papers had statistically non-significant results. From these studies, 12 (66.66%) had spin in both results and conclusion sections. Furthermore, the spin intensity increased during 2010-2023 and 38.29% of abstracts had spin in both results and conclusion sections. CONCLUSION: Overall poor adherence to CONSORT-A was observed, with spin detected in several RCTs featuring non-significant primary endpoints in obstetrics and gynecology literature.


Endometriosis , Randomized Controlled Trials as Topic , Humans , Female , Randomized Controlled Trials as Topic/standards , Research Design/standards , Pelvic Pain , Abstracting and Indexing/standards
7.
Am J Reprod Immunol ; 91(5): e13856, 2024 May.
Article En | MEDLINE | ID: mdl-38709906

INTRODUCTION: Endometriosis is a chronic inflammatory disease that leads to a series of pathological reactions. The basis is a changed proinflammatory activated immune system, which results in more pronounced oxidative stress, disturbed function of proteolysis and cell apoptosis. These processes are crucial in the development of the disease because their dysfunctional activities cause the progression of the disease. It is believed that the proteins excreted in the urine interact with each other and promote pathological processes in endometriosis. METHODS: We analyzed the urine proteome of patients and aimed to detect a potential protein biomarker for endometriosis in the urine proteome. We collected urine samples from 16 patients with endometriosis and 16 patients in the control group with functional ovarian cysts. The diagnosis for all patients was confirmed through pathohistological analysis. After the preanalytical preparation of the urine, chromatography and mass spectrometry (LC-MS/MS) used the technology of urine proteome analysis. RESULTS: The main finding was a significantly different concentration of 14 proteins in the urine samples. We recorded a considerably higher concentration of proteins that have a significant role in activating the immune system (SELL), iron metabolism (HAMP) and cell apoptosis (CHGA) in endometriosis compared to controls. Proteins having an antioxidant function (SOD1) and a role in proteolysis of the extracellular matrix (MMP-9) were significantly reduced in endometriosis compared to controls. CONCLUSION: Consistent with the known pathogenesis of endometriosis, the study results complement the pathological responses that occur with disease progression.


Biomarkers , Endometriosis , Humans , Endometriosis/urine , Endometriosis/diagnosis , Female , Biomarkers/urine , Adult , Superoxide Dismutase-1/urine , Tandem Mass Spectrometry , Proteome , Matrix Metalloproteinase 9/urine , Proteomics/methods , Chromatography, Liquid , Oxidative Stress
8.
Front Endocrinol (Lausanne) ; 15: 1352770, 2024.
Article En | MEDLINE | ID: mdl-38699387

Background: The efficiency of different first-line treatments, such as first-line surgery and assisted reproductive technology (ART), in women with deep infiltrating endometriosis (DIE) is still unclear due to a lack of direct comparative trials. This systematic review and meta-analysis aim to elucidate and compare the efficacies of first-line treatments in patients with DIE, with an emphasis on fertility outcomes. Methods: An exhaustive search of PubMed Central, SCOPUS, EMBASE, MEDLINE, Cochrane trial registry, Google Scholar, and Clinicaltrials.gov databases was done to identify studies directly comparing first-line surgery and assisted reproductive technology (ART) for DIE, and reporting fertility-related outcomes. Pooled estimates for each of the binary outcomes were reported as odds ratios (ORs) with 95% confidence intervals (CIs). The results were pooled using a random-effects model with the Mantel-Haenszel technique. Results: Our results show that pregnancy rate per patient (OR, 1.47; 95% CI, 0.59 to 3.63), pregnancy rate per cycle (OR, 1.16; 95% CI, 0.45 to 2.99), and live births per patient (OR, 1.66; 95% CI, 0.56 to 4.91) were comparable in DIE patients, treated with surgery or ART as a first line of treatment. When both complete and incomplete surgical DIE excision procedures were taken into account, surgery was associated with a significant enhancement in the pregnancy rate per patient (OR, 1.63; 95% CI, 1.11 to 2.40). Conclusion: The available evidence suggests that both first-line surgery and ART can be effective DIE treatments with similar fertility outcomes. However, further analysis reveals that excluding studies involving endometriomas significantly alters the understanding of treatment efficacy between surgery and ART for DIE-associated infertility. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=426061, identifier CRD42023426061.


Endometriosis , Infertility, Female , Pregnancy Rate , Reproductive Techniques, Assisted , Humans , Endometriosis/surgery , Female , Pregnancy , Infertility, Female/surgery , Infertility, Female/therapy
9.
FASEB J ; 38(9): e23622, 2024 May 15.
Article En | MEDLINE | ID: mdl-38703029

Endometriosis (EMs)-related infertility commonly has decreased endometrial receptivity and normal decidualization is the basis for establishing and maintaining endometrial receptivity. However, the potential molecular regulatory mechanisms of impaired endometrial decidualization in patients with EMs have not been fully clarified. We confirmed the existence of reduced endometrial receptivity in patients with EMs by scanning electron microscopy and quantitative real-time PCR. Here we identified an lncRNA, named BMPR1B-AS1, which is significantly downregulated in eutopic endometrium in EMs patients and plays an essential role in decidual formation. Furthermore, RNA pull-down, mass spectrometry, RNA immunoprecipitation, and rescue analyses revealed that BMPR1B-AS1 positively regulates decidual formation through interaction with the RNA-binding protein insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Downregulation of IGF2BP2 led to a decreased stability of BMPR1B-AS1 and inhibition of activation of the SMAD1/5/9 pathway, an inhibitory effect which diminished decidualization in human endometrial stromal cells (hESCs) decidualization. In conclusion, our identified a novel regulatory mechanism in which the IGF2BP2-BMPR1B-AS1-SMAD1/5/9 axis plays a key role in the regulation of decidualization, providing insights into the potential link between abnormal decidualization and infertility in patients with EMs, which will be of clinical significance for the management and treatment of infertility in patients with EMs.


Endometriosis , RNA, Long Noncoding , RNA-Binding Proteins , Adult , Female , Humans , Bone Morphogenetic Protein Receptors, Type I/metabolism , Bone Morphogenetic Protein Receptors, Type I/genetics , Decidua/metabolism , Decidua/pathology , Endometriosis/metabolism , Endometriosis/genetics , Endometriosis/pathology , Endometrium/metabolism , Endometrium/pathology , Infertility, Female/metabolism , Infertility, Female/genetics , Infertility, Female/pathology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Signal Transduction , Stromal Cells/metabolism , Smad Proteins , Young Adult
10.
Zhonghua Jie He He Hu Xi Za Zhi ; 47(5): 460-463, 2024 May 12.
Article Zh | MEDLINE | ID: mdl-38706069

Hemorrhagic pleural effusion (PE) is common in clinical practice. According to the guidelines, the etiological diagnosis of PE should focus on the identification of common diseases. In most cases, the etiology of PE can be determined by clinical history, physical examination, laboratory and imaging examinations, and pleural biopsy or video-assisted thoracic surgery (VAST). We reported a rare case of a 32-year-old woman with recurrent unilateral hemorrhagic pleural effusion (highly correlated with menstrual cycle) and chest pain that was diagnosed as thoracic endometriosis syndrome (TES) by pathological biopsy and immunohistochemistry. Later she underwent surgery combined with hormone therapy. During the follow-up, the right PE decreased, and she had no chest pain. Therefore, women of reproductive age with regular unilateral bloody pleural effusions should be alert to TES.


Endometriosis , Pleural Effusion , Humans , Female , Adult , Endometriosis/complications , Endometriosis/diagnosis , Pleural Effusion/etiology , Pleural Effusion/diagnosis , Recurrence , Hemorrhage/etiology , Hemorrhage/diagnosis
11.
Front Endocrinol (Lausanne) ; 15: 1397279, 2024.
Article En | MEDLINE | ID: mdl-38800489

Currently, three crucial questions regarding the reliability of ovarian reserve measures in women with ovarian endometrioma during the reproductive age are being discussed. Firstly, the effects of endometriotic cystectomy on short and long-term ovarian reserve. Secondly, the accuracy of serum anti-Müllerian hormone (AMH) and antral follicle count (AFC) in estimating ovarian reserve in these cases. Thirdly, the impact of endometrioma itself on the ovarian reserve over time in such cases. The purpose of the present review is to critically assess available systematic reviews and meta-analyses that have explored these questions. Nine eligible reviews were found following a systematic search on PubMed.com and similarly assessed. These reviews varied considerably regarding the level of evidence, as per an identical comprehensive scoring system. Moderate to high-quality evidence demonstrates that endometriotic cystectomy, by the stripping technique, adversely affects ovarian reserve in the short and long term, up to 9-18 months post-surgery. Damage to ovarian reserve was considerable but more pronounced in bilateral cases than unilateral cases, equivalent to 39.5% and 57.0%, respectively. Repeat endometriotic cystectomy is detrimental to ovarian reserve. The impact of endometrioma diameter on ovarian reserve before or after surgery is still unclear. Moderate to high-quality evidence, relying on simultaneous assessment of both ovarian reserve measures, shows that AMH is sensitive while AFC is not in cases undergoing ovarian cystectomy. AMH should be the biomarker of choice for counseling and managing women with endometrioma in their reproductive age, especially before surgery. While there is some evidence to show that endometrioma per se may harm ovarian reserve, this evidence is not robust, and there is good-quality evidence to challenge this notion. It is necessary to conduct further targeted RCTs, systematic reviews, and meta-analyses based on solid methodological grounds to increase the level of evidence, refine quantitative estimates, investigate open questions, and decrease heterogeneity.


Anti-Mullerian Hormone , Endometriosis , Ovarian Follicle , Ovarian Reserve , Humans , Female , Endometriosis/surgery , Endometriosis/blood , Endometriosis/pathology , Anti-Mullerian Hormone/blood , Ovarian Reserve/physiology , Ovarian Follicle/pathology , Ovarian Diseases/surgery , Ovarian Diseases/blood , Ovarian Diseases/pathology , Systematic Reviews as Topic
12.
Taiwan J Obstet Gynecol ; 63(3): 350-356, 2024 May.
Article En | MEDLINE | ID: mdl-38802198

OBJECTIVE: Endometriosis is associated with higher risk of ectopic pregnancy, premature delivery, miscarriage, and other adverse maternal and fetal complications. This study aimed to assess the impact of endometriosis on maternal and fetal outcomes of singleton pregnancies in a large nationally representative database. MATERIALS AND METHODS: This population-based, retrospective observational study extracted the data of women aged 20-49 years with singleton, spontaneously conceived pregnancies from the US Nationwide Inpatient Sample (NIS) database from 2005 to 2018. Included subjects were divided into those with ICD codes for endometriosis and those without (non-endometriosis group). Data of maternal and fetal outcomes were compared between groups and analyzed using regression analysis. RESULTS: After excluding 17,124 women who conceived with assisted reproductive technology (ART), 162,155 women with multiple pregnancies, and 27,847 with abnormal trend weight values (TRENDWT), a total of 8,584,269 women were eligible. After propensity score matching (PMS) case-control 1:4 by age, 45,560 remained (9112 (0.1%) with endometriosis, 36,448 without) and were included in the analysis. The mean age of women before matching was 28.7 years, and 30.5 years after matching. The most common comorbidity was chronic pulmonary disease (3.6%). Smoking frequency was higher in women with endometriosis compared to those without (4.8% vs. 2.4%). Multivariable analysis adjusted for confounders revealed that endometriosis was associated with significantly higher risk of maternal complications, including pre-eclampsia and eclampsia, antepartum hemorrhage, placenta previa, Cesarean delivery, post-partum hemorrhage, disseminated intravascular coagulation (DIC), transfusion, hemoperitoneum, and hospital stays ≥6 days. For fetal outcomes, endometriosis was associated with higher risk of intrauterine growth restriction (IUGR), premature birth, birth defects and abortion. CONCLUSION: Endometriosis during pregnancy is associated with maternal and fetal complications. Study findings may serve as a benchmark for expanding medical assistance for endometriosis-affected pregnant women.


Endometriosis , Pregnancy Complications , Humans , Female , Pregnancy , Endometriosis/epidemiology , Endometriosis/complications , Adult , Retrospective Studies , United States/epidemiology , Pregnancy Complications/epidemiology , Middle Aged , Young Adult , Pregnancy Outcome/epidemiology , Databases, Factual , Premature Birth/epidemiology , Risk Factors , Case-Control Studies , Cesarean Section/statistics & numerical data
13.
Front Endocrinol (Lausanne) ; 15: 1359236, 2024.
Article En | MEDLINE | ID: mdl-38742190

Background: Previous study suggested evidence for coexistence and similarities between endometriosis and polycystic ovary syndrome (PCOS), but it is unclear regarding the shared genetic architecture and causality underlying the phenotypic similarities observed for endometriosis and PCOS. Methods: By leveraging summary statistics from public genome-wide association studies regarding endometriosis (European-based: N=470,866) and PCOS (European-based: N=210,870), we explored the genetic correlation that shared between endometriosis and PCOS using linkage disequilibrium score regression. Shared risk SNPs were derived using PLACO (Pleiotropic analysis under composite null hypothesis) and FUMA (Functional Mapping and Annotation of Genetic Associations). The potential causal association between endometriosis and PCOS was investigated using two-sample Mendelian randomization (MR). Linkage disequilibrium score for the specific expression of genes analysis (LDSC-SEG) were performed for tissue enrichment analysis. The expression profiles of the risk gene in tissues were further examined. Results: A positive genetic association was observed between endometriosis and PCOS. 12 significant pleiotropic loci shared between endometriosis and PCOS were identified. Genetic associations between endometriosis and PCOS were particularly enriched in uterus, endometrium and fallopian tube. Two-sample MR analysis further indicated a potential causative effect of endometriosis on PCOS, and vice versa. Microarray and RNA-seq verified the expressions of SYNE1 and DNM3 were significantly altered in the endometrium of patients with endometriosis or PCOS compared to those of control subjects. Conclusion: Our study indicates the genetic correlation and shared risk genes between PCOS and endometriosis. These findings provide insights into the potential mechanisms behind their comorbidity and the future development of therapeutics.


Endometriosis , Genetic Predisposition to Disease , Genome-Wide Association Study , Polycystic Ovary Syndrome , Polymorphism, Single Nucleotide , Humans , Polycystic Ovary Syndrome/genetics , Endometriosis/genetics , Female , Linkage Disequilibrium , Mendelian Randomization Analysis
14.
Molecules ; 29(9)2024 May 01.
Article En | MEDLINE | ID: mdl-38731586

Nanomedicine has revolutionized drug delivery in the last two decades. Nanoparticles appear to be a promising drug delivery platform in the treatment of various gynecological disorders including uterine leiomyoma, endometriosis, polycystic ovarian syndrome (PCOS), and menopause. Nanoparticles are tiny (mean size < 1000 nm), biodegradable, biocompatible, non-toxic, safe, and relatively inexpensive materials commonly used in imaging and the drug delivery of various therapeutics, such as chemotherapeutics, small molecule inhibitors, immune mediators, protein peptides and non-coding RNA. We performed a literature review of published studies to examine the role of nanoparticles in treating uterine leiomyoma, endometriosis, PCOS, and menopause. In uterine leiomyoma, nanoparticles containing 2-methoxyestradiole and simvastatin, promising uterine fibroid treatments, have been effective in significantly inhibiting tumor growth compared to controls in in vivo mouse models with patient-derived leiomyoma xenografts. Nanoparticles have also shown efficacy in delivering magnetic hyperthermia to ablate endometriotic tissue. Moreover, nanoparticles can be used to deliver hormones and have shown efficacy as a mechanism for transdermal hormone replacement therapy in individuals with menopause. In this review, we aim to summarize research findings and report the efficacy of nanoparticles and nanotherapeutics in the treatment of various benign gynecologic conditions.


Genital Diseases, Female , Nanomedicine , Nanoparticles , Humans , Female , Nanomedicine/methods , Nanoparticles/chemistry , Animals , Genital Diseases, Female/drug therapy , Drug Delivery Systems , Leiomyoma/drug therapy , Endometriosis/drug therapy , Polycystic Ovary Syndrome/drug therapy
15.
Am J Reprod Immunol ; 91(5): e13855, 2024 May.
Article En | MEDLINE | ID: mdl-38745499

Endometriosis (EM) is one of the diseases related to retrograded menstruation and hemoglobin. Heme, released from hemoglobin, is degraded by heme oxygenase-1 (HO-1). In EM lesions, heme metabolites regulate processes such as inflammation, redox balance, autophagy, dysmenorrhea, malignancy, and invasion, where macrophages (Mø) play a fundamental role in their interactions. Regulation occurs at molecular, cellular, and pathological levels. Numerous studies suggest that heme is an indispensable component in EM and may contribute to its pathogenesis. The regulatory role of heme in EM encompasses cytokines, signaling pathways, and kinases that mediate cellular responses to external stimuli. HO-1, a catalytic enzyme in the catabolic phase of heme, mitigates heme's cytotoxicity in EM due to its antioxidant, anti-inflammatory, and anti-proliferative properties. Certain compounds may intervene in EM by targeting heme metabolism, guiding the development of appropriate treatments for all stages of endometriosis.


Endometriosis , Heme Oxygenase-1 , Heme , Endometriosis/metabolism , Endometriosis/drug therapy , Female , Humans , Heme/metabolism , Heme Oxygenase-1/metabolism , Animals , Signal Transduction , Macrophages/metabolism , Macrophages/immunology , Autophagy , Cytokines/metabolism
16.
Int J Med Robot ; 20(3): e2636, 2024 Jun.
Article En | MEDLINE | ID: mdl-38757434

BACKGROUND: To assess the feasibility of use of indocyanine green (ICG) in identifying and minimising urinary tract injury during surgical resection of endometriosis through robotic transvaginal natural orifice transluminal endoscopy surgery (RvNOTES). METHODS: We conducted a retrospective case series in two academic tertiary care hospitals. We examined 53 patients who underwent RvNOTES hysterectomy with planned endometriosis resection. RESULTS: The study involved 53 patients undergoing RvNOTES with ICG fluorescence for endometriosis resection. Mean patient age was 37.98 ± 6.65 years. Operative time averaged 181.32 ± 53.94 min, with estimated blood loss at 45.57 ± 33.62 mL. Postoperative stay averaged 0.23 ± 0.47 days. No ICG-related complications occurred. CONCLUSION: No complications occurred with ICG fluorescence in RvNOTES. It appears to be a safe option for ureteral localisation and preservation. ICG fluorescence is widely used in diverse medical specialities for identifying ureters during complex surgeries. Larger studies are needed to firmly establish its advantages in intraoperative ureteral visualisation during RvNOTES for deep infiltrative endometriosis.


Endometriosis , Feasibility Studies , Indocyanine Green , Natural Orifice Endoscopic Surgery , Robotic Surgical Procedures , Ureter , Humans , Female , Endometriosis/surgery , Endometriosis/diagnostic imaging , Robotic Surgical Procedures/methods , Adult , Retrospective Studies , Natural Orifice Endoscopic Surgery/methods , Ureter/surgery , Middle Aged , Fluorescence , Vagina/surgery , Operative Time , Hysterectomy/methods
17.
J Robot Surg ; 18(1): 212, 2024 May 16.
Article En | MEDLINE | ID: mdl-38753180

Endometriosis is a benign inflammatory onco-mimetic disease affecting 10-15% of women in the world. When it is refractory to medical treatments, surgery may be required. Usually, laparoscopy is the preferred approach, but robotic surgery has gained popularity in the last 15 years. This study aims to evaluate the safety and efficacy of robotic-assisted laparoscopic surgery (RAS) versus conventional laparoscopic surgery (LPS) in the treatment of endometriosis. This study adheres to PRISMA guidelines and is registered with PROSPERO. Studies reporting perioperative data comparing RAS and LPS surgery in patients with endometriosis querying PubMed, Google Scholar and ClinicalTrials.gov were included in the analysis. The Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2) was used for the quality assessment of the selected articles. Fourteen studies were identified, including 2709 patients with endometriosis stage I-IV for the meta-analysis. There were no significant differences between RAS and LPS in terms of intraoperative and postoperative complications, conversion rate and estimated blood loss. However, patients in the RAS group have a longer operative time (p < 0.0001) and longer hospital stay (p = 0.020) than those in the laparoscopic group. Robotic surgery is not inferior to laparoscopy in patients with endometriosis in terms of surgical outcomes; however, RAS requires longer operative times and longer hospital stay. The benefits of robotic surgery should be sought in the easiest potential integration of robotic platforms with new technologies. Prospective studies comparing laparoscopy to the new robotic systems are desirable for greater robustness of scientific evidence.


Endometriosis , Laparoscopy , Operative Time , Robotic Surgical Procedures , Endometriosis/surgery , Humans , Female , Robotic Surgical Procedures/methods , Laparoscopy/methods , Treatment Outcome , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Length of Stay , Blood Loss, Surgical/statistics & numerical data
18.
BMJ ; 385: e079006, 2024 05 15.
Article En | MEDLINE | ID: mdl-38749550

OBJECTIVES: To evaluate the clinical effectiveness of long acting progestogens compared with the combined oral contraceptive pill in preventing recurrence of endometriosis related pain. DESIGN: The PRE-EMPT (preventing recurrence of endometriosis) pragmatic, parallel group, open label, randomised controlled trial. SETTING: 34 UK hospitals. PARTICIPANTS: 405 women of reproductive age undergoing conservative surgery for endometriosis. INTERVENTIONS: Participants were randomised in a 1:1 ratio using a secure internet facility to a long acting progestogen (depot medroxyprogesterone acetate or levonorgestrel releasing intrauterine system) or the combined oral contraceptive pill. MAIN OUTCOME MEASURES: The primary outcome was pain measured three years after randomisation using the pain domain of the Endometriosis Health Profile 30 (EHP-30) questionnaire. Secondary outcomes (evaluated at six months, one, two, and three years) included the four core and six modular domains of the EHP-30, and treatment failure (further therapeutic surgery or second line medical treatment). RESULTS: 405 women were randomised to receive a long acting progestogen (n=205) or combined oral contraceptive pill (n=200). At three years, there was no difference in pain scores between the groups (adjusted mean difference -0.8, 95% confidence interval -5.7 to 4.2, P=0.76), which had improved by around 40% in both groups compared with preoperative values (an average of 24 and 23 points for long acting progestogen and combined oral contraceptive pill groups, respectively). Most of the other domains of the EHP-30 also showed improvement at all time points compared with preoperative scores, without evidence of any differences between groups. Women randomised to a long acting progestogen underwent fewer surgical procedures or second line treatments compared with those randomised to the combined oral contraceptive pill group (73 v 97; hazard ratio 0.67, 95% confidence interval 0.44 to 1.00). CONCLUSIONS: Postoperative prescription of a long acting progestogen or the combined oral contraceptive pill results in similar levels of improvement in endometriosis related pain at three years, with both groups showing around a 40% improvement compared with preoperative levels. While women can be reassured that both options are effective, the reduced risk of repeat surgery for endometriosis and hysterectomy might make long acting reversible progestogens preferable for some. TRIAL REGISTRATION: ISRCTN registry ISRCTN97865475.


Contraceptives, Oral, Combined , Endometriosis , Levonorgestrel , Medroxyprogesterone Acetate , Humans , Female , Endometriosis/surgery , Endometriosis/drug therapy , Endometriosis/complications , Contraceptives, Oral, Combined/therapeutic use , Contraceptives, Oral, Combined/administration & dosage , Adult , Levonorgestrel/administration & dosage , Levonorgestrel/therapeutic use , Medroxyprogesterone Acetate/administration & dosage , Medroxyprogesterone Acetate/therapeutic use , Pelvic Pain/drug therapy , Pelvic Pain/prevention & control , Pelvic Pain/etiology , Progestins/administration & dosage , Progestins/therapeutic use , Pain Measurement , Secondary Prevention/methods , Treatment Outcome , Young Adult , Intrauterine Devices, Medicated
19.
Eur J Obstet Gynecol Reprod Biol ; 297: 227-232, 2024 Jun.
Article En | MEDLINE | ID: mdl-38691975

AIM: To assess the benefit of prophylactic abdominal drainage (AD) after colorectal surgery for endometriosis. METHODS: We conducted a retrospective study of 215 patients who underwent colorectal surgery for endometriosis using a mini-invasive approach in our center from February 2019 to July 2023. A propensity score matched (PSM) analysis (1:1 ratio) identified two groups of patients with similar characteristics. Postoperative outcomes were then compared. RESULTS: In the unmatched cohort, 151 patients (70 %) had AD at the end of surgery and 64 (30 %) did not. Clinical characteristics and surgical procedures were comparable between the groups after PSM. After PSM, AD was associated with a longer hospital stay (p < 0.001) and a greater number of postoperative complications (p = 0.03). There were no differences for readmission, repeat surgery, or severe postoperative complications. CONCLUSION: In this retrospective cohort of patients undergoing colorectal resection for endometriosis using a mini-invasive approach, prophylactic AD was not found to be beneficial.


Drainage , Endometriosis , Postoperative Complications , Propensity Score , Humans , Female , Endometriosis/surgery , Retrospective Studies , Adult , Drainage/methods , Postoperative Complications/prevention & control , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Length of Stay/statistics & numerical data
20.
Eur J Obstet Gynecol Reprod Biol ; 297: 214-220, 2024 Jun.
Article En | MEDLINE | ID: mdl-38691973

OBJECTIVE: To analyze the factors that might influence the pregnancy rate in patients with infertility related to endometriosis (EMs) after undergoing laparoscopic surgery, providing guidance for our clinical diagnostic and therapeutic decision-making. METHODS: A retrospective analysis was conducted on clinical records and 1-year postoperative pregnancy outcomes of 335 patients diagnosed with endometriosis-related infertility via laparoscopic surgery, admitted to our department from January 2018 to December 2020. RESULTS: The overall pregnancy rate for patients with endometriosis (EMs) related infertility 1-year post-surgery was 57.3 %, with the highest pregnancy rate observed between 3 to 6 months after surgery. Factors such as Body Mass Index (BMI) (P = 0.515), presence of dysmenorrhea (P = 0.515), previous pelvic surgery (P = 0.247), type of EMs pathology (P = 0.893), and preoperative result of serum carbohydrate antigen 125 (CA125)(P = 0.615)had no statistically significant effect on postoperative pregnancy rates. The duration of infertility (P = 0.029), coexistence of adenomyosis (P = 0.042), surgery duration (P = 0.015), intraoperative blood loss (P = 0.050), preoperative result of serum anti-Müllerian hormone (AMH) (P = 0.002) and age greater than 35 (P = 0.000) significantly impacted postoperative pregnancy rates. The post-surgery pregnancy rate in patients with mild (Stage I-II) EMs was notably higher than those with moderate to severe (Stage III-IV) EMs (P = 0.009). Age (P = 0.002), EMs stage (P = 0.018), intraoperative blood loss (P = 0.010) and adenomyosis (P = 0.022) were the factors that affected the postoperative live birth rate. CONCLUSION: For patients with EMs-related infertility undergoing laparoscopic surgery, factors such as age > 35 years, infertility duration > 3 years, concurrent adenomyosis, severe EMs, surgery duration ≥ 2 h, intraoperative blood loss ≥ 50 ml, and low AMH before surgery are detrimental for the pregnancy rate within the first postoperative year. However, BMI, dysmenorrhea, past history of pelvic surgery, EMs pathology types (ovarian, peritoneal, deep infiltrating),and preoperative result of serum CA125 barely show any statistical difference in their effect on postoperative pregnancy rates. In terms of postoperative live birth rate, age > 35 years, severe EMs, intraoperative blood loss ≥ 50 ml, and adenomyosis were adverse factors.


Endometriosis , Infertility, Female , Laparoscopy , Pregnancy Rate , Humans , Female , Endometriosis/surgery , Endometriosis/complications , Endometriosis/blood , Pregnancy , Adult , Retrospective Studies , Infertility, Female/surgery , Infertility, Female/etiology , Infertility, Female/blood
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