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Chen Y, Liu C, Wang X, Liu Y, Liu H. Global, Regional and National Burden of Infertility due to Endometriosis: Results From the Global Burden of Disease Study 2021 and Forecast to 2044. BJOG 2025; 132:944-960. [PMID: 39996398 DOI: 10.1111/1471-0528.18108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Revised: 02/07/2025] [Accepted: 02/09/2025] [Indexed: 02/26/2025]
Abstract
OBJECTIVE To analyse global prevalence data for infertility due to endometriosis from 1990 to 2021, emphasising health inequalities. DESIGN Population-based study. SETTING Data from the Global Burden of Disease (GBD) database. POPULATION Individuals diagnosed with infertility due to endometriosis. METHODS A statistical method was employed to evaluate changes in disease prevalence over time. We also analysed how disease prevalence varies by age, time period and birth cohort. A model was used to predict future trends. Additionally, we examined the relationship between prevalence and the socio-demographic index (SDI) levels across countries. Finally, we conducted a decomposition analysis to identify key factors driving changes and assessed health inequality. MAIN OUTCOME MEASURES The burden of infertility due to endometriosis. RESULTS The global burden of infertility due to endometriosis in 2021 showed a downward trend, and the low SDI region had a notably higher burden. High risk was observed in the 25-29 age group in the age effects analysis. Period risks almost kept decreasing over these years, and for cohort effects, the later born individuals showed an overall lower risk than the earlier born individuals. Cross-country inequality analysis revealed significant disparities, with countries in lower SDI categories bearing a higher burden. CONCLUSIONS The global burden of infertility due to endometriosis has become a significant public health concern over recent decades. Governments should adapt prevention strategies to fit their specific national contexts.
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Affiliation(s)
- Yue Chen
- Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Cheng Liu
- Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Xiuping Wang
- Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Yi Liu
- Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Hengwei Liu
- Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, China
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Hong Y. Prioritization of potential drug targets in ovarian-related diseases: Mendelian randomization and colocalization analyses. F&S SCIENCE 2025; 6:164-176. [PMID: 39988236 DOI: 10.1016/j.xfss.2025.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 02/13/2025] [Accepted: 02/14/2025] [Indexed: 02/25/2025]
Abstract
OBJECTIVE To identify key genes and potential drug targets for ovarian-related diseases through genome-wide Mendelian randomization (MR) and colocalization analyses. DESIGN We conducted a comprehensive two-sample MR analysis to estimate the causal effects of blood expression quantitative trait loci (eQTLs) on ovarian-related diseases, followed by colocalization analyses to verify the robustness of the expression instrumental variables (IVs). Phenome-wide association studies (PheWAS) were also performed to evaluate the horizontal pleiotropy of potential drug targets and possible side effects. SUBJECTS Large cohorts of European ancestry. EXPOSURE The exposure in this study was the genetic variants (eQTLs) associated with gene expression levels, considered a form of lifelong exposure. Expression quantitative trait loci data were obtained from the eQTLGen Consortium, encompassing 16,987 genes and 31,684 cis-eQTLs derived from blood samples of healthy individuals of European ancestry. MAIN OUTCOME MEASURES The primary outcome measures were the identification of genes causally associated with ovarian-related diseases and the validation of these genes as potential therapeutic targets. RESULTS Our study revealed that specific genes such as CD163L1, PPP3CA, MTAP, F12, NRM, BANK1, ZNF66, GNA15, and SLC6A9 were associated with ovarian endometriosis, ovarian cysts, and polycystic ovarian syndrome. Through MR and colocalization analyses, we identified potential drug targets, including CTNNB1, PTPN7, and ABCB4, with strong evidence of colocalization with ovarian-related diseases. Sensitivity analyses confirmed the robustness of our findings, showing no evidence of horizontal pleiotropy or heterogeneity. CONCLUSION This research highlights the significance of precision medicine approaches in identifying genetic factors underlying ovarian-related diseases and provides a foundation for developing targeted therapies, enhancing diagnostic accuracy, and improving treatment strategies for ovarian-related diseases.
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Affiliation(s)
- Yanggang Hong
- The Second School of Medicine, Wenzhou Medical University, Zhejiang, China.
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Venkatesh SS, Wittemans LBL, Palmer DS, Baya NA, Ferreira T, Hill B, Lassen FH, Parker MJ, Reibe S, Elhakeem A, Banasik K, Bruun MT, Erikstrup C, Aagard Jensen B, Juul A, Mikkelsen C, Nielsen HS, Ostrowski SR, Pedersen OB, Rohde PD, Sørensen E, Ullum H, Westergaard D, Haraldsson A, Holm H, Jonsdottir I, Olafsson I, Steingrimsdottir T, Steinthorsdottir V, Thorleifsson G, Figueredo J, Karjalainen MK, Pasanen A, Jacobs BM, Kalantzis G, Hubers N, Lippincott M, Fraser A, Lawlor DA, Timpson NJ, Nyegaard M, Stefansson K, Magi R, Laivuori H, van Heel DA, Boomsma DI, Balasubramanian R, Seminara SB, Chan YM, Laisk T, Lindgren CM. Genome-wide analyses identify 25 infertility loci and relationships with reproductive traits across the allele frequency spectrum. Nat Genet 2025:10.1038/s41588-025-02156-8. [PMID: 40229599 DOI: 10.1038/s41588-025-02156-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Accepted: 03/07/2025] [Indexed: 04/16/2025]
Abstract
Genome-wide association studies (GWASs) may help inform the etiology of infertility. Here, we perform GWAS meta-analyses across seven cohorts in up to 42,629 cases and 740,619 controls and identify 25 genetic risk loci for male and female infertility. We additionally identify up to 269 genetic loci associated with follicle-stimulating hormone, luteinizing hormone, estradiol and testosterone through sex-specific GWAS meta-analyses (n = 6,095-246,862). Exome sequencing analyses reveal that women carrying testosterone-lowering rare variants in some genes are at risk of infertility. However, we find no local or genome-wide genetic correlation between female infertility and reproductive hormones. While infertility is genetically correlated with endometriosis and polycystic ovary syndrome, we find limited genetic overlap between infertility and obesity. Finally, we show that the evolutionary persistence of infertility-risk alleles may be explained by directional selection. Taken together, we provide a comprehensive view of the genetic determinants of infertility across multiple diagnostic criteria.
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Affiliation(s)
- Samvida S Venkatesh
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
| | - Laura B L Wittemans
- Novo Nordisk Research Centre Oxford, Oxford, UK
- Nuffield Department of Women's and Reproductive Health, Medical Sciences Division, University of Oxford, Oxford, UK
| | - Duncan S Palmer
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK
- Nuffield Department of Population Health, Medical Sciences Division, University of Oxford, Oxford, UK
| | - Nikolas A Baya
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Teresa Ferreira
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK
| | - Barney Hill
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK
- Nuffield Department of Population Health, Medical Sciences Division, University of Oxford, Oxford, UK
| | - Frederik Heymann Lassen
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Melody J Parker
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK
- Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
| | - Saskia Reibe
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK
- Nuffield Department of Population Health, Medical Sciences Division, University of Oxford, Oxford, UK
| | - Ahmed Elhakeem
- MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK
- Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK
| | - Karina Banasik
- Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark
- Department of Obstetrics and Gynecology, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark
| | - Mie T Bruun
- Department of Clinical Immunology, Odense University Hospital, Odense, Denmark
| | - Christian Erikstrup
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Health, Aarhus University, Aarhus, Denmark
| | - Bitten Aagard Jensen
- Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark
| | - Anders Juul
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark
| | - Christina Mikkelsen
- Department of Clinical Immunology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, Copenhagen University, Copenhagen, Denmark
| | - Henriette S Nielsen
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Obstetrics and Gynecology, The Fertility Clinic, Hvidovre University Hospital, Copenhagen, Denmark
| | - Sisse R Ostrowski
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Immunology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark
| | - Ole B Pedersen
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Immunology, Zealand University Hospital-Køge, Køge, Denmark
| | - Palle Duun Rohde
- Genomic Medicine, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
| | - Erik Sørensen
- Department of Clinical Immunology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark
| | | | - David Westergaard
- Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark
- Department of Obstetrics and Gynecology, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark
| | - Asgeir Haraldsson
- Faculty of Medicine, University of Iceland, Reykjavik, Iceland
- Children's Hospital Iceland, Landspitali University Hospital, Reykjavik, Iceland
| | - Hilma Holm
- deCODE genetics/Amgen Inc., Reykjavik, Iceland
| | - Ingileif Jonsdottir
- Faculty of Medicine, University of Iceland, Reykjavik, Iceland
- deCODE genetics/Amgen Inc., Reykjavik, Iceland
| | - Isleifur Olafsson
- Department of Clinical Biochemistry, Landspitali University Hospital, Reykjavik, Iceland
| | - Thora Steingrimsdottir
- Faculty of Medicine, University of Iceland, Reykjavik, Iceland
- Department of Obstetrics and Gynecology, Landspitali University Hospital, Reykjavik, Iceland
| | | | | | - Jessica Figueredo
- Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia
| | - Minna K Karjalainen
- Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland
- Research Unit of Population Health, Faculty of Medicine, University of Oulu, Oulu, Finland
- Northern Finland Birth Cohorts, Arctic Biobank, Infrastructure for Population Studies, Faculty of Medicine, University of Oulu, Oulu, Finland
| | - Anu Pasanen
- Research Unit of Clinical Medicine, Medical Research Center Oulu, University of Oulu, and Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland
| | - Benjamin M Jacobs
- Centre for Preventive Neurology, Wolfson Institute of Population Health, Queen Mary University London, London, UK
| | | | - Nikki Hubers
- Department of Biological Psychology, Netherlands Twin Register, Vrije Universiteit, Amsterdam, The Netherlands
- Amsterdam Reproduction and Development Institute, Amsterdam, The Netherlands
- Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit, Amsterdam, The Netherlands
| | - Margaret Lippincott
- Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Abigail Fraser
- MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK
- Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK
| | - Deborah A Lawlor
- MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK
- Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK
| | - Nicholas J Timpson
- MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK
- Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK
| | - Mette Nyegaard
- Genomic Medicine, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
- Statens Serum Institut, Copenhagen, Denmark
| | - Kari Stefansson
- Faculty of Medicine, University of Iceland, Reykjavik, Iceland
- deCODE genetics/Amgen Inc., Reykjavik, Iceland
| | - Reedik Magi
- Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia
| | - Hannele Laivuori
- Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland
- Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Department of Obstetrics and Gynecology, Tampere University Hospital, The Wellbeing Services County of Pirkanmaa, Tampere, Finland
- Center for Child, Adolescent, and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | | | - Dorret I Boomsma
- Amsterdam Reproduction and Development Institute, Amsterdam, The Netherlands
- Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit, Amsterdam, The Netherlands
| | - Ravikumar Balasubramanian
- Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Stephanie B Seminara
- Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Yee-Ming Chan
- Harvard Medical School, Boston, MA, USA
- Division of Endocrinology, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA
| | - Triin Laisk
- Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia
| | - Cecilia M Lindgren
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
- Nuffield Department of Women's and Reproductive Health, Medical Sciences Division, University of Oxford, Oxford, UK.
- Broad Institute of Harvard and MIT, Cambridge, MA, USA.
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Rasp E, Rönö K, But A, Gissler M, Härkki P, Heikinheimo O, Saavalainen L. Burden of somatic morbidity associated with a surgically verified diagnosis of endometriosis at a young age: a register-based follow-up cohort study in Finland. Hum Reprod 2025; 40:623-632. [PMID: 39986333 PMCID: PMC11965793 DOI: 10.1093/humrep/deaf032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 12/22/2024] [Indexed: 02/24/2025] Open
Abstract
STUDY QUESTION How does the burden of somatic disorders compare between women with surgically verified endometriosis diagnosed in adolescence or early adulthood, and matched women without a history of endometriosis? SUMMARY ANSWER Women with endometriosis diagnosed at a young age had a higher incidence of several somatic disorders and a higher number of hospital visits compared to women without endometriosis. WHAT IS KNOWN ALREADY Endometriosis is associated with an increased risk of several somatic disorders, including autoimmune, inflammatory, and pain-related disorders with higher utility of health care resources. There may be differences in the experience of pain relating to the subtypes of endometriosis. Depression and anxiety are linked to endometriosis and increase overall somatic comorbidity. STUDY DESIGN, SIZE, DURATION Longitudinal retrospective register-based cohort study utilizing episode data from specialized care; 2680 women under 25 years with a surgical of diagnosis endometriosis in 1998-2012, and 5338 reference women of the same age and municipality followed up from the index day to the end of 2019, emigration, death or the outcome of interest. PARTICIPANTS/MATERIALS, SETTING, METHODS We analysed incidence rates, cumulative incidence rates, and crude hazard rate ratios (HR) with 95% CIs across 15 groups of somatic disorders. Subgroup analyses were conducted among women with endometriosis, by (i) type of endometriosis-ovarian only (n = 601) versus combined types (n = 2079), and (ii) pre-existing diagnosis of depression or anxiety (n = 270) versus those without such diagnoses (n = 2410). MAIN RESULTS AND THE ROLE OF CHANCE Women reached a median age of 38 (IQR 34-42) years after a median follow-up of almost 16 (12, 19) years. Compared to the reference cohort, women with endometriosis had a higher incidence of several somatic disorders during the follow-up. By the age of 40 years, 38% of women with endometriosis and 9% of the reference cohort had diagnoses of infertility (HR 5.88 [95% CI 5.24-6.61]). The corresponding figures for genital tract infections were 24% and 6% (4.64 [4.03-5.36]), symptoms and signs of pain 62% and 28% (3.27 [3.04-3.51]), migraine 15% and 6.4% (2.49 [2.13-2.92]), and chronic pain conditions 33% and 19% (2.01 [1.83-2.22]), respectively. In women with endometriosis, a higher incidence was seen also for dyspareunia, uterine myomas, celiac disease, asthma, anaemia, high blood pressure, hypercholesterolemia or cardiovascular diseases; autoimmune diseases, and disorders of the thyroid gland. For women with ovarian endometriosis only, we observed a lower HR of high blood pressure, hypercholesterolemia or cardiovascular diseases, asthma, migraine, and pain-related disorders compared to those with other or combined types of endometriosis. Within the endometriosis cohort, women with pre-existing diagnoses of depression or anxiety had higher HRs of several somatic disorders compared to those without such diagnoses. The number of hospital visits after the index day was higher in women with endometriosis when compared to the reference cohort (40 vs 18). LIMITATIONS, REASONS FOR CAUTION Confounding bias may arise from the reliance on registry-based hospital diagnoses, as women undergoing surgery are already engaged with health care, and, subsequently, more likely to receive new diagnoses. Furthermore, the homogenous population of Finland limits the generalizability of these findings. WIDER IMPLICATIONS OF THE FINDINGS Surgical diagnosis of endometriosis at a young age is associated with a burden of somatic disorders, emphasizing importance of comprehensive approach to management of endometriosis and endometriosis-related conditions. Further studies are needed to clarify the varying reasons behind these associations. However, the results of this study suggest that pain and mental health may play a key role in the development of subsequent somatic disorders. Therefore, careful management of primary dysmenorrhea and mental health in young women is essential. STUDY FUNDING/COMPETING INTEREST(S) Funding was received from the Hospital District of Helsinki and Uusimaa, and from Finska Läkaresällskapet. E.R. acknowledges financial support from The Finnish Society of Research for Obstetrics and Gynaecology and The Finnish Medical Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. O.H. serves occasionally on advisory boards for Bayer AG, Gedeon Richter, and Roche, has received travel support from Gedeon Richter, has received consulting fees from Orion Pharma and Nordic Pharma, and has helped to organize and lecture at educational events for Bayer AG and Gedeon Richter. The other authors report no conflict of interest concerning the present work. TRIAL REGISTRATION NUMBER N/A.
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Affiliation(s)
- Elina Rasp
- Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Kristiina Rönö
- Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Anna But
- Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Mika Gissler
- Department of Data and Analytics, Finnish Institute for Health and Welfare (THL), Helsinki, Finland
- Academic Primary Health Care Centre, Stockholm, Sweden
- Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
| | - Päivi Härkki
- Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Oskari Heikinheimo
- Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Liisu Saavalainen
- Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Yan J, Peng Y, Huang S, Fei W, Chen Y, Zheng C, Zhang M, Zhao M. Treatment of endometriosis with mifepristone mediated by nanostructured lipid carriers. Drug Deliv Transl Res 2025; 15:1181-1192. [PMID: 38992183 DOI: 10.1007/s13346-024-01661-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/23/2024] [Indexed: 07/13/2024]
Abstract
Mifepristone, a progesterone receptor antagonist, was initially used to terminate early pregnancy. As scientific research advanced, it emerged to be effective in the treatment of various tumors and tumor-like conditions such as endometriosis. Despite the therapeutic potential of mifepristone, its therapeutic effect is still far from ideal because the drug is difficult to dissolve and to accumulate in the target tissue sites. To address this issue, mifepristone-loaded nanostructured lipid carriers (Mif-NLC) were prepared by a simple solvent diffusion method and their anti-endometriosis performance and mechanisms were initially investigated. By optimizing the preparation protocol, we obtained uniform and spheroidal Mif-NLC with an average particle size of 280 nm. The encapsulation rate and drug loading capacity were 64.67% ± 0.15% and 2.7% ± 0.014%, respectively, as measured by UV spectrophotometry. The in vitro release kinetics indicated that mifepristone was released from NLC in a sustained-release manner. Compared with free mifepristone, Mif-NLC exhibited enhanced cellular uptake and inhibition of invasion activity in primary mesenchymal cells of endometriosis. A certain reduction in the size of endometriotic cysts was observed in animals compared to controls. The induction of autophagy via Mif-NLC may serve as the molecular mechanism underlying this effect. Furthermore, observation of uterine structures showed negligible toxic effects. This suggested that mifepristone encapsulated in NLC can improve its bioavailability and anti-endometriosis efficacy, which provided a new strategy for the treatment of endometriosis.
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Affiliation(s)
- Jingjing Yan
- Department of Pharmacy, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Yujie Peng
- Research Center for Clinical Pharmacy, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
| | - Shiyao Huang
- Department of Pharmacy, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Weidong Fei
- Department of Pharmacy, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Yue Chen
- Department of Pharmacy, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Caihong Zheng
- Department of Pharmacy, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Meng Zhang
- Department of Pharmacy, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
| | - Mengdan Zhao
- Department of Pharmacy, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
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Nguyen AD, Marshall HL, Sidle MW, Galaviz VD, Sticco PL, Downing KT. Factors Associated With Spontaneous Conception Leading to Live Birth in Infertility Patients After Endometriosis Surgery. J Minim Invasive Gynecol 2025:S1553-4650(25)00095-0. [PMID: 40127888 DOI: 10.1016/j.jmig.2025.03.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 03/17/2025] [Accepted: 03/18/2025] [Indexed: 03/26/2025]
Abstract
STUDY OBJECTIVE To determine factors associated with spontaneous conception leading to live birth in infertility patients after endometriosis surgery. DESIGN Retrospective cohort study. SETTING Multi-hospital health system of Catholic Health in Long Island, NY. PARTICIPANTS Infertility patients, between ages 18 and 45, who underwent endometriosis surgery with complete excision or ablation with or without excision and continued follow-up care for at least 1 year between January 1st, 2016 and March 31st 2022. MAIN RESULTS Of the 100 patients, 50 achieved spontaneous conception and 40 achieved live birth within 1 year of surgery. Age less than 35 at the time of surgery was found to have an increased likelihood of live birth (RR 3.1, 95% CI 1.3-7.2). Being overweight (RR 1.0, 95% CI 0.4-2.2) or obese (RR 1.2, 95% CI 0.4-3.1) did not affect the likelihood of live birth. Surgery within 24 months of infertility diagnosis did not increase the likelihood of a successful delivery (RR 2.0, 95% CI 0.9-4.5). The pregnancy rate for AAGL Stage I, II, III, IV endometriosis were 42% (18/32), 32% (8/25), 46% (6/13), 42% (8/19) respectively. The logistic regression model indicated that live birth after spontaneous conception was significantly associated with younger age at the time of surgery and complete excision of endometriosis. Patients were 3.2 times (95% CI 1.3-7.8) more likely of having a live birth if they were less than 35 years old at the time of surgery. Complete excision of endometriosis conferred a 4.1-fold (95% CI 1.1-14.9) increased likelihood of a live birth. CONCLUSION Two factors increased the likelihood of live birth after endometriosis surgery: age at the time of surgery and complete excision of endometriosis. We cautiously recommend patients attempting spontaneous conception find an endometriosis surgeon proficient in excisional techniques. If they are under 35, there may be additional benefit from surgery.
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Affiliation(s)
- Anthony D Nguyen
- Department of Obstetrics and Gynecology, Good Samaritan University Hospital (Nguyen, Marshall, Galaviz, Sticco and Downing), West Islip, New York.
| | - Hannah L Marshall
- Department of Obstetrics and Gynecology, Good Samaritan University Hospital (Nguyen, Marshall, Galaviz, Sticco and Downing), West Islip, New York
| | - Meg W Sidle
- Institutional Research and Effectiveness, University of Pikeville (Sidle), Pikeville, Kentucky
| | - Veronica D Galaviz
- Department of Obstetrics and Gynecology, Good Samaritan University Hospital (Nguyen, Marshall, Galaviz, Sticco and Downing), West Islip, New York; Department of Obstetrics and Gynecology, Westchester Medical Center (Galaviz), Valhalla, New York
| | - Peter L Sticco
- Department of Obstetrics and Gynecology, Good Samaritan University Hospital (Nguyen, Marshall, Galaviz, Sticco and Downing), West Islip, New York
| | - Keith T Downing
- Department of Obstetrics and Gynecology, Good Samaritan University Hospital (Nguyen, Marshall, Galaviz, Sticco and Downing), West Islip, New York
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7
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Vallée A, Ceccaldi PF, Carbonnel M, Horsman S, Murtada R, Moawad G, Feki A, Ayoubi JM. Comparative pregnancy rate after colorectal resection versus other surgical procedures for deep infiltrating rectal endometriosis: a systematic review and meta-analysis. Sci Rep 2025; 15:9369. [PMID: 40102483 PMCID: PMC11920280 DOI: 10.1038/s41598-025-93705-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Accepted: 03/10/2025] [Indexed: 03/20/2025] Open
Abstract
The debate around colorectal surgery for endometriosis has been ongoing, but to date no meta-analysis has investigated the impact of the different surgical approaches on the pregnancy rate. The aim of this meta-analysis study was to determine in women with deep infiltrating rectal endometriosis, how does colorectal resection surgery compare to other surgical techniques (e.g., rectal shaving, disc excision) in terms of pregnancy rates. We searched PubMed, Web of Science, Cochrane library and Clinical Trials for relevant studies published from inception to December 2024. We performed a systematic review and meta-analysis of all English language full-text articles addressing colorectal resection compared with other management of deep infiltrating rectal endometriosis and presenting pregnancy outcomes. We included a study when it (i) provided data on surgical management (shaving, disc excision, and/or colorectal resection) and (ii) detailed the pregnancy outcomes in each subgroup. Four authors independently performed the initial search to evaluate the eligibility criteria. Four authors extracted the data and a fifth author checked this extraction. Of the 113 full-text articles assessed for eligibility, we included 13 in the meta-analysis. These studies represented a total of 3,248 patients. Pregnancy information was available for 2,131 patients: 1073 colorectal resection, 502 shaving, 172 disc excisions, and 384 other practices (expectant management). Colorectal resection was associated with a lower pregnancy rate compared with the other techniques (N = 2,131, odds ratio [OR] = 0.64 [95% confidence interval 0.52-0.79], p < 0.001, I2 = 35%). There were similar results when comparing colorectal resection with rectal shaving (N = 952, OR = 0.51 [95% confidence interval 0.36-0.73], p < 0.001, I2 = 0%), but not when comparing colorectal resection with disc excision (N = 432, OR = 0.65 [95% confidence interval 0.37-1.13], p = 0.13). Conclusions Rectal resection for endometriosis is associated with a lower pregnancy rate compared with other type of surgery, such as shaving. Trial registration: PROSPERO registration number CRD42024512328.
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Affiliation(s)
- Alexandre Vallée
- Department of Epidemiology and Public Health, Foch hospital, 92150, Suresnes, France.
| | - Pierre-François Ceccaldi
- Unité de Recherche en Biomatériaux Innovants Et Interfaces (URB2i), Université Paris Cité, Paris, France
- Department of Obstetrics, Gynecology and Reproductive Medicine, Foch Hospital, Suresnes, France
| | - Marie Carbonnel
- Department of Obstetrics, Gynecology and Reproductive Medicine, Foch Hospital, Suresnes, France
- Medical School, University of Versailles, Saint-Quentin-en-Yvelines (UVSQ), Versailles, France
| | - Silvia Horsman
- Department of Obstetrics, Gynecology and Reproductive Medicine, Foch Hospital, Suresnes, France
| | - Rouba Murtada
- Department of Obstetrics, Gynecology and Reproductive Medicine, Foch Hospital, Suresnes, France
| | - Gaby Moawad
- Department of Obstetrics and Gynecology, The George Washington University Hospital, Washington, DC, 20037, USA
| | - Anis Feki
- Department of Obstetrics and Gynecology, HFR-Fribourg, Chemin des Pensionnats 2-6, 1708, Fribourg, Switzerland
| | - Jean-Marc Ayoubi
- Department of Obstetrics, Gynecology and Reproductive Medicine, Foch Hospital, Suresnes, France
- Medical School, University of Versailles, Saint-Quentin-en-Yvelines (UVSQ), Versailles, France
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8
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Arsalan HM, Mumtaz H, Lagana AS. Biomarkers of endometriosis. Adv Clin Chem 2025; 126:73-120. [PMID: 40185537 DOI: 10.1016/bs.acc.2025.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/07/2025]
Abstract
Endometriosis represents a diverse disease characterized by three distinct phenotypes: superficial peritoneal lesions, ovarian endometriomas, and deep infiltrating endometriosis. The most widely accepted pathophysiological hypothesis for endometriosis is rooted in retrograde menstruation, a phenomenon observed in most patients. Endometriosis is closely linked to infertility, but having endometriosis does not necessarily imply infertility. The disease can impact fertility through various mechanisms affecting the pelvic cavity, ovaries, and the uterus itself. MicroRNAs (miRNAs) indeed represent a fascinating and essential component of the regulatory machinery within cells. Discovered in the early 1990s, miRNAs have since been identified as critical players in gene expression control. Unfortunately, ovarian endometrioma is a common gynecologic disorder for which specific serum markers are currently lacking. Some have examined urocortin for its ability to differentiate endometriomas from other benign ovarian cysts. Another potential marker, Cancer Antigen 125 (CA-125) is a well-established indicator for epithelial cell ovarian cancer and its levels can be elevated in conditions such as endometriosis. CA-125 is derived from coelomic epithelia, including the endometrium, fallopian tube, ovary, and peritoneum. In this review we examine the pathophysiologic basis for endometriosis and highlight potential markers to more fully characterize the underlying biochemical processes linked to this multifaceted disease state.
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Affiliation(s)
- Hafiz Muhammad Arsalan
- Faculty of General Medicine, Altamimi International Medical University, Bishkek, Kyrgyzstan.
| | - Hina Mumtaz
- Department of Biochemistry, University of Central Punjab, Lahore, Pakistan.
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9
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Moïse A, Dzeitova M, de Landsheere L, Nisolle M, Brichant G. Endometriosis and Infertility: Gynecological Examination Practical Guide. J Clin Med 2025; 14:1904. [PMID: 40142712 PMCID: PMC11943251 DOI: 10.3390/jcm14061904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2025] [Revised: 03/06/2025] [Accepted: 03/06/2025] [Indexed: 03/28/2025] Open
Abstract
Endometriosis, a prevalent gynecological condition affecting 10-15% of reproductive-age women, involves the growth of endometrial-like tissue outside the uterine cavity. This chronic inflammatory disease can significantly impact fertility by disrupting ovulation, tubal transport, and implantation. Clinical manifestations vary widely, ranging from asymptomatic cases to severe pelvic pain, dysmenorrhea, and dyspareunia. Accurate diagnosis remains challenging, often requiring a combination of patient history, clinical examination, and imaging studies. This paper will discuss the clinical approach to endometriosis during a first-line gynecological appointment, focusing on patient history, including detailed assessment of menstrual, pelvic, and bowel symptoms, and clinical examination; thorough gynecological examination, including abdominal and pelvic palpation, speculum examination, and bimanual examination; imaging evaluation (particularly of the role of ultrasound in identifying and characterizing endometriotic lesions, including the use of the #ENZIAN classification for deep infiltrating endometriosis and evaluation of fertility impact); and discussion of the Endometriosis Fertility Index (EFI) as a tool for assessing fertility potential. This comprehensive approach aims to guide clinicians in identifying and managing endometriosis effectively, improving patient outcomes and optimizing fertility management strategies. Methods: A literature search for suitable articles published from January 1974 to 2024 in the English language was performed using PubMed. Results: Endometriosis is associated with infertility rates ranging from 20% to 68%, with mechanisms including pelvic adhesions, chronic inflammation, and immune dysregulation. The revised American Society for Reproductive Medicine (rASRM) classification and #ENZIAN classification were identified as essential tools for staging and characterizing the disease. Transvaginal ultrasound (TVS) demonstrated high diagnostic accuracy for deep infiltrating endometriosis, with a sensitivity of up to 96% and specificity of 99%. EFI emerged as a valuable predictor of natural conception post-surgery. Additionally, the review underscores the frequent co-occurrence of adenomyosis in women with endometriosis, which may further compromise fertility. Despite advancements in imaging techniques and classification systems, the variability in symptom presentation and disease progression continues to challenge early diagnosis and effective management. Conclusions: Endometriosis is a prevalent gynecological condition affecting women of reproductive age and is associated with infertility. This paper describes the diagnostic approach to endometriosis during a first-line gynecological appointment, focusing on clinical history, physical examination, and the role of imaging, particularly ultrasound, in identifying and characterizing endometriosis lesions. The adoption of standardized classification systems such as #ENZIAN and EFI enhances disease staging and fertility prognosis, allowing for tailored treatment strategies. Despite improvements in non-invasive diagnostic methods, challenges persist in correlating symptom severity with disease extent, necessitating continued research into biomarkers and novel imaging techniques. Additionally, the frequent coexistence of adenomyosis further complicates fertility outcomes, underscoring the need for comprehensive management strategies. Further research is needed to enhance early detection strategies and optimize fertility preservation techniques for affected women.
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Affiliation(s)
- Alice Moïse
- Department of Obstetrics and Gynecology, Hopital de La Citadelle, University of Liège, 4000 Liège, Belgium; (L.d.L.); (M.N.); (G.B.)
| | | | - Laurent de Landsheere
- Department of Obstetrics and Gynecology, Hopital de La Citadelle, University of Liège, 4000 Liège, Belgium; (L.d.L.); (M.N.); (G.B.)
| | - Michelle Nisolle
- Department of Obstetrics and Gynecology, Hopital de La Citadelle, University of Liège, 4000 Liège, Belgium; (L.d.L.); (M.N.); (G.B.)
| | - Géraldine Brichant
- Department of Obstetrics and Gynecology, Hopital de La Citadelle, University of Liège, 4000 Liège, Belgium; (L.d.L.); (M.N.); (G.B.)
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10
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Mandeville J, Earnshaw VA, Zhang C, Cardoso LF, Gupta J. Associations between stigma and depression among college-attending women with endometriosis symptoms. JOURNAL OF AMERICAN COLLEGE HEALTH : J OF ACH 2025; 73:989-999. [PMID: 39514816 DOI: 10.1080/07448481.2024.2422319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 04/30/2024] [Accepted: 10/20/2024] [Indexed: 11/16/2024]
Abstract
Background: Endometriosis is a debilitating and highly stigmatized chronic condition. The relationship between stigma and depressive symptoms among college-attending women with endometriosis symptoms was examined. Method: Data were analyzed from a cross-sectional online survey of undergraduate women (N = 424). Mean anticipated, internalized, and enacted stigma values were calculated. Logistic regression assessed the relationship between stigma score and depressive symptoms. Results: Mean stigma scores were 1.98 (anticipated), 1.46 (internalized), and 1.59 (enacted) on a 5-point scale (1 being the lowest and 5 being the highest); 24.1% reported moderately severe/severe depressive symptoms. In adjusted models, stigma was associated with an increased likelihood of moderately severe/severe depressive symptoms (anticipated (aOR = 1.96, 95% CI:1.49-2.59); internalized (aOR =2.67, 95% CI: 1.88-3.85); enacted (aOR = 1.28, 95% CI: 1.16-1.42)). Conclusion: College attending-women with endometriosis symptoms experience stigma which is significantly associated with depressive symptoms. Stigma reducing interventions are warranted and may have mental health benefits.
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Affiliation(s)
- Julia Mandeville
- College of Public Health, Department of Global and Community Health, George Mason University, Fairfax, Virginia, USA
| | - Valerie A Earnshaw
- Department of Human Development and Family Sciences, College of Education and Human Development, University of Delaware, Newark, Delaware, USA
| | - Cheyu Zhang
- College of Public Health, Department of Global and Community Health, George Mason University, Fairfax, Virginia, USA
| | | | - Jhumka Gupta
- College of Public Health, Department of Global and Community Health, George Mason University, Fairfax, Virginia, USA
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11
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Wang J, Li J, Han H, Wang C, Shi T, Yang X. miR-375-3p predicts the severity of endometriosis and regulates cellular progression by targeting NOX4. Mol Cell Probes 2025; 79:101999. [PMID: 39672281 DOI: 10.1016/j.mcp.2024.101999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 12/09/2024] [Accepted: 12/09/2024] [Indexed: 12/15/2024]
Abstract
BACKGROUND Due to the complex pathogenesis of endometriosis, its early screening and development prediction are still challenging problems in the clinic. OBJECTIVES This study evaluated the significance of miR-375-3p in endometriosis onset, progression, and recurrence, aiming to identify a novel biomarker for disease diagnosis and prognosis. MATERIALS AND METHODS The study enrolled 100 patients with endometriosis and 80 healthy females. The serum miR-375-3p levels were compared between the two groups, and its diagnostic significance and predictive value were assessed by ROC and Cox regression analyses. The effect of miR-375-3p on endometriosis cell growth and motility was evaluated by CCK8 and Transwell assays. RESULTS Endometriosis patients showed a lower serum miR-375-3p level relative to healthy females, and more severe the disease condition, lower the miR-375-3p in endometrial tissues is. Reducing serum miR-375-3p could discriminate endometriosis patients sensitively and specifically. Additionally, miR-375-3p was identified as a predictor for the recurrence of endometriosis together with stage, lesion size, and the levels of related hormones. In endometriosis cells, miR-375-3p was demonstrated to target NOX4 and negatively regulated its expression. Overexpressing miR-375-3p significantly suppressed cell proliferation, migration, and invasion, which was reversed by NOX4. CONCLUSION Decreasing miR-375-3p served as a biomarker for endometriosis onset, development, and recurrence. miR-375-3p regulated endometriosis cell growth and motility via negatively modulating NOX4.
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Affiliation(s)
- Junmei Wang
- Department of Ultrasound 2, Xinxiang Central Hospital (The Fourth Clinical College of Xinxiang Medical University), Xinxiang, 453000, China.
| | - Jianling Li
- Department of Ultrasound 2, Xinxiang Central Hospital (The Fourth Clinical College of Xinxiang Medical University), Xinxiang, 453000, China
| | - Hua Han
- Department of Ultrasound 2, Xinxiang Central Hospital (The Fourth Clinical College of Xinxiang Medical University), Xinxiang, 453000, China
| | - Changhua Wang
- Department of Ultrasound, People's Hospital of Zhengzhou, Zhengzhou, 450002, China
| | - Taiying Shi
- Department of Ultrasound 2, Xinxiang Central Hospital (The Fourth Clinical College of Xinxiang Medical University), Xinxiang, 453000, China
| | - Xueyun Yang
- Department of Ultrasound 2, Xinxiang Central Hospital (The Fourth Clinical College of Xinxiang Medical University), Xinxiang, 453000, China
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12
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Wang Z, Mao Y, Wang Z, Li S, Hong Z, Zhou R, Xu S, Xiong Y, Zhang Y. Histone lactylation-mediated overexpression of RASD2 promotes endometriosis progression via upregulating the SUMOylation of CTPS1. Am J Physiol Cell Physiol 2025; 328:C500-C513. [PMID: 39672102 DOI: 10.1152/ajpcell.00493.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 11/26/2024] [Accepted: 11/26/2024] [Indexed: 12/15/2024]
Abstract
Histone lactylation is crucial in a variety of physiopathological processes; however, the function and mechanism of histone lactylation in endometriosis remain poorly understood. Therefore, the objective of this investigation was to illuminate the function and mechanism of histone lactylation in endometriosis. Immunohistochemistry was used to investigate the expression of histone lactylation. Cell Counting Kit-8 assay (CCK8), Transwell assay, and endometriosis mouse models were used to investigate the effects of histone lactylation in vitro and in vivo. Transcriptomics and immunoprecipitation-mass spectrometry (IP-MS), Western blot, co-immunoprecipitation (Co-IP), quantitative reverse transcription polymerase chain reaction (qRT-PCR), and chromatin immunoprecipitation-qPCR (ChIP-qPCR) were used to explore the intrinsic mechanisms. In this study, we found that histone lactylation was upregulated in endometriosis and could promote endometriosis progression both in vivo and in vitro. Mechanistically, histone lactylation H3K18la promoted the transcription of Ras homolog enriched in striatum (RASD2), and RASD2, in turn, increased the stability of CTP synthase 1 (CTPS1) by promoting the SUMOylation and inhibiting the ubiquitination of CTPS1, thereby promoting endometriosis progression. Overall, our findings indicated that histone lactylation could promote the progression of endometriosis through the RASD2/CTPS1 axis. This investigation uncovered a novel mechanism and identified prospective targets for endometriosis diagnosis and therapy.NEW & NOTEWORTHY Our finding reveals a novel mechanism that promotes the progression of endometriosis, namely the histone lactylation/RASD2/CTPS1 axis. This finding suggests that inhibiting histone lactylation or inhibiting RASD2 and CTPS1 might be a potential therapeutic strategy to inhibit endometriosis lesion growth.
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Affiliation(s)
- Ziwei Wang
- Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China
- Clinical Medicine Research Center of Prenatal Diagnosis and Birth Health in Hubei Province, Wuhan, Hubei, People's Republic of China
- Wuhan Clinical Research Center for Reproductive Science and Birth Health, Wuhan, Hubei, People's Republic of China
| | - Yanhong Mao
- Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China
- Clinical Medicine Research Center of Prenatal Diagnosis and Birth Health in Hubei Province, Wuhan, Hubei, People's Republic of China
- Wuhan Clinical Research Center for Reproductive Science and Birth Health, Wuhan, Hubei, People's Republic of China
| | - Zihan Wang
- Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China
- Clinical Medicine Research Center of Prenatal Diagnosis and Birth Health in Hubei Province, Wuhan, Hubei, People's Republic of China
- Wuhan Clinical Research Center for Reproductive Science and Birth Health, Wuhan, Hubei, People's Republic of China
| | - Shuwei Li
- Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China
- Clinical Medicine Research Center of Prenatal Diagnosis and Birth Health in Hubei Province, Wuhan, Hubei, People's Republic of China
- Wuhan Clinical Research Center for Reproductive Science and Birth Health, Wuhan, Hubei, People's Republic of China
| | - Zhidan Hong
- Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China
- Clinical Medicine Research Center of Prenatal Diagnosis and Birth Health in Hubei Province, Wuhan, Hubei, People's Republic of China
- Wuhan Clinical Research Center for Reproductive Science and Birth Health, Wuhan, Hubei, People's Republic of China
| | - Rong Zhou
- Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China
- Clinical Medicine Research Center of Prenatal Diagnosis and Birth Health in Hubei Province, Wuhan, Hubei, People's Republic of China
- Wuhan Clinical Research Center for Reproductive Science and Birth Health, Wuhan, Hubei, People's Republic of China
| | - Shaoyuan Xu
- Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China
- Clinical Medicine Research Center of Prenatal Diagnosis and Birth Health in Hubei Province, Wuhan, Hubei, People's Republic of China
- Wuhan Clinical Research Center for Reproductive Science and Birth Health, Wuhan, Hubei, People's Republic of China
| | - Yao Xiong
- Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China
- Clinical Medicine Research Center of Prenatal Diagnosis and Birth Health in Hubei Province, Wuhan, Hubei, People's Republic of China
- Wuhan Clinical Research Center for Reproductive Science and Birth Health, Wuhan, Hubei, People's Republic of China
| | - Yuanzhen Zhang
- Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China
- Clinical Medicine Research Center of Prenatal Diagnosis and Birth Health in Hubei Province, Wuhan, Hubei, People's Republic of China
- Wuhan Clinical Research Center for Reproductive Science and Birth Health, Wuhan, Hubei, People's Republic of China
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13
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Cetera GE, Merli CEM, Vercellini P. A Multimodal Approach to Symptomatic Endometriosis: A Proposed Algorithm for Clinical Management. Reprod Sci 2025; 32:289-299. [PMID: 39775786 DOI: 10.1007/s43032-024-01763-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 12/09/2024] [Indexed: 01/11/2025]
Abstract
Recent research has proven that peripheral (PS) and central sensitization (CS), mental health, and myofascial dysfunction all play a role, alongside nociception, in the genesis and in the perpetuation of endometriosis' symptoms. However, such components of pain are still largely ignored in clinical practice, although not considering such contributors may entail serious consequences on women's health, including the choice of unnecessary surgery and leaving the real causes of pain untreated. At the present time, we are facing a paradox by which 25-40% of women who undergo laparoscopic surgery for pelvic pain do not have an obvious diagnosis, while the percentage of women with endometriosis who have signs of CS, of depressive or anxiety disorders, or who have an increased pelvic muscle tone ammounts to 41-55%, 15-88% and 28-73%, respectively. Moving from the widely-accepted stepwise approach suggested for endometriosis management, which consists in the initial prescription of low-dose combined oral contraceptives (COCs) or of a progestin monotherapy, followed by GnRH analogues and, ultimately, by surgery, when COCs and progestins have proven ineffective or are not tolerated or contraindicated, we propose an integration of such model which takes into account the identification and the simultaneous treatment of all pain contributors. Our objective is to encourage physicians' awareness of the need of a multidisciplinary, multimodal approach to endometriosis-related pain, and ultimately to promote a reduction in the number of unnecessary surgeries.
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Affiliation(s)
- Giulia Emily Cetera
- Gynecology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
- Academic Center for Research On Adenomyosis and Endometriosis, Department of Clinical Sciences and Community Health, Università Degli Studi Di Milano, Milan, Italy.
| | | | - Paolo Vercellini
- Gynecology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Academic Center for Research On Adenomyosis and Endometriosis, Department of Clinical Sciences and Community Health, Università Degli Studi Di Milano, Milan, Italy
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14
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Liu S, Li X, Gu Z, Wu J, Jia S, Shi J, Dai Y, Wu Y, Yan H, Zhang J, You Y, Xue X, Liu L, Lang J, Wang X, Leng J. Single-cell and spatial transcriptomic profiling revealed niche interactions sustaining growth of endometriotic lesions. CELL GENOMICS 2025; 5:100737. [PMID: 39788102 PMCID: PMC11770218 DOI: 10.1016/j.xgen.2024.100737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 10/25/2024] [Accepted: 12/06/2024] [Indexed: 01/12/2025]
Abstract
Endometriosis is a chronic condition with limited therapeutic options. The molecular aberrations promoting ectopic attachment and interactions with the local microenvironment sustaining lesion growth have been unclear, prohibiting development of targeted therapies. Here, we performed single-cell and spatial transcriptomic profiling of ectopic lesions and eutopic endometrium in endometriosis. We found that ectopic endometrial stromal (EnS) cells retained cyclical gene expression patterns of their eutopic counterparts while exhibiting unique gene expression that contributes to the pathogenesis of endometriosis. We identified two distinct ovarian stromal cells (OSCs) localized at different zones of the lesion, showing differential gene expression profiles associated with fibrosis and inflammation, respectively. We also identified WNT5A upregulation and aberrant activation of non-canonical WNT signaling in endometrial stromal cells that may contribute to the lesion establishment, offering novel targets for therapeutic intervention. These data will enhance our understanding of the molecular mechanisms underlying endometriosis and paves the way for developing non-hormonal treatments.
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Affiliation(s)
- Song Liu
- Center for Bioinformatics, National Infrastructures for Translational Medicine, Institute of Clinical Medicine & Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Xiaoyan Li
- National Clinical Research Center for Obstetric & Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Zhiyue Gu
- National Clinical Research Center for Obstetric & Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Jiayu Wu
- Center for Bioinformatics, National Infrastructures for Translational Medicine, Institute of Clinical Medicine & Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Shuangzheng Jia
- Department of Gynecologic Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China
| | - Jinghua Shi
- National Clinical Research Center for Obstetric & Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Yi Dai
- National Clinical Research Center for Obstetric & Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Yushi Wu
- National Clinical Research Center for Obstetric & Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Hailan Yan
- National Clinical Research Center for Obstetric & Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Jing Zhang
- National Clinical Research Center for Obstetric & Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Yan You
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Xiaowei Xue
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Lulu Liu
- Biomedical Engineering Facility of National Infrastructures for Translational Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Jinghe Lang
- National Clinical Research Center for Obstetric & Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Xiaoyue Wang
- Center for Bioinformatics, National Infrastructures for Translational Medicine, Institute of Clinical Medicine & Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
| | - Jinhua Leng
- National Clinical Research Center for Obstetric & Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
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15
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Jennings BS, Hewison M. Vitamin D and Endometriosis: Is There a Mechanistic Link? Cell Biochem Funct 2025; 43:e70037. [PMID: 39739404 DOI: 10.1002/cbf.70037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 11/26/2024] [Accepted: 12/13/2024] [Indexed: 01/02/2025]
Abstract
Endometriosis is a prevalent chronic gynaecological disorder, but its cause is still unclear, and both genetic and environmental factors may contribute disease aetiology. Prominent amongst the latter is vitamin D which can be obtained either by the action of sunlight on skin or from dietary sources. Serum levels of the main circulating form of vitamin D, 25-hydroxvitamin D (25(OH)D), have been reported to be inversely correlated with endometriosis, suggesting that vitamin D-deficiency may be a risk factor for the disease. Crucially, the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D) is known to exert many functions beyond its established role in the endocrinology of mineral homoeostasis and prevention of rickets. Several of these extra-skeletal effects of 1,25(OH)2D may impact the risk and progression of endometriosis. The following review details the studies that have assessed associations between vitamin D status/supplementation and endometriosis severity and disease progression, but also describes the mechanistic targets for 1,25(OH)2D in endometriosis with specific reference to immunomodulatory responses and effects on angiogenesis. Endometriosis is an under-reported health issue with poor non-invasive options for diagnosis. Given that vitamin D-deficiency may trigger or exacerbate key pathophysiological responses linked to endometriosis, analysis of vitamin D status in women may provide an alternative risk marker for endometriosis. Treatment options for endometriosis are also limited and the review will also consider whether vitamin D supplementation has a role in the management of endometriosis, either in prevention or treatment.
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Affiliation(s)
- Bethany Scout Jennings
- Department of Metabolism and Systems Science, School of Medical Sciences, University of Birmingham, Birmingham, UK
| | - Martin Hewison
- Department of Metabolism and Systems Science, School of Medical Sciences, University of Birmingham, Birmingham, UK
- Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
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16
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Yan H, Li X, Dai Y, Shi J, Wu Y, Gu Z, Zhang C, Li Q, Zhang B, Lv S, Leng J. Bladder Endometriosis: Symptoms and Pregnancy Outcomes. J Minim Invasive Gynecol 2025; 32:22-30.e1. [PMID: 39270975 DOI: 10.1016/j.jmig.2024.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 08/29/2024] [Accepted: 09/04/2024] [Indexed: 09/15/2024]
Abstract
OBJECTIVE To investigate the clinical features of bladder endometriosis and factors associated with urinary symptoms, pregnancy outcomes, and long-term effects of symptom relief and recurrence. DESIGN A single-center retrospective cohort study. SETTING A tertiary referral hospital. PARTICIPANTS Forty-seven patients who were surgically confirmed to have bladder endometriosis at Peking Union Medical College Hospital between January 2012 and December 2023 were included in this study. INTERVENTIONS A retrospective study of the clinical and pathological features and reproductive outcomes in patients with bladder endometriosis. MEASUREMENTS AND MAIN RESULTS Among 47 patients with bladder endometriosis, 27 (57.4%) presented with urinary symptoms, including urinary frequency, urgency, dysuria, and hematuria. Patients with urinary symptoms were more likely to have previous cesarean sections (odds ratio [OR] 4.5, 95% confidence interval [CI] 1.1-19.2, p = .032) and experience dysmenorrhea compared to those without (p = .008, OR 5.3, 95% CI 1.5-18.8). Anterior compartment obliteration was another factor associated with urinary symptoms (OR 7.2, 95% CI 1.3-40.4, p = .016). Bladder lesions located within 1 cm of the ureteral orifice (OR 7.2, 95% CI 1.3-40.4, p = .020) and the deeper invasive layer of lesions (mucosal layer, OR 6.1, 95% CI 1.4-25.8, p = .009) were also found to be associated with symptoms. Regarding reproductive outcomes, 12 patients desired to conceive. Of the patients who desired pregnancy, 66.7% achieved pregnancy; 5 spontaneously and 3 after IVF treatment. The miscarriage rate among patients with bladder endometriosis was 25.0% in the age range of 27-40 years. Additionally, all patients experienced symptom relief after one year of follow-up. Only two patients experienced bladder endometriosis recurrence. CONCLUSIONS Previous cesarean section, dysmenorrhea, anterior compartment obliteration, lesion in the trigone, and mucosal layer invasion were identified as factors associated with urinary symptoms. Although some patients conceived successfully after surgery, disentangling the independent effect of bladder endometriosis on fertility remains challenging.
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Affiliation(s)
- Hailan Yan
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (Yan, Li, Dai, Shi, Wu, Gu, Zhang, Li, Zhang, Lv, and Leng), Beijing, China; National Clinical Research Center for Obstetric & Gynecologic Diseases (Yan, Li, Dai, Shi, Wu, Gu, Zhang, Li, Zhang, Lv, and Leng), Beijing, China
| | - Xiaoyan Li
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (Yan, Li, Dai, Shi, Wu, Gu, Zhang, Li, Zhang, Lv, and Leng), Beijing, China; National Clinical Research Center for Obstetric & Gynecologic Diseases (Yan, Li, Dai, Shi, Wu, Gu, Zhang, Li, Zhang, Lv, and Leng), Beijing, China
| | - Yi Dai
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (Yan, Li, Dai, Shi, Wu, Gu, Zhang, Li, Zhang, Lv, and Leng), Beijing, China; National Clinical Research Center for Obstetric & Gynecologic Diseases (Yan, Li, Dai, Shi, Wu, Gu, Zhang, Li, Zhang, Lv, and Leng), Beijing, China
| | - Jinghua Shi
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (Yan, Li, Dai, Shi, Wu, Gu, Zhang, Li, Zhang, Lv, and Leng), Beijing, China; National Clinical Research Center for Obstetric & Gynecologic Diseases (Yan, Li, Dai, Shi, Wu, Gu, Zhang, Li, Zhang, Lv, and Leng), Beijing, China
| | - Yushi Wu
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (Yan, Li, Dai, Shi, Wu, Gu, Zhang, Li, Zhang, Lv, and Leng), Beijing, China; National Clinical Research Center for Obstetric & Gynecologic Diseases (Yan, Li, Dai, Shi, Wu, Gu, Zhang, Li, Zhang, Lv, and Leng), Beijing, China
| | - Zhiyue Gu
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (Yan, Li, Dai, Shi, Wu, Gu, Zhang, Li, Zhang, Lv, and Leng), Beijing, China; National Clinical Research Center for Obstetric & Gynecologic Diseases (Yan, Li, Dai, Shi, Wu, Gu, Zhang, Li, Zhang, Lv, and Leng), Beijing, China
| | - Chenyu Zhang
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (Yan, Li, Dai, Shi, Wu, Gu, Zhang, Li, Zhang, Lv, and Leng), Beijing, China; National Clinical Research Center for Obstetric & Gynecologic Diseases (Yan, Li, Dai, Shi, Wu, Gu, Zhang, Li, Zhang, Lv, and Leng), Beijing, China
| | - Qiutong Li
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (Yan, Li, Dai, Shi, Wu, Gu, Zhang, Li, Zhang, Lv, and Leng), Beijing, China; National Clinical Research Center for Obstetric & Gynecologic Diseases (Yan, Li, Dai, Shi, Wu, Gu, Zhang, Li, Zhang, Lv, and Leng), Beijing, China
| | - Biyun Zhang
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (Yan, Li, Dai, Shi, Wu, Gu, Zhang, Li, Zhang, Lv, and Leng), Beijing, China; National Clinical Research Center for Obstetric & Gynecologic Diseases (Yan, Li, Dai, Shi, Wu, Gu, Zhang, Li, Zhang, Lv, and Leng), Beijing, China
| | - Shiqing Lv
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (Yan, Li, Dai, Shi, Wu, Gu, Zhang, Li, Zhang, Lv, and Leng), Beijing, China; National Clinical Research Center for Obstetric & Gynecologic Diseases (Yan, Li, Dai, Shi, Wu, Gu, Zhang, Li, Zhang, Lv, and Leng), Beijing, China
| | - Jinhua Leng
- Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (Yan, Li, Dai, Shi, Wu, Gu, Zhang, Li, Zhang, Lv, and Leng), Beijing, China; National Clinical Research Center for Obstetric & Gynecologic Diseases (Yan, Li, Dai, Shi, Wu, Gu, Zhang, Li, Zhang, Lv, and Leng), Beijing, China.
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17
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Tahmasbi Rad M, Graf N, Akpinar-Isci D, Wilhelm LM, Becker S, Gasimli K. Laparoscopic Endometriosis Surgery in Patients with Infertility: Identifying Surgical and Non-Surgical Variables Affecting Postoperative Pregnancy. Long-term Follow-up in a University Endometriosis Center. Geburtshilfe Frauenheilkd 2025; 85:80-88. [PMID: 39758121 PMCID: PMC11695095 DOI: 10.1055/a-2460-6470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 11/02/2024] [Indexed: 01/07/2025] Open
Abstract
Background Endometriosis is a disease which affects the quality of life and fertility of many young women. Choosing the right time for surgery is important for the outcome of patients. We evaluated the surgical variables affecting postoperative pregnancy rates. Method This study is a retrospective analysis of women treated for endometriosis in Frankfurt University Hospital between 2007 and 2017. A total of 695 patients underwent laparoscopic surgery, of whom 125 patients fulfilled the inclusion criteria of wanting to have a child for more than one year. Finally, 102 patients (82%) with surgery and infertility were followed up for 70 months. Results We found a cumulative pregnancy rate of 69.6% after 38 months in our patients. The duration of infertility before surgery had a significant effect on postoperative pregnancy rates. There was no significant difference between the different kinds of surgical techniques, but complete treatment of all visible lesions significantly increased the chance of pregnancy (hazard ratio 2.2). Repeated abdominal operations reduced the chance of postoperative pregnancy and prolonged the time to pregnancy. Conclusions In patients with endometriosis and infertility, both laparoscopic surgery with complete resection of all visible lesions and the timing of surgery are important to achieve pregnancy. Early intervention with careful planning of the operation is critical. It is important to avoid repeated operations to achieve the best results regarding pregnancy.
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Affiliation(s)
- Morva Tahmasbi Rad
- Department of Obstetrics and Gynecology, University of Frankfurt, Frankfurt am Main, Germany
| | - Nele Graf
- Department of Obstetrics and Gynecology, University of Frankfurt, Frankfurt am Main, Germany
| | - Dilara Akpinar-Isci
- Department of Obstetrics and Gynecology, University of Frankfurt, Frankfurt am Main, Germany
| | - Lisa Marie Wilhelm
- Department of Obstetrics and Gynecology, University of Frankfurt, Frankfurt am Main, Germany
| | - Sven Becker
- Department of Obstetrics and Gynecology, University of Frankfurt, Frankfurt am Main, Germany
| | - Khayal Gasimli
- Department of Obstetrics and Gynecology, University of Frankfurt, Frankfurt am Main, Germany
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18
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Nati ID, Ciortea R, Malutan A, Oancea M, Iuhas C, Bucuri C, Roman M, Ormindean C, Gombos L, Mihu D. Dyspareunia and Biomarkers: A Case Study of Sexual Dysfunction in Moderate Endometriosis. Int J Mol Sci 2024; 26:162. [PMID: 39796020 PMCID: PMC11720033 DOI: 10.3390/ijms26010162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Revised: 12/23/2024] [Accepted: 12/26/2024] [Indexed: 01/13/2025] Open
Abstract
Endometriosis, a chronic hormone-dependent condition affecting 10% of women globally, impacts pelvic organs and occasionally distant sites, causing pain, infertility, and sexual dysfunction. Biomarkers such as IL-8, IL-10, and BDNF influence inflammation, nerve sensitization, and pain. This study investigates their relationship with sexual quality of life, focusing on dyspareunia and related dysfunctions, as assessed using the Female Sexual Function Index (FSFI). Dyspareunia, a prominent symptom of endometriosis, is linked to lower FSFI scores in domains such as desire (mean 3.38), satisfaction (mean 3.28), and pain (mean 3.07). Elevated IL-8 tissue levels negatively correlated with desire (r = -0.649, p < 0.05) and satisfaction (r = -0.813, p < 0.01). Similarly, higher BDNF tissue levels were associated with increased pain (r = -0.435, p < 0.01) and reduced satisfaction (r = -0.252, p < 0.05). Patient factors such as higher endometriosis severity scores (mean 26.3, p < 0.05) and surgical history correlated with lower desire and satisfaction. Conversely, physical activity improved pain scores (p < 0.01) and enhanced desire and lubrication (p < 0.05), likely through reduced inflammation and better circulation. These findings highlight the complex interplay between biomarkers, individual factors, and sexual dysfunction in endometriosis, underscoring the need for personalized therapeutic approaches.
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Affiliation(s)
- Ionel Daniel Nati
- 2nd Department of Obstetric and Ginecology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400610 Cluj-Napoca, Romania; (I.D.N.); (R.C.); (M.O.); (C.I.); (M.R.); (C.O.); (D.M.)
| | - Razvan Ciortea
- 2nd Department of Obstetric and Ginecology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400610 Cluj-Napoca, Romania; (I.D.N.); (R.C.); (M.O.); (C.I.); (M.R.); (C.O.); (D.M.)
| | - Andrei Malutan
- 2nd Department of Obstetric and Ginecology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400610 Cluj-Napoca, Romania; (I.D.N.); (R.C.); (M.O.); (C.I.); (M.R.); (C.O.); (D.M.)
| | - Mihaela Oancea
- 2nd Department of Obstetric and Ginecology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400610 Cluj-Napoca, Romania; (I.D.N.); (R.C.); (M.O.); (C.I.); (M.R.); (C.O.); (D.M.)
| | - Cristian Iuhas
- 2nd Department of Obstetric and Ginecology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400610 Cluj-Napoca, Romania; (I.D.N.); (R.C.); (M.O.); (C.I.); (M.R.); (C.O.); (D.M.)
| | - Carmen Bucuri
- Emergency Military Clinical Hospital “Dr Constantin Papilian”, 400610 Cluj-Napoca, Romania
| | - Maria Roman
- 2nd Department of Obstetric and Ginecology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400610 Cluj-Napoca, Romania; (I.D.N.); (R.C.); (M.O.); (C.I.); (M.R.); (C.O.); (D.M.)
| | - Cristina Ormindean
- 2nd Department of Obstetric and Ginecology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400610 Cluj-Napoca, Romania; (I.D.N.); (R.C.); (M.O.); (C.I.); (M.R.); (C.O.); (D.M.)
| | - Leon Gombos
- Faculty of Physical Education and Sport, Bogdan-Vodă University of Cluj Napoca, 400394 Cluj-Napoca, Romania
| | - Dan Mihu
- 2nd Department of Obstetric and Ginecology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400610 Cluj-Napoca, Romania; (I.D.N.); (R.C.); (M.O.); (C.I.); (M.R.); (C.O.); (D.M.)
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19
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Pandey C, Maunder A, Liu J, Vaddiparthi V, Costello MF, Bahri-Khomami M, Mousa A, Ee C. The Role of Nutrient Supplements in Female Infertility: An Umbrella Review and Hierarchical Evidence Synthesis. Nutrients 2024; 17:57. [PMID: 39796491 PMCID: PMC11722770 DOI: 10.3390/nu17010057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 12/05/2024] [Accepted: 12/25/2024] [Indexed: 01/13/2025] Open
Abstract
BACKGROUND AND OBJECTIVES Nutrient supplements are commonly used to improve fertility outcomes by women with infertility trying to conceive spontaneously or utilising medically assisted reproduction (MAR). However, despite their widespread use and perceived safety, there is a lack of clear guidance on the efficacy and safety of these supplements for female infertility. The aim of this umbrella review was to identify the best available and most recent evidence on the efficacy and safety of nutrient supplements for female infertility to provide evidence-based guidance for clinicians and reproductive couples. METHODS Five electronic databases were searched for umbrella reviews, meta-analyses, and systematic reviews of randomised controlled trials on nutrient supplements for female infertility, published from August 2017 to January 2024. The primary outcomes were live birth, and clinical and biochemical pregnancy rates. Secondary outcomes were adverse effects including miscarriage and ectopic or multiple pregnancy. Quality assessment was performed using the A MeaSurement Tool to Assess systematic Reviews Version 2.0 (AMSTAR 2), and the certainty of evidence for outcomes were assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, where possible. RESULTS Four meta-analyses were included. Multiple micronutrients and antioxidants increased live birth rates in women utilising MAR and/or trying to conceive spontaneously compared to placebo, standard or no treatment (odds ratio (OR) 2.59 and 1.81 respectively) with very low certainty evidence. L-carnitine, coQ10, melatonin, myo-inositol, NAC and vitamin D increased clinical pregnancy rates in women with PCOS and/or undergoing MAR compared to placebo, standard or no treatment (odds ratio (OR) 11.14, 2.49, 1.66, relative risk (RR) 1.52, OR 2.15, and 1.49 respectively) with very low certainty evidence. Vitamin D did not increase biochemical pregnancy rates in women utilising MAR with very low certainty evidence. NAC, vitamin D, and pooled antioxidants had no effect on miscarriage rates or multiple pregnancy rates in women trying to conceive spontaneously or utilising MAR, with low to very low certainty evidence. Pooled antioxidants had no effect on ectopic pregnancy rates in women trying to conceive spontaneously or utilising MAR, with low certainty evidence. CONCLUSIONS The available evidence is insufficient to recommend nutrient supplementation to improve female infertility in women trying to conceive naturally and those utilising MAR. However, there is currently no indication that these nutrients pose any risk of significant harm. REGISTRATION PROSPERO (CRD42022365966) 20 October 2022.
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Affiliation(s)
- Chhiti Pandey
- NICM Health Research Institute, Western Sydney University, Penrith, NSW 2751, Australia; (C.P.); (A.M.); (J.L.); (V.V.)
| | - Alison Maunder
- NICM Health Research Institute, Western Sydney University, Penrith, NSW 2751, Australia; (C.P.); (A.M.); (J.L.); (V.V.)
| | - Jing Liu
- NICM Health Research Institute, Western Sydney University, Penrith, NSW 2751, Australia; (C.P.); (A.M.); (J.L.); (V.V.)
| | - Vaishnavi Vaddiparthi
- NICM Health Research Institute, Western Sydney University, Penrith, NSW 2751, Australia; (C.P.); (A.M.); (J.L.); (V.V.)
| | - Michael F. Costello
- Women’s Health, University of New South Wales and Royal Hospital for Women and Monash IVF, Sydney, NSW 2031, Australia;
| | - Mahnaz Bahri-Khomami
- Monash Centre for Health Research and Implementation, Monash University, Melbourne, VIC 3168, Australia; (M.B.-K.); (A.M.)
| | - Aya Mousa
- Monash Centre for Health Research and Implementation, Monash University, Melbourne, VIC 3168, Australia; (M.B.-K.); (A.M.)
| | - Carolyn Ee
- NICM Health Research Institute, Western Sydney University, Penrith, NSW 2751, Australia; (C.P.); (A.M.); (J.L.); (V.V.)
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20
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Mappa I, Page ZP, Di Mascio D, Patelli C, D'Antonio F, Giancotti A, Gebbia F, Mariani G, Cozzolino M, Muzii L, Rizzo G. The Effect of Endometriosis on In Vitro Fertilization Outcomes: A Systematic Review and Meta-Analysis. Healthcare (Basel) 2024; 12:2435. [PMID: 39685057 DOI: 10.3390/healthcare12232435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 11/27/2024] [Accepted: 11/29/2024] [Indexed: 12/18/2024] Open
Abstract
OBJECTIVES The purpose of this study was to evaluate the impact of endometriosis on various outcomes of in vitro fertilization (IVF), including live birth rates, clinical pregnancy rates, fertilization rates, and implantation rates, through a systematic review and meta-analysis. METHODS Systematic searches were carried out using PubMed, MEDLINE, Cochrane Central Register of Controlled Trials, Scopus, EMBASE, and Web of Science from January 2010 to November 2023. Studies comparing IVF outcomes in women with and without endometriosis were included. The primary outcome was live birth rate; secondary outcomes included clinical pregnancy, fertilization, and implantation rates. Data were extracted and analyzed using odds ratio (OR) and 95% confidence interval (CI) with fixed or random-effects models, depending on heterogeneity. RESULTS From 1340 studies initially identified, 40 studies met the inclusion criteria, encompassing 8970 women with endometriosis and 42,946 control participants. There were no significant differences between the endometriosis and control groups in terms of live birth rate (OR 1.03, 95% CI 0.75-1.41, p = 0.84), clinical pregnancy rate (OR 0.86, 95% CI 0.72-1.02, p = 0.1), or fertilization rate (OR 0.96, 95% CI 0.79-1.15, p = 0.64). However, endometriosis was associated with a significantly lower implantation rate (OR 0.85, 95% CI 0.74-0.97, p = 0.02). CONCLUSIONS Endometriosis significantly negatively affects implantation rates in women undergoing IVF, despite the absence of significant differences in live birth, clinical pregnancy, and fertilization rates. Further research is needed to evaluate the impact of different stages of endometriosis on IVF outcomes and to develop optimized management protocols for these patients.
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Affiliation(s)
- Ilenia Mappa
- Department of Obstetrics and Gynecology, Fondazione Policlinico di Tor Vergata, University of Rome Tor Vergata, 00133 Roma, Italy
| | - Zoe Pauline Page
- Department of Obstetrics and Gynecology, Fondazione Policlinico di Tor Vergata, University of Rome Tor Vergata, 00133 Roma, Italy
| | - Daniele Di Mascio
- Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, 00185 Roma, Italy
| | - Chiara Patelli
- Department of Obstetrics and Gynecology, University of Verona, 37129 Verona, Italy
| | - Francesco D'Antonio
- Department of Obstetrics and Gynecology, University of Chieti, 66013 Chieti, Italy
| | - Antonella Giancotti
- Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, 00185 Roma, Italy
| | - Francesco Gebbia
- IVIRMA Global Research Alliance, IVI Roma-Rome, 00197 Roma, Italy
| | - Giulia Mariani
- IVIRMA Global Research Alliance, IVI Roma-Rome, 00197 Roma, Italy
| | - Mauro Cozzolino
- IVIRMA Global Research Alliance, IVI Roma-Rome, 00197 Roma, Italy
| | - Ludovico Muzii
- Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, 00185 Roma, Italy
| | - Giuseppe Rizzo
- Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, 00185 Roma, Italy
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Lu J, Wang X, Shi X, Jiang J, Liu L, Liu L, Ren C, Lu C, Yu Z. PAK5-mediated PKM2 phosphorylation is critical for anaerobic glycolysis in endometriosis. Front Med 2024; 18:1054-1067. [PMID: 39331255 DOI: 10.1007/s11684-024-1069-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Accepted: 02/08/2024] [Indexed: 09/28/2024]
Abstract
P21-activated kinase 5 (PAK5) belongs to the PAK-II subfamily, which is an important regulator of cell survival, adhesion, and motility. However, the functions of PAK5 in endometriosis remain unclear. Here, PAK5 is strikingly upregulated in endometriosis. Furthermore, the knockdown of PAK5 or its inhibitor GNE 2861 blocks the development of endometriosis, which is equally demonstrated in PAK5-knockout mice. In addition, PAK5 promotes glycolysis by enhancing the protein stability of pyruvate kinase 2 (PKM2) in endometriotic cells, which is a key enzyme for glucose metabolism. Moreover, the phosphorylation of PKM2 at Ser519 by PAK5 mediates endometriosis cell proliferation and metastasis. Collectively, PAK5 plays an indispensable role in endometriosis. Our findings demonstrate that PAK5 is an important target for the treatment of endometriosis.
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Affiliation(s)
- Jiayi Lu
- Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University, Weifang, 261042, China
- School of Clinical Medicine, Shandong Second Medical University, Weifang, 261053, China
| | - Xiaoyun Wang
- Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University, Weifang, 261042, China
- School of Clinical Medicine, Shandong Second Medical University, Weifang, 261053, China
| | - Xiaodan Shi
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China
| | - Junyi Jiang
- Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University, Weifang, 261042, China
- School of Clinical Medicine, Shandong Second Medical University, Weifang, 261053, China
| | - Lan Liu
- Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University, Weifang, 261042, China
- School of Clinical Medicine, Shandong Second Medical University, Weifang, 261053, China
| | - Lu Liu
- Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University, Weifang, 261042, China
- School of Clinical Medicine, Shandong Second Medical University, Weifang, 261053, China
| | - Chune Ren
- Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University, Weifang, 261042, China.
| | - Chao Lu
- Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University, Weifang, 261042, China.
| | - Zhenhai Yu
- Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University, Weifang, 261042, China.
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22
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Song L, Yang C, Ji G, Hu R. The role and potential treatment of macrophages in patients with infertility and endometriosis. J Reprod Immunol 2024; 166:104384. [PMID: 39442472 DOI: 10.1016/j.jri.2024.104384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Revised: 10/04/2024] [Accepted: 10/12/2024] [Indexed: 10/25/2024]
Abstract
Endometriosis is characterized as a macrophage-related ailment due to its strong link with immune dysfunction. Understanding the status of macrophage polarization in the context of endometriosis-related infertility is crucial for advancing diagnostic and therapeutic strategies. Our comprehensive review delves into the foundational understanding of macrophages and their profound influence on both endometriosis and infertility. Additionally, we illuminate the complex role of macrophages in infertility and endometriosis specifically. Finally, we focused on four critical dimensions: follicular fluid, the intraperitoneal environment, endometrial receptivity, and strategies for managing endometriosis. It is clear that throughout the progression of endometriosis, the diverse polarization states of macrophages play a pivotal role in the internal reproductive environment of infertile individuals grappling with this condition. Modulating macrophage polarization in the reproductive environment of endometriosis patients could address infertility challenges more effectively, offering a promising pathway for treating infertility associated with endometriosis.
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Affiliation(s)
- Linlin Song
- Department of Gynecology, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China; Reproductive Medicine Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China; Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China
| | - Caihong Yang
- Department of Gynecology, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China; Reproductive Medicine Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China
| | - Guiyi Ji
- Reproductive Medicine Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China; Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China; Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia, 750004, China
| | - Rong Hu
- Reproductive Medicine Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China; Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China; Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia, 750004, China.
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23
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Kalra R, McDonnell R, Stewart F, Hart RJ, Hickey M, Farquhar C. Excisional surgery versus ablative surgery for ovarian endometrioma. Cochrane Database Syst Rev 2024; 11:CD004992. [PMID: 39588841 PMCID: PMC11590177 DOI: 10.1002/14651858.cd004992.pub4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2024]
Abstract
BACKGROUND Endometrioma are endometriotic deposits within the ovary. Laparoscopic management of endometriomas is associated with shorter hospital stay, faster recovery, and decreased hospital costs compared with laparotomy. The previous version of this systematic review (2008), including randomised controlled trials (RCTs) of surgical interventions for endometrioma, concluded that laparoscopic cystectomy (excision) was preferable to drainage and ablation of endometrioma. We aimed to update the evidence comparing excision with drainage and ablation for improving pain and fertility-related outcomes. OBJECTIVES To evaluate the safety and efficacy of laparoscopic excision (cystectomy) compared with laparoscopic drainage and ablation of endometrioma in women of reproductive age. SEARCH METHODS We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycInfo, two trials registries, grey literature sources, and conference proceedings on 19 December 2022. We also checked the reference lists of relevant papers and contacted leaders in the field of endoscopic surgery for any additional trials. SELECTION CRITERIA Eligible studies were RCTs that compared excision with drainage and ablation of endometriomas. DATA COLLECTION AND ANALYSIS Two review authors independently assessed study eligibility, extracted data, assessed risk of bias, and applied the GRADE approach to rate the certainty of evidence. MAIN RESULTS We identified nine studies (involving 578 women) that investigated laparoscopic excision versus drainage and ablation of endometriomas measuring at least 3 cm in diameter. Participants were women of reproductive age who presented to an outpatient gynaecology clinic with pain, infertility, or both. For most outcomes, we downgraded the certainty of evidence for risk of bias due to lack of blinding and for imprecision due to low participant numbers. At up to two years after surgery, excisional surgery compared with ablative surgery may reduce the risk of dysmenorrhoea recurrence (OR 0.25, 95% CI 0.12 to 0.52; 2 studies, 140 women; low-certainty evidence;). Recurrence of dysmenorrhoea may occur in 49% of women after ablative surgery compared with 10% to 34% after excisional surgery. At up to two years after surgery, excisional surgery compared with ablative surgery may reduce the risk of dyspareunia recurrence (OR 0.09, 95% CI 0.03 to 0.22; 2 studies, 131 women; low-certainty evidence). Recurrence of dyspareunia may occur in 58% of women after ablative surgery compared with 4% to 23% after excisional surgery. At one year after surgery, excisional surgery may reduce the risk of endometrioma recurrence compared with ablative surgery (OR 0.17, 95% CI 0.09 to 0.34; 4 studies, 264 women; low-certainty evidence). Recurrence of endometrioma may occur in 37% of women after ablative surgery compared with 5% to 17% after excisional surgery. At one year after surgery, excisional surgery may reduce the need for further endometrioma surgery compared with ablative surgery (OR 0.16, 95% CI 0.07 to 0.41; 2 studies, 178 women; low-certainty evidence). Our results suggest that 32% of women require further endometrioma surgery after ablative surgery compared with 3% to 16% after excisional surgery. There may be little or no difference between excisional surgery and ablative surgery in terms of their effect on spontaneous pregnancy during the first year after surgery (OR 1.27, 95% CI 0.33 to 4.87; 3 studies, 101 women; low-certainty evidence). Five studies reported that there were no conversions to laparotomy. No studies provided data about any other surgical complications or adverse effects. AUTHORS' CONCLUSIONS Surgical management of endometrioma with excision (cystectomy) may be more effective than drainage and ablation for reducing painful menstrual periods, pain during sexual intercourse, endometrioma recurrence, and the need for further endometrioma surgery. However, there may be little or no difference between the techniques in their effect on subsequent pregnancy rates. We found limited evidence on the safety of excisional surgery compared with ablative surgery. Future trials should recruit adequate numbers of women and measure outcomes relating to adverse events and clinical pregnancy.
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Affiliation(s)
- Rashi Kalra
- Department of Obstetrics and Gynaecology, King Edward Memorial Hospital, Perth, Australia
| | | | - Fiona Stewart
- c/o Cochrane Incontinence, Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Roger J Hart
- School of Women's and Infants' Health, The University of Western Australia, King Edward Memorial Hospital and Fertility Specialists of Western Australia, Subiaco, Perth, Australia
| | - Martha Hickey
- The University of Melbourne, The Royal Women's Hospital, Melbourne, Australia
| | - Cindy Farquhar
- Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand
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Wang YX, Farland LV, Gaskins AJ, Wang S, Terry KL, Rexrode KM, Rich-Edwards JW, Tamimi R, Chavarro JE, Missmer SA. Endometriosis and uterine fibroids and risk of premature mortality: prospective cohort study. BMJ 2024; 387:e078797. [PMID: 39567014 PMCID: PMC11577545 DOI: 10.1136/bmj-2023-078797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/26/2024] [Indexed: 11/22/2024]
Abstract
OBJECTIVE To prospectively assess the effect of endometriosis and uterine fibroids on the long term risk of premature mortality (younger than 70 years). DESIGN Prospective cohort study SETTING: The Nurses' Health Study II, United States (1989-2019). PARTICIPANTS 110 091 women aged 25-42 years in 1989 without a history of hysterectomy before endometriosis or fibroids diagnosis, cardiovascular diseases, or cancer. MAIN OUTCOME MEASURES Hazard ratios (estimated by Cox proportional hazards models) for total and cause specific premature mortality according to laparoscopically confirmed endometriosis or ultrasound or hysterectomy confirmed uterine fibroids reported in biennial questionnaires. RESULTS 4356 premature deaths were recorded during 2 994 354 person years of follow-up (27.2 years per person), including 1459 from cancer, 304 from cardiovascular diseases, and 90 from respiratory diseases. The crude incidence of all cause premature mortality for women with and without laparoscopically confirmed endometriosis was 2.01 and 1.40 per 1000 person years, respectively. In age adjusted models, laparoscopically confirmed endometriosis was associated with a hazard ratio of 1.19 (95% confidence interval 1.09 to 1.30) for premature death; these models were strengthened after also adjusting for potential confounders including behavioral factors (1.31, 1.20 to 1.44). Cause specific mortality analyses showed that the association was largely driven by mortality from senility and ill-defined diseases (1.80, 1.19 to 2.73), non-malignant respiratory diseases (1.95, 1.11 to 3.41), diseases of the nervous system and sense organs (2.50, 1.40 to 4.44), and malignant neoplasm of gynecological organs (2.76, 1.79 to 4.26). Ultrasound or hysterectomy confirmed uterine fibroids were not associated with all cause premature mortality (1.03, 0.95 to 1.11), but were associated with a greater risk of mortality from malignant neoplasm of gynecological organs (2.32, 1.59 to 3.40) in cause specific mortality analyses. The risk of mortality caused by cardiovascular and respiratory diseases varied according to joint categories of endometriosis and uterine fibroids, with an increased risk of all cause premature mortality among women reporting both endometriosis and uterine fibroids. CONCLUSION Women with a history of endometriosis and uterine fibroids might have an increased long term risk of premature mortality extending beyond their reproductive lifespan. These conditions were also associated with an increased risk of death due to gynecological cancers. Endometriosis was associated with a greater risk of non-cancer mortality. These findings highlight the importance for primary care providers to consider these gynecological disorders in their assessment of women's health.
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Affiliation(s)
- Yi-Xin Wang
- Department of Environmental Health, School of Public Health, Shanghai Jiao Tong University, Shanghai, China
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Leslie V Farland
- Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health and Department of Obstetrics and Gynecology, College of Medicine-Tucson, University of Arizona, Tucson, AZ, USA
| | - Audrey J Gaskins
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Siwen Wang
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Kathryn L Terry
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Kathryn M Rexrode
- Division of Women's Health, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Janet W Rich-Edwards
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Division of Women's Health, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Rulla Tamimi
- Division of Epidemiology, Population Health Sciences, Weill Cornell Medicine, New York, NY, USA
| | - Jorge E Chavarro
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Stacey A Missmer
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Obstetrics and Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI, USA
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25
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Balasubramanian V, Saravanan R, Balamurugan SSS, Rajendran S, Joseph LD, Dev B, Srinivasan B, Balunathan N, Shanmugasundaram G, Gopisetty G, Ganesan K, Rayala SK, Venkatraman G. Genetic alteration of mRNA editing enzyme APOBEC3B in the pathogenesis of ovarian endometriosis. Reprod Biomed Online 2024; 49:104111. [PMID: 39197402 DOI: 10.1016/j.rbmo.2024.104111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 03/24/2024] [Accepted: 05/09/2024] [Indexed: 09/01/2024]
Abstract
RESEARCH QUESTION What are the specific genetic alterations and associated network in endometriotic cells responsible for the disease pathogenesis? DESIGN Case control experimental study involving 45 women with endometriosis who underwent laparoscopic surgery (case) and 45 normal samples from women undergoing total abdominal hysterectomy (control). The endometrial samples were subjected to whole exome sequencing (WES) of endometriotic tissue and copy number variation analysis. Validation of gene hits were obtained from WES using polymerase chain reaction techniques, immunological techniques, in-silico tools and transgenic cell line models. RESULTS Germline heterozygous deletion of mRNA editing enzyme subunit APOBEC3B was identified in about 96% of endometriosis samples. The presence of germline deletion was confirmed with blood, endometrium and normal ovary samples obtained from the same patient. APOBEC3B deletions resulted in a hybrid protein that activates A1CF. APOBEC3B deletion can be a major cause of changes in the endometriotic microenvironment, and contributes to the pathogenesis and manifestation of the disease. The effect of APOBEC3B deletion was proved by in-vitro experiments in a cell line model, which displayed endometriosis-like characteristics. APOBEC3B germline deletion plays a major role in the pathogenesis of endometriosis, which is evident by the activation of A1CF, an increase in epithelial to mesenchymal transition, cellular proliferation, inflammation markers and a decrease in apoptosis markers. CONCLUSION The deleterious effects caused by APOBEC3B deletion in endometriosis were identified and confirmed. These results might provide a base for identifying the complete pathogenetic mechanism of endometriosis, thereby moving a step closer to better diagnosis and treatment options.
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Affiliation(s)
- Vaishnavi Balasubramanian
- Department of Human Genetics, Sri Ramachandra Faculty of Biomedical Sciences and Technology, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai-600116, India
| | - Roshni Saravanan
- Department of Human Genetics, Sri Ramachandra Faculty of Biomedical Sciences and Technology, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai-600116, India
| | - Srikanth Swamy Swaroop Balamurugan
- Department of Human Genetics, Sri Ramachandra Faculty of Biomedical Sciences and Technology, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai-600116, India
| | - Swetha Rajendran
- Department of Human Genetics, Sri Ramachandra Faculty of Biomedical Sciences and Technology, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai-600116, India
| | - Leena Dennis Joseph
- Department of Pathology, Sri Ramachandra Medical College, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, 600116, India
| | - Bhawna Dev
- Department of Radiology, Sri Ramachandra Medical College Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, 600116, India
| | - Bhuvana Srinivasan
- Department of Obstetrics and Gynecology, Sri Ramachandra Medical College Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, 600095, India
| | - Nandhini Balunathan
- Department of Human Genetics, Sri Ramachandra Faculty of Biomedical Sciences and Technology, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai-600116, India
| | | | - Gopal Gopisetty
- Department of Molecular Oncology, Cancer Institute (W.I.A), Adayar, Chennai, 600036, India
| | - Kumaresan Ganesan
- Unit of Excellence in Cancer Genetics, Department of Genetics, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, 625021, India
| | - Suresh Kumar Rayala
- Department of Biotechnology, Indian Institute of Technology Madras, Chennai, 600036, India..
| | - Ganesh Venkatraman
- Department of Bio-Medical Sciences, School of Bio Sciences & Technology, Vellore Institute of Technology Vellore, Vellore, 632014, India..
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Liu H, Dai X, Li N, Zhang L, Wang Z, Ren K, Li Y, Sun X, Wan J. Injectable Magnetic Hydrogel Incorporated with Anti-Inflammatory Peptide for Efficient Magnetothermal Treatment of Endometriosis. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2409778. [PMID: 39373358 PMCID: PMC11600196 DOI: 10.1002/advs.202409778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 09/24/2024] [Indexed: 10/08/2024]
Abstract
Endometriosis is a prevalent gynecological condition characterized by chronic pelvic pain, dysmenorrhea, and infertility, affecting ≈176 million women of reproductive age worldwide. Current treatments, including pharmacological and surgical interventions, are often associated with significant side effects and high recurrence rates. Consequently, there is an urgent need for innovative and safer therapeutic approaches. In this study, an injectable magnetic hydrogel nanosystem is developed designed for the dual-purpose magnetothermal and anti-inflammatory treatment of endometriosis. This hydrogel incorporates Fe3O4 nanoparticles alongside an anti-inflammatory peptide. Upon magnetic activation, the Fe3O4 nanoparticles induce a localized hyperthermic response, raising the temperature of endometriotic lesions to 63.3 °C, effectively destroying endometriotic cells. Concurrently, the thermally responsive hydrogel facilitates the controlled release of the anti-inflammatory peptide, thus modulating the inflammatory milieu. The biocompatibility and complete in vivo degradability of the hydrogel further enhance its therapeutic potential. The in vivo studies demonstrated that this injectable magnetic hydrogel system achieved a 90% reduction in the volume of endometriotic lesions and significantly decreased inflammatory markers, offering a promising non-invasive treatment modality for endometriosis. By integrating precise lesion ablation with the modulation of the inflammatory microenvironment, this system represents a novel approach to the clinical management of endometriosis.
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Affiliation(s)
- Huaichao Liu
- Department of GynecologyJi Nan Key Laboratory of Diagnosis and Treatment of Major Gynaecological DiseaseShandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan250021China
| | - Xiaohui Dai
- School of Chemistry and Pharmaceutical EngineeringMedical Science and Technology Innovation CenterShandong First Medical University and Shandong Academy of Medical SciencesJinan250000China
| | - Na Li
- Department of GynecologyJi Nan Key Laboratory of Diagnosis and Treatment of Major Gynaecological DiseaseShandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan250021China
| | - Le Zhang
- Department of GynecologyJi Nan Key Laboratory of Diagnosis and Treatment of Major Gynaecological DiseaseShandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan250021China
| | - Zihan Wang
- Department of GynecologyJi Nan Key Laboratory of Diagnosis and Treatment of Major Gynaecological DiseaseShandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan250021China
| | - Ke Ren
- School of Chemistry and Pharmaceutical EngineeringMedical Science and Technology Innovation CenterShandong First Medical University and Shandong Academy of Medical SciencesJinan250000China
| | - Yulei Li
- Department of GynecologyJi Nan Key Laboratory of Diagnosis and Treatment of Major Gynaecological DiseaseShandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan250021China
| | - Xiao Sun
- Department of GynecologyJi Nan Key Laboratory of Diagnosis and Treatment of Major Gynaecological DiseaseShandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan250021China
| | - Jipeng Wan
- Department of GynecologyJi Nan Key Laboratory of Diagnosis and Treatment of Major Gynaecological DiseaseShandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan250021China
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Santulli P, Bourdon M, Desportes C, Maignien C, Pocate-Cheriet K, Patrat C, Marcellin L, Chapron C. Assessment of the Pelvic Pain Experienced by Infertile Women is of Prime Importance for Diagnosing Endometriosis. J Minim Invasive Gynecol 2024; 31:943-950.e1. [PMID: 39033906 DOI: 10.1016/j.jmig.2024.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Revised: 07/03/2024] [Accepted: 07/13/2024] [Indexed: 07/23/2024]
Abstract
OBJECTIVE To provide evidence regarding the significance of painful symptoms among women suffering from infertility. DESIGN An observational retrospective cross-sectional study. SETTINGS University hospital-based research center. PATIENTS Infertile patients aged between 18 and 42 years surgically explored for benign gynecological conditions between 01-2004 and 12-2020. INTERVENTIONS For each patient, a standardized questionnaire was completed during a face-to-face interview conducted by the surgeon in the month preceding the surgery. Preoperative assessment the pain symptoms was recorded. Pain intensity was assessed with a 10cm visual analog scale (VAS). The pain was considered to be severe when the VAS score was ≥ 7. MEASUREMENTS AND MAIN RESULTS Surgery was performed in 839 infertile women. 451 women had severe pelvic pain. Infertile patients with severe pain significantly more often had endometriosis (67.4% versus 30.7% respectively; p <.001) than infertile women without severe pelvic pain, and especially deep infiltrating lesions (43.2% versus 8.5% respectively; p <.001). Moreover, these women more often had intestinal endometriosis lesions (28.4% vs 1.8%; p <.001). After multivariable regression analysis, the presence of endometriosis, irrespective of the phenotype (superficial lesions (OR1.84 [1.19-2.86] and/or ovarian endometrioma OR 2.79 [1.70-4.59] and/or deep infiltrating endometriosis OR 4.49 [2.69-7.51]), and the presence of at least one intestine endometriosis lesion (OR6.49 [2.69-7.51] were significantly associated with severe pelvic pain. CONCLUSION Severe pelvic pain is significantly associated with endometriosis and especially deep infiltrating lesions in a population of infertile women. These results demonstrate the importance of thorough questioning regarding pelvic pain symptoms during the initial management of infertile patients.
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Affiliation(s)
- Pietro Santulli
- Université de Paris Cité, Faculté de Santé, Faculté de Médecine Paris Centre, Paris, France (Drs. Santulli, Bourdon, Desportes, Patrat, Marcellin, and Chapron); Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Cité, Centre Hospitalier Universitaire (CHU) Cochin, Service de Gynécologie-Obstétrique II et de Médecine de la Reproduction, Paris, France (Drs. Santulli, Bourdon, Desportes, Maignien, Marcellin, and Chapron); Department "Development, Reproduction and Cancer", Institut Cochin, INSERM U1016, Paris, France (Drs. Santulli, Bourdon, Patrat, Marcellin, and Chapron).
| | - Mathilde Bourdon
- Université de Paris Cité, Faculté de Santé, Faculté de Médecine Paris Centre, Paris, France (Drs. Santulli, Bourdon, Desportes, Patrat, Marcellin, and Chapron); Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Cité, Centre Hospitalier Universitaire (CHU) Cochin, Service de Gynécologie-Obstétrique II et de Médecine de la Reproduction, Paris, France (Drs. Santulli, Bourdon, Desportes, Maignien, Marcellin, and Chapron); Department "Development, Reproduction and Cancer", Institut Cochin, INSERM U1016, Paris, France (Drs. Santulli, Bourdon, Patrat, Marcellin, and Chapron)
| | - Cassandre Desportes
- Université de Paris Cité, Faculté de Santé, Faculté de Médecine Paris Centre, Paris, France (Drs. Santulli, Bourdon, Desportes, Patrat, Marcellin, and Chapron); Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Cité, Centre Hospitalier Universitaire (CHU) Cochin, Service de Gynécologie-Obstétrique II et de Médecine de la Reproduction, Paris, France (Drs. Santulli, Bourdon, Desportes, Maignien, Marcellin, and Chapron)
| | - Chloé Maignien
- Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Cité, Centre Hospitalier Universitaire (CHU) Cochin, Service de Gynécologie-Obstétrique II et de Médecine de la Reproduction, Paris, France (Drs. Santulli, Bourdon, Desportes, Maignien, Marcellin, and Chapron)
| | - Khaled Pocate-Cheriet
- Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Cité, Centre Hospitalier Universitaire (CHU) Cochin, Service de Biologie de la Reproduction-CECOS, Paris, France (Pocate-Cheriet, and Patrat)
| | - Catherine Patrat
- Université de Paris Cité, Faculté de Santé, Faculté de Médecine Paris Centre, Paris, France (Drs. Santulli, Bourdon, Desportes, Patrat, Marcellin, and Chapron); Department "Development, Reproduction and Cancer", Institut Cochin, INSERM U1016, Paris, France (Drs. Santulli, Bourdon, Patrat, Marcellin, and Chapron); Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Cité, Centre Hospitalier Universitaire (CHU) Cochin, Service de Biologie de la Reproduction-CECOS, Paris, France (Pocate-Cheriet, and Patrat)
| | - Louis Marcellin
- Université de Paris Cité, Faculté de Santé, Faculté de Médecine Paris Centre, Paris, France (Drs. Santulli, Bourdon, Desportes, Patrat, Marcellin, and Chapron); Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Cité, Centre Hospitalier Universitaire (CHU) Cochin, Service de Gynécologie-Obstétrique II et de Médecine de la Reproduction, Paris, France (Drs. Santulli, Bourdon, Desportes, Maignien, Marcellin, and Chapron); Department "Development, Reproduction and Cancer", Institut Cochin, INSERM U1016, Paris, France (Drs. Santulli, Bourdon, Patrat, Marcellin, and Chapron)
| | - Charles Chapron
- Université de Paris Cité, Faculté de Santé, Faculté de Médecine Paris Centre, Paris, France (Drs. Santulli, Bourdon, Desportes, Patrat, Marcellin, and Chapron); Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Cité, Centre Hospitalier Universitaire (CHU) Cochin, Service de Gynécologie-Obstétrique II et de Médecine de la Reproduction, Paris, France (Drs. Santulli, Bourdon, Desportes, Maignien, Marcellin, and Chapron); Department "Development, Reproduction and Cancer", Institut Cochin, INSERM U1016, Paris, France (Drs. Santulli, Bourdon, Patrat, Marcellin, and Chapron)
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28
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Ji S, Li Y, Liang G, Zhang H, Yan L, Zhao X, Chen L, Zhang J. Chemokine ligand 2 may contribute to damage of fallopian tube epithelium in women with tubal endometriosis. Reprod Biomed Online 2024; 50:104499. [PMID: 40267758 DOI: 10.1016/j.rbmo.2024.104499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Revised: 10/12/2024] [Accepted: 10/15/2024] [Indexed: 04/25/2025]
Abstract
RESEARCH QUESTION How does tubal endometriosis (TEM) impact the morphology and ultrastructure of tubal epithelium, and what are the underlying pathophysiological mechanisms of TEM? DESIGN Epithelial samples of fallopian tube were collected from patients with and without TEM (TEM group, n = 27; control group, n=28). Morphological characteristics, ultrastructure, percentage of ciliated cells and ciliary beat frequency (CBF) were assessed via haematoxylin and eosin staining, electron microscopy and high-speed camera. mRNA microarray analysis was conducted to identify differentially expressed genes (DEG) in tubal epithelium, which were further validated using quantitative polymerase chain reaction (qPCR), immunohistochemistry and Western blotting. The effects of recombinant chemokine ligand 2 (CCL2) protein on primary human fallopian tube epithelial cells (FTEC) were examined in vitro. RESULTS Patients with TEM exhibited abnormalities in the morphology and ultrastructure of tubal epithelium, with a significantly reduced percentage of ciliated cells (P < 0.0001) and CBF (P < 0.0001) compared with control patients. Among the 765 DEG identified in tubal epithelium, 512 genes were up-regulated and 253 genes were down-regulated in the TEM group. Validation using qPCR (P = 0.0288), immunohistochemistry and Western blotting (P = 0.0150) confirmed significant up-regulation of CCL2 expression in the TEM group. In-vitro experiments revealed that recombinant CCL2 protein significantly reduced CBF (100 ng/ml versus blank control: P < 0.0001), differentiation of ciliated cells (25 ng/ml versus blank control: P = 0.0206, 50 ng/ml versus blank control: P < 0.0001, 100 ng/ml versus blank control: P < 0.001) and ciliary length (P < 0.0001) in FTEC, suggesting a role for CCL2 in the development of the TEM-related pathological phenotype. CONCLUSIONS These findings indicate that CCL2 may contribute to the pathological phenotype associated with TEM, and could be a crucial signalling molecule in damage of tubal epithelium in patients with TEM.
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Affiliation(s)
- Sifan Ji
- Department of Obstetrics and Gynaecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
| | - Yamei Li
- Department of Obstetrics and Gynaecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
| | - Guiling Liang
- Department of Obstetrics and Gynaecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
| | - Huiyu Zhang
- Department of Obstetrics and Gynaecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
| | - Li Yan
- Department of Obstetrics and Gynaecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
| | - Xiaoya Zhao
- Department of Obstetrics and Gynaecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
| | - Luting Chen
- Department of Obstetrics and Gynaecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China.
| | - Jian Zhang
- Department of Obstetrics and Gynaecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China.
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29
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Trinchant R, García-Velasco JA. Oocyte Quality in Women with Endometriosis. Gynecol Obstet Invest 2024; 90:173-181. [PMID: 39348802 DOI: 10.1159/000541615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Accepted: 09/23/2024] [Indexed: 10/02/2024]
Abstract
BACKGROUND Endometriosis is a chronic gynecological condition that affects approximately 10% of women of reproductive age globally. It is associated with significant morbidity due to symptoms such as pelvic pain and infertility. Current knowledge suggests that endometriosis impacts oocyte quality, a critical factor for successful fertilization and pregnancy. Despite extensive research, the exact mechanisms remain unclear, and further updates are necessary to optimize treatment strategies. OBJECTIVES This review aims to summarize current evidence regarding the impact of endometriosis on oocyte quality and its subsequent effects on fertility outcomes, particularly in the context of in vitro fertilization (IVF). METHODS A comprehensive search was conducted in PubMed using the terms "endometriosis AND oocyte quality," "endometriosis AND infertility, and "endometriosis AND IVF." The review included studies published up to July 2024. OUTCOME The review findings indicate that endometriosis may be associated with decreased oocyte quality, characterized by impaired morphological features and molecular abnormalities. These defects potentially lead to lower fertilization rates, impaired embryo development, and reduced pregnancy outcomes. However, some studies suggest that with controlled factors such as age and ovarian reserve, IVF outcomes may be comparable to those without endometriosis. CONCLUSIONS AND OUTLOOK For clinicians and scientists working in medically assisted reproduction, understanding the impact of endometriosis on oocyte quality is crucial for improving fertility treatment outcomes. Advances in assisted reproductive technologies and personalized treatment approaches may mitigate these adverse effects. The potential for using artificial intelligence to assess oocyte quality presents a promising avenue for future research, as currently there is no direct and objective measure to assess this parameter.
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Affiliation(s)
- Rafael Trinchant
- IVIRMA Global Research Alliance, IVIRMA Mallorca, Mallorca, Spain
- Escuela Internacional de Doctorado, Rey Juan Carlos University, Madrid, Spain
| | - Juan Antonio García-Velasco
- IVIRMA Global Research Alliance, IVIRMA Madrid, Madrid, Spain
- IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain
- Medical Specialties and Public Health, Rey Juan Carlos University, Madrid, Spain
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Wei L, Wang S, Xu S, Zhang C. The interplay between systemic inflammatory factors and endometriosis: A bidirectional mendelian randomization study. J Reprod Immunol 2024; 165:104293. [PMID: 38986231 DOI: 10.1016/j.jri.2024.104293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 06/08/2024] [Accepted: 06/27/2024] [Indexed: 07/12/2024]
Abstract
OBJECTIVE To utilize vast genetic data to reveal the interplay between 41 systemic inflammatory factors and endometriosis. DESIGN Bidirectional Mendelian randomization study. MAINS OUTCOME MEASURES This study obtained believable genetic instrumental variables for systemic inflammatory factors. The effect of systemic inflammatory factors on different endometriosis phenotypes, and the effect of endometriosis on the concentrations of systemic inflammatory factors were investigated. RESULTS In this mendelian randomization study, we found 20 causal relationships involving 18 systemic inflammatory factors and it was shown that Monocyte chemotactic protein-1, Macrophage inflammatory protein-1a, Granulocyte colony-stimulating factor, Macrophage migration inhibitory factor, Interleukin-4, Interleukin-5, Interleukin-8, Interleukin-9, Interleukin-12p70, Interleukin-16, and Interleukin-17 may be the upstream causes of endometriosis (P<0.05). Additionally, if the definition of exposure in the mendelian randomization was endometriosis, it could suggestively cause an increase in Eotaxin, cutaneous T-cell attracting chemokine, and Interferon gamma-induced protein 10 levels, and a decrease in growth-regulated oncogene-alpha, Interleukin-2 receptor, alpha subunit, platelet-derived growth factor BB, and Interleukin-18 (P<0.05). Reverse causality was not observed between a single systemic inflammatory factor and endometriosis. CONCLUSIONS Our findings indicate that several systemic inflammatory factors may act as the initiator at the onset of endometriosis. Additionally, several other inflammatory factors are far more probable to involved downstream during disease development.
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Affiliation(s)
- Longlong Wei
- Department of Reproductive Medicine Center, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China; Department of Reproductive Medicine Center, Henan Provincial People's Hospital, Zhengzhou, Henan, China
| | - Shuna Wang
- Department of Reproductive Medicine Center, Henan Provincial People's Hospital, Zhengzhou, Henan, China
| | - Siyue Xu
- Department of Reproductive Medicine Center, Henan Provincial People's Hospital, Zhengzhou, Henan, China
| | - Cuilian Zhang
- Department of Reproductive Medicine Center, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China; Department of Reproductive Medicine Center, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
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Gao X, Shao W, Wang J, Gao H, Zhang X, Xia C, Li M, Liu S. Integrin β3 enhances glycolysis and increases lactate production in endometriosis. J Reprod Immunol 2024; 165:104312. [PMID: 39094215 DOI: 10.1016/j.jri.2024.104312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 07/16/2024] [Accepted: 07/23/2024] [Indexed: 08/04/2024]
Abstract
BACKGROUND Endometriosis (EMs) is a chronic disease characterized by endometrial-like tissue present outside of the uterus. Macrophages have been confirmed to participate in the development of EMs. Integrin β3 (ITGB3), a β-subunit of the integrin family, is crucial in tumor progression. In this study, we investigated the pivotal role of ITGB3 in endometrial stromal cells (ESCs) and its influence on the development of EMs, particularly focusing on the regulatory impact of macrophages. METHODS In this study, we used western blot, Real-time qPCR, Immunohistochemistry to detected the high expression of ITGB3 in ESCs. ITGB3-overexpression ESCs (ITGB3-OE) was constructed and detected by RNA-seq with normal ESCs. ATP and lactate expression assay, transwell migration assay, wound healing, cell adhesion assay and other molecular biology techniques were used to explore the potential mechanisms. In vivo, we constructed the EMs mouse model and injected with cilengitite to inhibit ITGB3. RESULTS Here, we found ITGB3 highly expressed in ectopic lesions in EMs. The increasing ITGB3 resulted in activating the glycolysis, which produced more ATP and lactate in ITGB3-OE. After culturing with lactate, the migration, proliferation and invasion ability of ESCs were enhanced, while the result in 2-DG was reversed. In vivo, the results showed that after antagonizing ITGB3, the number of ectopic lesions was decrease. CONCLUSIONS Our findings indicate that ITGB3 up-regulated by macrophages are able to regulate the glycolysis to promote the development of EMs and lactate enhances the ability of proliferation, migration, invasion and adhesion of EMs iv vivo and in vitro.
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Affiliation(s)
- Xiaoxiao Gao
- Department of Obstetrics and Gynecology, Jinshan Hospital of Fudan University, Shanghai 201508, People's Republic of China
| | - Wei Shao
- Department of Obstetrics and Gynecology, Jinshan Hospital of Fudan University, Shanghai 201508, People's Republic of China
| | - Jiaqi Wang
- Department of Obstetrics and Gynecology, Jinshan Hospital of Fudan University, Shanghai 201508, People's Republic of China
| | - Han Gao
- Department of Obstetrics and Gynecology, Jinshan Hospital of Fudan University, Shanghai 201508, People's Republic of China
| | - Xiaolu Zhang
- Department of Obstetrics and Gynecology, Jinshan Hospital of Fudan University, Shanghai 201508, People's Republic of China
| | - Chen Xia
- Department of Obstetrics and Gynecology, Jinshan Hospital of Fudan University, Shanghai 201508, People's Republic of China
| | - Mingqing Li
- Department of Reproductive Immunology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, People's Republic of China.
| | - Songping Liu
- Department of Obstetrics and Gynecology, Jinshan Hospital of Fudan University, Shanghai 201508, People's Republic of China.
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Ouyang J, Dong H, Wei C, Yu R, Yang S, Xu H. Reproductive outcome after laparoscopic ovarian cystectomy using barbed sutures versus conventional smooth sutures: A retrospective cohort study. Int J Gynaecol Obstet 2024; 166:1351-1358. [PMID: 38607329 DOI: 10.1002/ijgo.15523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 03/12/2024] [Accepted: 03/24/2024] [Indexed: 04/13/2024]
Abstract
OBJECTIVE To investigate the effects of barbed and conventional sutures on reproductive outcomes and ovarian reserve after laparoscopic treatment for benign non-endometrioma ovarian cysts. METHODS This retrospective study was conducted at an affiliated women's hospital between May 2017 and December 2019. Patients with benign non-endometriotic ovarian cysts undergoing laparoscopic cystectomy were included. RESULTS Patients received barbed sutures (221 patients) or conventional smooth sutures (203 patients) intraoperatively. The two groups had comparable baseline characteristics. The surgical duration and ovarian suturing time were significantly shorter in the barbed suture group than in the conventional smooth suture group (P < 0.001 and P = 0.002, respectively). The rate of postoperative hemoglobin decline and serum anti-Müllerian hormone decline were similar between the two groups (P > 0.05). A total of 316 (74.53%) patients experienced at least one pregnancy postoperatively: 170 (76.92%) and 146 (71.92%) patients in the barbed suture and conventional smooth suture groups, respectively (χ2 = 1.395, P = 0.238). Multivariate Poisson regression demonstrated that barbed sutures had no significant effect on the overall postoperative pregnancy rate (adjusted incidence rate ratio, 1.10; 95% confidence interval, 0.93-1.36; P = 0.382). CONCLUSION In patients with benign non-endometriotic ovarian cysts undergoing laparoscopic ovarian cystectomy, barbed sutures had a reproductive outcome similar to that of conventional smooth sutures while providing higher surgical efficiency without adverse effects on the postoperative ovarian reserve. Barbed sutures are probably a viable option to conventional smooth sutures.
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Affiliation(s)
- Jing Ouyang
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
| | - Huan Dong
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
| | - Chenxuan Wei
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
| | - Ruoer Yu
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
| | - Siqin Yang
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
| | - Hong Xu
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
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Ellis K, Armour W, Wood R. 'I never see anyone like myself represented in discussions about endometriosis': priorities of LGBTQIA + endometriosis patients in New Zealand. CULTURE, HEALTH & SEXUALITY 2024:1-21. [PMID: 39196785 DOI: 10.1080/13691058.2024.2394650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Accepted: 08/16/2024] [Indexed: 08/30/2024]
Abstract
Limited information is available regarding the experiences and perspectives of LGBTQIA + patients internationally, and no literature exists for New Zealand. Twenty-eight LGBTQIA + endometriosis patients took part in asynchronous, online text-based discussions about their experiences navigating endometriosis diagnosis and management in Aotearoa New Zealand. Their qualitative responses were coded in an iterative thematic manner. The mean delay to diagnosis of this cohort was 10.2 ± 5.6 years from symptom onset, longer than previously reported delays in Aotearoa New Zealand. Participants shared a strong discomfort with the predominant focus of endometriosis management strategies on penetrative sex and pregnancy, and the sense they were dismissed if prioritising these functions was not their priority. Several potential improvements to current treatment and care for LGBTQIA + endometriosis patients were generally agreed upon by the cohort, including research to better understand a practice approach for managing the symptoms of transmasculine patients; expanding the management strategies for patients who are not prioritising fertility and penetrative sex; improving awareness of LGBTQIA + people and experiences amongst medical practitioners to reduce homophobia, transphobia, misogyny, misgendering and mistreatment in care; and the development of gender-neutral spaces for the support of patients who feel uncomfortable in cisgender women-centric endometriosis spaces.
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Affiliation(s)
- Katherine Ellis
- Department of Chemical and Process Engineering, University of Canterbury, Christchurch, New Zealand
- Endometriosis New Zealand, Christchurch, New Zealand
| | | | - Rachael Wood
- Department of Chemical and Process Engineering, University of Canterbury, Christchurch, New Zealand
- Biomolecular Interaction Centre, University of Canterbury, Christchurch, New Zealand
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Nati ID, Malutan A, Ciortea R, Oancea M, Bucuri C, Roman M, Ormindean C, Milon AG, Mihu D. Exploring the Influence of IL-8, IL-10, Patient-Reported Pain, and Physical Activity on Endometriosis Severity. Diagnostics (Basel) 2024; 14:1822. [PMID: 39202309 PMCID: PMC11353965 DOI: 10.3390/diagnostics14161822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 08/18/2024] [Accepted: 08/19/2024] [Indexed: 09/03/2024] Open
Abstract
Endometriosis is known to be a chronic, debilitating disease. The pathophysiological mechanisms of endometriosis development include local chronic inflammation and a certain degree of local immune deficit. We investigated the relationship between the endometriosis severity, IL-8, IL-10, BDNF, VEGF-A serum and tissue levels, patient-related pain, and physical activity in a cohort of 46 patients diagnosed with endometriosis who underwent surgery. The same panel of biomarkers was investigated in a control group of 44 reproductive-aged patients with non-endometriotic gynecological pathology who underwent surgical intervention. Our data show a high statistical significance between tissue expression of IL-8, IL-10, patient-related pain, and the severity of endometriosis. No relationship was identified between serum or tissue levels of VEGF-A and BDNF and the severity of endometriosis. These results validate the presence of local chronic inflammation and immune deficit, thereby creating, alongside other studies in the field, an opportunity for the development of innovative and personalized treatment approaches in endometriosis.
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Affiliation(s)
- Ionel Daniel Nati
- 2nd Department of Obstetric and Ginecology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400610 Cluj-Napoca, Romania; (I.D.N.)
| | - Andrei Malutan
- 2nd Department of Obstetric and Ginecology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400610 Cluj-Napoca, Romania; (I.D.N.)
| | - Razvan Ciortea
- 2nd Department of Obstetric and Ginecology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400610 Cluj-Napoca, Romania; (I.D.N.)
| | - Mihaela Oancea
- 2nd Department of Obstetric and Ginecology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400610 Cluj-Napoca, Romania; (I.D.N.)
| | - Carmen Bucuri
- 2nd Department of Obstetric and Ginecology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400610 Cluj-Napoca, Romania; (I.D.N.)
- Emergency Military Clinical Hospital “Dr Constantin Papilian”, 400610 Cluj-Napoca, Romania
| | - Maria Roman
- 2nd Department of Obstetric and Ginecology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400610 Cluj-Napoca, Romania; (I.D.N.)
| | - Cristina Ormindean
- 2nd Department of Obstetric and Ginecology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400610 Cluj-Napoca, Romania; (I.D.N.)
| | - Alexandra Gabriela Milon
- Faculty of Physical Education and Sport, Bogdan-Vodă University of Cluj Napoca, 400394 Cluj-Napoca, Romania
| | - Dan Mihu
- 2nd Department of Obstetric and Ginecology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400610 Cluj-Napoca, Romania; (I.D.N.)
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Chauhan JK, Dubey PK, Rai S, Tripathi A. Induction and characterization of a rat model of endometriosis. Sci Rep 2024; 14:18827. [PMID: 39138257 PMCID: PMC11322168 DOI: 10.1038/s41598-024-69440-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Accepted: 08/05/2024] [Indexed: 08/15/2024] Open
Abstract
Endometriosis is a common condition that affects 5% to 10% of women during their reproductive years, although the aetiology and pathophysiology are still unknown. This study aimed to create an endometriosis model in rats to investigate the efficacy of natural and synthetic medications in treating endometriosis. An in vivo endometriotic model was established using a surgical induction method and the endocrine-disrupting drug diethylstilbestrol (DES). In brief, the experiment is categorised into three different groups. Each group contains five rats. The first group had no surgery, while in the in the second group of rats (n = 5), two small tissue grafts were fixed at the right and left walls of the abdomen. But in the in the third group of rats (n = 5), two small pieces of tissue have been grafted on the right and left abdomen walls by surgically along with DES treatments. Noninvasive photoacoustic imaging (PAI) was employed in the study to measure factors such as haemoglobin levels, oxygen saturation, and the size of endometriotic lesions. Histopathological analysis was carried out utilising staining techniques such as Hematoxylin and Eosin, Masson's Trichrome, and Periodic Acid Schiff, as well as immunohistochemistry with marker antibodies. Molecular markers in uterine tissue were examined using Western blots and real-time PCR. The developed endometriosis rat model showed a significant increase in the expression of anti-apoptotic Bcl-2, angiogenic marker VEGF and pro-inflammatory (COX-2 and IL-6) protein markers. In contrast to the control group, the treatment group had considerably lower Caspase-3 expression levels. Photoacoustic imaging (PAI) data demonstrated a constant increase in lesion size, as well as a decrease in oxygen saturation levels. The findings suggest that the in vivo endometriosis rat model may accurately assess the efficacy of natural or synthetic endometriosis treatments. This model may help in the improvement of disease understanding and the development of targeted therapeutic drugs.
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Affiliation(s)
| | - Pawan K Dubey
- Centre for Genetic Disorders, Banaras Hindu University, Varanasi, 221005, UP, India
| | - Sangeeta Rai
- Department of Obstetrics and Gynecology, Institute of Medical Science, Banaras Hindu University, Varanasi, 221005, UP, India
| | - Anima Tripathi
- Department of Zoology, MMV, Banaras Hindu University, Varanasi, 221005, UP, India.
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Molina A, Carter A, Alexander L, Davé A, Riley K. Holistic approach to care for patients with endometriosis. Curr Opin Obstet Gynecol 2024; 36:266-272. [PMID: 38837362 DOI: 10.1097/gco.0000000000000970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/07/2024]
Abstract
PURPOSE OF REVIEW Endometriosis is a chronic, often debilitating, disease which is typically managed with surgery and hormonal medications. However, many patients feel they lack agency when managing endometriosis symptoms. The purpose of this review is to discuss the mental and physical management strategies, the long-term health consequences, and the role of a multidisciplinary team in the treatment of endometriosis. RECENT FINDINGS Evidence is becoming more robust regarding the role of complementary care and physical activity in the management of endometriosis. Health risks such as infertility are well known and newer evidence is evolving regarding perinatal and cardiovascular health risks. There are also trends towards multiple specialist involvement in the care of endometriosis and the benefit of interdisciplinary collaboration. SUMMARY Endometriosis is a frequently recurrent condition requiring not only meticulous medical and surgical care, but also coordinated longitudinal disease management and impact mitigation. Gynecologists should be aware of the short-term and long-term implications of the disease to empower patients on the management of their overall health.
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Affiliation(s)
- Andrea Molina
- Department of Minimally Invasive Gynecologic Surgery, Penn State Health
| | - Ashlie Carter
- Department of Minimally Invasive Gynecologic Surgery, Penn State Health
| | - Lacy Alexander
- Department of Kinesiology, Penn State, College of Health and Human Development, Pennsylvania, USA
| | - Arpit Davé
- Department of Minimally Invasive Gynecologic Surgery, Penn State Health
| | - Kristin Riley
- Department of Minimally Invasive Gynecologic Surgery, Penn State Health
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Bourdon M, Sorel M, Maignien C, Guibourdenche J, Patrat C, Marcellin L, Jobin T, Chapron C, Santulli P. Progesterone levels do not differ between patients with or without endometriosis/adenomyosis both in those who conceive after hormone replacement therapy-frozen embryo transfer cycles and those who do not. Hum Reprod 2024; 39:1692-1700. [PMID: 38850031 DOI: 10.1093/humrep/deae114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 04/19/2024] [Indexed: 06/09/2024] Open
Abstract
STUDY QUESTION Do women with endometriosis who achieve a live birth (LB) after HRT-frozen embryo transfer (HRT-FET) have different progesterone levels on the day of transfer compared to unaffected women? SUMMARY ANSWER In women achieving a LB after HRT-FET, serum progesterone levels on the day of the transfer did not differ between patients with endometriosis and unaffected patients. WHAT IS KNOWN ALREADY In HRT-FET, several studies have highlighted the correlation between serum progesterone levels at the time of FET and LB rates. In the pathophysiology of endometriosis, progesterone resistance is typically described in the eutopic endometrium. This has led to the hypothesis that women with endometriosis may require higher progesterone levels to achieve a LB, especially in HRT-FET cycles without a corpus luteum. STUDY DESIGN, SIZE, DURATION We conducted an observational cohort study at the university-based reproductive medicine center of our institution, focusing on women who underwent a single autologous frozen blastocyst transfer after HRT using exogenous estradiol and micronized vaginal progesterone for endometrial preparation between January 2019 and December 2021. Women were included only once during the study period. Serum progesterone levels were measured on the morning of the FET by a single laboratory. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients were divided into groups based on whether they had endometriosis or not and whether they achieved a LB. The diagnosis of endometriosis was based on published imaging criteria (transvaginal sonography/magnetic resonance imaging) and/or confirmed histology. The primary outcome was progesterone levels on the day of the HRT-FET leading to a LB in patients with endometriosis compared to unaffected women. Subgroup analyses were performed based on the presence of deep infiltrating endometriosis or adenomyosis. MAIN RESULTS AND THE ROLE OF CHANCE A total of 1784 patients were included. The mean age of the women was 35.1 ± 4.1 (SD) years. Five hundred and sixty women had endometriosis, while 1224 did not. About 179/560 (32.0%) with endometriosis and 381/1224 (31.2%) without endometriosis achieved a LB. Among women who achieved a LB after HRT-FET, there was no significant difference in the mean progesterone level on the day of the HRT-FET between those with endometriosis and those without (13.6 ± 4.3 ng/ml vs 13.2 ± 4.4 ng/ml, respectively; P = 0.302). In the subgroup of women with deep infiltrating endometriosis (n = 142) and adenomyosis (n = 100), the mean progesterone level was 13.1 ± 4.1 ng/ml and 12.6 ± 3.7 ng/ml, respectively, with no significant difference compared to endometriosis-free patients. After adjusting for BMI, parity, duration of infertility, tobacco use, and geographic origin, neither the presence of endometriosis (coefficient 0.38; 95% CI: -0.63 to 1.40; P = 0.457) nor the presence of adenomyosis (coefficient 0.97; 95% CI: -0.24 to 2.19; P = 0.114) was associated with the progesterone level on the day of HRT-FET. Among women who did not conceive, there was no significant difference in the mean progesterone level on the day of the HRT-FET between those with endometriosis and those without (P = 0.709). LIMITATIONS, REASONS FOR CAUTION The primary limitation of our study is associated with its observational design. Extrapolating our results to other laboratories or different routes and/or dosages of administering progesterone also requires validation. WIDER IMPLICATIONS OF THE FINDINGS This study shows that patients diagnosed with endometriosis do not require higher progesterone levels on the day of a frozen blastocyst transfer to achieve a LB in hormonal replacement therapy cycles. STUDY FUNDING/COMPETING INTEREST(S) None declared. TRIAL REGISTRATION NUMBER N/A.
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Affiliation(s)
- M Bourdon
- Faculté de Santé, University of Paris Cité, Paris, France
- Department of Gynecology, Obstetrics II, and Reproductive Medicine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Paris, France
- Department of Development, Reproduction, and Cancer, Cochin Institute, INSERM U1016, Paris, France
| | - M Sorel
- Department of Gynecology, Obstetrics II, and Reproductive Medicine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Paris, France
| | - C Maignien
- Department of Gynecology, Obstetrics II, and Reproductive Medicine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Paris, France
| | - J Guibourdenche
- Faculté de Santé, University of Paris Cité, Paris, France
- Department of Biological Endocrinology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Paris, France
| | - C Patrat
- Faculté de Santé, University of Paris Cité, Paris, France
- Department of Histology and Reproductive Biology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Paris, France
| | - L Marcellin
- Faculté de Santé, University of Paris Cité, Paris, France
- Department of Gynecology, Obstetrics II, and Reproductive Medicine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Paris, France
- Department of Development, Reproduction, and Cancer, Cochin Institute, INSERM U1016, Paris, France
| | - T Jobin
- Department of Gynecology, Obstetrics II, and Reproductive Medicine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Paris, France
| | - C Chapron
- Faculté de Santé, University of Paris Cité, Paris, France
- Department of Gynecology, Obstetrics II, and Reproductive Medicine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Paris, France
- Department of Development, Reproduction, and Cancer, Cochin Institute, INSERM U1016, Paris, France
| | - P Santulli
- Faculté de Santé, University of Paris Cité, Paris, France
- Department of Gynecology, Obstetrics II, and Reproductive Medicine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Paris, France
- Department of Development, Reproduction, and Cancer, Cochin Institute, INSERM U1016, Paris, France
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Tripathi A, Arsha S, Thapa A, Thapa S, Chand S, Frishman WH, Aronow WS. Cardiovascular Implications of Gynecological Disorders: Bridging the Gap Between Gynecology and Cardiology. Cardiol Rev 2024:00045415-990000000-00303. [PMID: 39078163 DOI: 10.1097/crd.0000000000000759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/31/2024]
Abstract
Gynecological disorders such as endometriosis, polycystic ovary syndrome, and gynecological cancers are increasingly recognized as potential risk factors for cardiovascular disease (CVD). Endometriosis, a chronic inflammatory condition, exhibits shared pathogenic mechanisms with CVD, including endothelial dysfunction and an atherogenic lipid profile. Emerging evidence suggests a link between endometriosis and an elevated risk of cardiovascular events such as myocardial infarction, ischemic heart disease, and hypertension. Polycystic ovary syndrome, characterized by hormonal imbalances and metabolic derangements, is associated with an increased risk of hypertension, myocardial infarction, and structural cardiac abnormalities, even after controlling for obesity. Gynecological cancers, such as ovarian, endometrial, and cervical cancers, are also associated with an increased burden of cardiovascular comorbidities and mortality. Cancer treatments, including chemotherapy and radiation therapy, can further contribute to cardiovascular toxicity. Understanding the interplay between gynecological disorders and CVD is crucial for identifying high-risk individuals, implementing preventive strategies, and providing comprehensive care. A multidisciplinary approach involving gynecologists, cardiologists, and other specialists is essential for optimizing the management of these complex conditions and improving overall patient outcomes.
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Affiliation(s)
- Ashish Tripathi
- From the Department of Medicine, Westchester Medical Center, Valhalla, NY
| | - Sanjana Arsha
- From the Department of Medicine, Westchester Medical Center, Valhalla, NY
| | - Anish Thapa
- Department of Medicine, Universal College of Medical Sciences, Bhairhawa, Nepal
| | - Sangharsha Thapa
- From the Department of Medicine, Westchester Medical Center, Valhalla, NY
| | - Swati Chand
- Department of Cardiology, Westchester Medical Center, Valhalla, NY
| | | | - Wilbert S Aronow
- Department of Cardiology, Westchester Medical Center, Valhalla, NY
- Department of Medicine, New York Medical College, Valhalla, NY
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Yang P, Miao Y, Wang T, Sun J. Identification of diagnostic markers related to inflammatory response and cellular senescence in endometriosis using machine learning and in vitro experiment. Inflamm Res 2024; 73:1107-1122. [PMID: 38704432 DOI: 10.1007/s00011-024-01886-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 04/11/2024] [Accepted: 04/16/2024] [Indexed: 05/06/2024] Open
Abstract
OBJECTIVE To understand the association between chronic inflammation, cellular senescence, and immunological infiltration in endometriosis. METHODS Datasets from GEO comprising 108 endometriosis and 97 healthy human samples and the human endometrial stromal cell. Differentially expressed genes were identified using Limma and WGCNA. Inflammatory response-related subtypes were constructed using consensus clustering analysis. The CIBERSORT algorithm and correlation analyses assessed immune cell infiltration. LASSO, SVM-RFE, and RF identified diagnostic genes. Functional enrichment analysis and multifactor regulatory networks established functional effects. Nomograms, internal and external validations, and in vitro experiments validated the diagnostic genes. RESULTS Inflammatory response subtypes were highly correlated with the immune activities of B and NK cells. Sixteen genes were associated with inflammatory response and cellular senescence and six diagnostic genes (NLK, RAD51, TIMELESS, TBX3, MET, and BTG3) were identified. The six diagnostic gene models had an area under the curve of 0.828 and their expression was significantly downregulated in endometriosis samples. Low expression of NLK and BTG3 promoted the proliferation, migration, and invasion of endometriotic cells. CONCLUSIONS Inflammatory response subtypes were successfully constructed for endometriosis. Six diagnostic genes related to inflammatory response and cellular senescence were identified and validated. Our study provides novel insights for inflammatory response in endometriosis and markers for endometriosis diagnosis and treatment.
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Affiliation(s)
- Pusheng Yang
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Tongji University, Shanghai, 200092, China
| | - Yaxin Miao
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Tongji University, Shanghai, 200092, China
| | - Tao Wang
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Tongji University, Shanghai, 200092, China
| | - Jing Sun
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Tongji University, Shanghai, 200092, China.
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Bourdon M, Peigné M, Maignien C, de Villardi de Montlaur D, Solignac C, Darné B, Languille S, Bendifallah S, Santulli P. Impact of Endometriosis Surgery on In Vitro Fertilization/Intracytoplasmic Sperm Injection Outcomes: a Systematic Review and Meta-analysis. Reprod Sci 2024; 31:1431-1455. [PMID: 38168857 DOI: 10.1007/s43032-023-01421-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 12/04/2023] [Indexed: 01/05/2024]
Abstract
Endometriosis-related infertility remains a therapeutic challenge. A burning issue in this field of research is determining whether pre-assisted reproductive technology (ART) surgery may be of some benefit in terms of reproductive outcomes. This systematic review and meta-analysis aimed at comparing ongoing pregnancy rates (OPR) and/or live birth rates (LBR) in patients who underwent endometriosis surgery before ART (IVF/ICSI) in comparison with patients who underwent first-line ART (IVF/ICSI). Searches were conducted from January 1990 to June 2021 on PubMed, Embase, and Cochrane Library using the following search terms: endometriosis, surgery, reproductive outcomes, and IVF/ICSI. The primary outcomes were OPR or LBR. A total of 19 studies were included in the meta-analysis. No statistically significant differences in LBR [0.91[0.63, 1.30]; I2 = 66%; n = 11], OPR [1.28[0.66, 2.49]; I2 = 60%; n = 3], and early pregnancy loss rate [0.88[0.62, 1.25]; I2 = 0%; n = 7] per cycle were found when comparing patients who underwent endometriosis surgery before IVF/ICSI and those who did not. After the exclusion of the studies with high risks of bias, the LBR per cycle was significantly reduced in the case of surgical treatment before IVF/ICSI [0.53[0.33, 0.86]; I2 = 30%; n = 4]. These data urge the clinician to carefully weigh the pros and cons before referring infertile patients with endometriosis to surgery before IVF, highlighting the key role of multidisciplinary referral centers.
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Affiliation(s)
- M Bourdon
- Department of Gynecology Obstetrics II and Reproductive Medicine (Professor Chapron), Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Université de Paris Cité, Faculté de Santé, Paris, France
- Department 3I "Infection, Immunité Et Inflammation", Institut Cochin, INSERM U1016, Paris, France
| | - M Peigné
- Department of Reproductive Médecine and Fertility Preservation, AP-HP, Hopital Jean Verdier, Université Sorbonne Paris Nord, Faculté de Santé, Bondy, France
| | - C Maignien
- Department of Gynecology Obstetrics II and Reproductive Medicine (Professor Chapron), Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Université de Paris Cité, Faculté de Santé, Paris, France
| | | | - C Solignac
- Gedeon Richter France, 75008, Paris, France
| | - B Darné
- Monitoring Force, 78600, Maisons-Laffitte, France
| | - S Languille
- Monitoring Force, 78600, Maisons-Laffitte, France
| | - S Bendifallah
- Department of Gynecology Obstetrics and Reproductive Medicine, AP-HP, Hôpital Tenon, Hôpitaux Universitaires Est Parisien, Faculté de Santé, Paris, France
| | - Pietro Santulli
- Department of Gynecology Obstetrics II and Reproductive Medicine (Professor Chapron), Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Université de Paris Cité, Faculté de Santé, Paris, France.
- Department 3I "Infection, Immunité Et Inflammation", Institut Cochin, INSERM U1016, Paris, France.
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Katta M, Maged AM, Ogila AI, Ragab WS. Impact of treatment interventions of endometriomas prior to in vitro fertilization: a systematic review and meta-analysis. MIDDLE EAST FERTILITY SOCIETY JOURNAL 2024; 29:27. [DOI: 10.1186/s43043-024-00189-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 05/21/2024] [Indexed: 05/10/2025] Open
Abstract
Abstract
Background
Treatment of endometrioma before in vitro fertilization (IVF) is challenging as it may affect ovarian response to induction.
Objective
A systematic review to search for the available optimal management of ovarian endometrioma before ovulation induction in IVF.
Search strategy
Screening of the MEDLINE, Web of Science, EMBASE, Cochrane database, and the clinical trial registration sites, covering the period from their inception up to June 2023 was done by two reviewers independently using the keywords ovarian endometrioma, ovarian endometriosis, endometrioma/surgery, endometrioma/hormonal treatment, randomized controlled trial(s), case-controlled studies, and cohort studies.
Selection criteria
All types of studies were included. Participants included were women with unilateral or bilateral ovarian endometriomas candidate for IVF/ICSI. We included 18 studies in the review. Three studies were randomized controlled parallel studies, six were prospective cohort, and nine were retrospective cohort studies.
Data collection and analysis
Data from all included studies were extracted by two authors (A. M., A. O.) independently. Data extracted included sample size, population characteristics including age, BMI, duration of infertility, ovarian reserve markers, cyst size, and bilaterality and induction protocol used.
Main results
We found 18 studies. Women with untreated endometrioma had significantly higher numbers of MII oocytes (the mean difference (MD) effect estimate was − 0.53 with [− 1.04, − 0.01] 95% CI and 0.04 P-value), higher number of obtained embryos (MD effect estimate was − 0.25 with [− 0.38, − 0.11] 95%CI and < 0.001 P-value), and required lower doses of gonadotropins for induction (MD effect estimate was 361.14 with [168.13, 5554.15] 95% CI and < 0.001 P-value) compared to those who had undergone surgical management of endometrioma. However, live birth (OR effect estimate was 0.79 with [0.54, 1.18] 95% CI and 0.25 P-value), clinical pregnancy (OR effect estimate was 0.95 with [0.72, 1.26] 95% CI and 0.73 P-value), miscarriage (OR effect estimate was 0.74 with [0.33, 1.63] 95% CI and 0.45 P-value), cancellation rates (OR effect estimate was 1.62 with [0.57, 4.66] 95% CI and 0.37 P-value), and the duration of stimulation (MD effect estimate was 0.19 with [− 0.42, − 0.81] 95% CI and 0.54 P-value) did not show any significant difference between the two groups of women. Hormonal treatment of endometrioma was associated with higher ongoing pregnancy rate (OR effect estimate was 3.39 with [1.83, 6.26] 95% CI and < 0.001 P-value), higher clinical pregnancy rate (OR effect estimate was 3.36 with [2.01, 5.63] 95% CI and < 0.001 P-value), and higher numbers of MII oocytes (MD effect estimate was 2.04 with [0.72, 3.36] 95% CI and 0.003 P-value) when compared to women who did not receive such therapy. These effects were evident in treatment with GnRH agonists, OCPs (oral contraceptive pills), and dienogest, while the miscarriage and cycle cancellation rates did not show these differences.
Conclusions
The optimal approach for treating endometrioma prior to IVF is not clear yet due to lack of well-designed randomized controlled trials.
Registration number
CRD42020151736.
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Que X, Ren L, Yang L, Wang L, Li J, Wu R, Chen Q. Long noncoding RNA BMPR1B-AS1 stability regulated by IGF2BP2 affects the decidualization in endometriosis patients through the SMAD1/5/9 pathway. FASEB J 2024; 38:e23622. [PMID: 38703029 DOI: 10.1096/fj.202302195r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 03/19/2024] [Accepted: 04/08/2024] [Indexed: 05/06/2024]
Abstract
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.
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Affiliation(s)
- Xiaohong Que
- The School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, China
- Clinical Medical Research Center for Gynecology and Reproductive Health of Fujian Province, Laboratory of Research and Diagnosis of Gynecological Diseases of Xiamen City, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
- The Graduate School of Fujian Medical University, Fuzhou, Fujian, China
| | - Lulu Ren
- The School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, China
- Clinical Medical Research Center for Gynecology and Reproductive Health of Fujian Province, Laboratory of Research and Diagnosis of Gynecological Diseases of Xiamen City, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
- Reproductive Medical Center, the First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
| | - Lin Yang
- Clinical Medical Research Center for Gynecology and Reproductive Health of Fujian Province, Laboratory of Research and Diagnosis of Gynecological Diseases of Xiamen City, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
| | - Lemeng Wang
- Clinical Medical Research Center for Gynecology and Reproductive Health of Fujian Province, Laboratory of Research and Diagnosis of Gynecological Diseases of Xiamen City, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
- School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Junzui Li
- Clinical Medical Research Center for Gynecology and Reproductive Health of Fujian Province, Laboratory of Research and Diagnosis of Gynecological Diseases of Xiamen City, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
- School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Rongfeng Wu
- The School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, China
- Clinical Medical Research Center for Gynecology and Reproductive Health of Fujian Province, Laboratory of Research and Diagnosis of Gynecological Diseases of Xiamen City, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
- Reproductive Medical Center, the First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
- School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Qionghua Chen
- The School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, China
- Clinical Medical Research Center for Gynecology and Reproductive Health of Fujian Province, Laboratory of Research and Diagnosis of Gynecological Diseases of Xiamen City, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
- The Graduate School of Fujian Medical University, Fuzhou, Fujian, China
- School of Medicine, Xiamen University, Xiamen, Fujian, China
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Gete DG, Doust J, Mortlock S, Montgomery G, Mishra GD. Risk of Iron Deficiency in Women With Endometriosis: A Population-Based Prospective Cohort Study. Womens Health Issues 2024; 34:317-324. [PMID: 38658289 DOI: 10.1016/j.whi.2024.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 02/25/2024] [Accepted: 03/15/2024] [Indexed: 04/26/2024]
Abstract
BACKGROUND Endometriosis may be linked to the risk of iron deficiency through chronic systemic inflammation or heavy menstrual bleeding. No longitudinal studies, however, have examined the relationship between endometriosis and the risk of iron deficiency. METHODS This study included 3,294 participants born from 1973 to 1978 and followed as part of the Australian Longitudinal Study on Women's Health from 2000 to 2018. Participants with endometriosis were identified using self-reported longitudinal surveys linked to administrative health records. During each survey, participants were also asked to report the diagnosis of iron deficiency, and we validated diagnoses using an administrative health database. Generalized estimating equations for binary responses with an autoregressive correlation matrix were used to examine the association between endometriosis and the risk of iron deficiency over the seven time points. FINDINGS We found that women with endometriosis had a significantly higher risk of iron deficiency than those without endometriosis after adjusting for sociodemographic, lifestyle, reproductive, and nutrition factors (adjusted odds ratio [aOR] = 1.46; 95% confidence interval [CI] [1.29, 1.66]; p < .0001). Women with a surgically confirmed diagnosis and those with clinically suspected endometriosis had a higher risk of iron deficiency (aOR = 1.38; 95% CI [1.17, 1.64] and aOR = 1.53; 95% CI [1.30, 1.81]), respectively. These associations, however, were slightly attenuated (by 8%) when adjusted for the presence of heavy menstrual bleeding. CONCLUSIONS Women with endometriosis are at a higher risk of developing iron deficiency than those without endometriosis. The findings suggest that iron deficiency should be concomitantly addressed during initial diagnosis and successive management of endometriosis.
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Affiliation(s)
- Dereje G Gete
- Australian Women and Girls' Health Research Centre, School of Public Health, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
| | - Jenny Doust
- Australian Women and Girls' Health Research Centre, School of Public Health, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Sally Mortlock
- Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia
| | - Grant Montgomery
- Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia
| | - Gita D Mishra
- Australian Women and Girls' Health Research Centre, School of Public Health, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
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Gjorgoska M, Rizner TL. The effect of androgens on the risk of endometriosis sub-phenotypes and ovarian neoplasms: A Mendelian randomization study. J Steroid Biochem Mol Biol 2024; 239:106482. [PMID: 38369034 DOI: 10.1016/j.jsbmb.2024.106482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 02/07/2024] [Accepted: 02/08/2024] [Indexed: 02/20/2024]
Abstract
Endometriosis is a complex gynecological pathology with a broad spectrum of symptoms, affecting around 10% of reproductive-aged women. Ovarian cancer (OC) is a heterogeneous disease for which we lack effective diagnostic and therapeutic strategies. The etiology and pathogenesis of both diseases remain ambiguous. Androgens in endometriosis could have a distinct role beyond serving as estrogen sources, whereas in the case of serous OC could be important in the formation of precursor lesions which ultimately lead to tumor formation. Here we performed two-sample Mendelian randomization (MR) analysis to examine the causal relationship between the androgen precursor - dehydroepiandrosterone sulphate (DHEAS), bioactive androgen - testosterone (T), androgen metabolite - androsterone sulphate, steroid hormone binding globulin (SHBG) and albumin and the risk of endometrioses of various sub-phenotypes and ovarian neoplasms across the benign-borderline-malignant spectrum. Stringent quality control procedures were followed to select eligible instrumental variables that were strongly associated with the selected exposures, sensitivity analyses were performed to assess the heterogeneities, horizontal pleiotropy, and stabilities of SNPs in endometriosis and ovarian neoplasms. We discovered an inverse association between genetically predicted levels of all androgens and risk of endometriosis, the same trend was most evident in the ovarian sub-phenotype. Total T levels were also inversely associated with peritoneal sub-phenotype of endometriosis. Likewise, T was causally associated with decreased risk of clear-cell OC, an endometriosis-associated OC subtype, and with malignant serous OC of both low- and high-grade, but with higher risk of their counterpart of low malignant potential. These findings support further investigation of androgen's action at a molecular level in ovary-associated endometriotic lesions, clear cell ovarian tumors and serous precursor lesions.
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Affiliation(s)
- Marija Gjorgoska
- Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Tea Lanisnik Rizner
- Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
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Alson S, Henic E, Jokubkiene L, Sladkevicius P. Endometriosis diagnosed by ultrasound is associated with lower live birth rates in women undergoing their first in vitro fertilization/intracytoplasmic sperm injection treatment. Fertil Steril 2024; 121:832-841. [PMID: 38246403 DOI: 10.1016/j.fertnstert.2024.01.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 01/09/2024] [Accepted: 01/15/2024] [Indexed: 01/23/2024]
Abstract
OBJECTIVE To study the cumulative live birth rate (CLBR) after the first in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment in women with or without deep-infiltrating endometriosis (DIE) and/or endometrioma diagnosed by transvaginal ultrasonography (TVUS), using the International Deep Endometriosis Analysis (IDEA) group definitions. DESIGN Prospective observational cohort study at a university hospital. PATIENTS(S) In total, 1,040 women with subfertility aged 25 to ≤39 years were undergoing their first IVF/ICSI treatment between January 2019 and October 2022. Of these, 234 (22.5%; 95% confidence interval [CI], 20.0-25.0) women were diagnosed with DIE and/or endometrioma at systematic TVUS before starting their treatment. INTERVENTION(S) All women underwent their first IVF or ICSI treatment. Fresh and/or frozen embryos from the first cycle were used until pregnancy was achieved or no embryos remained. MAIN OUTCOME MEASURE(S) Cumulative live birth rate after the first IVF/ICSI cycle in women with or without DIE and/or endometrioma. RESULT(S) The CLBR after the first IVF/ICSI treatment in the total cohort of women was 426/1,040 (41.0%; 95% CI, 38.0-44.0). Women with DIE and/or endometrioma had a lower CLBR (78/234, 33.3%; 95% CI, 27.3-39.4) than women without the disease (348/806, 43.2%; 95% CI, 39.8-46.6). The crude relative risk (RR) for cumulative live birth for women with DIE and/or endometrioma was 0.77; 95% CI, 0.63-0.94, and after adjustments were made for age, body mass index, s-antimüllerian hormone, stimulation protocol, and day for embryo transfer, the adjusted RR was 0.63; 95% CI, 0.48-0.82. There was no difference in the number of retrieved mature oocytes, fertilization rate, or good quality embryos between the 2 groups. CONCLUSION The presence of DIE and/or endometrioma diagnosed by TVUS lowers the chance of live birth in women undergoing their first IVF/ICSI treatment.
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Affiliation(s)
- Sara Alson
- Obstetric, Gynecological and Prenatal Ultrasound research, Department of Clinical Sciences, Malmö, Lund University, Sweden; Department of Obstetrics and Gynecology, Skåne University Hospital, Malmö, Sweden; Reproductive Medicine Center, Skåne University Hospital, Malmö, Sweden.
| | - Emir Henic
- Reproductive Medicine Center, Skåne University Hospital, Malmö, Sweden; Department of Translational Medicine, Lund University, Malmö, Sweden
| | - Ligita Jokubkiene
- Obstetric, Gynecological and Prenatal Ultrasound research, Department of Clinical Sciences, Malmö, Lund University, Sweden; Department of Obstetrics and Gynecology, Skåne University Hospital, Malmö, Sweden
| | - Povilas Sladkevicius
- Obstetric, Gynecological and Prenatal Ultrasound research, Department of Clinical Sciences, Malmö, Lund University, Sweden; Department of Obstetrics and Gynecology, Skåne University Hospital, Malmö, Sweden
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Wu J, Li Z, Wu Y, Cui N. The crosstalk between exosomes and ferroptosis: a review. Cell Death Discov 2024; 10:170. [PMID: 38594265 PMCID: PMC11004161 DOI: 10.1038/s41420-024-01938-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 03/17/2024] [Accepted: 03/28/2024] [Indexed: 04/11/2024] Open
Abstract
Exosomes are a subtype of extracellular vesicles composed of bioactive molecules, including nucleic acids, proteins, and lipids. Exosomes are generated by the fusion of intracellular multivesicular bodies (MVBs) with the cell membrane and subsequently released into the extracellular space to participate in intercellular communication and diverse biological processes within target cells. As a crucial mediator, exosomes have been implicated in regulating ferroptosis-an iron-dependent programmed cell death characterized by lipid peroxide accumulation induced by reactive oxygen species. The involvement of exosomes in iron, lipid, and amino acid metabolism contributes to their regulatory role in specific mechanisms underlying how exosomes modulate ferroptosis, which remains incompletely understood, and some related studies are still preliminary. Therefore, targeting the regulation of ferroptosis by exosomes holds promise for future clinical treatment strategies across various diseases. This review aims to provide insights into the pathophysiology and mechanisms governing the interaction between exosomes and ferroptosis and their implications in disease development and treatment to serve as a reference for further research.
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Affiliation(s)
- Jiao Wu
- Oncology Department of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Zhongyu Li
- Department of Internal Medicine, Eye Hospital China Academy of Chinese Medical Sciences, Beijing, China.
| | - Yu Wu
- Oncology Department of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
| | - Ning Cui
- Oncology Department of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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Abu-Zaid A, Gari A, Sabban H, Alshahrani MS, Khadawardi K, Badghish E, AlSghan R, Bukhari IA, Alyousef A, Abuzaid M, Alsharif SA, Alomar O, Alamery AH, Baradwan S. Comparison of Letrozole and Clomiphene Citrate in Pregnancy Outcomes in Patients with Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis. Reprod Sci 2024; 31:883-905. [PMID: 38030814 DOI: 10.1007/s43032-023-01404-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Accepted: 11/04/2023] [Indexed: 12/01/2023]
Abstract
Clomiphene citrate (CC) and letrozole are the predominant medical interventions for the management of infertility in patients with polycystic ovary syndrome (PCOS). To comprehensively summarize the evidence, a systematic review and meta-analysis of randomized clinical trials (RCTs) was carried out to assess the effect of letrozole and CC on pregnancy outcomes in PCOS patients. We searched PubMed/MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials from inception to January 2023. We included RCTs conducted on PCOS women comparing letrozole to CC and assessing endometrial thickness, the number and size of follicles, and ovulation and pregnancy rates. The endpoints were summarized as risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI) using the random-effects model. Heterogeneity was examined using the I2 statistic. Fifty trials met our inclusion criteria. The mean endometrial thickness was significantly higher in the letrozole group compared to CC group (SMD: 0.89; 95% CI: 0.49, 1.28; I2=97.72%); however, the number of follicles was higher in the CC group (SMD: -0.56; 95% CI: -0.96, -0.17; I2=96.34%). Furthermore, letrozole intake induced higher ovulation rate (RR: 1.20; 95% CI: 1.13, 1.26; I2=54.49%) and pregnancy rate (RR: 1.44; 95% CI: 1.28, 1.62; I2=65.58%) compared to CC. Compared to CC, letrozole has a positive effect on endometrial thickness, monofollicular development, and ovulation and pregnancy rates suggesting that letrozole may be a strong alternative to CC as a first-line medical intervention for chronic anovulation in PCOS women. Larger studies are warranted to further clarify these findings.
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Affiliation(s)
- Ahmed Abu-Zaid
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
| | - Abdulrahim Gari
- Department of Obstetrics and Gynecology, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
- Department of Obstetrics and Gynecology, Almurjan Hospital, Jeddah, Saudi Arabia
| | - Hussein Sabban
- Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia
- Department of Obstetrics and Gynecology, Faculty of Medicine at Rabigh, King Abdulaziz University, Rabigh, Saudi Arabia
| | - Majed Saeed Alshahrani
- Department of Obstetrics and Gynecology, Faculty of Medicine, Najran University, Najran, Saudi Arabia
| | - Khalid Khadawardi
- Department of Obstetrics and Gynecology, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Ehab Badghish
- Department of Obstetrics and Gynecology, Maternity and Children Hospital, Makkah, Saudi Arabia
| | - Rayan AlSghan
- Department of Obstetrics and Gynecology, Maternity and Children Hospital, AlKharj, Saudi Arabia
| | - Ibtihal Abdulaziz Bukhari
- Department of Obstetrics and Gynecology, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Abdullah Alyousef
- Department of Obstetrics and Gynecology, King Abdullah bin Abdulaziz University Hospital, Riyadh, Saudi Arabia
| | - Mohammed Abuzaid
- Department of Obstetrics and Gynecology, Muhayil General Hospital, Muhayil, Saudi Arabia
| | - Saud Abdullah Alsharif
- Department of Obstetrics and Gynecology, College of Medicine, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia
| | - Osama Alomar
- Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Aliyah Hadi Alamery
- Department of Obstetrics and Gynecology, Specialized Medical Center, Riyadh, Saudi Arabia
| | - Saeed Baradwan
- Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia
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Rubod C, de Prémare C, Kerbage Y, Kyheng M, Plouvier P, Chossegros C, Robin G. Does surgery for colorectal endometriosis prior to IVF±ICSI have an impact on cumulative live birth rates? Reprod Biomed Online 2024; 48:103649. [PMID: 38335899 DOI: 10.1016/j.rbmo.2023.103649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Revised: 10/23/2023] [Accepted: 10/26/2023] [Indexed: 02/12/2024]
Abstract
RESEARCH QUESTION Does colorectal endometriosis surgery prior to IVF ± intracytoplasmic sperm injection (ICSI) impact cumulative live birth rates? DESIGN This retrospective, monocentric study (Lille University Hospital) was conducted between 1 January 2007 and 31 December 2018. Two groups of patients from the JFIV database were included: a group undergoing IVF±ICSI alone (120 patients, 215 oocyte retrievals), and a group undergoing surgery and then IVF±ICSI (69 patients, 109 oocyte retrievals). The mode of management was decided after a multidisciplinary team meeting. Different criteria such as age (cut-off 35 years), anti-Müllerian hormone concentration (cut off 2 ng/ml), imaging results and the patient's symptomatology were considered: the most symptomatic patients underwent surgery prior to IVF±ICSI. The cumulative clinical pregnancy and live birth rates obtained after four IVF attempts were estimated and compared between the two groups using competing risk survival methods. RESULTS The cumulative live birth rates after four IVF attempts in the two groups were not statistically significantly different (50.8% in the IVF±ICSI group versus 52.2% in the surgery followed by IVF±ICSI group, P = 0.43). The results for the cumulative clinical pregnancy rates were the same (56.7% in the IVF±ICSI group versus 58% in the surgery followed by IVF±ICSI group, P = 0.47). CONCLUSION The study shows that cumulative live birth and pregnancy rates were similar in infertile patients with colorectal endometriosis who underwent IVF±ICSI either with or without prior colorectal endometriosis surgery.
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Affiliation(s)
- Chrystèle Rubod
- Service de chirurgie gynécologique, CHU Lille, Lille, France.; Univ. Lille, CHU Lille, Lille, France
| | | | - Yohan Kerbage
- Service de chirurgie gynécologique, CHU Lille, Lille, France
| | - Maeva Kyheng
- Service de Biostatistiques, CHU Lille, Lille, France
| | - Pauline Plouvier
- Service d'Assistance Médicale à la Procréation et Préservation de la Fertilité, CHU Lille, Lille, France
| | | | - Geoffroy Robin
- Univ. Lille, CHU Lille, Lille, France.; Service d'Assistance Médicale à la Procréation et Préservation de la Fertilité, CHU Lille, Lille, France
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49
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Venkatesh SS, Wittemans LBL, Palmer DS, Baya NA, Ferreira T, Hill B, Lassen FH, Parker MJ, Reibe S, Elhakeem A, Banasik K, Bruun MT, Erikstrup C, Jensen BA, Juul A, Mikkelsen C, Nielsen HS, Ostrowski SR, Pedersen OB, Rohde PD, Sorensen E, Ullum H, Westergaard D, Haraldsson A, Holm H, Jonsdottir I, Olafsson I, Steingrimsdottir T, Steinthorsdottir V, Thorleifsson G, Figueredo J, Karjalainen MK, Pasanen A, Jacobs BM, Hubers N, Lippincott M, Fraser A, Lawlor DA, Timpson NJ, Nyegaard M, Stefansson K, Magi R, Laivuori H, van Heel DA, Boomsma DI, Balasubramanian R, Seminara SB, Chan YM, Laisk T, Lindgren CM. Genome-wide analyses identify 21 infertility loci and over 400 reproductive hormone loci across the allele frequency spectrum. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.03.19.24304530. [PMID: 38562841 PMCID: PMC10984039 DOI: 10.1101/2024.03.19.24304530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/04/2024]
Abstract
Genome-wide association studies (GWASs) may help inform treatments for infertility, whose causes remain unknown in many cases. Here we present GWAS meta-analyses across six cohorts for male and female infertility in up to 41,200 cases and 687,005 controls. We identified 21 genetic risk loci for infertility (P≤5E-08), of which 12 have not been reported for any reproductive condition. We found positive genetic correlations between endometriosis and all-cause female infertility (r g=0.585, P=8.98E-14), and between polycystic ovary syndrome and anovulatory infertility (r g=0.403, P=2.16E-03). The evolutionary persistence of female infertility-risk alleles in EBAG9 may be explained by recent directional selection. We additionally identified up to 269 genetic loci associated with follicle-stimulating hormone (FSH), luteinising hormone, oestradiol, and testosterone through sex-specific GWAS meta-analyses (N=6,095-246,862). While hormone-associated variants near FSHB and ARL14EP colocalised with signals for anovulatory infertility, we found no r g between female infertility and reproductive hormones (P>0.05). Exome sequencing analyses in the UK Biobank (N=197,340) revealed that women carrying testosterone-lowering rare variants in GPC2 were at higher risk of infertility (OR=2.63, P=1.25E-03). Taken together, our results suggest that while individual genes associated with hormone regulation may be relevant for fertility, there is limited genetic evidence for correlation between reproductive hormones and infertility at the population level. We provide the first comprehensive view of the genetic architecture of infertility across multiple diagnostic criteria in men and women, and characterise its relationship to other health conditions.
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Affiliation(s)
- Samvida S Venkatesh
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7LF, United Kingdom
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, United Kingdom
| | - Laura B L Wittemans
- Novo Nordisk Research Centre Oxford, Oxford, United Kingdom
- Nuffield Department of Women's and Reproductive Health, Medical Sciences Division, University of Oxford, United Kingdom
| | - Duncan S Palmer
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7LF, United Kingdom
- Nuffield Department of Population Health, Medical Sciences Division, University of Oxford, Oxford, United Kingdom
| | - Nikolas A Baya
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7LF, United Kingdom
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, United Kingdom
| | - Teresa Ferreira
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7LF, United Kingdom
| | - Barney Hill
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7LF, United Kingdom
- Nuffield Department of Population Health, Medical Sciences Division, University of Oxford, Oxford, United Kingdom
| | - Frederik Heymann Lassen
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7LF, United Kingdom
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, United Kingdom
| | - Melody J Parker
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7LF, United Kingdom
- Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
| | - Saskia Reibe
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7LF, United Kingdom
- Nuffield Department of Population Health, Medical Sciences Division, University of Oxford, Oxford, United Kingdom
| | - Ahmed Elhakeem
- MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom
- Population Health Science, Bristol Medical School, University of Bristol, Bristol, United Kingdom
| | - Karina Banasik
- Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark
- Department of Obstetrics and Gynecology, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark
| | - Mie T Bruun
- Department of Clinical Immunology, Odense University Hospital, Odense, Denmark
| | - Christian Erikstrup
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Health, Aarhus University, Aarhus, Denmark
| | - Bitten A Jensen
- Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark
| | - Anders Juul
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen; Copenhagen, Denmark
- Department of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark
| | - Christina Mikkelsen
- Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, Copenhagen University, Copenhagen, Denmark
| | - Henriette S Nielsen
- Department of Obstetrics and Gynecology, The Fertility Clinic, Hvidovre University Hospital, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Sisse R Ostrowski
- Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Ole B Pedersen
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Immunology, Zealand University Hospital, Kge, Denmark
| | - Palle D Rohde
- Genomic Medicine, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
| | - Erik Sorensen
- Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | | | - David Westergaard
- Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark
- Department of Obstetrics and Gynecology, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark
| | - Asgeir Haraldsson
- Faculty of Medicine, University of Iceland, Reykjavik, Iceland
- Children's Hospital Iceland, Landspitali University Hospital, Reykjavik, Iceland
| | - Hilma Holm
- deCODE genetics/Amgen, Inc., Reykjavik, Iceland
| | - Ingileif Jonsdottir
- Faculty of Medicine, University of Iceland, Reykjavik, Iceland
- deCODE genetics/Amgen, Inc., Reykjavik, Iceland
| | - Isleifur Olafsson
- Department of Clinical Biochemistry, Landspitali University Hospital, Reykjavik, Iceland
| | - Thora Steingrimsdottir
- Faculty of Medicine, University of Iceland, Reykjavik, Iceland
- Department of Obstetrics and Gynecology, Landspitali University Hospital, Reykjavik, Iceland
| | | | | | - Jessica Figueredo
- Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia
| | - Minna K Karjalainen
- Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland
- Research Unit of Population Health, Faculty of Medicine, University of Oulu, Finland
- Northern Finland Birth Cohorts, Arctic Biobank, Infrastructure for Population Studies, Faculty of Medicine, University of Oulu, Oulu, Finland
| | - Anu Pasanen
- Research Unit of Clinical Medicine, Medical Research Center Oulu, University of Oulu, and Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland
| | - Benjamin M Jacobs
- Centre for Preventive Neurology, Wolfson Institute of Population Health, Queen Mary University London, London, EC1M 6BQ, United Kingdom
| | - Nikki Hubers
- Department of Biological Psychology, Netherlands Twin Register, Vrije Universiteit, Amsterdam, The Netherlands
- Amsterdam Reproduction and Development Institute, Amsterdam, The Netherlands
| | - Margaret Lippincott
- Harvard Reproductive Sciences Center and Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- Harvard Medical School, Boston, Massachusetts, United States of America
| | - Abigail Fraser
- MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom
- Population Health Science, Bristol Medical School, University of Bristol, Bristol, United Kingdom
| | - Deborah A Lawlor
- MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom
- Population Health Science, Bristol Medical School, University of Bristol, Bristol, United Kingdom
| | - Nicholas J Timpson
- MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom
- Population Health Science, Bristol Medical School, University of Bristol, Bristol, United Kingdom
| | - Mette Nyegaard
- Genomic Medicine, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
| | - Kari Stefansson
- Faculty of Medicine, University of Iceland, Reykjavik, Iceland
- deCODE genetics/Amgen, Inc., Reykjavik, Iceland
| | - Reedik Magi
- Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia
| | - Hannele Laivuori
- Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland
- Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Department of Obstetrics and Gynecology, Tampere University Hospital, Finland
- Center for Child, Adolescent, and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Finland
| | - David A van Heel
- Blizard Institute, Queen Mary University London, London, E1 2AT, United Kingdom
| | - Dorret I Boomsma
- Department of Biological Psychology, Netherlands Twin Register, Vrije Universiteit, Amsterdam, The Netherlands
- Amsterdam Reproduction and Development Institute, Amsterdam, The Netherlands
| | - Ravikumar Balasubramanian
- Harvard Reproductive Sciences Center and Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- Harvard Medical School, Boston, Massachusetts, United States of America
| | - Stephanie B Seminara
- Harvard Reproductive Sciences Center and Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- Harvard Medical School, Boston, Massachusetts, United States of America
| | - Yee-Ming Chan
- Harvard Medical School, Boston, Massachusetts, United States of America
- Division of Endocrinology, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, United States of America
| | - Triin Laisk
- Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia
| | - Cecilia M Lindgren
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7LF, United Kingdom
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, United Kingdom
- Nuffield Department of Women's and Reproductive Health, Medical Sciences Division, University of Oxford, United Kingdom
- Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America
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50
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Grigoriadis G, Daniilidis A, Merlot B, Stratakis K, Dennis T, Crestani A, Chanavaz-Lacheray I, Roman H. Surgical treatment of deep endometriosis: Impact on spontaneous conception. Best Pract Res Clin Obstet Gynaecol 2024; 93:102455. [PMID: 38181664 DOI: 10.1016/j.bpobgyn.2024.102455] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Accepted: 12/31/2023] [Indexed: 01/07/2024]
Abstract
Deep endometriosis (DE) is the most severe form of endometriosis and is commonly associated with infertility. Surgical treatment of DE appears to increase chances of spontaneous conception in appropriately selected patients wishing to conceive. Identifying, however, the exact impact of DE, and its surgical removal, on natural conception is highly challenging. The surgical approach should be favoured in symptomatic patients with pregnancy intention. Limited data from infertile patients suggest that outcomes may not differ from patients without known infertility. Complex DE surgery carries a risk of serious complications, therefore, it should be performed in centers of expertise. Such complications may, however, not have a significant negative impact on fertility outcomes, according to limited available data. Data on obstetric outcomes of spontaneous conceptions after DE surgery are too scarce. In asymptomatic, infertile patients the debate between primary surgery or Artifial Reproductive Technology is ongoing, until randomized studies report their results.
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Affiliation(s)
| | - Angelos Daniilidis
- 1st Department in Obstetrics and Gynecology, Papageorgiou General Hospital, School of Medicine, Aristotle University of Thessaloniki, 54643, Thessaloniki, Greece
| | - Benjamin Merlot
- Institut Franco-Europeen Multidisciplinaire d'Endometriose (IFEMEndo), Endometriosis Centre, CliniqueTivoli-Ducos, 33000, Bordeaux, France; Department of Obstetrics and Gynecology, Aarhus University, 8000, Aarhus, Denmark
| | - Konstantinos Stratakis
- 1st Surgical Department, Peripheral General Hospital Giorgos Gennimatas, 11527, Athens, Greece
| | - Thomas Dennis
- Institut Franco-Europeen Multidisciplinaire d'Endometriose (IFEMEndo), Endometriosis Centre, CliniqueTivoli-Ducos, 33000, Bordeaux, France
| | - Adrien Crestani
- Institut Franco-Europeen Multidisciplinaire d'Endometriose (IFEMEndo), Endometriosis Centre, CliniqueTivoli-Ducos, 33000, Bordeaux, France
| | - Isabella Chanavaz-Lacheray
- Institut Franco-Europeen Multidisciplinaire d'Endometriose (IFEMEndo), Endometriosis Centre, CliniqueTivoli-Ducos, 33000, Bordeaux, France
| | - Horace Roman
- Institut Franco-Europeen Multidisciplinaire d'Endometriose (IFEMEndo), Endometriosis Centre, CliniqueTivoli-Ducos, 33000, Bordeaux, France; Franco-European Multidisciplinary Endometriosis Institute (IFEMEndo), Middle East Clinic, Burjeel Medical City, Abu Dhabi, 7400, United Arab Emirates; Department of Obstetrics and Gynecology, Aarhus University, 8000, Aarhus, Denmark.
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