1. Hum Reprod Update. 2023 Sep 5;29(5):655-674.doi: 10.1093/humupd/dmad009.

Insights from Mendelian randomization and genetic correlation analyses into the relationship between endometriosis and its comorbidities

Isabelle M McGrath ¹, Grant W Montgomery ¹, Sally Mortlock ¹

Abstract

Background: Endometriosis remains a poorly understood disease, despite its high prevalence and debilitating symptoms. The overlap in symptoms and the increased risk of multiple other traits in women with endometriosis is becoming increasingly apparent through epidemiological data. Genetic studies offer a method of investigating these comorbid relationships through the assessment of causal relationships with Mendelian randomization (MR), as well as identification of shared genetic variants and genes involved across traits. This has the capacity to identify risk factors for endometriosis as well as provide insight into the aetiology of disease.

Objective and rationale: We aim to review the current literature assessing the relationship between endometriosis and other traits using genomic data, primarily through the methods of MR and genetic correlation. We critically examine the limitations of these studies in accordance with the assumptions of the utilized methods.

Search methods: The PubMed database was used to search for peer-reviewed original research articles using the terms ‘Mendelian randomization endometriosis’ and ‘”genetic correlation” endometriosis’. Additionally, a Google Scholar search using the terms ‘”endometriosis” “mendelian randomization” “genetic correlation”‘ was performed. All relevant publications (n = 21) published up until 7 October 2022 were included in this review. Upon compilation of all traits with published MR and/or genetic correlation with endometriosis, additional epidemiological and genetic information on their comorbidity with endometriosis was sourced by searching for the trait in conjunction with ‘endometriosis’ on Google Scholar.

Outcomes: The association between endometriosis and multiple pain, gynaecological, cancer, inflammatory, gastrointestinal, psychological, and anthropometric traits has been assessed using MR analysis and genetic correlation analysis. Genetic correlation analyses provide evidence that genetic factors contributing to endometriosis are shared with multiple traits: migraine, uterine fibroids, subtypes of ovarian cancer, melanoma, asthma, gastro-oesophageal reflux disease, gastritis/duodenitis, and depression, suggesting the involvement of multiple biological mechanisms in endometriosis. The assessment of causality with MR has revealed several potential causes (e.g. depression) and outcomes (e.g. ovarian cancer and uterine fibroids) of a genetic predisposition to endometriosis; however, interpretation of these results requires consideration of potential violations of the MR assumptions.

Wider implications: Genomic studies have demonstrated that there is a molecular basis for the co-occurrence of endometriosis with other traits. Dissection of this overlap has identified shared genes and pathways, which provide insight into the biology of endometriosis. Thoughtful MR studies are necessary to ascertain causality of the comorbidities of endometriosis. Given the significant diagnostic delay of endometriosis of 7-11 years, determining risk factors is necessary to aid diagnosis and reduce the disease burden. Identification of traits for which endometriosis is a risk factor is important for holistic treatment and counselling of the patient. The use of genomic data to disentangle the overlap of endometriosis with other traits has provided insights into the aetiology of endometriosis.

Keywords: Mendelian randomization; comorbidity; endometriosis; genetic correlation; genetics; genomics; gynaecology.

2. Front Biosci (Landmark Ed). 2023 Aug 15;28(8):166.doi: 10.31083/j.fbl2808166.

The Role of Peritoneal Immunity in Peritoneal Endometriosis and Related Infertility

Qiongxiao Huang ¹, Yiqi Yu ¹, Weihai Xu ¹, Shishi Li ¹, Yier Zhou ¹, Jing Shu ¹

Abstract

Endometriosis is defined as a disorder in which the glands and stroma of the endometrium grow and shed periodically outside the uterine cavity. Highly prevalent in women of reproductive age, the most common clinical manifestations are chronic pelvic pain and infertility. The pathogenesis of endometriosis may be multifactorial, including factors of anatomy, immunity, inflammation, hormones (estrogen), oxidative stress, genetics, epigenetics, and environment. There are generally three types of endometriotic disease, namely peritoneal, ovarian, and deep infiltration. For the same patient, there may be a single or multiple types concurrently. The different manifestations of these types suggests that they each have their own etiology. Numerous studies have shown that the evasion of endometrial cells from peritoneal immune surveillance helps establish and maintain peritoneal endometriosis, but the specific mechanism is not well understood. Likewise, the molecular mechanisms of endometriosis-related infertility have not been clearly elucidated. This review attempts to identify the role of peritoneal immunity in peritoneal endometriosis and related infertility, especially in the aspects of molecular mechanisms.

Keywords: endometriosis; immune; lymphocyte; macrophage; peritoneum.

3. Front Endocrinol (Lausanne). 2023 Aug 16;14:1226687.doi: 10.3389/fendo.2023.1226687.eCollection 2023.

Decreased oocyte quality in patients with endometriosis is closely related to abnormal granulosa cells

Weisen Fan ¹, Zheng Yuan ², Muzhen Li ³, Yingjie Zhang ¹, Fengjuan Nan ²

Abstract

Infertility and menstrual abnormalities in endometriosis patients are frequently caused by aberrant follicular growth or a reduced ovarian reserve. Endometriosis typically does not directly harm the oocyte, but rather inhibits the function of granulosa cells, resulting in a decrease in oocyte quality. Granulosa cells, as oocyte nanny cells, can regulate meiosis, provide the most basic resources required for oocyte development, and influence ovulation. Endometriosis affects oocyte development and quality by causing granulosa cells apoptosis, inflammation, oxidative stress, steroid synthesis obstacle, and aberrant mitochondrial energy metabolism. These aberrant states frequently interact with one another, however there is currently relatively little research in this field to understand the mechanism of linkage between abnormal states.

Keywords: endometriosis; granulosa cells; infertility; mechanism; oocytes.

4. Cell Death Discov. 2023 Aug 22;9(1):306.doi: 10.1038/s41420-023-01606-8.

Double-edged roles of ferroptosis in endometriosis and endometriosis-related infertility

Yangshuo Li ^# 1, Yalun He ^# 1, Wen Cheng ^# 1, Zhihao Zhou ¹, Zhexin Ni ^2 3, Chaoqin Yu ⁴

Abstract

Endometriosis is strongly associated with infertility. Several mechanisms have been reported in an attempt to elucidate the pathophysiological effects that lead to reduced fertility in women with endometriosis. However, the mechanisms by which endometriosis affects fertility have not been fully elucidated. Ferroptosis is a novel form of nonapoptotic cell death that is characterized by iron-dependent lipid peroxidation membrane damage. In past reports, elevated iron levels in ectopic lesions, peritoneal fluid and follicular fluid have been reported in patients with endometriosis. The high-iron environment is closely associated with ferroptosis, which appears to exhibit a double-edged effect on endometriosis. Ferroptosis can cause damage to ovarian granulosa cells, oocytes, and embryos, leading to endometriosis-related infertility. This article summarizes the main pathways and regulatory mechanisms of ferroptosis and explores the possible mechanisms of the formation of an iron-overloaded environment in endometriotic ectopic lesions, peritoneal fluid and follicular fluid. Finally, we reviewed recent studies on the main and potential mechanisms of ferroptosis in endometriosis and endometriosis-related infertility.

5. Eur J Obstet Gynecol Reprod Biol X. 2023 Aug 14;19:100228. doi: 10.1016/j.eurox.2023.100228.eCollection 2023 Sep.

Stigma and mental health in endometriosis

H Deniz Kocas ¹, Lisa R Rubin ¹, Marci Lobel ²

Abstract

This review provides an overview of patient experiences of endometriosis, endometriosis-related types and sources of stigma pertaining to menstruation, chronic pain, and infertility, and their impact on patients’ mental health with particular implications for patient care. Because endometriosis is a complex disease with multifactorial etiology, complicated pathophysiology, and a spectrum of clinical features, diagnosis of endometriosis is typically a lengthy process, and many patients experience initial misdiagnosis. A hallmark symptom is severe menstrual pain with other symptoms including chronic pelvic pain, dysmenorrhea, and infertility. Prior research documents that the diagnostic odyssey, complex management, disabling and unpredictable nature of the disease, and painful symptom profile affect multiple life domains of patients, resulting in poor physical, social, and psychological functioning and clinically-significant rates of anxiety and depression for many. More recently, stigma has been recognized as a potent contributor to poor mental health in endometriosis patients, but existing research is limited and largely atheoretical. We identify major sources of stigma related to endometriosis, including menstrual stigma, chronic pain stigma, and infertility stigma, and their likely impact on patients and health care provision. An integrative theoretical approach is described to facilitate research on the prevalence and effects of endometriosis stigma and their explanatory mechanisms, highlighting specific well-validated psychological instruments to assess stigma. Implications for patient care are emphasized. Better understanding of stigma and mental health in people with endometriosis will enhance the standard of care for this patient population.

Keywords: Chronic pain; Endometriosis; Infertility; Menstruation; Mental health; Stigma.

6. J Clin Med. 2023 Aug 29;12(17):5624.doi: 10.3390/jcm12175624.

Endometriosis and Adolescence: The Impact of Dysmenorrhea

Francesco G Martire ^1 2, Emilio Piccione ³, Caterina Exacoustos ⁴, Errico Zupi ²

Abstract

Endometriosis affects approximately 10% of premenopausal women worldwide. Despite its impact on quality of life, the delay in diagnosing this chronic disease is well known. Many patients with endometriosis report having suffered from dysmenorrhea and chronic pelvic pain in adolescence or at a young age. However, this painful symptom is often highly underestimated and considered a normal and transient symptom in young women. The real prevalence of endometriosis in adolescence remains uncertain. Some authors recently described at least one ultrasound feature of endometriosis in 13.3% of a general population of adolescent girls, which increased to 35.3% in young girls with severe dysmenorrhea. Dysmenorrhea is classified as primary dysmenorrhea or secondary dysmenorrhea. Primary dysmenorrhea is defined as a menstrual pain without organic disease, while secondary dysmenorrhea is defined as a menstrual pain associated with organic pelvic pathology. Since endometriosis represents the main cause of secondary dysmenorrhea in adolescents and young women, it is important to determine whether the patient has primary dysmenorrhea or additional suggestive symptoms related to endometriosis. Endometriosis in adolescent patients is a challenging problem with clinical and pathological differences compared with its presentation in premenopausal women. Adolescents and young women with dysmenorrhea and painful symptoms that suggest endometriosis should be referred to dedicated endometriosis centers for an early diagnosis and appropriate medical and surgical management. This paper aims to describe the role of dysmenorrhea in adolescents and the management of these young patients to confirm or exclude endometriosis.

Keywords: adolescence; diagnosis; dysmenorrhea; endometriosis; management.

7. J Clin Med. 2023 Aug 21;12(16):5416.doi: 10.3390/jcm12165416.

Robotic Surgery for Bladder Endometriosis: A Systematic Review and Approach

Marco Aurelio Pinho Oliveira ¹, Thiers Soares Raymundo ^1 2, Thiago Dantas Pereira ¹, Ricardo José de Souza ¹, Felipe Vaz Lima ³, Rudy Leon De Wilde ⁴, Leila Cristina Brollo ¹

Abstract

Introduction: Women with bladder endometriosis often present with more advanced stages of endometriosis. Robotic surgery has emerged as a promising approach to the management of bladder endometriosis. This systematic review aims to analyze the current literature on robotic surgery for bladder endometriosis and describe our systematic approach to surgical treatment.

Methods: This review followed the PRISMA guidelines, which ensured a comprehensive and transparent approach to selecting and evaluating relevant studies. We conducted a thorough literature search to identify studies that investigated the use of robotic surgery for bladder endometriosis. Relevant databases were searched, and inclusion and exclusion criteria were applied to select eligible studies. Data extraction and analysis were performed to assess the outcomes and effectiveness of robotic surgery for the treatment of bladder endometriosis.

Results: We did not find any randomized clinical trials with the use of robotics in the treatment of bladder endometriosis. We found only two retrospective studies comparing robotic surgery with laparoscopy, and another retrospective study comparing robotic surgery, laparoscopy, and laparotomy in the treatment of bladder endometriosis. All the other 12 studies were solely case reports. Despite the lack of robust evidence in the literature, the studies demonstrated that robotic surgery is feasible and is associated with reduced postoperative pain, shorter hospital stays, and faster recovery.

Conclusions: The utilization of robotic technology is a promising option for the surgical management of bladder endometriosis. We advocate a surgical systematic approach for the robotic treatment of bladder endometriosis. Robotic technology, with its 3D vision, instrumental degrees of freedom, and precision, particularly in suturing, may provide potential benefits over traditional laparoscopy.

Keywords: bladder endometriosis; minimally invasive approach; robotic surgery; surgical treatment; systematic review.

8. Schmerz. 2023 Aug 25.doi: 10.1007/s00482-023-00747-0. Online ahead of print.

[Holistic treatment of endometriosis]

[Article in German]

Sylvia Mechsner ¹

Abstract 

in English, German

Background: The pain phenomena caused by endometriosis are manifold. In addition to nociceptive pain there is also a nociplastic reaction with central sensitization. Atypical symptoms, such as acyclic lower abdominal pain, radiating pain, nonspecific bladder and intestinal complaints or even depression increasingly occur in addition to the classical cyclic complaints, such as severe dysmenorrhea, cyclic lower abdominal pain, dyspareunia, dysuria and dyschezia. Due to the diffuse range of symptoms, affected patients often consult not just gynecologists but also specialists from other disciplines (internal medicine, gastroenterology, orthopedics, pain therapy, psychology etc.).

Objective: The complexity of endometriosis is presented. The resulting approaches to multimodal interdisciplinary holistic treatment are described.

Results: Interdisciplinary concepts should be involved in the optimal treatment of endometriosis patients along with hormonal and surgical treatment, mostly under the supervision of a gynecologist and pain management, dietary changes, psychological support and physiotherapeutic management should also be included. This article provides an overview of possible treatment strategies for chronic symptomatic endometriosis.

Conclusion: Based on multimodal treatment strategies and regarding the complex pathophysiological alterations of this disease, the complex complaints that significantly impair the quality of life of endometriosis patients can be greatly improved.

Keywords: Central nervous system sensitization; Chronic pain; Combined modality therapy; Nociceptive pain; Nociplastic pain.

9. Biomedicines. 2023 Aug 7;11(8):2210.doi: 10.3390/biomedicines11082210.

Molecular Mechanisms of Endometriosis Revealed Using Omics Data

Seong Beom Cho ¹

Abstract

Endometriosis is a gynecological disorder prevalent in women of reproductive age. The primary symptoms include dysmenorrhea, irregular menstruation, and infertility. However, the pathogenesis of endometriosis remains unclear. With the advent of high-throughput technologies, various omics experiments have been conducted to identify genes related to the pathophysiology of endometriosis. This review highlights the molecular mechanisms underlying endometriosis using omics. When genes identified in omics experiments were compared with endometriosis disease genes identified in independent studies, the number of overlapping genes was moderate. However, the characteristics of these genes were found to be equivalent when functional gene set enrichment analysis was performed using gene ontology and biological pathway information. These findings indicate that omics technology provides invaluable information regarding the pathophysiology of endometriosis. Moreover, the functional characteristics revealed using enrichment analysis provide important clues for discovering endometriosis disease genes in future research.

Keywords: biological pathway; disease gene; endometriosis; gene ontology; high-throughput data.

10. Biomolecules. 2023 Aug 16;13(8):1253.doi: 10.3390/biom13081253.

Endometriosis-Associated Ovarian Carcinomas: How PI3K/AKT/mTOR Pathway Affects Their Pathogenesis

Tatiana S Driva ¹, Christoph Schatz ², Johannes Haybaeck ^2 3

Abstract

Ovarian clear cell (OCCC) and endometrioid (EnOC) carcinomas are often subsumed under the umbrella term “endometriosis-associated ovarian cancer” (EAOC), since they frequently arise from ectopic endometrium settled in the ovaries. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is known to be aberrantly activated both in endometriosis and EAOC; however, its role in the progression of endometriosis to ovarian cancer remains unclear. In fact, cancer-associated alterations in the mTOR pathway may be found in normal uterine epithelium, likely acting as a first step towards ovarian cancer, through the intermediary stage of endometriosis. This review aims to summarize the current knowledge regarding mTOR signaling dysregulation in the uterine endometrium, endometriosis, and EAOC while focusing on the interconnections between the PI3K/AKT/mTOR pathway and other signaling molecules that give rise to synergistic molecular mechanisms triggering ovarian cancer development in the presence of endometriosis.

Keywords: ARID1A mutations; PI3K/AKT/mTOR pathway; endometriosis; endometrium; ovarian cancer.

11. Arch Gynecol Obstet. 2023 Aug 25.doi: 10.1007/s00404-023-07151-0.Online ahead of print.

Diagnostic and therapeutic approaches for endometriosis: a patent landscape

Maninder Singh ¹, Reena Jassal ², Preeti Khetarpal ³

Abstract

Objective: The aim of this review is to analyze the patent filings and to systematize the main technological trends in patent protection for the diagnosis and therapeutics for endometriosis. Patent literature has also been explored to identify active inventors and applicants in this field.

Methodology: Patent search was carried out in the freely accessible patent search databases namely, patentscope using various combinations of the keywords “Endometriosis OR Adenomyosis” AND “Diagnostic OR Therapeutics” were used along with wildcard search queries in the “Title”, “Abstract” and “Descriptions” fields.

Results: A patent search revealed 144 patents describing inventions for diagnostic and therapeutic purposes of endometriosis. These patents include 26 patent applications in the diagnostic utility and 116 patent applications under the therapeutic approaches. Out of these 116 patent applications, 43 describe traditional medicines for endometriosis. Two patent applications describe inventions that can fall into both categories.

Conclusion: Efforts are being made to improve current diagnostic instruments. Hormonal alteration methods is the most common field of invention, followed by surgical interventions for therapeutics. A general trend of increase in patent application filings has been observed with a slight decrease in recent years.

Keywords: Adenomyosis; Diagnostics; Endometriosis; Patent; Therapeutics.

12. Sex Med Rev. 2023 Aug 5;qead033.doi: 10.1093/sxmrev/qead033. Online ahead of print.

Neuroproliferative dyspareunia in endometriosis and vestibulodynia

Agnes N Mwaura ¹, Nisha Marshall ¹, Michael S Anglesio ¹, Paul J Yong ¹

Abstract

Introduction: Endometriosis is a common cause of deep dyspareunia, while provoked vestibulodynia is a common cause of superficial dyspareunia. The etiology of dyspareunia in both conditions is multifactorial and may include the role of local nerve growth (neurogenesis or neuroproliferation) that sensitizes pelvic structures and leads to pain with contact.

Objectives: To review the evidence for neuroproliferative dyspareunia in endometriosis and provoked vestibulodynia.

Methods: Narrative review.

Results: The pelvic peritoneum and vulvar vestibule receive somatic and autonomic innervation. Various markers have been utilized for nerve subtypes, including pan-neuronal markers and those specific for sensory and autonomic nerve fibers. The nerve growth factor family includes neurotrophic factors, such as nerve growth factor and brain-derived neurotrophic factor, and their receptors. Studies of endometriosis and provoked vestibulodynia have demonstrated the presence of nerve fibers around endometriosis epithelium/stroma in the pelvic peritoneum and within the vulvar vestibule. The number of nerve fibers is higher in these pain conditions as compared with control tissue. Nerve growth factor expression by endometriosis stroma and by immune cells in the vulvar vestibule may be involved in local neuroproliferation. Local inflammation is implicated in this neuroproliferation, with potential roles of interleukin 1β and mast cells in both conditions. Several studies have shown a correlation between nerve fibers around endometriosis and dyspareunia severity, but studies are lacking in provoked vestibulodynia. There are several possible clinical ramifications of neuroproliferative dyspareunia in endometriosis and provoked vestibulodynia, in terms of history, examination, biopsy, and surgical and medical treatment.

Conclusions: A neuroproliferative subtype of dyspareunia may be implicated in endometriosis and provoked vestibulodynia. Additional research is needed to validate this concept and to integrate it into clinical studies. Neuroproliferative pathways could serve as novel therapeutic targets for the treatment of dyspareunia in endometriosis and provoked vestibulodynia.

Keywords: dyspareunia; endometriosis; nerve growth factor; neuroproliferation; provoked vestibulodynia; vulvodynia.

13. Curr Opin Anaesthesiol. 2023 Oct 1;36(5):595-601.doi: 10.1097/ACO.0000000000001305.Epub 2023 Aug 13.

Endometriosis – a painful disease

Lydia Coxon ¹, Emma Evans, Katy Vincent

Abstract

Purpose of review: This review looks to overview advances in endometriosis-associated pain, both in understanding the pain mechanisms involved and increasing treatment options with well designed clinical trials and meta-analyses.

Recent findings: Our understanding of endometriosis-associated pain has progressed from a purely nociceptive model to an awareness that both neuropathic and nociplastic mechanisms can be present for some people with endometriosis. Clinical trials and meta-analyses have demonstrated efficacy of surgical treatments and hormonal therapies. It is notable that currently, the basic science and clinical trials are not cross-fertilising.

Summary: Following growth in other areas of chronic pain, there have been significant advances in our understanding of endometriosis-associated pain. However, there remains lots to explore and we are currently a long way from our goal of timely personalized holistic multidisciplinary treatment for all sufferers of endometriosis-associated pain.

14. Microorganisms. 2023 Aug 15;11(8):2089.doi: 10.3390/microorganisms11082089.

Microbiota in Irritable Bowel Syndrome and Endometriosis: Birds of a Feather Flock Together-A Review

Noemi Salmeri ¹, Emanuele Sinagra ², Carolina Dolci ¹, Giovanni Buzzaccarini ¹, Giulio Sozzi ³, Miriam Sutera ³, Massimo Candiani ¹, Federica Ungaro ⁴, Luca Massimino ⁴, Silvio Danese ⁴, Francesco Vito Mandarino ⁴

Abstract

Endometriosis and irritable bowel syndrome (IBS) are chronic conditions affecting up to 10% of the global population, imposing significant burdens on healthcare systems and patient quality of life. Interestingly, around 20% of endometriosis patients also present with symptoms indicative of IBS. The pathogenesis of both these multifactorial conditions remains to be fully elucidated, but connections to gut microbiota are becoming more apparent. Emerging research underscores significant differences in the gut microbiota composition between healthy individuals and those suffering from either endometriosis or IBS. Intestinal dysbiosis appears pivotal in both conditions, exerting an influence via similar mechanisms. It impacts intestinal permeability, triggers inflammatory reactions, and initiates immune responses. Furthermore, it is entwined in a bidirectional relationship with the brain, as part of the gut-brain axis, whereby dysbiosis influences and is influenced by mental health and pain perception. Recent years have witnessed the development of microbiota-focused therapies, such as low FODMAP diets, prebiotics, probiotics, antibiotics, and fecal microbiota transplantation, designed to tackle dysbiosis and relieve symptoms. While promising, these treatments present inconsistent data, highlighting the need for further research. This review explores the evidence of gut dysbiosis in IBS and endometriosis, underscoring the similar role of microbiota in both conditions. A deeper understanding of this common mechanism may enable enhanced diagnostics and therapeutic advancements.

Keywords: dysbiosis; endometriosis; female genital tract; gut–brain; irritable bowel syndrome; microbiome; microbiota; pain.

15. Eur J Obstet Gynecol Reprod Biol X. 2023 Aug 9;19:100224.doi: 10.1016/j.eurox.2023.100224.eCollection 2023 Sep.

Endometriosis and dyspareunia: Solving the enigma

Jose Carlos Vilches Jimenez ¹, Lucas Lozano Romero ², Ignacio Brunel Garcia ¹, Manuel Lozano Sanchez ¹, Rodrigo Orozco Fernandez ¹

Abstract

Introduction: Endometriosis is a chronic oestrogen-dependent disease that affects 1 in 10 women of childbearing age. Half of these women have deep dyspareunia. The presence of this symptom has been shown to negatively affect your quality of life. There are few studies in the literature that address this issue and its pathophysiology remains poorly understood.

Materials and methods: A case-control study has been carried out in order to assess the multi-causality of dyspareunia in patients with endometriosis. All the patients were assessed in a unit specialising in endometriosis and pelvic pain and their disease was staged using high-resolution ultrasound following the criteria of the IDEA group. The patients were divided into two groups, patients with dyspareunia n = 45 (cases) and those without it n = 55 (controls).

Results: The only element that was statistically significant in explaining the dyspareunia was the presence of nodules in the retrocervical region with p = 0.000. The odds ratio of dyspareunia in the cases group was 5.3 (95 % CI 2.2-12.5).

Conclusions: Dyspareunia in patients with endometriosis is strongly dependent on the presence of nodules in the retrocervical region, although there are other factors involved that remain unknown, so more studies are still needed to understand and optimally address this symptom.

Keywords: Dyspareunia; Endometriosis; Pelvic pain; Retrocervical; Torus.

16. J Clin Med. 2023 Aug 19;12(16):5392.doi: 10.3390/jcm12165392.

Endometriosis and Adverse Pregnancy Outcomes: A Nationwide Population-Based Study

Hee Jeung Lim ^1 2, Jiyu Sun ³, Banhyang Min ^1 2, Myungeun Song ^1 2, Tae Hun Kim ^1 2, Byoung Jae Kim ^1 2, Kyu Ri Hwang ^1 2, Taek Sang Lee ^1 2, Hye Won Jeon ^1 2, Sun Min Kim ^1 2

Abstract

Endometriosis is a major cause of infertility, and considering its pathophysiology, it is expected to affect pregnancy outcomes as well. This study aimed to evaluate whether endometriosis is associated with adverse pregnancy outcomes after successful conception. Data from singleton pregnancy deliveries between January 2014 and October 2019 were obtained from the Korean Health Insurance Review and Assessment Service database. We compared the clinical characteristics and adverse pregnancy outcomes of women with and without endometriosis. A total of 1,251,597 pregnant women were enrolled; of these, 32,951 (2.6%) were assigned to the endometriosis group. Women with endometriosis had significantly more adverse pregnancy outcomes than those without endometriosis. Adverse pregnancy outcomes associated with endometriosis included preterm labor, preterm birth, preeclampsia, fetal growth restriction, placenta previa, placental abruption, antepartum and postpartum hemorrhage, and stillbirth. This study also showed an increased risk of postpartum hemorrhage, blood transfusion, uterine artery embolization, and cesarean hysterectomy in the endometriosis group compared to the non- endometriosis group. The cesarean delivery rate was significantly higher in the endometriosis group than in the non-endometriosis group, even after excluding cases of antenatal obstetric complications that could increase the risk of cesarean delivery. Women with endometriosis not only have difficulty conceiving, but also have a significantly higher risk of adverse pregnancy outcomes.

Keywords: cesarean delivery; endometriosis; placenta previa; placental abruption; postpartum hemorrhage; preeclampsia; pregnancy outcome; stillbirth.

17. Curr Opin Obstet Gynecol. 2023 Oct 1;35(5):434-439.doi: 10.1097/GCO.0000000000000902.Epub 2023 Aug 17.

Perioperative hormone treatment of endometriosis

William Farkas ¹, Alexandros Lazaridis ², Funlayo Odejinmi ³, Martin Hirsch ¹

Abstract

Purpose of review: The use of hormonally suppressive medication to reduce levels of reproductive hormones around the time of surgery is widely used in the management of endometriosis. This review summarizes the current evidence concerning the perioperative use of hormonal treatment in the management of endometriosis.

Recent findings: European Society of Human Reproduction and Embryology (ESHRE) guidanceSurgical Outcomes and Complications of Laparoscopic Hysterectomy for Endometriosis: A Multicentre Cohort StudyPre and postsurgical medical therapy for endometriosis surgery. Cochrane 2020Postoperative hormonal treatment for prevention of endometrioma recurrence after ovarian cystectomy: a systematic review and network meta-analysis. BJOG 2021.

Summary: The literature highlights the importance of hormonal treatment for symptom relief, reduced surgical complications and postoperative benefits, including a reduction in pain, disease recurrence and improved pregnancy rates. The treatment of endometriosis can be broadly categorized into medical, commonly using hormonal suppression medications and surgical, in which endometriosis tissue is excised or ablated. This review aims to outline current management strategies and examines the relationship between the two treatment modalities.

18. BMC Womens Health. 2023 Aug 15;23(1):432.doi: 10.1186/s12905-023-02563-1.

Roles of increased NUCKS1 expression in endometriosis

Bo Li ¹, Bocen Chen ², Xiaoli Wang ³, Man Xiao ², Kan Zhang ¹, Wenjiao Ye ¹, Da Zhao ¹, Xiaohua Wang ¹, Yan Yu ¹, Jun Li ¹, Xun Xu ¹, Wenhui Zhang ⁴, Yanhua Zhang ⁵

Abstract

Background: Endometriosis is still a difficult problem for women. The Nuclear Ubiquitous Casein and cyclin-dependent Kinase Substrate 1 (NUCKS1) gene is located on human chromosome 1q32.1. It encodes the NUCKS1 protein, a 27 kDa nuclear DNA binding protein that plays an important role in cell growth and proliferation. NUCKS1 plays an important role in the development of many diseases. However, its role in endometriosis is unclear.

Methods: Ectopic endometrial tissues and normal tissue specimens were collected, and the expression of NUCKS1, NF-κB and PI3K was detected by RT-qPCR and immunohistochemistry. Inhibition of NUCKS1 in hEM15A cells, study the changes in cell viability, apoptosis, migration and protein expression by CCK8 assay, flow cytometry, wound-healing assay, western blot and ELISA techniques. The comparison of differences between the two groups was implemented using unpaired sample t test or Mann-whitney U test. One-way analysis of variance or Kruskal-wallis test was used for comparisons among the three groups.

Results: (1) NUCKS1 is highly expressed in endometriosis tissues. (2) Inhibition of NUCKS1 decreases cell viability and capability of migration, and increases apoptosis in endometriosis cells. (3) Expressions of NF-κB and PI3K are increased in endometriosis tissues, and inhibition of NUCKS1 decreases the expression levels of PI3K and NF-κB in endometriosis cells. (4) Inhibition of NUCKS1 decreases the expression of VEGF.

Conclusion: (1) NUCKS1 is overexpressed in endometriosis, and inhibition of NUCKS1 inhibits cell viability and capability of migration, and increases apoptosis. (2) NUCKS1 promotes the progress of endometriosis through activating PI3K and NF-κB pathways, and VEFG is also involved in this process.

Keywords: Endometriosis; NF-kappa B; NUCKS1; Phosphatidylinositol 3-Kinase.

19. WIREs Mech Dis. 2023 Aug 2;e1624.doi: 10.1002/wsbm.1624. Online ahead of print.

Recent insights explaining susceptibility to endometriosis-From genetics to environment

Ana Sofia Pais, Teresa Almeida-Santos 

Abstract

Endometriosis is a disease with a heterogeneous pathogenesis, explained by multiple theories, and also with a polymorphic presentation. The purpose of this literature review is to systematize the genetic, inflammatory, and environmental factors related to the pathophysiology of endometriosis. Current evidence suggests that endometriosis is a complex inherited genetic condition, in which the genes that determine susceptibility to the disease interact with the environment to develop different phenotypes. Genetic variants associated with risk of endometriosis have been identified in several genome-wide association studies, in addition to a group of genes related to the pathophysiology of endometriosis, namely the estrogen, progesterone and androgen receptors and the cytochrome P450 gene, as well as the p53 gene. The role of inflammation is controversial; however, it is an essential process, both in the initiation and perpetuation of the disease, in and outside the pelvis. Alterations in reactive oxygen species pathways that consequently determine oxidative stress are typical in the inflammatory environment of endometriosis. The role of environmental factors is a relatively new and broad-spectrum topic, with inconsistent evidence. Multiple factors have been studied such as endocrine-disrupting chemicals, metals, intrauterine exposure to diethylstilbesterol and lifestyle risk factors. In conclusion, endometriosis remains a mysterious condition, with multifactorial factors involved in its pathophysiology. The progress that has been made in the genetic predisposition to endometriosis may allow the establishment of new therapeutic targets. On the other hand, understanding the role of the environment in this disease may allow preventive intervention, minimizing its incidence and/or severity. This article is categorized under: Reproductive System Diseases > Molecular and Cellular Physiology Reproductive System Diseases > Environmental Factors Reproductive System Diseases > Genetics/Genomics/Epigenetics.

Keywords: endometriosis; environment; genetic predisposition; inflammation; pathogenesis.

20. Sci Rep. 2023 Aug 17;13(1):13412.doi: 10.1038/s41598-023-40647-y.

Causal relationship between endometriosis with infertility and ankylosing spondylitis

Jian-Xiong Wang ^# 1, Yue Shen ^# 1, Xi-le Wang ¹, Lin-Li Ma ¹, Sheng-Qian Xu ²

Abstract

Retrospective studies have identified an increased risk of ankylosing spondylitis (AS) in endometriosis patients. The purpose of this study was to investigate the causal relationship between clinical phenotypes of endometriosis and AS using mendelian randomized analysis (MR). MR was performed using data from genome-wide association studies (GWASs). Heterogeneity, pleiotropy and sensitivity analyses were performed to evaluate the robustness of the results by MR Egger and inverse variance weighted (IVW), leave-one-out analysis. IVW, IVW-MRE (inverse variance weighted multiplicative random effects), weighted median and MR Egger were used to explore the relationship between endometriosis and AS. The IVW analysis showed a causal relationship between infertile endometriosis and AS (OR = 0.8334, P = 0.02191), and the same result was observed with IVW-MRE (OR = 0.8334, P = 0.0007933). However, further stratified analysis showed that no matter which statistical method was used, ovarian endometriosis (IVW: OR = 0.1662, P = 0.4986; IVW-MRE: OR = 0.1662, P = 0.4986; MR Egger: OR = – 0.9577, P = 0.2798; Weighted median: OR = 0.2628, P = 0.3452), pelvic peritoneum endometriosis (IVW: OR = 0.4363, P = 0.225; IVW-MRE: OR = 0.4363, P = 0.225, MR Egger: OR = 4.159, P = 0.1705; Weighted median: OR = 0.4112, P = 0.2714), rectovaginal endometriosis (IVW: OR = 0.1365, P = 0.805; IVW-MRE: OR = 0.1365, P = 0.805) there was no causal relationship between endometriosis and AS. This study suggested that patients with infertility endometriosis are at increased risk for AS. This study supports clinicians to pay more attention to the occurrence of AS in endometriosis patients with infertility.

21. Int J Mol Sci. 2023 Aug 11;24(16):12663.doi: 10.3390/ijms241612663.

Molecular and Cellular Advances in Endometriosis Research: Paving the Way for Future Directions

Antonio Simone Laganà ¹, Federico Ferrari ², Donatella Mangione ¹, Fabio Fiorino ¹, Alessandra Vassiliadis ¹, Renato Venezia ¹

Abstract

Molecular and cellular research in the field of endometriosis is moving forward in giant steps […].

Conflict of interest statement

The authors declare no conflict of interest.

22. Int J Mol Sci. 2023 Aug 17;24(16):12869.doi: 10.3390/ijms241612869.

Expression of HOXA10 Gene in Women with Endometriosis: A Systematic Review

Nurunnajah Lazim ¹, Marjanu Hikmah Elias ^1 2, Zulazmi Sutaji ^1 2, Abdul Kadir Abdul Karim ¹, Mohammad Azrai Abu ¹, Azizah Ugusman ³, Saiful Effendi Syafruddin ⁴, Mohd Helmy Mokhtar ³, Mohd Faizal Ahmad ¹

Abstract

The homeobox A10 (HOXA10) gene is known to be related to endometriosis; however, due to a lack of knowledge/evidence in the pathogenesis of endometriosis, the mechanisms that link HOXA10 to endometriosis still need to be clarified. This review addresses the difference in the expression of the HOXA10 gene in endometriotic women versus non-endometriotic women across populations by country and discusses its influences on women’s fertility. An organized search of electronic databases was conducted in Scopus, ScienceDirect, PubMed, and Web of Science. The keywords used were (HOXA10 OR “homeobox A10” OR PL OR HOX1 OR HOX1H OR HOX1.8) AND (“gene expression”) AND (endometriosis). The initial search resulted in 623 articles, 10 of which were included in this review. All ten papers included in this study were rated fair in terms of the quality of the studies conducted. The expression of the HOXA10 gene was found to be downregulated in most studies. However, one study provided evidence of the downregulation and upregulation of HOXA10 gene expression due to the localization of endometriotic lesions. Measuring the expression of the HOXA10 gene in women is clinically essential to predicting endometriosis, endometrial receptivity, and the development of pinopodes in the endometrium during the luteal phase.

Keywords: HOX; HOXA10; endometriosis; endometrium; gene; gene expression.

23. Endocrinology. 2023 Aug 31;bqad133.doi: 10.1210/endocr/bqad133. Online ahead of print.

Flavonoids Quercetin and Kaempferol Are NR4A1 Antagonists and Suppress Endometriosis in Female Mice

Lei Zhang ¹, Kumaravel Mohankumar ¹, Gregory Martin ¹, Fuada Mariyam ¹, Yuri Park ², Sang Jun Han ², Stephen Safe ¹

Abstract

Nuclear receptor 4A1 (NR4A1) plays an important role in endometriosis progression; levels of NR4A1 in endometriotic lesions are higher than in normal endometrium, and substituted bis-indole analogs (NR4A1) antagonists suppress endometriosis progression in mice with endometriosis. In addition, flavonoids kaempferol and quercetin are natural products that directly bind NR4A1 and significantly repress the intrinsic NR4A1-dependent transcriptional activity in human endometriotic epithelial and stromal cells and Ishikawa endometrial cancer cells. NR4A1 knockdown and inhibition of NR4A1 by kaempferol and quercetin suppressed proliferation of human endometriotic epithelial cells and Ishikawa cells by inhibiting EGFR/c-Myc/survivin-mediated growth-promoting and survival pathways, mTOR signaling and αSMA/CTGF/COL1A1/FN-mediated fibrosis signaling but increasing TXNDC5/SESN2-mediated oxidative/ER stress signaling. In human endometriotic stromal cells, NR4A1 knockdown and inhibition of NR4A1 by kaempferol and quercetin primarily inhibited mTOR signaling by suppressing proliferation of human endometrial stromal cells. In addition, kaempferol and quercetin treatment also effectively suppressed the growth of endometriotic lesions in mice with endometriosis compared to the vehicle without any body weight changes. Therefore, kaempferol and quercetin are NR4A1 antagonists with potential as nutritional therapy for endometriosis.

Keywords: NR4A1 antagonists; Quercetin; endometriosis; kaempferol.

24. Int J Fertil Steril. 2023 Aug 7;17(4):226-230.doi: 10.22074/ijfs.2023.557683.1329.

Interleukin-6 as A Useful Predictor of Endometriosis-Associated Infertility: A Systematic Review

Giosue Giordano Incognito ¹, Federica Di Guardo ², Ferdinando Antonio Gulino ³, Fortunato Genovese ², Domenico Benvenuto ⁴, Chiara Lello ⁵, Marco Palumbo ²

Abstract

Endometriosis is a chronic inflammatory disease defined by the presence of endometrial-like tissue outside the uterine cavity. Several authors have reported on the association between changes in inflammatory marker levels and the maintenance or progression of endometriosis and associated infertility. Interleukin-6 (IL-6) is the most studied cytokine in endometriosis and has important functions in reproductive physiology. The aim of this study is to review systematically available evidence about altered IL-6 concentrations in endometriosis-related infertility. This is a systematic review including all studies until December 2022 in which IL-6 in serum, peritoneal fluid, follicular fluid, or endometrial biopsy specimens was measured and that correlated their findings with endometriosis- associated infertility. Fifteen studies were included in the systematic review. There seems to be a correlation between elevated serum and peritoneal fluid IL-6 concentrations and the occurrence of endometriosis-associated infertility. IL-6 may be a potential diagnostic or biomarker tool for the prediction of endometriosis-related infertility. However, the numerous biases affecting the available studies, and challenges in endometriosis research reproducibility must be considered. Future investigations should pay attention to factors that may affect the results, such as the choice of suitable control groups, and carefully consider other pathological conditions affecting the patients, endometriosis stage, and type of lesion.

Keywords: Endometriosis; Interleukin-6; infertility.

25. J Cell Mol Med. 2023 Aug 25.doi: 10.1111/jcmm.17921. Online ahead of print.

Digestive system deep infiltrating endometriosis: What do we know

Wenze Yin ¹, Xiaoqing Li ², Peng Liu ³, Yingjie Li ⁴, Jin Liu ², Shan Yu ², Sheng Tai ¹

Abstract

Digestive system infiltrating endometriosis (DSIE) is an uncommon form of endometriosis in the digestive system. DSIE often occurs in the intestines (especially the sigmoid rectum), liver, gallbladder and pancreas. Clinically, DSIE presents with the same symptoms as endometriosis, including cyclic pain, bleeding and infertility, in addition to specific biliary/intestinal obstruction and gastrointestinal bleeding. Compared to general endometriosis, DSIE has unique biological behaviour and pathophysiological mechanisms. Most DSIEs are deep invasive endometrioses, characterized by metastasis to the lymph nodes and lymphatic vessels, angiogenesis, peripheral nerve recruitment, fibrosis and invasion of surrounding tissues. DSIE-related peripheral angiogenesis is divided into three patterns: angiogenesis, vasculogenesis and inosculation. These patterns are regulated by interactions between multiple hypoxia-hormone cytokines. The nerve growth factors regulate the extensive neurofibril recruitment in DSIE lesions, which accounts for severe symptoms of deep pain. They are also associated with fibrosis and the aggressiveness of DSIE. Cyclic changes in DSIE lesions, recurrent inflammation and oxidative stress promote repeated tissue injury and repair (ReTIAR) mechanisms in the lesions, accelerating fibril formation and cancer-related mutations. Similar to malignant tumours, DSIE can also exhibit aggressiveness derived from collective cell migration mediated by E-cadherin and N-cadherin. This often makes DSIE misdiagnosed as a malignant tumour of the digestive system in clinical practice. In addition to surgery, novel treatments are urgently required to effectively eradicate this lesion.

Keywords: aetiology; digestive system; endometriosis; intestines; molecular mechanisms.

26. Reprod Biol Endocrinol. 2023 Aug 29;21(1):79.doi: 10.1186/s12958-023-01126-1.

Antioxidant vitamins supplementation reduce endometriosis related pelvic pain in humans: a systematic review and meta-analysis

Sai-Hua Zheng ¹, Xiu-Xia Chen ¹, Yi Chen ¹, Zhi-Cong Wu ¹, Xian-Qian Chen ^# 2, Xue-Lian Li 

Abstract

Objective: This study aimed to clarify the effect of antioxidant vitamins supplementation on endometriosis-related pain.

Methods: A systematic search of PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNK) databases was conducted to identify relevant studies published in English and Chinese up to 16 March 2023. The search terms used were “endometriosis” OR “endometrioma” OR “endometrium” AND “antioxidant” OR “Vitamin C” OR “Vitamin E” OR “Vitamin D” OR “25-OHD” OR “25(OH)D” OR “25-hydroxyvitamin D”. Eligible studies were randomized controlled trials (RCTs) that assessed pain scores using the Visual Analogue Scale (VAS). Mean differences or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the effect of antioxidant vitamins supplementation on endometriosis. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.

Results: A total of 13 RCTs involving 589 patients were included in this meta-analysis. We identified 11 studies that evaluated the effect of antioxidant vitamins supplementation on endometriosis-related pain. The results indicated that the supplementation of antioxidant vitamins can effectively alleviate endometriosis-related pain. Subgroup analysis showed that the supplementation of vitamin E (with or without vitamin C) had a positive effect on improving clinical pelvic pain in patients with chronic pelvic pain. Conversely, supplementation of vitamin D was associated with a reduction in pelvic pain in endometriosis patients, but the difference was not statistically significant compared to the placebo. Additionally, we observed changes in oxidative stress markers following vitamin supplementation. Plasma malondialdehyde (MDA) concentration decreased in patients with endometriosis after antioxidant vitamin supplementation, and the plasma MDA level was inversely correlated with the time and dose of vitamin E and C supplementation. Furthermore, the inflammatory markers in peritoneal fluid, including RANTES, interleukin-6, and monocyte chemoattractant protein-1, significantly decreased after antioxidant therapy. These findings suggest that antioxidant vitamins may alleviate pain in endometriosis patients by reducing inflammation.

Conclusions: The included studies support the potential role of antioxidant vitamins in the management of endometriosis. Supplementation with antioxidant vitamins effectively reduced the severity of dysmenorrhea, improved dyspareunia and pelvic pain, and enhanced quality of life in these patients. Therefore, antioxidant vitamin therapy could be considered as an alternative treatment method, either alone or in combination with other approaches, for endometriosis-related pain.

Trial registration: PROSPERO registration number: CRD42023415198.

Keywords: Antioxidant; Endometriosis; Pain; Supplementation; Vitamin C; Vitamin D; Vitamin E.

27. J Med Internet Res. 2023 Aug 15;25:e45381.doi: 10.2196/45381.

Users’ Concerns About Endometriosis on Social Media: Sentiment Analysis and Topic Modeling Study

Rahul Goel ¹, Vijayachitra Modhukur ^2 3, Katrin Täär ⁴, Andres Salumets, Rajesh Sharma ¹, Maire Peters

Abstract

Background: Endometriosis is a debilitating and difficult-to-diagnose gynecological disease. Owing to limited information and awareness, women often rely on social media platforms as a support system to engage in discussions regarding their disease-related concerns.

Objective: This study aimed to apply computational techniques to social media posts to identify discussion topics about endometriosis and to identify themes that require more attention from health care professionals and researchers. We also aimed to explore whether, amid the challenging nature of the disease, there are themes within the endometriosis community that gather posts with positive sentiments.

Methods: We retrospectively extracted posts from the subreddits r/Endo and r/endometriosis from January 2011 to April 2022. We analyzed 45,693 Reddit posts using sentiment analysis and topic modeling-based methods in machine learning.

Results: Since 2011, the number of posts and comments has increased steadily. The posts were categorized into 11 categories, and the highest number of posts were related to either asking for information (Question); sharing the experiences (Rant/Vent); or diagnosing and treating endometriosis, especially surgery (Surgery related). Sentiment analysis revealed that 92.09% (42,077/45,693) of posts were associated with negative sentiments, only 2.3% (1053/45,693) expressed positive feelings, and there were no categories with more positive than negative posts. Topic modeling revealed 27 major topics, and the most popular topics were Surgery, Questions/Advice, Diagnosis, and Pain. The Survey/Research topic, which brought together most research-related posts, was the last in terms of posts.

Conclusions: Our study shows that posts on social media platforms can provide insights into the concerns of women with endometriosis symptoms. The analysis of the posts confirmed that women with endometriosis have to face negative emotions and pain daily. The large number of posts related to asking questions shows that women do not receive sufficient information from physicians and need community support to cope with the disease. Health care professionals should pay more attention to the symptoms and diagnosis of endometriosis, discuss these topics with patients to reduce their dissatisfaction with doctors, and contribute more to the overall well-being of women with endometriosis. Researchers should also become more involved in social media and share new science-based knowledge regarding endometriosis.

Keywords: Reddit; endometriosis; latent Dirichlet allocation; pain; sentiment analysis; social media; surgery; topic modeling; user engagement.

28. Aust J Gen Pract. 2023 Aug;52(8):547-555.doi: 10.31128/AJGP-10-22-6579.

Challenges in diagnosing and managing endometriosis in general practice: A Western Australian qualitative study

Jacqueline Frayne ¹, Talila Milroy ², Magdalena Simonis ³, Alan Lam ⁴

Abstract

Background and objectives: To reduce diagnostic delay for women with endometriosis-related symptoms, we need to understand general practitioners’ (GPs) perspectives on the challenges they face in diagnosing and managing endometriosis.

Method: Qualitative interviews were conducted with nine Western Australian GPs to explore their knowledge, experiences and challenges with the diagnosis and management of endometriosis.

Results: Three themes were identified as challenges: eliciting symptoms, with subthemes of multiple and complex symptoms, clinician experience and awareness, time constraints and screening opportunities; delivering patient-centred care, with subthemes of cultural factors and health literary, perceived gender biases and women’s choices and priorities; and system and service, which included learning on the job, clearer diagnostic pathways, access to services and collaborative care models.

Discussion: GPs can be better supported in dealing with endometriosis through raising awareness and education; recognition of endometriosis as a complex chronic condition; and the development of pragmatic guidelines, with increased access to local centres for excellent and collaborative care.

29. Gynecol Endocrinol. 2023 Aug 18;39(1):2242956.doi: 10.1080/09513590.2023.2242956.

Oxidative stress markers cannot be used as endometriosis biomarkers in infertile patients

Vid Janša ^1 2, Joško Osredkar ^3 4, Ivan Verdenik ¹, Tea Lanišnik Rižner ⁵, Helena Ban Frangež ^1 2

Abstract

Objectives: Endometriosis is a common benign gynaecological disease that significantly compromises the quality of life of patients. To date, invasive surgery is the method of choice to visually and histologically confirm endometriosis. Thus, there is a major interest to develop noninvasive diagnostic tools. Oxidative stress is one of the proposed mechanisms of pathogenesis and may be involved in pelvic pain, dysmenorrhea, dyspareunia, and infertility in endometriosis patients. Thus, markers of oxidative stress may serve as diagnostic biomarkers for endometriosis.

Design: This prospective case-control study assessed erythrocyte superoxide dismutase (SOD), erythrocyte glutathione peroxidase (GPX), serum hexanoyl lysine (HEL) and peritoneal fluid HEL.

Participants/materials, setting, and methods: We enrolled 86 women with primary infertility; the case group included 57 women with endometriosis, and the control group included 29 women with unexplained primary infertility. All the patients underwent laparoscopy, and the diagnosis was confirmed histologically. RANDOX and RANSEL reagents were used to determine the levels of SOD and GPX, respectively, and ELISA was used to determine the levels of HEL.

Results: We found no statistically significant differences in the erythrocyte levels of GPX (p value 0.623) or SOD (p value 0.122) or the serum or peritoneal fluid levels of HEL (p value 0.562 and 0.329 accordingly).

Conclusions: SOD, GPX, and HEL levels most likely do not differ between patients with unexplained infertility and patients with endometriosis.

Keywords: Oxidative stress biomarkers; endometriosis; glutathione peroxidase; hexanoyl lysine; superoxide dismutase.

30. Insights Imaging. 2023 Aug 15;14(1):136.doi: 10.1186/s13244-023-01468-9.

Differences in the position of endometriosis-associated and non-associated ovarian cancer relative to the uterus

Tsukasa Saida ¹, Kensaku Mori ², Toshitaka Ishiguro ², Yukihisa Saida ³, Toyomi Satoh ⁴, Takahito Nakajima ²

Abstract

Background: Preoperative assessment of the histological type of ovarian cancer is essential to determine the appropriate treatment strategy. Tumor location may be helpful in this regard. The purpose of this study was to compare the position of endometriosis-associated (EAOCs) and non-associated (non-EAOCs) ovarian cancer relative to the uterus using MRI.

Methods: This retrospective study included patients with pathologically confirmed malignant epithelial ovarian tumors who underwent MRI at our hospital between January 2015 and January 2023. T2-weighted images of the sagittal and axial sections of the long axis of the uterine body were used for the analysis. Three blinded experienced radiologists independently interpreted the images and assessed whether the ovarian tumor was attached to the uterus, and the angle between the uterus and the tumor was measured. The presence of attachment and the measured angles were compared for each histology. In addition, the angles between EAOCs, including endometrioid carcinomas (ECs) and clear cell carcinomas (CCCs), were compared with non-EAOCs.

Results: In total, 184 women (mean age, 56 years; age range, 20-91 years) were evaluated. High-grade serous carcinomas (HGSCs) were significantly smaller than the others and had significantly less uterine attachment than CCCs (p < 0.01 for all readers). According to the mean of the measured angles, CCCs were positioned significantly more posteriorly than HGSCs and mucinous carcinomas (p < 0.02), and EAOCs were positioned significantly more posteriorly to the uterus than non-EAOCs (p < 0.01).

Conclusion: HGSCs are often not attached to the uterus, and EAOCs are positioned more posteriorly to the uterus than non-EAOCs.

Critical relevance statement: High-grade serous carcinomas were often not attached to the uterus, and endometriosis-associated ovarian cancers were positioned more posteriorly to the uterus than non-endometriosis-associated ovarian cancers.

Key points: • The position of the ovarian tumor can be determined using MRI. • High-grade serous carcinomas had less attachment to the uterus. • Endometriosis-associated cancers were positioned more posteriorly to the uterus. • The location of ovarian tumors is helpful in estimating histology.

Keywords: Carcinoma; Location; Magnetic resonance imaging; Ovary.

31. Eur J Med Res. 2023 Aug 30;28(1):305.doi: 10.1186/s40001-023-01280-7.

Effects of dysregulated glucose metabolism on the occurrence and ART outcome of endometriosis

Jian-Peng Chen ^# 1, Yan-Ye Zhang ^# 1, Jia-Ni Jin ¹, Yue Ying ¹, Zhi-Min Song ¹, Qi-Qi Xu ¹, Mi-Xue Tu ¹, Xiao-Hang Ye ¹, Huan-Na Tang ¹, Fei-Da Ni ¹, Yan-Yun Ying ¹, Jing-Yi Li ^2 3, Dan Zhang 

 

Abstract

Background: Endometriosis is associated with systemic metabolic indicators, including body mass index (BMI), glucose metabolism and lipid metabolism, while the association between metabolic indexes and the occurrence and assisted reproductive technology (ART) outcome of endometriosis is unclear. We aimed to evaluate the characteristics of systemic metabolic indexes of endometriosis patients with infertility and their effects on pregnancy outcome after ART treatment.

Methods: A retrospective cohort study involve 412 endometriosis patients and 1551 controls was conducted. Primary outcome was metabolic indexes, and secondary measures consisted of the influence of metabolic indexes on the number of retrieved oocytes and ART outcomes.

Results: Endometriosis patients had higher insulin (INS) [6.90(5.10-9.50) vs 6.50(4.80-8.90) μU/mL, P = 0.005]. A prediction model for endometriosis combining the number of previous pregnancies, CA125, fasting blood glucose (Glu) and INS, had a sensitivity of 73.9%, specificity of 67.8% and area under curve (AUC) of 0.77. There were no significant differences in ART outcomes and complications during pregnancy. The serum levels of Glu before pregnancy were associated with GDM both in endometriosis group (aOR 12.95, 95% CI 1.69-99.42, P = 0.014) and in control group (aOR 4.15, 95% CI 1.50-11.53, P = 0.006).

Conclusions: We found serum Glu is related to the number of retrieved oocytes in control group, serum INS is related to the number of retrieved oocytes in endometriosis group, while serum Glu and INS before pregnancy are related to the occurrence of GDM in two groups. A prediction model based on metabolic indexes was established, representing a promising non-invasive method to predict endometriosis patients with known pregnancy history.

Keywords: ART outcomes; Endometriosis; GDM; Metabolic indicator; Number of retrieved oocytes.

32. Molecules. 2023 Aug 8;28(16):5945.doi: 10.3390/molecules28165945.

Effects of Quince Gel and Hesperidin Mixture on Experimental Endometriosis

Işılay Sezen Ermiş ¹, Engin Deveci ², Fırat Aşır ²

Abstract

Objectives: Endometriosis (EM) is the presence of endometrial tissue outside the uterus. This study aimed to examine the effects of quince gel and hesperidin treatment on uterine tissue in an experimental endometriosis model.

Materials and methods: Thirty-two rats were categorized into four groups as sham, EM, EM+quince gel (QG), and EM+QG+Hesperidin (HES). The endometriosis (EM) model was induced with surgical intervention. Estradiol benzoate (EB) was used to induce endometrial hyperplasia. In the EM group, EB was given to rats for 7 days. The EM+QG group received 2 cc QG for 21 days. HES treatment was given for 21 days after EM induction. At the end of the experiment, blood was taken from the animals and the serum total antioxidant status (TAS) and total oxidant status (TOS) values were studied. Uterine tissues were dissected and processed for histological paraffin embedding. Tissues were fixed in 4% glutaraldehyde solution and processed for ultrastructural analysis.

Results: After EM, QG and HES treatment significantly increased the TAS and decreased the TOS value. EM caused epithelial and glandular degeneration, thinning of the basal membranes, and vascular dilatation with increased fibrosis and edema. QG+HES restored the pathology and showed protective effects in uterine tissues. Caspase-3 expression was increased in the epithelium, glands, and muscle layers of the EM group. In EM+QG+HES, hesperidin protected cell survival and decreased Caspase-3 expression in uterine tissues. TNF-α expression was intense in inflammatory cells and the muscle layer in the EM group. HES reduced inflammation by decreasing the TNF-α expression. MAPK expression was increased after EM induction in epithelial, glandular, and inflammatory cells in the EM group. After HES treatment, MAPK expression was mainly negative in cells of uterine tissue in the EM+QG+HES group. Ultrastructurally, in the EM group, organelles were disrupted and dilated and degenerated after EM induction. QG and HES treatment improved cellular organelles.

Conclusion: Local vaginal applications can be an alternative treatment method in the endometriosis model via QG+HES treatment promoting cell proliferation and angiogenesis and preventing cell death.

Keywords: TAS; TOS; histochemistry; morphometry; ultrastructural.

33. Reprod Biol. 2023 Aug 21;23(4):100796.doi: 10.1016/j.repbio.2023.100796.Online ahead of print.

Circulating miR-3613-5p but not miR-125b-5p, miR-199a-3p, and miR-451a are biomarkers of endometriosis

Izabela Walasik ¹, Klaudia Klicka ², Tomasz M Grzywa ³, Iwona Szymusik ⁴, Paweł Włodarski ⁵, Mirosław Wielgoś ⁶, Bronisława Pietrzak ⁶, Artur Ludwin ¹

Abstract

Objective: This study aimed to assess the utility of circulating miR-125b-5p, miR-199a-3p, miR-451a, and miR-3613-5p as biomarkers of endometriosis.

Study design: Patients with stage III or IV of endometriosis according to the revised American Society of Reproductive Medicine (rASRM) staging classification, as well as control women, were recruited. We created a prospective study conducted on a group of 48 patients (n = 25 controls, n = 24 endometriosis) who had laparoscopic surgery. Blood samples were taken and plasma miRNA levels were measured by quantitative real-time polymerase chain reaction (RT-qPCR) and assessed with AUC and ROC curves.

Results: MiR-451a and miR-3613-5p were significantly decreased in the plasma of endometriosis patients. miR-451a had a receiver-operating characteristic (ROC) area under the curve 0.8283 and miR-3613-5p had a ROC area under the curve 0.7617. The concentration of circulating miR-125b-5p and miR-199-3p did not differ between endometriosis patients and controls. Plasma miRNA levels did not change with BMI, smoking status, fertility problems, or menstrual pain according to the VAS scale (p > 0.05).

Conclusion: Circulating miR-451a and miR-3613-5p levels significantly differed between endometriosis and controls. However, the levels of miR-451a were discordant with previous studies. Therefore, miR-3613-5p may have better potential as the endometriosis biomarker. Circulating miR-125b-5p and miR-199a-3p cannot be used as reliable markers of endometriosis.

Keywords: Biomarkers; Endometriosis; miR-125b-5p; miR-199a-3p; miR-3613-5p; miR-451a; miRNA.

34. Minerva Obstet Gynecol. 2023 Aug;75(4):387-389.doi: 10.23736/S2724-606X.22.05089-8.

Primary vulvar endometriosis in postmenopausal woman: a case report and review of the literature

Giuseppe Sarpietro ¹, Maria G Matarazzo ², Giada M Vecchio ³, Gaia Palermo ², Antonio Cianci ²

Abstract

Endometriosis is a benign, estrogen-dependent condition that commonly affects women during the reproductive age. Postmenopausal endometriosis is a rare condition because of the absence of estrogenic hormone production. Furthermore, extrapelvic endometriosis is a rare and complex phenomenon. For this reason, it is usually a misdiagnosed disease. An 84-year-old female patient with no medical history of endometriosis or dysmenorrhea and no hormone replacement therapy was found to have a 4.4×3 cm tender, mobile mass on the left labium majus detached from the underlying perineal muscle. The patient underwent surgical excision under sedation and local anesthesia. The mass was easily removed intact and was not adherent to the vagina or the perineal muscles. Surgical resection of the lesion should be performed in order to remove the lesion and to confirm the diagnosis histologically. The diagnosis of long-standing endometriotic cyst was made. Primary vulvo-perineal endometriosis is a rare and difficult diagnosis especially in postmenopausal women without previous surgical procedures and no history of endometriosis. A better awareness of symptoms and signs of uncommon locations of extrapelvic endometriosis should be encouraged in order to optimize patient care. Finally, more research is needed to elucidate the pathogenesis of endometriosis in postmenopausal women.

35. J Ultrasound Med. 2023 Aug 14.doi: 10.1002/jum.16318.Online ahead of print.

Deep Infiltrating Endometriosis: A Pictorial Essay

Abdullah Nadeem ¹, Alexander Habte ², Areeba Ahsan ¹, Rabeea Tariq ¹, Areeba Aamir Ali Basaria ¹

Abstract

Deep infiltrating endometriosis (DIE) is a subperitoneal intrusion of endometrial tissue. Resulting endometrial nodules may develop on the uterosacral ligament, urinary tract, rectovaginal, and retrocervical areas, and less commonly in the urinary bladder, thoracic, and neural regions. Genetics, age, and environmental factors determine the progression of the disease. DIE manifests with numerous symptoms, which are similar to unrelated diseases, namely dysmenorrhea, dyspareunia, urinary tract infections, and infertility. Transvaginal ultrasound, magnetic resonance imaging, computed tomography, and physical examination may detect and differentiate endometriosis lesions from other diseases. Its clinical management typically involves laparoscopic surgery and hormonal therapy. These are designed to improve the quality of life and to address individual reproductive goals. This pictorial essay aims to provide clinical cases to highlight the characteristic radiological findings in each diagnostic modality and in addition to elucidate the current clinical management of DIE.

Keywords: CT; DIE; MRI; deep infiltrating endometriosis; endometrioma; endometriosis; nodules; ultrasound (TVUS).

36. Front Endocrinol (Lausanne). 2023 Aug 9;14:1162786.doi: 10.3389/fendo.2023.1162786.eCollection 2023.

Transcriptomic analyses of ovarian clear-cell carcinoma with concurrent endometriosis

Kaitlyn E Collins ^1 2, Xiyin Wang ^3 4, Yuliya Klymenko ^2 3, Noah B Davis ³, Maria C Martinez ⁵, Chi Zhang ^6 7, Kaman So ^6 7, Aaron Buechlein ⁸, Douglas B Rusch ⁸, Chad J Creighton ⁹, Shannon M Hawkins 

Abstract

Introduction: Endometriosis, a benign inflammatory disease whereby endometrial-like tissue grows outside the uterus, is a risk factor for endometriosis-associated ovarian cancers. In particular, ovarian endometriomas, cystic lesions of deeply invasive endometriosis, are considered the precursor lesion for ovarian clear-cell carcinoma (OCCC).

Methods: To explore this transcriptomic landscape, OCCC from women with pathology-proven concurrent endometriosis (n = 4) were compared to benign endometriomas (n = 4) by bulk RNA and small-RNA sequencing.

Results: Analysis of protein-coding genes identified 2449 upregulated and 3131 downregulated protein-coding genes (DESeq2, P< 0.05, log2 fold-change > |1|) in OCCC with concurrent endometriosis compared to endometriomas. Gene set enrichment analysis showed upregulation of pathways involved in cell cycle regulation and DNA replication and downregulation of pathways involved in cytokine receptor signaling and matrisome. Comparison of pathway activation scores between the clinical samples and publicly-available datasets for OCCC cell lines revealed significant molecular similarities between OCCC with concurrent endometriosis and OVTOKO, OVISE, RMG1, OVMANA, TOV21G, IGROV1, and JHOC5 cell lines. Analysis of miRNAs revealed 64 upregulated and 61 downregulated mature miRNA molecules (DESeq2, P< 0.05, log2 fold-change > |1|). MiR-10a-5p represented over 21% of the miRNA molecules in OCCC with endometriosis and was significantly upregulated (NGS: log2fold change = 4.37, P = 2.43e-18; QPCR: 8.1-fold change, P< 0.05). Correlation between miR-10a expression level in OCCC cell lines and IC50 (50% inhibitory concentration) of carboplatin in vitro revealed a positive correlation (R^{2 =} 0.93). MiR-10a overexpression in vitro resulted in a significant decrease in proliferation (n = 6; P< 0.05) compared to transfection with a non-targeting control miRNA. Similarly, the cell-cycle analysis revealed a significant shift in cells from S and G₂ to G₁ (n = 6; P< 0.0001). Bioinformatic analysis predicted that miR-10a-5p target genes that were downregulated in OCCC with endometriosis were involved in receptor signaling pathways, proliferation, and cell cycle progression. MiR-10a overexpression in vitro was correlated with decreased expression of predicted miR-10a target genes critical for proliferation, cell-cycle regulation, and cell survival including [SERPINE1 (3-fold downregulated; P<0.05), CDK6 (2.4-fold downregulated; P< 0.05), and RAP2A (2-3-fold downregulated; P< 0.05)].

Discussion: These studies in OCCC suggest that miR-10a-5p is an impactful, potentially oncogenic molecule, which warrants further studies.

Keywords: endometriosis; miRNA; ovarian clear-cell carcinoma; ovarian endometrioma; transcriptomic profiling.

37. Commun Biol. 2023 Aug 16;6(1):780.doi: 10.1038/s42003-023-05070-z.

Global endometrial DNA methylation analysis reveals insights into mQTL regulation and associated endometriosis disease risk and endometrial function

Sally Mortlock ^# 1, Sahar Houshdaran ^# 2, Idit Kosti ^# 3, Nilufer Rahmioglu ^# 4 5, Camran Nezhat ^6 7 8, Allison F Vitonis ⁹, Shan V Andrews ³, Parker Grosjean ³, Manish Paranjpe ³, Andrew W Horne ¹⁰, Alison Jacoby ², Jeannette Lager ², Jessica Opoku-Anane ², Kim Chi Vo ², Evelina Manvelyan ², Sushmita Sen ², Zhanna Ghukasyan ², Frances Collins ¹⁰, Xavier Santamaria ^11 12, Philippa Saunders ¹³, Kord Kober, Allan F McRae ¹⁵, Kathryn L Terry, Júlia Vallvé-Juanico ^2 12, Christian Becker ⁵, Peter A W Rogers ¹⁸, Juan C Irwin ², Krina Zondervan ^4 5, Grant W Montgomery ¹⁵, Stacey Missmer , Marina Sirota ^3 21, Linda Giudice ²²

Abstract

Endometriosis is a leading cause of pain and infertility affecting millions of women globally. Herein, we characterize variation in DNA methylation (DNAm) and its association with menstrual cycle phase, endometriosis, and genetic variants through analysis of genotype data and methylation in endometrial samples from 984 deeply-phenotyped participants. We estimate that 15.4% of the variation in endometriosis is captured by DNAm and identify significant differences in DNAm profiles associated with stage III/IV endometriosis, endometriosis sub-phenotypes and menstrual cycle phase, including opening of the window for embryo implantation. Menstrual cycle phase was a major source of DNAm variation suggesting cellular and hormonally-driven changes across the cycle can regulate genes and pathways responsible for endometrial physiology and function. DNAm quantitative trait locus (mQTL) analysis identified 118,185 independent cis-mQTLs including 51 associated with risk of endometriosis, highlighting candidate genes contributing to disease risk. Our work provides functional evidence for epigenetic targets contributing to endometriosis risk and pathogenesis. Data generated serve as a valuable resource for understanding tissue-specific effects of methylation on endometrial biology in health and disease.

38. BMC Womens Health. 2023 Aug 4;23(1):409.doi: 10.1186/s12905-023-02576-w.

“I think to myself ‘why now?'” – a qualitative study about endometriosis and pain in Austria

Manuela Gstoettner ¹, René Wenzl ², Ines Radler ³, Margret Jaeger ⁴

Erratum in

• Correction: “I think to myself ‘why now?'” – a qualitative study about endometriosis and pain in Austria.

Gstoettner M, Wenzl R, Radler I, Jaeger M.BMC Womens Health. 2023 Aug 28;23(1):455. doi: 10.1186/s12905-023-02610-x.PMID: 37641056 Free PMC article. No abstract available.

Abstract

Background: Endometriosis is a chronic, benign, and oestrogen-dependent condition and about 10-15% of all women of reproductive age are affected by endometriosis worldwide. It is not curable and pain is one of the most common symptoms of endometriosis and leads to low quality of life in affected women. To our knowledge, in German-speaking countries, no studies with qualitative methods approaches are available concerning women who suffer from pain caused by endometriosis and possible associated coping strategies. Our study aims to familiarise ourselves with the individual pain experience of selected women who suffer from endometriosis in Austria and their coping strategies.

Methods: A qualitative study design was based on problem-centred interviews for data collection and qualitative content analysis for data analysis. The research participants were women aged between 18 and 55 diagnosed with endometriosis and living in Austria. The interview period was from 27 February to 26 March 2019 and interviews lasted between 50 and 75 min.

Results: Eight categories were formulated, of which category 3 (thoughts and feelings regarding endometriosis and pain – ‘why?’), category 5 (effects and changes caused by endometriosis and pain – ‘quality of life’), category 7 (taboos – ‘don`t talk about it’), and category 8 (talking about it – ‘contact with others in the same position’) were relevant for this article. The remaining four categories [1-4] have already been published elsewhere.

Conclusion: Our data show that the social environment plays a fundamental role in coping strategies concerning pain caused by endometriosis. Women in our study reported that exchange with peers offers support. This opens a door for information events, patient organizations like support groups, and the inclusion of these in the supporting system. Involving occupational medicine and workplace health promotion departments in companies should be further goals to support affected women.

Keywords: Austria; Endometriosis; Pain; Qualitative methods; Social environment.

39. Arch Gynecol Obstet. 2023 Aug 28.doi: 10.1007/s00404-023-07193-4. Online ahead of print.

Evaluation of the effect of previous endometriosis surgery on clinical and surgical outcomes of subsequent endometriosis surgery

Fokkedien H M P Tummers ¹, Sophie I Peltenburg ², Jeroen Metzemaekers ², Frank Willem Jansen ^2 3, Mathijs D Blikkendaal ^4 5

Abstract

Purpose: Patients often undergo repeat surgery for endometriosis, due to recurrent or residual disease. Previous surgery is often considered a risk factor for worse surgical outcome. However, data are scarce concerning the influence of subsequent endometriosis surgery.

Methods: A retrospective study in a centre of expertise for endometriosis was conducted. All endometriosis subtypes and intra-operative steps were included. Detailed information regarding surgical history of patients was collected. Surgical time, intra-operative steps and major post-operative complications were obtained as outcome measures.

Results: 595 patients were included, of which 45.9% had previous endometriosis surgery. 7.9% had major post-operative complications and 4.4% intra-operative complications. The patient journey showed a median of 3 years between previous endometriosis surgeries. Each previous therapeutic laparotomic surgery resulted on average in 13 additional minutes (p = 0.013) of surgical time. Additionally, it resulted in more frequent performance of adhesiolysis (OR 2.96, p < 0.001) and in a higher risk for intra-operative complications (OR 1.81, p = 0.045), however no higher risk for major post-operative complications (OR 1.29, p = 0.418). Previous therapeutic laparoscopic endometriosis surgery, laparotomic and laparoscopic non-endometriosis surgery showed no association with surgical outcomes. Regardless of previous surgery, disc and segmental bowel resection showed a higher risk for major post-operative complications (OR 3.64, p = 0.017 respectively OR 3.50, p < 0.001).

Conclusion: Previous therapeutic laparotomic endometriosis surgery shows an association with longer surgical time, the need to perform adhesiolysis, and more intra-operative complications in the subsequent surgery for endometriosis. However, in a centre of expertise with experienced surgeons, no increased risk of major post-operative complications was observed.

Keywords: Complications; Endometriosis; Patient journey; Recurrence; Repeat surgery.

40. Hum Reprod. 2023 Aug 15;dead164.doi: 10.1093/humrep/dead164. Online ahead of print.

Utilization of healthcare prior to endometriosis diagnosis: a Danish case-control study

Anna Melgaard ¹, Claus Høstrup Vestergaard ², Ulrik Schiøler Kesmodel ³, Bettina Wulff Risør ^4 5, Axel Forman ⁶, Krina Zondervan ⁷, Bodil Hammer Bech ¹, Dorte Rytter ¹

Abstract

Study question: Do women with endometriosis have higher utilization of primary and secondary healthcare prior to diagnosis compared to women without endometriosis?

Summary answer: Women with a hospital-based diagnosis of endometriosis had an overall higher utilization of both primary and secondary healthcare in all 10 years prior to diagnosis.

What is known already: Endometriosis is associated with a diagnostic delay, but only a few studies have investigated the potential consequences of this delay with regard to the utilization of healthcare. To the best of our knowledge, no study has investigated it in a period corresponding to the estimated diagnostic delay.

Study design, size, duration: This national Danish registry-based case-control study included 129 696 women. Cases were women with a first-time hospital-based diagnosis of endometriosis between 1 January 2000 and 31 December 2017.

Participants/materials, setting, methods: We identified 21 616 cases using density sampling. Each case was matched on age at the date of diagnosis (index date) to five women without diagnosed endometriosis (n = 108 080). The utilization of healthcare was assessed for the 10 years before the index.

Main results and the role of chance: Cases had significantly higher use of healthcare in all 10 years preceding the index. The mean number of yearly contacts with the GP was 9.99 for cases and 7.85 for controls, with an adjusted incidence rate ratio of 1.28 (1.27; 1.29). For hospital contacts, the association increased slightly in the first 9 years and was most profound in the last year preceding index when the adjusted incidence rate ratio was 2.26 (95% CI 2.28; 2.31).

Limitations, reasons for caution: We were not able to include women with an endometriosis diagnosis from the general practitioner or private gynaecologist. Therefore, our results are only applicable to hospital-based diagnoses of endometriosis. We do not have information on the specific reasons for contacting the healthcare providers and we can therefore only speculate that the higher utilization of healthcare among cases was related to endometriosis.

Wider implications of the findings: This study is in agreement with the other known studies on the subject. Future studies should include specific reasons for contacting the healthcare system and thereby identify any specific contact patterns for women with endometriosis. With this knowledge, healthcare professionals could be better at relating certain healthcare seeking behaviour to endometriosis earlier and thereby reduce the time from onset of symptoms to diagnosis.

Study funding/competing interest(s): This study is supported by grants from the project ‘Finding Endometriosis using Machine Learning’ (FEMaLe/101017562), which has received funding from The European Union’s Horizon 2020 research and innovation program and Helsefonden (21-B-0141). K.Z. report grants from Bayer AG, Roche Inc. and Volition, royalties from Oxford-Bayer scientific collaboration in gynaecological therapies, non-financial collaboration with the World Endometriosis Society and World Endometriosis Research Foundation and is a Wellbeing of Women research advisory committee member. All this is outside the submitted work. The other authors have no conflict of interest to declare.

Trial registration number: N/A.

Keywords: case–control study; diagnostic delay; endometriosis; healthcare utilization; women’s health.

41. Biol Reprod. 2023 Aug 10;109(2):156-171.doi: 10.1093/biolre/ioad057.

A novel mechanism regulating pyroptosis-induced fibrosis in endometriosis via lnc-MALAT1/miR-141-3p/NLRP3 pathway†

Ying Xu ^1 2, Hengwei Liu ³, Wenqian Xiong ¹, Yuan Peng ⁴, Xiaoou Li ¹, Xuefeng Long ¹, Jie Jin ¹, Jiaxin Liang ¹, Ruiwen Weng ¹, Junjun Liu ¹, Ling Zhang ¹, Yi Liu ¹

Abstract

Endometriosis is a chronic inflammatory disease distinguished by ectopic endometrium and fibrosis. NLRP3 inflammasome and pyroptosis are present in endometriosis. Aberrant increase of Long noncoding (Lnc)-metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays a vital role in endometriosis. However, the relationship between lnc-MALAT1, pyroptosis, and fibrosis is not completely known. In the present study, we found that the pyroptosis levels in ectopic endometrium of patients with endometriosis were significantly increased, consistent with fibrosis levels. Lipopolysaccharide (LPS) + ATP could induce pyroptosis of primary endometrial stromal cells (ESCs), thereby releasing interleukin (IL)-1β and stimulating transforming growth factor (TGF)-β1-mediated fibrosis. NLRP3 inhibitor MCC950 had the same effect as TGF-β1 inhibitor SB-431542 in suppressing the fibrosis-inducing effect of LPS + ATP in vivo and in vitro. The abnormal increase of lnc-MALAT1 in ectopic endometrium was connected with NLRP3-mediated pyroptosis and fibrosis. Leveraging bioinformatic prediction and luciferase assays combined with western blotting and quantitative reverse transcriptase-polymerase chain reaction, we validated that lnc-MALAT1 sponges miR-141-3p to promote NLRP3 expression. Silencing lnc-MALAT1 in HESCs ameliorated NLRP3-mediated pyroptosis and IL-1β release, thereby relieving TGF-β1-mediated fibrosis. Consequently, our findings suggest that lnc-MALAT1 is critical for NLRP3-induced pyroptosis and fibrosis in endometriosis through sponging miR-141-3p, which may indicate a new therapeutic target of endometriosis treatment.

Keywords: endometriosis; fibrosis; lnc-MALAT1; miR-141-3p; pyroptosis.

42. Am J Med Sci. 2023 Oct;366(4):296-304.doi: 10.1016/j.amjms.2023.08.003. Epub 2023 Aug 6.

Pleural effusion secondary to endometriosis: A systematic review

José M Porcel ¹, Paula Sancho-Marquina ², Paula Monteagudo ², Silvia Bielsa ²

Abstract

Background: Endometriosis-associated pleural effusion is a rare occurrence with poorly defined clinical characteristics.

Methods: A systematic review was performed to examine all articles on endometriosis-associated pleural effusion extracted from 4 databases (PubMed, Embase, Web of Science and Scopus) from inception until November 2022.

Results: A total of 142 articles (isolated cases and small retrospective series) involving 176 patients (median age 33 years) with endometriosis-associated pleural effusion were included. The most frequent symptoms were dyspnea (67%), chest pain (55%) and abdominal pain (40%). Pleural effusion was predominantly unilateral (89%), right-sided (88.5%) and massive (56%). Ascites was evident in 42% of the cases. Pleural fluid had a bloody appearance in 99% of cases and always met the exudate criteria. Pleural fluid cytology identified only 9% of the patients, with pleural biopsy being the most common diagnostic procedure (74%). Most patients were treated with hormones (76%), thoracic surgery (60%) and abdominal surgery (27%). Effusion recurrence was observed in 26% of cases after a median follow-up of 1 year.

Conclusions: The presence of right-sided hemorrhagic pleural effusion in a young woman warrants an assessment for the possibility of endometriosis. Despite conventional treatment, effusion recurs in approximately a quarter of patients.

Keywords: Pleural effusion; Systematic review; Thoracic endometriosis.

43. Ginekol Pol. 2023 Aug 21.doi: 10.5603/gpl.95968. Online ahead of print.

MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in endometriosis – review of literature

Tomasz Szaflik ¹, Hanna Romanowicz ², Krzysztof Szyllo ¹, Beata Smolarz ³

Abstract

Endometriosis is a disease of the female genital organs, the causes of which are not fully understood. Recent studies have shown that non-coding RNAs (ncRNAs) like long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) can contribute to the pathogenesis of endometriosis. Profiling of miRNA and lncRNA expression is carried out using state-of-the-art molecular biology techniques (RT-PCR, sequencing, microarray analysis). The use of the latest technologies may make it possible to establish a genetic profile, which is a promising prospect for early diagnosis of endometriosis. In the future, genetic testing may become the gold diagnostic standard and eliminate invasive laparoscopy. In the case of endometriosis, it is important to extend the research to molecular aspects, which may facilitate the diagnosis of the disease or indicate new (based for example ncRNA) treatment methods. The paper presents the latest data on the importance of miRNA/lncRNA in endometriosis.

Keywords: endometriosis; lncRNA; miRNA.

44. J Surg Case Rep. 2023 Aug 14;2023(8):rjad455.doi: 10.1093/jscr/rjad455.eCollection 2023 Aug.

Large bowel perforation secondary to endometriosis

Lawrence Y Goriel ¹, David J Seok ¹, Silvy C Akrawe ¹, Yousif H Goriel ²

Abstract

Endometriosis is described as the implantation of ectopic, viable endometrium. Among the complications associated with this phenomenon, ectopic foci that localizes to the bowel can result in many presentations. An uncommon presentation of such an occurrence is a mass effect on the colon causing an obstruction. This case report describes the progression of endometriosiscausing mass effect in the colon and resulting in perforated hollow viscous. Hence, this demonstrates the importance of maintaining endometriosis as a differential diagnosis in women of childbearing age presenting with bowel obstruction. Although the presence of endometriosis as a cause of bowel obstruction has been reported in the literature, the presentation of large bowel perforation is rare. In this case, an extremely rare presentation of sigmoid obstruction with transverse colonic perforation is observed.

45. JOG Glob Rep. 2023 Aug 28;3(3):100259.doi: 10.1016/j.xagr.2023.100259.eCollection 2023 Aug.

Examining the co-occurrence of endometriosis and polycystic ovarian syndrome

Karen C Schliep ¹, Lina Ghabayen ¹, May Shaaban ¹, Felicity R Hughes ¹, Anna Z Pollack ², Joseph B Stanford ¹, Kristy Allen Brady ³, Amber Kiser ⁴, C Matthew Peterson ⁵

Abstract

Background: Polycystic ovarian syndrome and endometriosis are 2 of the most common reproductive disorders among women but are thought to be unrelated.

Objective: This study aimed to examine the overlap and common symptoms of polycystic ovarian syndrome and endometriosis.

Study design: The study population included the Endometriosis, Natural History, Diagnosis, and Outcomes Study (2007-2009) operative cohort: 473 women, aged 18 to 44 years, who underwent a diagnostic and/or therapeutic laparoscopy or laparotomy at 1 of 14 surgical centers located in Salt Lake City, Utah, or San Francisco, California, in addition to a population cohort composed of 127 women from the surgical centers’ catchment areas. Age and site-adjusted multinomial regression models were used to estimate adjusted prevalence ratios and 95% confidence intervals of reproductive history characteristics among women with endometriosis only, women with polycystic ovarian syndrome only, and women with both endometriosis and polycystic ovarian syndrome.

Results: Among the operative cohort, 35% had endometriosis only, 9% had polycystic ovarian syndrome only, and 5% had endometriosis and polycystic ovarian syndrome. Among the population cohort, 10% had endometriosis only, 8% had polycystic ovarian syndrome only, and 2% had endometriosis and polycystic ovarian syndrome. In the operative cohort, a history of subfertility was associated with a higher adjusted probability of having both conditions (adjusted prevalence ratio, 10.33; 95% confidence interval, 3.94-27.08), followed by having endometriosis only (adjusted prevalence ratio, 2.45; 95% confidence interval, 1.56-3.84) or polycystic ovarian syndrome only (adjusted prevalence ratio, 1.15; 95% confidence interval, 0.51-2.61), than having neither condition. In addition, experiencing chronic pelvic pain within the past 12 months was associated with a higher probability of having both conditions (adjusted prevalence ratio, 2.53; 95% confidence interval, 1.07-6.00) than having neither condition.

Conclusion: Among a cohort of women undergoing gynecologic laparoscopy or laparotomy, our study found that nearly 1 in 20 women had both an incident endometriosis diagnosis and symptoms consistent with polycystic ovarian syndrome. Among a population cohort of women not seeking gynecologic care, polycystic ovarian syndrome and endometriosis overlap prevalence was approximately 1 in 50 women.

Keywords: endometriosis; epidemiology; pelvic pain; polycystic ovarian syndrome; subfertility.

46. Rev Assoc Med Bras (1992). 2023 Aug 14;69(8):e20230316.doi: 10.1590/1806-9282.20230316.eCollection 2023.

Improved quality of life (EHP-30) in patients with endometriosis after surgical treatment

João Nogueira Neto ^1 2, Vinicius Gonçalves Melo ¹, Luna Carolina Silva Lima ¹, Miguel Vinicius Lima Reis Costa ¹, Leonardo Carvalho Silva ¹, Lyvia Maria Rodrigues de Sousa Gomes ^1 2, Glaúcia Iraúna de Melo Freire ², Plinio da Cunha Leal ^1 2, Caio Marcio Barros de Oliveira ^1 2, Ed Carlos Rey Moura ^1 2

Abstract

Objective: This study aimed to evaluate the quality of life of patients with endometriosis before and after surgical treatment.

Methods: An observational, longitudinal, and prospective study was conducted with 102 women with pelvic pain and endometriosis that was unimproved by clinical treatment and indicated for surgical treatment. The patients’ quality of life was assessed using the 30-item Endometriosis Health Profile (EHP-30) questionnaire before and 3 and 6 months after surgery. The statistical tests were analyzed using the Statistical Package for Social Sciences version 17.0, and the Friedman test was used.

Results: There was a reduction in EHP-30 scores 3 and 6 months after surgery compared to before surgery, as well as 6 months after surgery compared to 3 months after surgery, in the central questionnaire (PART 1) and in Sections A, B, C, E, and F (p<0.0001). For Section D, there was a reduction in scores 6 months after surgery compared to before surgery (p<0.0001).

Conclusion: Surgical treatment of endometriosis improves quality of life in several areas assessed by the EHP-30 questionnaire.

47. J Clin Med. 2023 Aug 11;12(16):5234.doi: 10.3390/jcm12165234.

Use of the Free Endometriosis Risk Advisor App as a Non-Invasive Screening Test for Endometriosis in Patients with Chronic Pelvic Pain and/or Unexplained Infertility

Camran Nezhat ^1 2 3, Ellie Armani ¹, Hsuan-Chih Carolina Chen ^1 2, Zahra Najmi ¹, Steven R Lindheim ^4 5 6, Ceana Nezhat ⁷

Abstract

Endometriosis is a prevalent condition that affects millions of individuals globally, leading to various symptoms and significant disruptions to their quality of life. However, the diagnosis of endometriosis often encounters delays, emphasizing the pressing need for non-invasive screening. This retrospective cross-sectional study aimed to evaluate the utility of the Endometriosis Risk Advisor (EndoRA) mobile application in screening for endometriosis in patients with chronic pelvic pain and/or unexplained infertility. The study consisted of 293 patients who met specific criteria: they were English-speaking individuals with chronic pelvic pain and/or unexplained infertility, owned smartphones, and had no prior diagnosis of endometriosis. The results demonstrated that the EndoRA score exhibited a high sensitivity of 93.1% but a low specificity of 5.9% in detecting endometriosis. The positive predictive value was 94.1%, while the negative predictive value was 5.0%. Although the study had limitations and potential selection bias, its findings suggest that EndoRA can serve as a valuable screening tool for high-risk individuals, enabling them to identify themselves as being at an increased risk for endometriosis. EndoRA’s non-invasive nature, free access, and easy accessibility have the potential to streamline evaluation and treatment processes, thereby empowering individuals to seek timely care and ultimately improving patient outcomes and overall well-being.

Keywords: chronic pelvic pain; endometriosis; free Endometriosis Risk Advisor mobile application; laparoscopic surgery; robotic surgery; unexplained infertility.

48. Cancer Epidemiol Biomarkers Prev. 2023 Aug 1;32(8):1087-1096.

doi: 10.1158/1055-9965.EPI-23-0121.

Folate Intake and Ovarian Cancer Risk among Women with Endometriosis: A Case-Control Study from the Ovarian Cancer Association Consortium

Kate Gersekowski ¹, Torukiri I Ibiebele ¹; Australian Ovarian Cancer Study Group; Jennifer A Doherty ², Holly R Harris ^3 4, Marc T Goodman ^5 6, Kathryn L Terry ^7 8, Anna H Wu ⁹, Elisa V Bandera ¹⁰, Bo Qin ¹⁰, Jue-Sheng Ong ¹¹, Jonathan P Tyrer ¹², Suzanne C Dixon-Suen ^13 14, Francesmary Modugno ^15 16 17, Harvey A Risch ¹⁸, Penelope M Webb ^1 19

Abstract

Background: Although folate intake has not been associated with an increased risk of ovarian cancer overall, studies of other cancer types have suggested that high folate intake may promote carcinogenesis in precancerous lesions. Women with endometriosis (a potential precancerous lesion) have an increased risk of developing ovarian cancer; however, whether high folate intake increases risk in this group is unknown.

Methods: We conducted a pooled analysis of six case-control studies from the Ovarian Cancer Association Consortium to investigate the association between folate intake and risk of ovarian cancer among women with and without self-reported endometriosis. We included 570 cases/558 controls with and 5,171/7,559 without endometriosis. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals for the association between folate intake (dietary, supplemental, and total) and ovarian cancer risk. Finally, we used Mendelian randomization (MR) to evaluate our results using genetic markers as a proxy for folate status.

Results: Higher dietary folate intake was associated with an increased risk of ovarian cancer for women with endometriosis [OR, 1.37 (1.01-1.86)] but not for women without endometriosis. There was no association between supplemental folate intake and ovarian cancer risk for women with or without endometriosis. A similar pattern was seen using MR.

Conclusions: High dietary folate intake may be associated with an increased risk of ovarian cancer among women with endometriosis.

Impact: Women with endometriosis with high folate diets may be at increased risk of ovarian cancer. Further research is needed on the potential cancer-promoting effects of folate in this group.

49. BMJ Open. 2023 Aug 24;13(8):e074259.doi: 10.1136/bmjopen-2023-074259.

Exploring regional healthcare utilisation and quality of care for endometriosis in rural areas in Hesse, Germany: a mixed methods study protocol

Lara Brauer ¹, Max Geraedts ²

Abstract

Introduction: The need of a regional healthcare monitoring in order to evaluate quality and utilisation of health services in smaller scale is internationally and in Germany well established. Little is known about variation in healthcare in rural German areas, especially for women’s health. In particular, endometriosis is highly prevalent and known to be unsatisfactorily treated. Thus, this study aims to investigate utilisation and quality of care, the influence of structural determinants on quality and the patient’s experiences on endometriosis healthcare in rural Hesse.

Methods and analysis: We will use a mixed methods approach to ensure reliable mapping of the care situation for endometriosis patients in seven counties in Central and Eastern Hesse. First, retrospective secondary utilisation data and quality indicators will be used to describe possible regional variation in the treatment of endometriosis in the outpatient and inpatient sector. Second, we compare structural determinants of regions with quality of care. Third, we conduct qualitative, semistructured interviews with endometriosis patients on their perspective and experiences in those chosen rural regions. Data will then be analysed using descriptive statistics, small area variation analyses and multifactorial analyses of variance (ANOVAs). The interview will be interpreted using the experience-focused phenomenological approach.

Ethics and dissemination: The study has been approved by the ethics committee of Philipps-University Marburg. Utilisation data and structural determinants are anonymised and partly aggregated. The interview will use tokens for pseudonymisation to prevent the collected data from being assigned to an individual person. Also, informed consent will be obtained from patients.The results of this study will be reported to the scientific community in peer-reviewed journals and at conferences. A summary of the key findings will be provided to the interviewed patients and the Endometriosis Association Germany.

Keywords: epidemiology; gynaecology; quality in health care.

50. Medicine (Baltimore). 2023 Aug 4;102(31):e34496.doi: 10.1097/MD.0000000000034496.

Efficacy and safety of different subsequent therapies after fertility preserving surgery for endometriosis: A systematic review and network meta-analysis

Yu Zheng ¹, Ruyue Ma ¹, Hong Xu ¹, Lian Wang ², Lei Zhang ¹, Huiqun Mao ¹, Ruiheng Zhao ¹

Abstract

Background: Endometriosis (EMT) is a benign and common estrogen-dependent disease. Hormonal therapy improves pain symptoms in most women with EMT. However, in many cases, laparoscopic fertility preservation surgery is considered a common treatment for EMT. The present study aimed to evaluate the efficacy and safety of dienogest, leuprolide, danazol, gestrinone, mifepristone and levonorgestrel intrauterine system (LNG-IUS) in relieving symptoms and delaying the recurrence of EMT cysts after fertility protection surgery.

Methods: We searched PubMed, the Cochrane Library, Web of Science, EMBase, China National Knowledge Infrastructure, VIP Database, China Biology Medicine disc, WanFang Data databases to collect randomized controlled trials (RCT) related to dienogest, leuprolide, danazol, gestrinone, mifepristone and LNG-IUS as a follow-up treatment after fertility preserving surgery for EMT. After literature screening, data extraction and quality evaluation, effective rate, recurrence rate, pregnancy rate and adverse reaction rate were used as outcome indicators to evaluate the efficacy and safety of drugs. Evidence networks included in the study were drawn and publication bias was assessed. The drugs most likely to be the best postoperative treatment were explored through mixed comparison of different drugs and efficacy ranking.

Result: Effective rate: dienogest, leprerelin, gestrinone and LNG-IUS were better than placebo after EMT fertility preservation surgery; dienogest was superior to mifepristone and danazol. LNG-IUS is superior to danazol. LNG-IUS has the highest potential for improving the effectiveness of EMT symptoms. Recurrence rate: the application of dienogest, leuprolide, gestrinone, mifepristone and LNG-IUS after EMT fertility preservation surgery was lower than that of placebo; dienogest and LNG-IUS were lower than danazol. The recurrence rate of dinorgestrel was the last place with the highest performance. Pregnancy rate: in the cases with fertility requirements, dienogest and,leuprolide were better than placebo after EMT fertility preservation surgery; dienogest was superior to danazol, gestrinone and mifepristone. Leuprolide is superior to danazol and gestrinone. The first rank of dienogest pregnancy rate was the highest. Adverse reaction rate: the application of dienogest, leuprolide, danazol, gestrinone, mifepristone and LNG-IUS after EMT fertility preservation surgery was higher than that of placebo. After placebo, LNG-IUS had the highest adverse reaction rate.

Conclusion: For patients after fertility preserving surgery for EMT, the recurrence rate of dienogest was the last place with highest preference. The first rank of dienogest pregnancy was the highest.

51. Reprod Biol. 2023 Sep;23(3):100788.doi: 10.1016/j.repbio.2023.100788. Epub 2023 Aug 4.

Promising effects of exosomes from menstrual blood-derived mesenchymal stem cells on endometriosis

Faezeh Davoodi Asl ¹, Seyedeh Saeideh Sahraei ², Naser Kalhor ¹, Hoda Fazaeli ¹, Mohsen Sheykhhasan ¹, Sanaz Soleimani Moud ³, Leila Naserpour ², Azar Sheikholeslami ⁴

Abstract

Endometriosis as a non-malignant gynecological disease leads to dysregulation of numerous cellular functions including apoptosis, angiogenesis, migration, proliferation, and inflammation. Accumulating evidence has shed light on the importance of endometrial stem cells within the menstrual blood which are involved in the establishment and progression of endometriotic lesions in a retrograde manner. According to the fact that the therapeutic benefits of mesenchymal stem cells are provided through paracrine functions, we used exosomes from menstrual blood-derived stem cells (MenSCs) for treating endometriotic stem cells to inhibit their lesion formation tendency. Menstrual blood samples from healthy and endometriosis women were collected. Isolated MenSCs by the density-gradient centrifugation method were characterized by flow cytometry. Secreted exosomes were isolated from healthy MenSCs (NE-MenSCs) and used to treat endometriotic cells (E-MenSCs). 72 h after treatment, different mechanisms and pathways including inflammation, proliferation, apoptosis, migration, and angiogenesis were analyzed using Real-Time PCR, ELISA, immunocytochemistry, annexin V/PI, and scratching assay. Exosome treatment significantly reduce the expression level of markers related to inflammation, proliferation, migration, and angiogenesis in E-MenSCs which are aberrantly expressed in endometriosis. Moreover, apoptosis was induced in E-MenSCs after treatment which was evaluated in both gene and protein levels. In this study, we give preliminary evidence for the potential of MenSCs-Exo in ameliorating endometriosis. Regarding our results, we suggest that after relevant clinical trial, MenSCs-derived exosomes can be considered as a better treatment option to improve endometriosis compared to common and conventional treatments and show their potential as a cell-free product in endometriosis repair.

Keywords: Endometriosis; Exosomes; Menstrual blood; Mesenchymal Stem Cells.

52. Int J Gynaecol Obstet. 2023 Aug 9.doi: 10.1002/ijgo.15019. Online ahead of print.

Vascular- and nerve-sparing bowel resection for deep endometriosis: A retrospective single-center study

Manuel Maria Ianieri ¹, Alessandra De Cicco Nardone ¹, Greta Benvenga ², Pierfrancesco Greco ², Pia Clara Pafundi ³, Maria Vittoria Alesi ², Federica Campolo ¹, Claudio Lodoli ⁴, Carlo Abatini ⁴, Miriam Attalla El Halabieh ⁴, Fabio Pacelli ^2 4, Giovanni Scambia ^1 2, Francesco Santullo ⁴

Abstract

Objective: Surgical management of bowel endometriosis is still controversial. Recently, many authors have pointed out the potential benefits of preserving the superior rectal artery, thus ensuring better perfusion of the anastomosis. The aim of this study was to evaluate the complication rate and functional outcomes of a bowel resection technique for deep endometriosis (DE) involving a nerve- and vascular-sparing approach.

Methods: A single-center retrospective study was conducted by enrolling patients who underwent segmental resection of the rectus sigmoid for DE in our department between September 2019 and April 2022. Intraoperative and postoperative complications were recorded for each woman, and functional outcomes relating to the pelvic organs were assessed using validated questionnaires (Knowles-Eccersley-Scott-Symptom [KESS] questionnaire and Gastro-Intestinal Quality of Life Index [GIQLI] for bowel function, Bristol Female Lower Urinary Tract Symptoms [BFLUTS] for urinary function, and Female Sexual Function Index [FSFI] for sexual function). These were evaluated preoperatively and postoperatively after 6 months from surgery.

Results: Sixty-one patients were enrolled. No patients had Clavien-Dindo grade 3 or 4 complications, there were no rectovaginal fistulas or ureteral lesions, and in no cases was it necessary to reoperate. Temporary bladder voiding deficits were reported in 8.2% of patients, which were treated with self-catheterizations, always resolving within 45 days of surgery. Gastrointestinal function evaluated by KESS and GIQLI improved significantly after surgery, whereas sexual function appeared to worsen, although without reaching the level of statistically significant validity.

Conclusion: Our vascular- and nerve-sparing segmental bowel resection technique for DE had a low intraoperative and postoperative complication rate and produced an improvement in gastrointestinal function after surgery.

Keywords: bowel endometriosis; bowel resection; complications; deep endometriosis; functional outcomes; vascular-sparing.

53. Front Immunol. 2023 Aug 22;14:1223828.doi: 10.3389/fimmu.2023.1223828.eCollection 2023.

The landscape of non-coding RNAs in the immunopathogenesis of Endometriosis

Mohammad Abbaszadeh ¹, Mohammadreza Karimi ¹, Samira Rajaei ¹

Abstract

Endometriosis is a complex disorder that is characterized by the abnormal growth of endometrial-like tissue outside the uterus. It is associated with chronic inflammation, severe pelvic pain, infertility, and significantly reduced quality of life. Although the exact mechanism of endometriosis remains unknown, inflammation and altered immunity are considered key factors in the immunopathogenesis of the disorder. Disturbances of immune responses result in reduced clearance of regurgitated endometrial cells, which elicits oxidative stress and progression of inflammation. Proinflammatory mediators could affect immune cells’ recruitment, fate, and function. Reciprocally, the activation of immune cells can promote inflammation. Aberrant expression of non-coding RNA (ncRNA) in patient and animal lesions could be suggestive of their role in endometriosis establishment. The engagement of these RNAs in regulating diverse biological processes, including inflammatory responses and activation of inflammasomes, altered immunity, cell proliferation, migration, invasion, and angiogenesis are widespread and far-reaching. Therefore, ncRNAs can be identified as a determining candidate regulating the inflammatory responses and immune system. This review aims in addition to predict the role of ncRNAs in the immunopathogenesis of endometriosis through regulating inflammation and altered immunity based on previous studies, it presents a comprehensive view of inflammation role in the pathogenesis of endometriosis.

Keywords: CircRNAs; endometriosis; inflammation; lncRNAs; miRNAs; non-coding RNAs; siRNAs.

54. J Clin Med. 2023 Aug 26;12(17):5578.doi: 10.3390/jcm12175578.

Thoracic Endometriosis Syndrome (TES) in Martinique, a French West Indies Island

Moustapha Agossou ¹, Bruno-Gilbert Sanchez ², Paul-Henri Alauzen ¹, Maud Olivier ², Elsa Cécilia-Joseph ³, Ludivine Chevallier ⁴, Mehdi Jean-Laurent ⁴, Aude Aline-Fardin ⁵, Moustapha Dramé ^6 7, Nicolas Venissac ⁸

Abstract

Introduction: Endometriosis is a female disease that affects 5-10% of women of childbearing age, with predominantly pelvic manifestations. It is currently declared as a public health priority in France. Thoracic endometriosis syndrome (TES) is the most common extra-pelvic manifestation.

Objective: The objective of this study was to describe the epidemiological and clinical characteristics, and outcomes of patients with TES in Martinique.

Patients and methods: We performed a descriptive, retrospective study including all patients managed at the University Hospital of Martinique for TES between 1 January 2004 and 31 December 2020.

Results: During the study period, we identified 479 cases of pneumothorax, of which 212 were women (44%). Sixty-three patients (30% of all female pneumothorax) were catamenial pneumothorax (CP) including 49 pneumothoraxes alone (78% of catamenial pneumothorax) and 14 hemopneumothorax (22% of catamenial pneumothorax). There were 71 cases of TES, including 49 pneumothoraxes (69%), 14 hemopneumothoraxes (20%) and 8 hemothorax (11%). The annual incidence of TES was 1.1 cases/100,000 inhabitants. The prevalence of TES was 1.2/1000 women aged from 15 to 45 years and the annual incidence of TES for this group was 6.9/100,000. The annual incidence of CP was 1 case/100,000 inhabitants. The average age at diagnosis was 36 ± 6 years. Eight patients (11%) had no prior diagnosis of pelvic endometriosis (PE). The mean age at pelvic endometriosis diagnosis was 29 ± 6 years. The mean time from symptom onset to diagnosis was 24 ± 50 weeks, and 53 ± 123 days from diagnosis to surgery. Thirty-two patients (47%) had prior abdominopelvic surgery. Seventeen patients (24%) presented other extra-pelvic localizations. When it came to management, 69/71 patients (97%) underwent surgery. Diaphragmatic nodules or perforations were found in 68/69 patients (98.5%). Histological confirmation was obtained in 55/65 patients who underwent resection (84.6%). Forty-four patients (62%) experienced recurrence. The mean time from the initial treatment to recurrence was 20 ± 33 months. The recurrence rate was 16/19 (84.2%) in patients who received medical therapy only, 11/17 (64.7%) in patients treated by surgery alone, and 17/31 (51.8%) in patients treated with surgery and medical therapy (p = 0.03).

Conclusions: We observed a very high incidence of TES in Martinique. The factors associated with this high incidence in this specific geographical area remain to be elucidated. The frequency of recurrence was lower in patients who received both hormone therapy and surgery.

Keywords: black people; catamenial pneumothorax; endometriosis; hemothorax; thoracic endometriosis syndrome.

55. J Assist Reprod Genet. 2023 Aug 9.doi: 10.1007/s10815-023-02903-y. Online ahead of print.

Identification of potential diagnostic biomarkers and therapeutic targets for endometriosis based on bioinformatics and machine learning analysis

Maryam Hosseini ¹, Behnaz Hammami ¹, Mohammad Kazemi ^2 3

Abstract

Purpose: Endometriosis (EMs) is a major gynecological condition in women. Due to the absence of definitive symptoms, its early detection is very challenging; thus, it is crucial to find biomarkers to ease its diagnosis and therapy. Here, we aimed to identify potential diagnostic and therapeutic targets for EMs by constructing a regulatory network and using machine learning approaches.

Methods: Three Gene Expression Omnibus (GEO) datasets were merged, and differentially expressed genes (DEGS) were identified after preprocessing steps. Using the DEGs, a transcription factor (TF)-mRNA-miRNA regulatory network was constructed, and hub genes were detected based on four different algorithms in CytoHubba. The hub genes were used to build a GaussianNB diagnostic model and also in docking analysis that were performed using Discovery Studio and AutoDock Vina software.

Results: A total of 119 DEGs were identified between EMs and non-EMs samples. A regulatory network consisting of 52 mRNAs, 249 miRNAs, and 37 TFs was then constructed. The diagnostic model was introduced using the hub genes selected from the network (GATA6, HMOX1, HS3ST1, NFASC, and PTGIS) that its area under the curve (AUC) was 0.98 and 0.92 in the training and validation cohorts, respectively. Based on docking analysis, two chemical compounds, rofecoxib and retinoic acid, had potential therapeutic effects on EMs.

Conclusion: In conclusion, this study identified potential diagnostic and therapeutic targets for EMs which demand more experimental confirmations.

Keywords: Diagnostic biomarkers; Docking analysis; Endometriosis; Gene expression; Machine learning.

56. J Proteomics. 2023 Aug 30;104995.doi: 10.1016/j.jprot.2023.104995. Online ahead of print.

DIA-based analysis of the menstrual blood proteome identifies association between CXCL5 and IL1RN and endometriosis

Sifan Ji ¹, Yuan Liu ², Li Yan ¹, Yiqin Zhang ¹, Yamei Li ¹, Qian Zhu ¹, Wei Xia ¹, Shunna Ge ³, Jian Zhang ⁴

Abstract

Endometriosis is a gynecological disease related to menstruation that affects nearly 10% of reproductive-age women. However, so far, there are no reliable diagnostic biomarkers for endometriosis, causing a delay in diagnosis of 6.7 ± 6.2 years. Menstrual blood is a non-invasive source of endometrial tissue that can be analyzed for biomarkers of endometriosis. In this study, menstrual blood samples were collected from women with (n = 8) and without (n = 8) endometriosis. Data Independent Acquisition (DIA)-based mass spectrometry and bioinformatic analysis were used to quantify and identify differentially expressed proteins (DEPs) using the thresholds of fold change >1.5 and P value <0.05. A total of 95 DEPs were identified in menstrual blood from women with endometriosis compared to women without endometriosis, of which 64 were up-regulated and 31 were down-regulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to functionally annotate DEPs. Protein-protein interaction (PPI) network analysis was then conducted to identify hub genes and the MCODE plugin placed CXCL1, CXCL3, CXCL5, CCL18, and IL1RN in the most significant cluster network. The expression of the above candidate proteins was confirmed by enzyme-linked immunosorbent assay (ELISA), among which CXCL5 and IL1RN protein expression was increased in patients with endometriosis, indicating that CXCL5 and IL1RN in menstrual blood may be useful biomarkers to diagnose endometriosis from non-invasive samples. SIGNIFICANCE: Endometriosis is a common gynecological disease that causes discomfort in many women. Unfortunately, the diagnosis of endometriosis is frequently delayed due to a lack of reliable non-invasive biomarkers. To our knowledge, this is the first time that DIA-MS was used to characterize the proteome and identify the differentially expressed proteins in menstrual blood from women with endometriosis. The results, as confirmed by ELISA, showed that CXCL5 and IL1RN protein expression is significantly increased in patients with endometriosis, indicating that these proteins can be used as biomarkers for endometriosis. This study contributes to the identification of putative endometriosis biomarkers from non-invasive samples and lays the groundwork for future research into the roles of CXCL5 and IL1RN in the pathogenesis of endometriosis.

Keywords: CXCL5; Data independent acquisition; Endometriosis; IL1RN; Menstrual blood; Proteomics.

57. Trends Mol Med. 2023 Aug 18;S1471-4914(23)00188-0.doi: 10.1016/j.molmed.2023.08.003.Online ahead of print.

Feel so bac: is Fusobacterium the suspect causing endometriosis?

Huan-Tzu Hou ¹, Ting-Chien Lin ², Meng-Hsing Wu ², Shaw-Jenq Tsai ³

Abstract

Recent work by Muraoka and colleagues reports that the Gram-negative anaerobic bacterium Fusobacterium nucleatum is detected in the uterus of 64% of women with endometriosis. Fusobacterium infection causes macrophage infiltration, transforming growth factor-β production, and transgelin upregulation in human and mouse endometria as well as endometriotic lesion development in a mouse model of endometriosis.

Keywords: bacterium infection; endometriosis; macrophage infiltration; transforming growth factor-β; transgelin.

58. Pain Med. 2023 Aug 1;24(8):1005-1007.doi: 10.1093/pm/pnad002.

Central sensitization in patients with deep endometriosis

Lara Quintas-Marquès ¹, Maria-Ángeles Martínez-Zamora ¹, Marta Camacho ¹, Meritxell Gràcia ¹, Mariona Rius ¹, Cristina Ros ¹, Ana Carrión ¹, Francisco Carmona ¹

No abstract available

59. Front Immunol. 2023 Aug 18;14:1130738.doi: 10.3389/fimmu.2023.1130738. eCollection 2023.

Identification of molecular subtypes and immune infiltration in endometriosis: a novel bioinformatics analysis and In vitro validation

Si-Ji Lv ¹, Jia-Ni Sun ¹, Lei Gan ², Jing Sun ¹

Abstract

Introduction: Endometriosis is a worldwide gynacological diseases, affecting in 6-10% of women of reproductive age. The aim of this study was to investigate the gene network and potential signatures of immune infiltration in endometriosis.

Methods: The expression profiles of GSE51981, GSE6364, and GSE7305 were obtained from the Gene Expression Omnibus (GEO) database. Core modules and central genes related to immune characteristics were identified using a weighted gene coexpression network analysis. Bioinformatics analysis was performed to identify central genes in immune infiltration. Protein-protein interaction (PPI) network was used to identify the hub genes. We then constructed subtypes of endometriosis samples and calculated their correlation with hub genes. qRTPCR and Western blotting were used to verify our findings.

Results: We identified 10 candidate hub genes (GZMB, PRF1, KIR2DL1, KIR2DL3, KIR3DL1, KIR2DL4, FGB, IGFBP1, RBP4, and PROK1) that were significantly correlated with immune infiltration. Our study established a detailed immune network and systematically elucidated the molecular mechanism underlying endometriosis from the aspect of immune infiltration.

Discussion: Our study provides comprehensive insights into the immunology involved in endometriosis and might contribute to the development of immunotherapy for endometriosis. Furthermore, our study sheds light on the underlying molecular mechanism of endometriosis and might help improve the diagnosis and treatment of this condition.

Keywords: WGCNA; endometriosis; immune cell subset; immune infiltration; molecular subtype; signature.

60. Int J Gynaecol Obstet. 2023 Aug 28.doi: 10.1002/ijgo.15062. Online ahead of print.

Multicenter evaluation of blood-based biomarkers for the detection of endometriosis and adenomyosis: A prospective non-interventional study

Stefanie Burghaus ¹, Predrag Drazic ², Monika Wölfler ³, Sylvia Mechsner ⁴, Magdalena Zeppernick ^5 6, Ivo Meinhold-Heerlein ^5 6, Michael D Mueller ⁷, Ralf Rothmund ⁸, Paola Vigano ⁹, Christian M Becker ¹⁰, Krina T Zondervan ^10 11, Matthias W Beckmann ¹, Peter A Fasching ¹, Sibylle Berner-Gatz ¹², Felix S Grünewald ¹², Martin Hund ¹³, Peter Kastner ¹², Martin Klammer ¹², Ruediger P Laubender ¹², Heike Wegmeyer ¹², Ursula-Henrike Wienhues-Thelen ¹², Stefan P Renner ^1 14

Abstract

Objective: To evaluate blood-based biomarkers to detect endometriosis and/or adenomyosis across nine European centers (June 2014-April 2018).

Methods: This prospective, non-interventional study assessed the diagnostic accuracy of 54 blood-based biomarker immunoassays in samples from 919 women (aged 18-45 years) with suspicion of endometriosis and/or adenomyosis versus symptomatic controls. Endometriosis was stratified by revised American Society for Reproductive Medicine stage. Symptomatic controls were “pathologic symptomatic controls” or “pathology-free symptomatic controls”. The main outcome measure was receiver operating characteristic-area under the curve (ROC-AUC) and Wilcoxon P values corrected for multiple testing (q values).

Results: CA-125 performed best in “all endometriosis cases” versus “all symptomatic controls” (AUC 0.645, 95% confidence interval [CI] 0.600-0.690, q < 0.001) and increased (P < 0.001) with disease stage. In “all endometriosis cases” versus “pathology-free symptomatic controls”, S100-A12 performed best (AUC 0.692, 95% CI 0.614-0.769, q = 0.001) followed by CA-125 (AUC 0.649, 95% CI 0.569-0.729, q = 0.021). In “adenomyosis only cases” versus “symptomatic controls” or “pathology-free symptomatic controls”, respectively, the top-performing biomarkers were sFRP-4 (AUC 0.615, 95% CI 0.551-0.678, q = 0.045) and S100-A12 (AUC 0.701, 95% CI 0.611-0.792, q = 0.004).

Conclusion: This study concluded that no biomarkers tested could diagnose or rule out endometriosis/adenomyosis with high certainty.

Keywords: CA-125; S100-A12; adenomyosis; blood-based biomarkers; diagnosis; endometriosis; sFRP-4.

61. Mol Cell Endocrinol. 2023 Sep 15;575:112040.doi: 10.1016/j.mce.2023.112040. Epub 2023 Aug 7.

Long non coding RNA, C8orf49, a novel diagnostic and prognostic biomarker, enhances PTEN/FZD4-mediated cell growth and metastasis by sponging miR-1323 in endometriosis

Meichen Yin ¹, Jianzhang Wang ¹, Xue Ying ¹, Zhou Fang ², Xinmei Zhang ³

Abstract

Lack of sensitive biomarkers in the early stages of endometriosis (EMs) results in delayed diagnosis and intervention. Long non-coding RNAs (lncRNAs) have prognostic and diagnostic values in various diseases. However, the prognostic and diagnostic effects of lncRNAs on EMs have rarely been discussed in EMs. In this study, we found that lncRNA C8orf49 was stably overexpressed in EMs tissues/plasma, and its expression greatly influenced dysmenorrhea (p = 2.2605E-9) and the revised American Society for Reproductive Medicine stage (p = 0.040765) of EMs. Multivariate logistic regression results revealed that C8orf49 expression was an independent risk factor for EMs [p = 6.4997E-17, 95% confidence interval (CI) = 0.000559-0.023853]. In primary endometrial stromal cells (ESCs), inhibition of C8orf49 could impede the proliferation and metastasis of ESCs. C8orf49 influenced the expression of PTEN/FZD4 by absorbing miR-1323, thus controlling ESCs activity. The results of a subcutaneous endometriosis animal model showed that the inhibition of C8orf49 restrained endometrial growth. Overall, C8orf49 functioned as an activator of EMs pathogenesis via the C8orf49/miR-1323/PTEN/FZD4 axis.

Keywords: C8orf49; Endometriosis; FZD4; PTEN; lncRNA; miR-1323.

62. SAGE Open Med Case Rep. 2023 Aug 25;11:2050313X231197009.doi: 10.1177/2050313X231197009.eCollection 2023.

Endometriosis in cesarean scars: A rare case report with clinical, imaging, and histopathological insights

Shailendra Katwal ¹, Sarad Katuwal ², Sushmita Bhandari ³

Abstract

Scar endometriosis is a rare form of endometriosis characterized by the presence of endometrial tissue in the abdominal wall following a cesarean delivery. We present a case report of a 38-year-old female with scar endometriosis and provide a comprehensive review of the literature on its clinical management. The patient presented with intermittent pain and swelling at the site of her previous cesarean section scar. Imaging studies revealed a nodular lesion with characteristic features of scar endometriosis. Fine needle aspiration cytology confirmed the diagnosis, ruling out malignancy. The patient underwent wide surgical resection of the mass, resulting in the resolution of symptoms and no recurrence during follow-up. Our case highlights the diagnostic challenge of scar endometriosis, which can mimic carcinoma, and emphasizes the importance of a multidisciplinary approach involving clinical evaluation, imaging, and histopathological examination for accurate diagnosis and optimal management of this condition.

Keywords: Endometriosis; gynaecology; radiology; scar.

63. Arch Gynecol Obstet. 2023 Aug 29.doi: 10.1007/s00404-023-07194-3. Online ahead of print.

Vulvar endometriosis: a rare primary location in adolescence

Ana Catarina Borges ¹, Natacha Sousa ², Cristina Nogueira-Silva ^2 3 4

No abstract available

Keywords: Adolescence; Endometriosis; Extrapelvic endometriosis; Vulvar lesion.

64. J Minim Invasive Gynecol. 2023 Aug 2;S1553-4650(23)00282-0.doi: 10.1016/j.jmig.2023.07.003.Online ahead of print.

Robot-assisted Laparoscopic Excision of Abdominal Wall Endometrioma Utilizing Intraoperative Ultrasound and Transabdominal Needle Placement

Trina Mansour ¹, Scott Young ², Megan N Wasson ³

Abstract

Objective: In patients with endometriosis, extra pelvic endometriosis is estimated to have an incidence of 11% and a rare subset of extra pelvic lesions include abdominal wall endometriosis with an incidence of 0.03% to 3.5% [1,2]. Evaluation for and surgical management of abdominal wall endometriosis are an essential skill set for the advanced gynecologic surgeon. In this video, we demonstrate a surgical technique for robot-assisted laparoscopic excision of abdominal wall endometriosis with intraoperative ultrasound-guided needle placement.

Design: Description and demonstration of surgical technique.

Setting: A patient with previous history of 2 cesarean sections and right lower quadrant cyclic abdominal wall pain; a tertiary care, academic center.

Interventions: Intraoperative ultrasound-guided needle placement to map location and boundaries of the lesion followed by minimally invasive resection of the lesion with the intermittent advancement and withdrawal of needles to confirm clear margins.

Conclusion: Minimally invasive resection of abdominal wall endometriosis using intraoperative ultrasound-guided needle placement is an effective technique to guide surgical dissection and allow for clear surgical margins and successful treatment of this rare condition.

Keywords: Abdominal wall endometriosis; Chronic pelvic pain; Endometriosis; Robotic surgery.

65. BMC Complement Med Ther. 2023 Aug 19;23(1):291.doi: 10.1186/s12906-023-04084-8.

Network pharmacology prediction and experimental verification of Rhubarb-Peach Kernel promoting apoptosis in endometriosis

Zi Liao ^# 1, Ya Lei ^# 1, Li Peng ², Xianyun Fu ³, Wei Wang ⁴, Dan Yang ⁴

Abstract

Background: “Rhubarb-Peach Kernel” herb pair (RP) one of the most frequently used drug pairs, has been used in traditional medicine in China to treat inflammation and diseases associated with pain. Although it is widely used clinically and has a remarkable curative effect, the mechanism of RP treatment for endometriosis (EMs) remains unclear due to its complicated components. The aim of this study was to investigate the anti-endometriosis effect of RP, with emphasis on apoptosis via network pharmacology prediction, molecular docking and experimental verification.

Methods: The related ingredients and targets of RP in treating EMs were screened out using Traditional Chinese Medicine Systems Pharmacology (TCMSP), Tool for Molecular mechanism of Traditional Chinese Medicine (BATMAN-TCM), and GeneCards database. The data of the protein-protein interaction (PPI) network was obtained by the Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) Database. The Metascape database was adopt for Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. After that, the molecular docking of the main active ingredients and apoptosis targets was performed. Finally, the pro-apoptotic effect of RP was verified in hEM15a cells.

Results: A total of 32 RP compounds were collected. Forty-two matching targets were picked out as the correlative targets of RP in treating EMs. Among these, 18 hub targets including P53, CASP3 were recognized by the PPI network. KEGG enrichment analysis discovered that the regulation of apoptosis was one of the potential mechanisms of RP against EMs. Anthraquinone compounds, flavonoids, and triterpenes in RP were identified as crucial active ingredients, involved in the pro-apoptotic effect, which were confirmed subsequently by molecular docking. Additionally, it was verified that RP treatment promoted apoptosis and inhibited the proliferation of EMs cells (assessed by MTT and Flow cytometry). Moreover, the induction of apoptosis in treated EMs cells may be due to the regulation of apoptosis-related protein expression, including P53, BAX, and CASP3.

Conclusions: The results of our study demonstrated that RP may exert its therapeutic effects on EMs through the potential mechanism of promoting apoptosis. Anthraquinones, flavonoids and triterpenoids are the possible pro-apoptotic components in RP.

Keywords: Endometriosis; Molecular docking; Network pharmacology; Rhubarb-Peach kernel; Vitro experiment.

66. PLoS One. 2023 Aug 10;18(8):e0289832.doi: 10.1371/journal.pone.0289832. eCollection 2023.

Risk factors for recurrent endometriosis after conservative surgery in a quaternary care center in southern Thailand

Pongpan Ngernprom ¹, Satit Klangsin ¹, Chitkasaem Suwanrath ¹, Krantarat Peeyananjarassri ¹

Abstract

Objectives: To determine the 2-year recurrence rate of endometriosis after conservative surgery and the risk factors for recurrence.

Methods: This study retrospectively analyzed women with endometriosis who underwent conservative surgery and had at least a 2-year follow-up at a quaternary care hospital in southern Thailand from January 2000 to December 2019. Recurrent endometriosis was defined as either presence of endometrioma with a diameter ≥ 2 cm for more than three consecutive menstrual cycles or relapse of pelvic pain with the same or higher visual analog scale (VAS) score as before surgery. Multivariate logistic regression analysis was used to identify the risk factors for recurrence.

Results: The median (interquartile range [IQR]) age was 34 (29, 38) years in 362 cases and nearly three-quarters (74.2%) were nulliparous. Cyclic pain was the most common clinical presentation (48.9%) and the median (IQR) VAS score of pelvic pain was 6 (5, 9). Ovarian cystectomy was the most common procedure (68.1%). The 2-year recurrent endometriosis rate after conservative surgery was 23.2%, and the overall recurrence rate was 56.4%. The risk factors of recurrence were preoperative moderate to severe pelvic pain (adjusted odds ratio [aOR] 1.93; 95% confidence interval [CI], 1.12-3.34; p = 0.017), adhesiolysis/ablation/ovarian cystectomy without unilateral oophorectomy (aOR 2.71; 95% CI, 1.40-5.23; p = 0.002), and duration of postoperative hormonal treatment < 24 months (aOR 10.58; 95% CI, 5.47-20.47; p < 0.001).

Conclusion: The 2-year recurrence rate after conservative surgery for endometriosis was 23.2%. Preoperative moderate to severe pelvic pain, procedures except unilateral oophorectomy, and postoperative hormonal treatment < 24 months were risk factors for recurrence.

67. Hum Reprod. 2023 Aug 1;38(8):1509-1519.doi: 10.1093/humrep/dead099.

Plasma proteomic profiles of pain subtypes in adolescents and young adults with endometriosis

Naoko Sasamoto ^1 2, Long Ngo ^3 4, Allison F Vitonis ^1 2, Simon T Dillon ^3 5, Christine B Sieberg ^6 7 8, Stacey A Missmer ^2 9 10, Towia A Libermann ^3 5, Kathryn L Terry ^1 2 10

Abstract

Study question: What are the similarities and differences in the systemic proteomic profiles by endometriosis-associated pain subtypes among adolescents and young adults with endometriosis?

Summary answer: Endometriosis-associated pain subtypes exhibited distinct plasma proteomic profiles.

What is known already: Endometriosis patients, especially those diagnosed in adolescents and young adults, are often plagued by various pain symptoms. However, it is not clear what biological processes underlie this heterogeneity.

Study design, size, duration: We conducted a cross-sectional analysis using data and plasma samples from 142 adolescent or young adult participants of the Women’s Health Study: From Adolescence to Adulthood cohort with laparoscopically confirmed endometriosis.

Participants/materials, setting, methods: We measured 1305 plasma protein levels by SomaScan. We classified self-reported endometriosis-associated pain into subtypes of dysmenorrhea, acyclic pelvic pain, life impacting pelvic pain, bladder pain, bowel pain, and widespread pain phenotype. We used logistic regression to calculate the odds ratios and 95% confidence intervals for differentially expressed proteins, adjusting for age, BMI, fasting status, and hormone use at blood draw. Ingenuity Pathway Analysis identified enriched biological pathways.

Main results and the role of chance: Our study population consisted mainly of adolescents and young adults (mean age at blood draw = 18 years), with nearly all (97%) scored as rASRM stage I/II at laparoscopic diagnosis of endometriosis, which is a common clinical presentation of endometriosis diagnosed at a younger age. Pain subtypes exhibited distinct plasma proteomic profiles. Multiple cell movement pathways were downregulated in cases with severe dysmenorrhea and life impacting pelvic pain compared to those without (P < 7.5×10-15). Endometriosis cases with acyclic pelvic pain had upregulation of immune cell adhesion pathways (P < 9.0×10-9), while those with bladder pain had upregulation of immune cell migration (P < 3.7×10-8) and those with bowel pain had downregulation (P < 6.5×10-7) of the immune cell migration pathways compared to those without. Having a wide-spread pain phenotype involved downregulation of multiple immune pathways (P < 8.0×10-10).

Limitations, reasons for caution: Our study was limited by the lack of an independent validation cohort. We were also only able to explore any presence of a pain subtype and could not evaluate multiple combinations by pain subtypes. Further mechanistic studies are warranted to elucidate the differences in pathophysiology by endometriosis-pain subtype.

Wider implications of the findings: The observed variation in plasma protein profiles by pain subtypes suggests different underlying molecular mechanisms, highlighting the need for potential consideration of pain subtypes for effectively treating endometriosis patients presenting with various pain symptoms.

Study funding/competing interest(s): This study was supported by the Department of Defense W81XWH1910318 and the 2017 Boston Center for Endometriosis Trainee Award. Financial support for establishment of and data collection within the A2A cohort were provided by the J. Willard and Alice S. Marriott Foundation. N.S., A.F.V., S.A.M., and K.L.T. have received funding from the Marriott Family Foundation. C.B.S. is funded by an R35 MIRA Award from NIGMS (5R35GM142676). S.A.M. and K.L.T. are supported by NICHD R01HD094842. S.A.M. reports serving as an advisory board member for AbbVie and Roche, Field Chief Editor for Frontiers in Reproductive Health, personal fees from Abbott for roundtable participation; none of these are related to this study. Other authors report no conflict of interest.

Trial registration number: N/A.

Keywords: acyclic pelvic pain; dysmenorrhea; endometriosis; pelvic pain; plasma biomarkers; proteome; proteomics; sub-phenotypes.

68. Asian J Surg. 2023 Aug 15;S1015-9584(23)01091-6.doi: 10.1016/j.asjsur.2023.07.085.Online ahead of print.

An atypical site endometriosis treated by multidisciplinary cooperation

Xue Dong ¹, Miao Huang ², Xin Tan ³, Tao Guo ⁴

Free article

No abstract available

69. Hum Reprod.2023 Aug 1;38(8):1520-1528. doi: 10.1093/humrep/dead120.

First live birth before surgical verification of endometriosis-a nationwide register study of 18 324 women

A Tuominen ^1 2, L Saavalainen ¹, M Niinimäki ^3 4 5, M Gissler ^6 7 8, A But ⁹, P Härkki ¹, O Heikinheimo ¹

Abstract

Study question: Do women with endometriosis have lower first live birth rate before surgical diagnosis than women without verified endometriosis?

Summary answer: Compared to reference women, the incidence of first live birth was lower in women prior to surgical verification of endometriosis irrespective of the type of endometriosis.

What is known already: Endometriosis is associated with pain and reduced fertility. The mechanism of infertility is partly explained by anatomical, endocrinological, and immunological changes. Over the past decades, the treatment of both endometriosis and infertility has evolved. Knowledge of fertility far before surgical diagnosis of endometriosis in large cohorts and of different types of endometriosis has been lacking. The diagnostic delay of endometriosis is long, 6-7 years.

Study design, size, duration: Retrospective population-based cohort study focused on the time period before the surgical verification of endometriosis. All women with surgical verification of endometriosis in 1998-2012 were identified from the Finnish Hospital Discharge Register and the reference cohort from the Central Population Register. Data on deliveries, gynecological care, and sociodemographic factors before the surgical diagnosis were gathered from Finnish national registers maintained by the Finnish Institute for Health and Welfare, the Digital and Population Data Services Agency, and Statistics Finland.

Participants/materials, setting, methods: All women aged 15-49 years at the time of surgical verification of endometriosis (ICD-10: N80.1-N80.9) in Finland during 1998-2012 were identified (n = 21 620). Of them, we excluded women born in 1980-1999 due to the proximity of the surgical diagnosis (n = 3286) and women left without reference (n = 10) for the final endometriosis cohort of 18 324 women. From the final cohort, we selected sub-cohorts of women with isolated diagnosis of ovarian (n = 6384), peritoneal (n = 5789), and deep (n = 1267) endometriosis. Reference women were matched by age and residence and lacked registered clinical or surgical diagnosis of endometriosis (n = 35 793). The follow-up started at the age of 15 years and ended at the first birth, sterilization, bilateral oophorectomy, hysterectomy, or until the surgical diagnosis of endometriosis or corresponding index day-whichever came first. Incidence rate (IR) and the incidence rate ratio (IRR) of first live birth before the surgical verification of endometriosis with corresponding CIs were calculated. In addition, we reported the fertility rate of parous women (the number of all children divided by the number of parous women in the cohort) until the surgical verification of endometriosis. The trends in first births were analysed according to the women’s birth cohort, type of endometriosis, and age.

Main results and the role of chance: Surgical diagnosis of endometriosis was set at the median age of 35.0 years (IQR 30.0-41.4). Altogether 7363 women (40.2%) with endometriosis and 23 718 (66.3%) women without endometriosis delivered a live born infant before the index day (surgery). The IRs of the first live birth per 100 person-years were 2.64 (95% CI 2.58-2.70) in the endometriosis cohort and 5.21 (95% CI 5.15-5.28) in the reference cohort. Between the endometriosis sub-cohorts, the IRs were similar. The IRR of the first live birth was 0.51 (95% CI 0.49-0.52) between the endometriosis and reference cohorts. Fertility rate per parous woman before the surgical diagnosis was 1.93 (SD 1.00) and 2.16 (SD 1.15) in the endometriosis and reference cohorts (P < 0.01). The median age at the first live birth was 25.5 (IQR 22.3-28.9) and 25.5 (IQR 22.3-28.6) years (P = 0.01), respectively. Between the endometriosis sub-cohorts, women in the ovarian sub-cohort were the oldest at the time of surgical diagnosis with the median age of 37.2 years (IQR 31.4-43.3), (P < 0.001). Altogether 44.1% (2814) of the women with ovarian, 39.4% (2282) with peritoneal, and 40.8% (517) with deep endometriosis delivered a live born infant before the diagnosis. IRRs between the endometriosis sub-cohorts did not differ. Fertility rate per parous woman was lowest, 1.88 (SD 0.95), in the ovarian sub-cohort compared to 1.98 (SD 1.07) in the peritoneal and 2.04 (SD 0.96) in deep endometriosis (P < 0.001). Women with ovarian endometriosis were oldest at first live birth compared to women in other sub-cohorts with a median age of 25.8 years (IQR 22.6-29.1) (P < 0.001). Cumulative distributions of first live birth were presented according to age at first live birth and birth cohorts of the participants.

Limitations, reasons for caution: The increasing age at first live birth, increasing practice of clinical diagnostics, conservative treatment of endometriosis, a possible effect of coexisting adenomyosis, and use of artificial reproductive treatments should be considered when assessing the results. In addition, the study is limited due to possible confounding effects of socioeconomic factors, such as level of education. It should be noted that, in this study, we assessed parity only during the years preceding the surgical verification of endometriosis.

Wider implications of the findings: The need for early diagnosis and relevant treatment of endometriosis appears clear given the impairment of fertility prior to its surgical verification.

Study funding/competing interest(s): The study was funded by the Hospital District of Helsinki and Uusimaa and by Finska Läkaresällskapet. The authors report no conflicts of interest. All authors have completed the ICMJE Disclosure form.

Trial registration number: N/A.

Keywords: delivery; endometriosis; fertility; infertility; surgical diagnosis.

70. Clin Nucl Med. 2023 Oct 1;48(10):e472-e473.doi: 10.1097/RLU.0000000000004787.Epub 2023 Aug 3.

18 F-FDG PET/CT to Spare Malignancy in a Rare Case of Lung Endometriosis

Amanda Padilla Bermejo ¹, Laura García Zoghby, Francisco José Pena Pardo, María Del Prado Talavera Rubio, Víctor Manuel Poblete García

Abstract

Lung endometriosis is a rare condition. A 44-year-old woman with known lung endometriosis and radiological follow-up showed progression of bilateral lung affection at control CT, with an enlarged solid nodule with respect to previous control. 18 F-FDG PET/CT was performed to assess that lesion and to guide biopsy. PET images showed the multiple known nodules with pathological tracer uptake.

71. Reprod Sci. 2023 Aug 16.doi: 10.1007/s43032-023-01316-7. Online ahead of print.

Prohibitin2/PHB2, Transcriptionally Regulated by GABPA, Inhibits Cell Growth via PRKN/Parkin-dependent Mitophagy in Endometriosis

Yupeng Deng ¹, Tong Lou ¹, Lili Kong ², Chongdong Liu ³

Abstract

Endometriosis (EMS) is a common benign gynecological disease affecting women of reproductive age. It is characterized by abnormal growth of endometrial tissue outside the uterine cavity, resulting in chronic pelvic pain and infertility. Endometrial physiological and pathological processes are intimately connected to autophagy. Mitophagy is an essential selective mode that protects cells from metabolic stress and hypoxia. Mitochondrial autophagy mediated by prohibitin 2 (PHB2) is dependent on the PRKN/Parkin pathway and is involved in numerous human diseases. Uncertainty remains as to whether mitophagy regulation by PHB2 contributes to the occurrence and progression of EMS. This study aims to investigate the mechanism underlying the role of PHB2 in EMS. This study detected the protein and mRNA expression of PHB2 in ectopic and normal endometrial tissues of ovarian EMS, in addition to ectopic endometrial cell line 12Z and endometrial stromal cell line KC02-44D for gene overexpression or knockdown. Cell function experiments and mitochondrial function experiments were conducted to investigate the role of PHB2 in the endometrium. Bioinformatic analysis and experiments were also used to investigate the upstream transcription factors that influence PHB2 expression. PHB2 was downregulated in ectopic endometrium, and PHB2 overexpression inhibited cell proliferation, migration, and invasion and promoted apoptosis. The upregulation of mitophagy markers, including Parkin and LC3II/I, and the downregulation of autophagy degradation markers P62 and TOMM20 in EMS suggest that PHB2 may contribute to cell proliferation, migration, invasion, and apoptosis via PRKN/Parkin-mediated mitophagy. Analysis and validation of bioinformatics data revealed that the transcription factor GABPA binds directly to the PHB2 promoter region and controls the transcriptional expression of PHB2. This study investigated the role of PHB2 in the onset of EMS. It inhibits EMS growth via PRKN/Parkin-mediated mitophagy, and GABPA controls the transcriptional disorder of PHB2. This study’s findings suggest a novel method for investigating the clinical potential of PHB2 in EMS.

Keywords: Endometriosis; GABPA; Mitophagy; PHB2; PRKN/Parkin.

72. Pharmaceutics. 2023 Aug 9;15(8):2108.doi: 10.3390/pharmaceutics15082108.

iRGD-Targeted Peptide Nanoparticles for Anti-Angiogenic RNAi-Based Therapy of Endometriosis

Anna Egorova ¹, Mariya Petrosyan ², Marianna Maretina ¹, Elena Bazian ², Iuliia Krylova ³, Vladislav Baranov ¹, Anton Kiselev ¹

Abstract

Anti-angiogenic RNAi-based therapy can be considered as a possible strategy for the treatment of endometriosis (EM), which is the most common gynecological disease. Targeted delivery of siRNA therapeutics is a prerequisite for successful treatment without adverse effects. Here we evaluated the RGD1-R6 peptide carrier as a non-viral vehicle for targeted siRNA delivery to endothelial cells in vitro and endometrial implants in vivo. The physicochemical properties of the siRNA complexes, cellular toxicity, and GFP and VEGFA gene silencing efficiency were studied, and anti-angiogenic effects were proved in cellular and animal models. The modification of siRNA complexes with iRGD ligand resulted in a two-fold increase in gene knockdown efficiency and three-fold decrease in endothelial cells’ migration in vitro. Modeling of EM in rats with the autotransplantation of endometrial tissue subcutaneously was carried out. Efficiency of anti-angiogenic EM therapy in vivo by anti-VEGF siRNA/RGD1-R6 complexes was evaluated by the implants’ volume measurement, CD34 immunohistochemical staining, and VEGFA gene expression analysis. We observed a two-fold decrease in endometriotic implants growth and a two-fold decrease in VEGFA gene expression in comparison with saline-treated implants. RNAi-mediated therapeutic effects were comparable with Dienogest treatment efficiency in a rat EM model. Taken together, these findings demonstrate the advantages of RGD1-R6 peptide carrier as a delivery system for RNAi-based therapy of EM.

Keywords: VEGFA; anti-angiogenic therapy; endometriosis; gene therapy; iRGD; integrins; peptide-based carriers; siRNA delivery.

73. Int J Environ Res Public Health. 2023 Aug 26;20(17):6659.doi: 10.3390/ijerph20176659.

Physical Activity in Women with Endometriosis: Less or More Compared with a Healthy Control?

Maike Katja Sachs ¹, Ioannis Dedes ², Samia El-Hadad ¹, Annika Haufe ¹, Dalia Rueff ¹, Alexandra Sabrina Kohl Schwartz ³, Felix Haeberlin ⁴, Stephanie von Orelli ⁵, Markus Eberhard ⁶, Brigitte Leeners ¹

Abstract

Background: Endometriosis, i.e., endometrial-like tissue outside the uterus, is a chronic inflammatory condition affecting physical functioning. However, the specific levels of physical activity (PA) in the context of endometriosis and different disease symptoms remain unclear.

Methods: This multi-center, cross-sectional study compared PA levels and influencing factors in endometriosis patients and non-endometriosis patients. Data were collected through questionnaires. Endometriosis was surgically confirmed. A statistical analysis was performed with appropriate tests.

Results: The study included 460 women with endometriosis and 460 age-matched women without this condition. The two groups did not differ significantly in terms of age, education level, or stable partnership. Women with endometriosis exhibited lower PA levels, practicing fewer hours of sports weekly and climbing fewer stairs daily compared to the control group. These differences remained significant after controlling for confounding factors. Factors such as endometriosis, current dysmenorrhea, and depression were associated with decreased PA.

Conclusions: These findings suggest that women with endometriosis engage in less PA compared to those without this condition. These results highlight the need for interventions to promote increased PA in endometriosis patients and harness the associated health benefits. Further research is warranted to explore the underlying mechanisms and develop tailored exercise therapies for this population.

Keywords: endometriosis; exercise; physical activity.

74. J Ovarian Res. 2023 Aug 16;16(1):166.doi: 10.1186/s13048-023-01245-8.

Impact of dienogest pretreatment on IVF-ET outcomes in patients with endometriosis: a systematic review and meta-analysis

Wenjing Shao ¹, Yuying Li ², Yanli Wang ³

Abstract

Background: To comprehensively evaluate the influence of dienogest (DNG) versus non-DNG pretreatment on in vitro fertilization and embryo transfer (IVF-ET) outcomes for patients with endometriosis.

Methods: PubMed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, and VIP were comprehensively searched for relevant publications until September 14, 2022. Primary outcomes included clinical pregnancy rate and live birth rate. Secondary outcomes included retrieved oocytes, mature oocytes, blastocysts, growing follicles, transferrable embryos, fertilization rate, implantation rate, and miscarriage rate. Subgroup analysis was performed according to different grouping methods and embryo types.

Results: Five studies of 568 females with endometriosis were involved in this systematic review and meta-analysis. DNG treatment exhibited similar effects to non-DNG treatment on either the primary or the secondary outcomes (all P > 0.05). The DNG group had a significantly greater clinical pregnancy rate than the non-hormonal treatment group (pooled relative risk [RR]: 2.055, 95% confidence interval [CI]: 1.275, 3.312, P = 0.003), and exhibited a significantly lower clinical pregnancy rate than the long gonadotropin-releasing hormone agonist (GnRH-a) group (RR: 0.542, 95%CI: 0.321, 0.916, P = 0.022). For patients undergoing fresh embryo transfer, the DNG group displayed a significantly greater clinical pregnancy rate versus the non-DNG group (pooled RR: 1.848, 95%CI: 1.234, 2.767, P = 0.003). Patients receiving DNG had a significantly greater live birth rate than those with non-hormonal treatment (pooled RR: 2.136, 95%CI: 1.223, 3.734, P = 0.008), while having a significantly lower live birth rate than the long GnRH-a group (RR: 0.441, 95%CI: 0.214, 0.907, P = 0.026). While using fresh embryos, patients with DNG treatment had an increased live birth rate, compared with those without DNG treatment (pooled RR: 2.132, 95%CI: 1.090, 4.169, P = 0.027).

Conclusion: DNG treatment may have similar effects to non-DNG treatment on IVF-ET outcomes. The clinical pregnancy rate and live birth rate after DNG treatment may be significantly higher than those after non-hormonal treatment. More evidence is warranted to corroborate these findings.

Keywords: Dienogest; Endometriosis; IVF-ET; Meta-analysis.

75. Hum Reprod. 2023 Aug 1;38(8):1499-1508.doi: 10.1093/humrep/dead119.

Severe pelvic pain is associated with sexual abuse experienced during childhood and/or adolescence irrespective of the presence of endometriosis

M Bourdon ^1 2 3, V Antoine ¹, U Combes ¹, L Maitrot-Mantelet ¹, L Marcellin ^1 2 3, C Maignien ¹, C Chapron, P Santulli

Abstract

Study question: Is endometriosis associated with childhood and/or adolescent sexual abuse?

Summary answer: Endometriosis is not associated with a history of sexual abuse, unlike the presence of severe pelvic pain.

What is known already: Several studies have highlighted a link between pelvic pain and sexual abuse during childhood/adolescence. Moreover, an inflammatory state has been described in patients with a history of childhood maltreatment. Given that inflammation and pelvic pain are two entities often encountered with endometriosis, several teams have investigated whether endometriosis is associated with abuse during childhood/adolescence. However, the results are conflicting, and the link between sexual abuse and the presence of endometriosis and/or pain is hard to disentangle.

Study design, size, duration: A survey nested in a cohort study of women surgically explored for benign gynecological indications at our institution between January 2013 and January 2017. For each patient, a standardized questionnaire was completed during a face-to-face interview with the surgeon in the month preceding the surgery. Pelvic pain symptoms (dysmenorrhea, deep dyspareunia, non-cyclic chronic pelvic pain, and gastrointestinal or lower urinary tract symptoms) and their intensities were assessed with a 10 cm visual analog scale (VAS). Pain was considered to be severe when the VAS score was ≥7.

Participants/materials, setting, methods: A 52-question survey was sent in September of 2017 to evaluate abuses, especially sexual abuse during childhood and/or adolescence, and the psychological state during childhood and adolescence. The survey was structured to cover the following sections: (i) abuses and other life events during childhood and adolescence; (ii) puberty and body changes; (iii) onset of sexuality; and (iv) family relationships during childhood and adolescence. The patients were divided into groups according to whether or not they exhibited histologically proven endometriosis. Statistical analyses were conducted using univariate and multivariate logistic regression models.

Main results and the role of chance: Two hundred and seventy-one patients answered all the questions of the survey: 168 with (endometriosis group) and 103 without endometriosis (control group). The mean ± SD overall population age was 32.2 ± 5.1 years. There were 136 (80.9%) and 48 (46.6%) women who experienced at least one severe pelvic pain symptom in the endometriosis and the control groups, respectively (P < 0.001). No differences were found between the two study groups regarding the following characteristics: (i) a history of sexual, physical, or emotional abuse; (ii) a history of abandonment or bereavement; (iii) the psychological state regarding puberty; and (iv) the family relationships. After multivariable analysis, we found no significant association between endometriosis and a history of sexual abuse during childhood and/or adolescence (P = 0.550). However, the presence of at least one severe pelvic pain symptom was independently associated with a history of sexual abuse (odds ratio = 3.6, 95% CI (1.2-10.4)).

Limitations, reasons for caution: Evaluation of the psychological state during childhood and/or adolescence can be subject to recall bias. In addition, selection bias is also a possibility given that some of the patients surveyed did not return the questionnaire.

Wider implications of the findings: Severe gynecological painful symptoms in women with or without histologically proven endometriosis may be linked to sexual abuse experienced during childhood and/or adolescence. Patient questioning about painful symptoms and abuses is important to provide comprehensive care to the patients, from a psychological to a somatic point of view.

Study funding/competing interest(s): No funding or competing interests.

Trial registration number: N/A.

Keywords: adolescence; childhood; endometriosis; gynecological surgery; pelvic pain; sexual abuse.

76. Medicine (Baltimore). 2023 Aug 25;102(34):e34845.doi: 10.1097/MD.0000000000034845.

Research into the mechanism of intervention of Wenjing decoction in endometriosis based on network pharmacology and molecular docking technology

Linhui Huang ¹, Wei Yang ², Minxue Su ³

Abstract

Background: Endometriosis (EMs) is a frequent disease in women and is the principal cause of infertility and dysmenorrhea. Due to its high recurrence rate and serious complications, more research on EMs is needed. We used network pharmacology and molecular docking technology to predict the key active components, targets, and signaling pathways of Wen Jing decoction (WJD) in the treatment of EMs.

Methods: The components and targets of WJD were collected and identified using the Traditional Chinese Medicine Systems Pharmacology Database and BATMAN-TCM. The EMs targets were obtained from GeneCards, OMIM, TTD, Kyoto encyclopedia of genes and genomes (KEGG) and GAD Databases; the Venny diagram was used to analyze the overlap between the targets of WJD and EMs; use Cytoscape 3.8.2 software to build a drug active ingredient-target protein interaction network; after downloading the data from the String online database, Cytoscape 3.8.2 software was used to draw the intersection target protein-protein interaction network diagram. Finally, microbiotic information mapping was used to analyze gene ontology function enrichment and KEGG pathway enrichment. Molecular docking was used to predict the binding affinity of the components of WJD to the targets of EMs.

Results: Seventy-eight active ingredients of WJD were screened, corresponding to 108 targets, 2626 EMs-related targets and 124 intersection targets. The results of gene ontology functional enrichment analysis showed that WJD could affect 709 biological processes, 131 molecular functions and 54 cell composition. The enrichment analysis of KEGG pathway yielded 185 pathways. The treatment of EMs by WJD has the characteristics of multiple targets and multiple pathways. Molecular docking with the AutoDock Vina platform found that 5 active ingredients of WJD were successfully docked with 6 common targets.

Conclusion: Based on network pharmacology and molecular docking, WJD was found to act on EMs through multi-targets and related signaling pathways.

77. J Robot Surg. 2023 Aug 22.doi: 10.1007/s11701-023-01691-y. Online ahead of print.

Changes in hospital consumption of opioid and non-opioid analgesics after colorectal endometriosis surgery

Adrien Crestani ¹, Amine Bibaoune ², Marjolaine Le Gac ³, Yohann Dabi ³, Kamila Kolanska ^3 4, Clément Ferrier ³, Sofiane Bendifallah ³, Cyril Touboul ³, Emile Darai ^3 2

Abstract

The aim of this study was to analyze postoperative consumption of analgesics during hospitalization following colorectal surgery for endometriosis. We conducted a retrospective study at Tenon University Hospital, Paris, France from February 2019 to December 2021. One hundred sixty-two patients underwent colorectal surgery: eighty-nine (55%) by robotic and seventy-three (45%) by conventional laparoscopy. The type of procedure had an impact on acetaminophen and nefopam consumed per day: consumption for colorectal shaving, discoid resection, and segmental resection was, respectively, 2(0.5), 2.1(0.6), 2.4(0.6) g/day (p = 10-3), and 25(7), 30(14), 31(11) mg/day (p = 0.03). The total amount of tramadol consumed was greater following robotic surgery compared with conventional laparoscopy (322(222) mg vs 242(292) mg, p = 0.04). We observed a switch in analgesic consumption over the years: tramadol was used by 70% of patients in 2019 but only by 7.1% in 2021 (p < 10-3); conversely, ketoprofen was not used in 2019, but was consumed by 57% of patients in 2021 (p < 10-3). A history of abdominal surgery (OR = 0.37 (0.16-0.78, p = 0.011) and having surgery in 2020 rather than in 2019 (OR = 0.10 (0.04-0.24, p < 10^-3)) and in 2021 than in 2019 (OR = 0.08 (0.03-0.20, p < 10^-3)) were the only variables independently associated with the risk of opioid use. We found that neither clinical characteristics nor intraoperative findings had an impact on opioid consumption in this setting, and that it was possible to rapidly modify in-hospital analgesic consumption modalities by significantly reducing opioid consumption in favor of NSAIDS or nefopam.

Keywords: Analgesic consumption; Colorectal surgery; Endometriosis; Opioids; Post-operative pain.

78. Int J Surg Case Rep. 2023 Aug 21;110:108703.doi: 10.1016/j.ijscr.2023.108703.Online ahead of print.

A Diagnostic Conundrum – Small bowel obstruction from undiagnosed endometriosis following uterine perforation

Erina Horikawa ¹, Carmen R Abbe ², Brian E Staley ³, Luay Ailabouni ⁴

Abstract

Introduction: Uterine perforation is a rare but recognized complication from dilation and curettage, a common therapeutic procedure for obstetric complications and emergencies. Limited cases exist on endometriosis occurring following rupture. Additionally, there are no reported cases of uterine rupture secondary to dilation and curettage leading to new onset endometriosis first presenting as a small bowel obstruction (SBO).

Presentation of case: A 42-year-old female with recurrent small bowel obstruction was found to have a stricture caused by endometriosis via diagnostic laparoscopy and pathology. Patient had a dilation and curettage for retained products of conception 11 years prior, complicated by uterine perforation. This patient never had a diagnosis of endometriosis prior to her SBO. Patient made an uneventful recovery after small bowel resection with resolving of SBO symptoms.

Discussion: Our case highlights the possibility of endometriosis due to previous uterine rupture as a cause for SBO in an otherwise healthy, female patient of reproductive age. There is a continued need for appropriate documentation of surgical complications on patient charts as well as considering postoperative complications when other etiologies of SBO are less likely.

Conclusion: Endometriosis should be considered as a differential in reproductive aged women presenting with a small bowel obstruction, with an increased index of suspicion if the patient has had previous obstetric surgical procedures.

Keywords: Endometriosis; Small bowel obstruction; Uterine perforation.

79. J Surg Case Rep. 2023 Aug 4;2023(8):rjad229.doi: 10.1093/jscr/rjad229.eCollection 2023 Aug.

Surgical approach to coexistent inguinal endometriosis and inguinal hernial defect: a case report

Nouf Almagushi ¹, Leen Almadhi ¹, Nadia Aljomah ², Ibrahim Albabtain ³

Abstract

The presence of ectopic endometrial and myometrial tissue is referred to as endometriosis. The majority of cases of inguinal endometriosis are linked to prior uterine surgery. We present a 39-year-old female presented to the general surgery clinic in June 2013 with mild right inguinal pain and swelling. Enhanced computed tomography scan of the abdominal and pelvis revealed an elongated cystic mass in the right groin region. Diagnostic laparoscopy was performed and the uterus, both ovaries, and pouch of Douglas were examined. Two endometrial deposits were detected: on in the superoposteriar part of the uterus and another below the base of the right fallopian tube. In addition to the right inguinal hernia, a cystic lesion was noted on the surface of the round ligament. The entire round ligament, including the canal of Nuck, and cyst were dissected and excised completely. The right inguinal hernia was repaired.

Keywords: cyst; endometriosis; inguinal hernia.

80. J Clin Med. 2023 Aug 21;12(16):5430.doi: 10.3390/jcm12165430.

Lipid Profile after Pharmacologic Discontinuation and Restoration of Menstruation in Women with Endometriosis: A 12-Month Observational Prospective Study

Athanasios D Anastasilakis ¹, Stergios A Polyzos ², Panagiotis A Vorkas ^3 4 5, Athina Gkiomisi ⁶, Maria P Yavropoulou ⁷, Martina Rauner ⁸, Panagiotis Nikolakopoulos ⁴, Stergios Papachatzopoulos ⁶, Polyzois Makras ⁹, Spyridon Gerou ¹⁰, Lorenz C Hofbauer ⁸, Andrea Palermo ¹¹, Elena Tsourdi ⁸

Abstract

The lipid profile is affected following menstrual cessation (MC). We aimed to evaluate the effects of goserelin-induced MC and subsequent menstrual restoration (MR) on lipid metabolism. Premenopausal women with histologically verified endometriosis (n = 15) received goserelin monthly for 6 months (6mο), resulting in MC, and were followed-up for another 6 months after MR (12mο). Serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein a ([Lp(a)] and lipidomics were measured at baseline, 6mo and 12mo. Shotgun quantitative deep lipidomics were determined at the level of lipid class category, subclass, species, and fatty acyl chain lengths and degree of saturation. TC (p = 0.006), LDL-C (p = 0.028), HDL-C (p= 0.002), and apoA1 (p = 0.013) increased during goserelin-induced MC and remained practically unchanged during MR. TG, apoB, and Lp(a) did not change. From the deep lipidomics analysis, multivariate statistical analysis demonstrated profound alterations in lipid species with MC, whereas no statistically valid models could be fitted for the restoration period. In conclusion, GnRH-analog-induced MC alters lipid profiles at various levels, from standard blood lipid and lipoprotein profiles to several lipid species as detected by lipidomics analysis. Changes largely persist for at least 6 m after MR.

Keywords: GnRH analog; endometriosis; goserelin; lipid; lipidomics; menstrual cessation.

81. Microb Pathog. 2023 Aug 15;183:106309.doi: 10.1016/j.micpath.2023.106309.Online ahead of print.

Translocation of vaginal and cervical low-abundance non-Lactobacillus bacteria notably associate with endometriosis: A pilot study

Qing Yang ¹, Yinan Wang ¹, Han Cai ¹, Qian Zhou ², Liping Zeng ¹, Shuaicheng Li ², Hui Du ¹, Weixia Wei ¹, Wei Zhang ¹, Wenkui Dai ³, Ruifang Wu ⁴

Abstract

The etiology remains to be understood for endometriosis (EMS) which affected health negatively for 10% of reproductive-age women globally. Emerging studies found the associations of EMS with genital microbiota dysbiosis. However, the role of vaginal and cervical microbiota is not fully understood for Chinese women. This study recruited forty Chinese women (21 healthy women and 19 EMS patients) to analyze vaginal and cervical microbiota using 16S rRNA amplicon sequencing method. For both sites, there were no significant differences for distribution of microbial samples between control and EMS group, which was concordant with dominated Lactobacillus in both groups. In contrast, we observed accumulation of several low-abundance genera in vaginal and cervical microbiota of EMS patients, such as Fannyhessea, Prevotella, Streptococcus, Bifidobacterium, Veillonella, Megasphaera and Sneathia. Random forest analysis found that translocation of these genera had the significant importance in differentiating EMS patients from controls. In addition, cervix/vagina ratio of these genera also associated with EMS severity. And these genera had notable associations with ascending infection-related functional pathways, including flagellar assembly, bacterial motility proteins, bacterial toxins and epithelial cell signaling in Helicobacter pylori infection. These findings suggest that translocation of specific genera between vaginal and cervical sites play a role in EMS.

Keywords: Cervical microbiota; Endometriosis; Low-abundance genus; Translocation; Vaginal microbiota.

82. Appl Immunohistochem Mol Morphol. 2023 Aug 30.doi: 10.1097/PAI.0000000000001148.Online ahead of print.

Hypoxia-inducible Factor-1α and mTOR as a Potential Therapeutic Target in Endometriosis: An Immunohistochemical Study

Dalia M Badary ¹, Hisham A Abou-Taleb ¹, Maha Ibrahim ²

Abstract

Background and study aim: We aim to study the immunohistochemical expression of both hypoxia-inducible factor-1α (HIF-1α) and mammalian target of rapamycin (mTOR) in endometriosis to provide new evidence for a targeted endometriosis therapy.

Patients and methods: This study comprised 106 endometriotic cases diagnosed clinically and histopathologically. The immunohistochemical method was done to determine the expression of HIF-1α and mTOR.

Results: Endometriotic glands showed significant cytoplasmic expression of both markers in patients with poor ovulation, severe endometriosis, and infertile for >2 years (P<0.001). Also, patients with intense and worst pain show significant immunohistochemical expression of both markers (P<0.001). There is a significant correlation between mTOR and HIF-1α expression in endometriotic tissue samples as P<0.001.

Conclusions: Our data suggest that both mTOR and its downstream target HIF-1α transcription factor are both disrupted in patients with endometriosis, which is consistent with aberrant activation of these pathways and their possible contribution to the pathogenesis of endometriosis. These results could offer a promising novel opportunity to be blocked therapeutically. As new management options need to be refined in particular in severe cases and infertile patients with endometriosis, therefore future studies are warranted to investigate treating endometriosis with mTOR inhibitors; the latter are already in clinical trials in phase III and IV, treating solid tumors as well as non-neoplastic disorders.

83. Reprod Sci. 2023 Aug 22.doi: 10.1007/s43032-023-01324-7. Online ahead of print.

Evaluation of Bowel Function of Women with Colorectal Endometriosis: a Cross-Sectional Study

Nara Abe Cairo Villa ¹, Cristina Laguna Benetti-Pinto ¹, Daniela Angerame Yela ²

Abstract

The objective was to evaluate bowel function in women with colorectal endometriosis according to treatment type. Cross-sectional study, carried out with 141 women with endometriosis, followed by the University of Campinas from May 2020 to April 2021. Women were divided into 3 groups according to the kind of treatment: 16 women with conservative surgery, 35 women with radical surgery treatment, and 90 women with clinical treatment. The clinical and sociodemographic characteristics of these women were evaluated. To access bowel outcome, we used the following questionnaires: the Bristol Stool Scale, the Bowel Function in the Community, the Gastrointestinal Quality of Life Index (GIQLI), and the Pelvic Floor Distress Inventory (PFDI-20). The mean treatment time was 32.24 ± 29.37 months. The women of the three groups had similar gastrointestinal quality of life index scores (p = 0.27) and pelvic floor distress inventory scores (p = 0.23). Women in the radical surgery group had a higher frequency of evacuatory effort and change in posture to evacuate (p = 0.01 and 0.009, respectively) than did those in the other groups. Women with constipation had worse quality of life and more pain than those without constipation. In conclusion, women with endometriosis treated with radical surgery (segmental resection) had a higher frequency of constipation. In addition, women with endometriosis and constipation had a worse quality of life and higher pain scores compared to those without constipation.

Keywords: Bowel outcome; Constipation; Endometriosis; Quality of life.

84. Reprod Sci. 2023 Aug 2.doi: 10.1007/s43032-023-01315-8. Online ahead of print.

Increased Expression of TGF-β1 Contributes to the Downregulation of Progesterone Receptor Expression in the Eutopic Endometrium of Infertile Women with Minimal/Mild Endometriosis

Lukanxuan Wu, Xin Huang, Ruiying Wang, Yujing Li, Huili Zhu ^1 2, Yunwei Ouyang ^1 2, Wei Huang 

Abstract

Endometriosis is a hormone-dependent disease associated with impaired immunoregulation. In our recent study, we have characterized the trascriptomic transformation of eutopic endometrium from patients with minimal/mild endometriosis and controls across the menstrual cycle. However, the regulatory mechanism of altered immune microenvironment in eutopic endometrial stromal cells (ESCs) remains unclear. Here, we want to explore the regulation of immune cell to progesterone resistance and endometrial receptivity in the eutopic ESCs by cytokine (TGF-β1), and to understand the effect of TGF-β1 on the decidualization of the eutopic ESCs. Primary culture of eutopic ESCs was performed to explore the effects of TGF-β1 on the expression of Smad and progesterone receptor (PR) and the in vitro decidualization. Additionally, co-immunoprecipitation (Co-IP) was used to explore the direct interaction between Smad and PR. We found an attenuate expression of PRB protein (p=0.026) after using TGF-β1 in eutopic ESCs, although the difference of PRA before and after treatment was not significant (p=0.678). Similarly, the results of qRT-PCR showed that the mRNA level of PR (p<0.001), PRB (p=0.003) and HOXA10 (p<0.001) decreased significantly after TGF-β1 treatment, but that increased (p<0.023, for all) after SB431542 treatment in the eutopic ESCs. Moreover, TGF-β1 has a negative effect on the in vitro decidualization of eutopic ESCs (p=0.003). And the group with treatment of both TGF-β1 and SB435142 in eutopic ESCs showed significant decidual-like changes with increased prolactin level (p=0.01). We did not observe any physical interaction between the PR and p-Smad3/Smad3 proteins by using Co-IP. By activating TGF-β/Smad signaling in eutopic ESCs, elevated TGF-β1 from CD45+ immune cells could attenuate expression of PR, and further decrease endometrial receptivity.

Keywords: Endometriosis; Eutopic endometrium; Immune cells; Progesterone receptor; TGF-β1.

85. Life Sci. 2023 Aug 24;331:122037.doi: 10.1016/j.lfs.2023.122037. Online ahead of print.

Parthenolide repressed endometriosis induced surgically in rats: Role of PTEN/PI3Kinase/AKT/GSK-3β/β-catenin signaling in inhibition of epithelial mesenchymal transition

Soad L Kabil ¹, Hayam E Rashed ², Noura Mostafa Mohamed ³, Nisreen E Elwany ⁴

Abstract

Aim: PI3K/AKT/GSK-3β/β-catenin signaling pathway is a triggering factor for epithelial to mesenchymal transition (EMT) which plays a pivotal role in the pathogenesis of endometriosis. Parthenolide is a sesquiterpene lactone extract that has anti-inflammatory, analgesic and anticancer properties. Hence, we investigated the effect of parthenolide against EMT in the endometrial tissue implants and immortalized epithelial endometriotic cell lines 12Z.

Main methods: Twenty- four female Rats with surgically induced endometriosis were treated with parthenolide (2, 4 mg/kg), for 4 weeks. Endometriotic cell line 12Z was used to identify the effect of parthenolide on the wound healing, cellular migration and invasion properties of endometriotic cells.

Key findings: Parthenolide decreased the endometriotic implant tissue expression of total PI3K, PI3K-p85, p-AKT, p/total AKT, p-GSK-3β, P/total GSK-3β, and nβ-catenin, as well as increased E-cadherin and decreased vimentin mRNA expression. Parthenolide upregulated PTEN immunoreactivity as well as the endometriotic tissue caspase-3, caspase-9, BAX levels while reducing Bcl2 level. Additionally, parthenolide decreased endometriotic tissue implants surface area and histopathological score of the epithelial growth.

Significance: Our findings showed that parthenolide in a dose dependent manner inhibited PI3K/AKT/GSK-3β/nβ-catenin cascade via enhancement of PTEN with subsequent inhibition of EMT evidenced by elevation of the epithelial marker, E-cadherin and reduction of mesenchymal marker, vimentin, of the endometriotic implants in addition to reversal of invasion and migration properties of epithelial endometriotic cell lines. These findings provide a valuable therapeutic approach for treatment of endometriosis.

Keywords: Endometriosis; Epithelial to mesenchymal transition; Parthenolide.

86. Case Rep Surg.2023 Aug 22;2023:5493232. doi: 10.1155/2023/5493232.eCollection 2023.

Robotic-Assisted Thoracic Surgery Approach to Thoracic Endometriosis Syndrome with Unilateral Diaphragmatic Palsy

Abiah Jacob ¹, Adeyemi Coker ^2 3, Steven Aleksandar Stamenkovic ¹

Abstract

Endometriosis is characterized by endometrial-like glands and stroma outside the uterine cavity, affecting women of reproductive age. Thoracic endometriosis syndrome (TES) is an entity producing a range of clinical and radiological manifestations, including catamenial pneumothorax, haemothorax, haemoptysis, and pulmonary nodules within the thoracic cavity or on the diaphragm. TES symptoms are nonspecific, warranting a high degree of clinical suspicion. Management includes hormone replacement therapy, surgical management, or a combination of both. We present a case of a 37-year-old woman who presented with TES and unilateral diaphragmatic palsy, managed with robotic-assisted thoracoscopic surgery and hormone replacement.

87. ACG Case Rep J. 2023 Aug 11;10(8):e01120.doi: 10.14309/crj.0000000000001120.eCollection 2023 Aug.

A Variation on a Rare Diagnosis: Rectosigmoid Endometriosis

Samuel Engman ¹, Frances Puello ¹, David A Labowitz ¹, Thanh Thien Ha Lan ¹

No abstract available