Research progress in endometriosis-associated ovarian cancer.

Endometriosis-associated ovarian cancer (EAOC) is a unique subtype of ovarian malignant tumor originating from endometriosis (EMS) malignant transformation, which has gradually become one of the hot topics in clinical and basic research in recent years. According to clinicopathological and epidemiological findings, precancerous lesions of ovarian clear cell carcinoma (OCCC) and ovarian endometrioid carcinoma (OEC) are considered as EMS. Given the large number of patients with endometriosis and its long time window for malignant transformation, sufficient attention should be paid to EAOC. At present, the pathogenesis of EAOC has not been clarified, no reliable biomarkers have been found in the diagnosis, and there is still a lack of basis and targets for stratified management and precise treatment in the treatment. At the same time, due to the long medical history of patients, the fast growth rate of cancer cells, and the possibility of eliminating the earliest endometriosis-associated ovarian cancer, it is difficult to find the corresponding histological evidence. As a result, few patients are finally diagnosed with EAOC, which increases the difficulty of in-depth study of EAOC. This article reviews the epidemiology, pathogenesis, risk factors, clinical diagnosis, new treatment strategies and prognosis of endometriosis-associated ovarian cancer, and prospects the future direction of basic research and clinical transformation, in order to achieve stratified management and personalized treatment of ovarian cancer patients.

Müllerian anomalies and endometriosis as potential explanatory models for the retrograde menstruation/implantation and the embryonic remnants/celomic metaplasia pathogenic theories: a systematic review and meta-analysis.

STUDY QUESTION: Does endometriosis prevalence differ in patients with obstructive Müllerian anomalies (OMA) versus those with nonobstructive Müllerian anomalies (NOMA), and in patients with NOMA versus those without Müllerian anomalies? SUMMARY ANSWER: The quantitative synthesis of published data demonstrates a substantially increased prevalence of endometriosis in patients with OMA compared with those with NOMA, and a similar prevalence in patients with NOMA and those without Müllerian anomalies. WHAT IS KNOWN ALREADY: The pathogenesis of endometriosis has not been definitively clarified yet. A higher prevalence of endometriosis in patients with OMA than in those with NOMA would support the retrograde menstruation (RM)/implantation theory, whereas a higher prevalence of endometriosis in the NOMA group than in the group without Müllerian anomalies would support the embryonic remnants/celomic metaplasia hypothesis. STUDY DESIGN, SIZE, DURATION: This systematic review with meta-analysis was restricted to full-length, English-language articles published in peer-reviewed journals between 1980 and 2023. The PubMed and EMBASE databases were searched using the keyword 'endometriosis' in combination with 'Müllerian anomalies', 'obstructive Müllerian anomalies', 'female genital malformations', 'retrograde menstruation', 'infertility', 'pelvic pain', and 'classification'. References from relevant publications were screened, and PubMed's 'similar articles' and 'cited by' functions were used. PARTICIPANTS/MATERIALS, SETTING, METHODS: Studies were selected if they reported the prevalence of surgically confirmed endometriosis in either individuals with OMA compared to those with NOMA, or patients with NOMA compared to those without Müllerian anomalies. Cohort and case-control studies and case series were deemed eligible for inclusion. Noncomparative studies, studies not reporting both the number of individuals with endometriosis and the total number of those with Müllerian anomalies or with other gynecological conditions, those including exclusively data on patients with absent or uncertain menstrual function (e.g. complete Müllerian agenesis category), or with imperforate hymen were excluded. Two reviewers independently abstracted data. The risk of bias was assessed with the Risk of Bias In Non-randomized Studies of Exposures tool. The overall certainty of the evidence was graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. MAIN RESULTS AND THE ROLE OF CHANCE: Seven retrospective studies were included. The overall mean estimate of endometriosis prevalence was 47% (95% CI, 36-58%) in patients with OMA, and 19% (95% CI, 15-24%) in patients with NOMA, with a common odds ratio (OR) of 4.72 (95% CI, 2.54-8.77). The overall mean estimate of endometriosis prevalence in patients with NOMA was 23% (95% CI, 20-27%), and that in patients without Müllerian anomalies was 21% (95% CI, 20-22%), with a common OR of 0.95 (95% CI, 0.57-1.58). The overall certainty of the evidence according to GRADE guidelines was judged as low for both comparisons. LIMITATIONS, REASON FOR CAUTION: Some NOMA subtypes may create a partial obstacle to menstrual efflux and/or generate dysfunctional myometrial contractions that favor transtubal reflux, thus increasing the risk of endometriosis and limiting the difference between OMA and NOMA. As infertility and pelvic pain are strongly associated with endometriosis, women with these symptoms are inappropriate controls. Confounding by indication could explain the lack of difference in endometriosis prevalence between patients with NOMA and those without Müllerian anomalies. WIDER IMPLICATIONS OF THE FINDINGS: The results of this meta-analysis support the validity of the RM theory but do not definitively rule out alternative hypotheses. Thus, RM may be considered the initiator for the development of endometriotic lesions, while not excluding the contribution of both inheritable and tissue-specific genetic and epigenetic modifications as disease-promoting factors. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this review. P.Ve. is a member of the Editorial Board of Human Reproduction Open, the Journal of Obstetrics and Gynaecology Canada, and the International Editorial Board of Acta Obstetricia et Gynecologica Scandinavica; has received royalties from Wolters Kluwer for chapters on endometriosis management in the clinical decision support resource UpToDate; and maintains both a public and private gynecological practice. E.S. discloses payments from Ferring for research grants and honoraria from Merck-Serono for lectures. All other authors declare they have no conflict of interest. REGISTRATION NUMBER: N/A.

Immune Dysregulation in Endometriomas: Implications for Inflammation.

The most common manifestation of endometriosis, a condition characterized by the presence of endometrial-like tissue outside of the uterus, is the endometrioma, a cystic ovarian lesion. It is a commonly occurring condition associated with chronic pelvic pain exacerbated prior to and during menstruation, as well as infertility. The exact pathomechanisms of the endometrioma are still not fully understood. Emerging evidence suggests a pivotal role of immune dysregulation in the pathogenesis of endometriomas, primarily influencing both local and systemic inflammatory processes. Among the factors implicated in the creation of the inflammatory milieu associated with endometriomas, alterations in both serum and local levels of several cytokines stand out, including IL-6, IL-8, and IL-1ß, along with abnormalities in the innate immune system. While numerous signaling pathways have been suggested to play a role in the inflammatory process linked to endometriomas, only NF-κB has been conclusively demonstrated to be involved. Additionally, increased oxidative stress, both resulting from and contributing to endometriomas, has been identified as a primary driver of both systemic and local inflammation associated with the condition. This article reviews the current understanding of immune dysfunctions in the endometrioma and their implications for inflammation.

Dissecting the shared genetic architecture between endometriosis and polycystic ovary syndrome.

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

Endometriosis, staging, infertility and assisted reproductive technology: time for a rethink.

How endometriosis causes infertility, with the exception of tubal dysfunction caused by adhesions, is unclear. The inflammatory milieu in the pelvis and impaired receptivity of the eutopic endometrium are considered to be possible factors. Anatomical staging systems fail to predict the fertility status of endometriosis patients. Data from assisted reproductive technology cycles consistently suggest that oocytes from patients with endometriosis have a normal potential to develop into euploid blastocysts. Moreover, oocyte or embryo recipients with endometriosis seem to have similar or slightly lower pregnancy and live birth rates compared with recipients without endometriosis, suggesting that eutopic endometrium is not or is only minimally affected, which may be caused by undiagnosed adenomyosis. In-vivo observations from women with endometriomas provide evidence against a detrimental effect of endometriomas on oocytes. Combined with the absence of an obvious improvement in fertility following the surgical destruction or excision of peritoneal endometriosis or from temporary medical suppression of the disease and the associated inflammation, the available evidence makes endometriosis-associated infertility questionable in the absence of tubal dysfunction caused by adhesions. It is likely that no anatomical staging will correlate with fertility beyond assessing tubal function. In patients with endometriosis assisted reproductive technology is as effective as for other indications.

The Burden of Pelvic Pain Associated with Endometriosis Among Women in Selected European Countries and the United States: A Restricted Systematic Review.

OBJECTIVE: To evaluate the burden of endometriosis-associated pelvic pain (EAPP) on health-related quality of life (HRQoL) among women living in similar socio-economic conditions. DATA SOURCES: Searches were performed in PubMed and Embase on 26 September 2022. The review was performed in conformity with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocol (PRISMA-P) and was registered on PROSPERO (ID: CRD42023370363). METHODS OF STUDY SELECTION: Due to the high volume of eligible publications following initial review, inclusion criteria were restricted to studies undertaken in France, Germany, Italy, Spain, the United Kingdom, and the United States. This restriction was applied before screening as these countries have broad social and economic similarities, and previous studies in the literature suggest pain reporting and experience are influenced by numerous socio-cultural factors. Eligible studies were those published between 2013 and 2022 and include a sample size of ≥50 participants. The search strategy identified all relevant publications relating to the burden of illness due to EAPP. A variety of terms are used in the literature to describe pain associated with endometriosis, and this was considered in the design of the search strategy and screening procedure. TABULATION, INTEGRATION, AND RESULTS: The database searches resulted in a total of 6139 records. After removal of duplicates, 3855 records were assessed further. A total of 27 publications were identified as eligible. 14 (52%) were from Italy; 5 (19%) were multinational studies, 4 (15%) were from the US, 3 (11%) were from Spain, and 1 (4%) was from Germany. Most studies were cross-sectional (n=15; 56%); 7 (26%) were case-control studies; 3 (11%) were cohort studies; and 2 (7%) were longitudinal studies. These publications collectively highlighted an association between EAPP and reduced HRQoL. Several studies showed that EAPP was associated with lower HRQoL when compared with endometriosis without pain and potentially with chronic pelvic pain caused by other conditions, although the evidence is limited in this case. Moreover, the studies reported detrimental effects on general HRQoL, mental health functioning, and sexual functioning, culminating in reduced work productivity and difficulties in performing everyday activities. The associations were generally similar across study populations, including adolescents, as well as younger and older women. Results were consistent across the range of different patient-reported outcome tools used to assess HRQoL. CONCLUSION: The existing literature suggests that, among women in selected European countries and the United States, EAPP is associated with reduced HRQoL, including impaired mental and sexual functioning, as well as reduced work performance and productivity; each of which may contribute to the societal burden of endometriosis.

Demographic Correlates of Endometriosis Diagnosis Among United States Women Aged 15-50.

OBJECTIVE: To compare demographic characteristics for women with and without a diagnosis of endometriosis. DESIGN: Data were collected from the National Survey of Family Growth - a publicly available survey designed and administered by the Centers for Disease Control, which uses a nationally-representative sample of the United States population. Univariate data were reported as survey-weighted percentages and means, and were analyzed using chi-square, t-tests, and logistic regression. Analyses accounted for complex survey design. SETTING: United States PARTICIPANTS: Interviews were conducted with 6,141 female respondents, aged 15-50, between 2017 and 2019. INTERVENTIONS: Data were collected through in-person interviews. RESULTS: Nationally, 5.7% reported a diagnosis of endometriosis (95% CI 4.6-6.9%). Those with endometriosis were older, with a mean age of 39 (95% CI 38.1-39.9), compared to 31.7 (95% CI 31.2-32.2) among those without (p < 0.0005). Endometriosis diagnosis was significantly associated with race. Compared to non-Hispanic White women, Hispanic women had an adjusted odds ratio (aOR) of 0.37 (95% CI 0.21-0.65) for diagnosis of endometriosis, and non-Hispanic Black women had an aOR of 0.54 (95% CI 0.35-0.84). We also observed a difference in diagnosis by health insurance: compared to those with private insurance or Medi-Gap coverage, those with Medicare or military insurance had an aOR for endometriosis diagnosis of 2.49 (95% CI 1.36-4.55). Finally, compared to those with less than a high school education, those who had completed high school or greater had an aOR for endometriosis diagnosis of 2.84 (95% CI 1.15-6.99). CONCLUSION: These disparities in endometriosis diagnosis suggest that intersecting barriers may preclude certain groups from accessing timely endometriosis diagnosis and management. Further studies are warranted to explore these hypothesis-generating data, and to identify and address specific barriers to equitable endometriosis diagnosis and management.

Vitamin D and reproductive disorders: a comprehensive review with a focus on endometriosis.

Vitamin D is a fat-soluble steroid hormone that was initially known only for regulating calcium and phosphorus levels and maintaining bone health. However, it was later discovered that many organs express vitamin D metabolizing enzymes and have a ligand for vitamin D, which regulates the expression of an extensive assortment of genes. As a result, vitamin D is indispensable for the proper function of organs, and its deficiency is believed to be a critical factor in symptoms and disorders such as cardiovascular diseases, autoimmune diseases, and cancers. The significance of vitamin D in reproductive tissues was recognized later, and studies have revealed its crucial role in male and female fertility, as well as proper reproductive function during pregnancy. Vitamin D deficiency has been identified as a risk factor for infertility, gonadal cancers, pregnancy complications, polycystic ovary syndrome, and endometriosis. However, data investigating the association between vitamin D levels and reproductive disorders, including endometriosis, have encountered inconsistencies. Therefore, the present study aims to review existing research on the effect of vitamin D on proper reproductive function, and the role of deficiency in reproductive diseases and specifically focuses on endometriosis.

Surgical outcomes in women diagnosed with deep endometriosis involving urological structures.

INTRODUCTION: The prevalence of endometriosis is estimated to be about 10% among women of reproductive age. In about 5-10% of these patients, involvement of urological structures will be developed due to deep endometriosis. Urologists should be familiar with the management of these patients, who will require multidisciplinary care with medical and surgical treatment. MATERIAL AND METHODS: Retrospective study of patients diagnosed with deep endometriosis involving urological structures who underwent surgery performed jointly with gynecology and colorectal surgery departments from June 2012 until June 2021 (60 cases). Urologic symptoms were grouped into 3 groupers for subsequent analysis (storage symptoms, voiding symptoms, and low back pain). RESULTS: Storage symptoms (frequency and urgency) are the most frequent urologic symptoms. Patients with storage symptoms and low back pain showed improvement after surgery. In contrast, patients with voiding symptoms did not improve with surgical treatment. CONCLUSIONS: The prevalence of endometriosis and the likelihood of involving urologic structures require the urologic community to be aware of the pathology. Patients with storage symptoms will improve following excision of the endometriotic nodules. The need for Partial cystectomies with ureteral reimplantation can be safely performed by laparoscopic or robotic approach, even in previously operated patients, without compromising long-term function.

Heme metabolism and HO-1 in the pathogenesis and potential intervention of endometriosis.

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

Transgender and gender diverse people with endometriosis: A perspective on affirming gynaecological care.

Transgender and gender diverse people presumed female at birth experience gynaecological conditions, such as chronic pelvic pain at elevated rates, estimated to impact between 51% and 72% of this population, compared to rates of up to 26.6% in cisgender women. The negative impact of these conditions is likely amplified due to limited access to safe and affirming healthcare. Despite this high prevalence rate, there is limited research investigating the prevalence, presentation or management options for trans and gender diverse people with endometriosis. Cisgender women with endometriosis report barriers to accessing care, with lengthy times to diagnosis and limited treatment options available. However, barriers for trans and gender diverse individuals are enhanced by physician bias and lack of education in gender-affirming care. This is reflected in stories of discrimination and denial of basic healthcare. A healthcare environment built on the presumption that gynaecological patients are women, others trans and gender diverse patients, which can result in avoidance of needed medical care. A lack of knowledge of gender-affirming care alongside healthcare provider bias highlights a need for gender-affirming care and bias reduction training in undergraduate healthcare provider curricula. Research to date assessing current curriculum in Australia and Aotearoa (New Zealand) shows limited inclusion of lesbian, gay, bisexual, trans, queer, intersex, asexual and other related identities content as a whole with gender-affirming care being among the least-frequently addressed topics. This review will detail barriers to accessing gender-affirming healthcare specific to gynaecology, interweaving the experiences of a non-binary individual seeking access to gender-affirming endometriosis care.

Transgender and gender diverse people with endometriosis: a perspective on affirming gynaecological careTransgender and gender diverse people have limited access to safe and affirming healthcare. Barriers to accessing care are particularly prominent for those presumed female at birth attempting to access gynaecological care for conditions, such as endometriosis or chronic pelvic pain (CPP). A key barrier to safe and affirming healthcare for this population is a lack of inclusion of trans and gender diverse health in healthcare provider curriculum. The dearth of healthcare providers knowledgeable in gender-affirming care results in healthcare discrimination and poorer health outcomes for trans and gender diverse people.

Multi-omics integration highlights the role of ubiquitination in endometriosis fibrosis.

BACKGROUND: Endometriosis, characterized by the presence of active endometrial-like tissues outside the uterus, causes symptoms like dysmenorrhea and infertility due to the fibrosis of endometrial cells, which involves excessive deposition of extracellular matrix (ECM) proteins. Ubiquitination, an important post-transcriptional modification, regulates various biological processes in human diseases. However, its role in the fibrosis process in endometriosis remains unclear. METHODS: We employed multi-omics approaches on two cohorts of endometriosis patients with 39 samples. GO terms and KEGG pathways enrichment analyses were used to investigate the functional changes involved in endometriosis. Pearson's correlation coefficient analysis was conducted to explore the relationship between global proteome and ubiquitylome in endometriosis. The protein expression levels of ubiquitin-, fibrosis-related proteins, and E3 ubiquitin-protein ligase TRIM33 were validated via Western blot. Transfecting human endometrial stroma cells (hESCs) with TRIM33 small interfering RNA (siRNA) in vitro to explore how TRIM33 affects fibrosis-related proteins. RESULTS: Integration of proteomics and transcriptomics showed genes with concurrent change of both mRNA and protein level which involved in ECM production in ectopic endometria. Ubiquitylomics distinguished 1647 and 1698 ubiquitinated lysine sites in the ectopic (EC) group compared to the normal (NC) and eutopic (EU) groups, respectively. Further multi-omics integration highlighted the essential role of ubiquitination in key fibrosis regulators in endometriosis. Correlation analysis between proteome and ubiquitylome showed correlation coefficients of 0.32 and 0.36 for ubiquitinated fibrosis proteins in EC/NC and EC/EU groups, respectively, indicating positive regulation of fibrosis-related protein expression by ubiquitination in ectopic lesions. We identified ubiquitination in 41 pivotal proteins within the fibrosis-related pathway of endometriosis. Finally, the elevated expression of TGFBR1/α-SMA/FAP/FN1/Collagen1 proteins in EC tissues were validated across independent samples. More importantly, we demonstrated that both the mRNA and protein levels of TRIM33 were reduced in endometriotic tissues. Knockdown of TRIM33 promoted TGFBR1/p-SMAD2/α-SMA/FN1 protein expressions in hESCs but did not significantly affect Collagen1/FAP levels, suggesting its inhibitory effect on fibrosis in vitro. CONCLUSIONS: This study, employing multi-omics approaches, provides novel insights into endometriosis ubiquitination profiles and reveals aberrant expression of the E3 ubiquitin ligase TRIM33 in endometriotic tissues, emphasizing their critical involvement in fibrosis pathogenesis and potential therapeutic targets.

Extracellular vesicles in endometriosis: role and potential.

Endometriosis is a chronic inflammatory gynecological disease, which profoundly jeopardizes women's quality of life and places a significant medical burden on society. The pathogenesis of endometriosis remains unclear, posing major clinical challenges in diagnosis and treatment. There is an urgent demand for the development of innovative non-invasive diagnostic techniques and the identification of therapeutic targets. Extracellular vesicles, recognized for transporting a diverse array of signaling molecules, have garnered extensive attention as a novel mode of intercellular communication. A burgeoning body of research indicates that extracellular vesicles play a pivotal role in the pathogenesis of endometriosis, which may provide possibility and prospect for both diagnosis and treatment. In light of this context, this article focuses on the involvement of extracellular vesicles in the pathogenesis of endometriosis, which deliver information among endometrial stromal cells, macrophages, mesenchymal stem cells, and other cells, and explores their potential applications in the diagnosis and treatment, conducing to the emergence of new strategies for clinical diagnosis and treatment.

Pregnancy-related complications in patients with endometriosis in different stages.

BACKGROUND: Endometriosis is one of the most common and costly diseases among women. This study was carried out to investigate pregnancy outcomes in women with endometriosis because of the high prevalence of endometriosis in reproductive ages and its effect on pregnancy-related complications outcomes. METHODS: This was a cross-sectional study performed on 379 pregnant women with endometriosis who were referred to the endometriosis clinic of the Avicenna Infertility Treatment Center from 2014 to 2020. Maternal and neonatal outcomes were assessed for the endometriosis group and healthy mothers. The group with endometriosis was further divided into two groups: those who underwent surgery and those who either received medication alone or were left untreated before becoming pregnant. The analysis of the data was done using SPSS 18. RESULTS: The mean age of the patients was 33.65 ± 7.9 years. The frequency of endometriosis stage (P = 0.622) and surgery (P = 0.400) in different age groups were not statistically significant. The highest rates of RIF and infertility were in stages 3 (N = 46, 17.2%) (P = 0.067), and 4 (N = 129, 48.3%) (P = 0.073), respectively, but these differences were not statistically different, and the highest rate of pregnancy with ART/spontaneous pregnancy was observed in stage 4 without significant differences (P = 0.259). Besides, the frequency of clinical/ectopic pregnancy and cesarean section was not statistically different across stages (P > 0.05). There is no significant relationship between endometriosis surgery and infertility (P = 0.089) and RIF (P = 0.232). Most of the people who had endometriosis surgery with assisted reproductive methods got pregnant, and this relationship was statistically significant (P = 0.002) in which 77.1% (N = 138) of ART and 63% (N = 264) of spontaneous pregnancies were reported in patients with endometriosis surgery. The rate of live births (59.4%) was not statistically significant for different endometriosis stages (P = 0.638). There was no stillbirth or neonatal death in this study. All cases with preeclampsia (N = 5) were reported in stage 4. 66.7% (N = 8) of the preterm labor was in stage 4 and 33.3% (N = 4) was in stage 3 (P = 0.005). Antepartum bleeding, antepartum hospital admission, preterm labor, gestational diabetes, gestational hypertension, abortion, placental complications and NICU admission were higher in stage 4, but this difference had no statistical difference. CONCLUSION: Endometriosis is significantly correlated with infertility. The highest rates of RIF and infertility are observed in stages 3 and 4 of endometriosis. The rate of pregnancy with ART/spontaneous pregnancy, preterm labor, preeclampsia and pregnancy-related complications is higher in stage 4. Most of the people who had endometriosis surgery with assisted reproductive methods got significantly pregnant. Clinical/ectopic pregnancy, cesarean sections, and live birth were not affected by the endometriosis stages.

Identification of urine biomarkers of endometriosis-Protein mass spectrometry.

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

Oocyte cryopreservation for women with endometriosis: Justification, indications, and reproductive outcomes.

Women with endometriosis often experience diminished ovarian reserve and a decreased number of oocytes retrieved. This reduction is exacerbated after surgery. Nevertheless, oocyte quality does not seem to be compromised in these patients. When embryos of good quality are obtained, in vitro fertilization outcomes are generally satisfactory. Oocyte cryopreservation may represent a fertility preservation option for women with planned and/or prior surgery, as it enables the collection of oocytes in advance. Given the diverse manifestations of endometriosis, which vary by type, age, and ovarian reserve, the decision to pursue oocyte cryopreservation should be weighed individually. Moreover, the potential benefits of this approach on future fertility must be carefully considered. Considering current guidelines, the most appropriate candidates for oocyte cryopreservation among women with endometriosis are: patients with bilateral endometriomas, typically larger than 3 cm; those with prior surgery for unilateral endometrioma who exhibit ipsilateral or contralateral recurrence; and those with unilateral endometrioma on a single ovary. However, the size criteria for endometrioma warrant further discussion. Conversely, oocyte cryopreservation is inadvisable for patients: with unilateral endometrioma smaller than 3 cm and good ovarian reserve; who have undergone surgery for bilateral endometriomas, regardless of recurrence; and who have diminished ovarian reserve. While consensus indicates that decisions regarding diminished ovarian reserve should be individualized, fertility preservation should often be considered for patients with serum anti-Müllerian hormone levels below 0.5 ng/mL. In such cases, a prolonged duration may be necessary to retrieve the desired 10 to 15 oocytes.

Tailoring radicality in diaphragmatic surgery for deep endometriosis: A matter of choice.

Diaphragmatic endometriosis (DpE) is a rare disease localization which represents an important clinical challenge. The main criticisms toward the proper DpE management consist of poor consensus on both surgical indications and the choice between different surgical techniques available to treat the disease. Furthermore, only weak recommendations are provided by current guidelines and surgical management is mostly based on surgeon's experience. As consequence, the lack of standardization about the surgical treatment led to the risk of under- or over-treatments in patients suffering from this form of endometriosis. The latest evidence-based data suggest to adopt a lesion-oriented surgical approach serving as a guide in daily surgical activities, in order to ensure a tailored radicality and reduce the rate of surgery-related complications. Diaphragmatic endometriosis surgery should be performed only by expert surgeons with an extensive oncogynecologic expertise since it represents a technically demanding procedure. A multidisciplinary approach is also mandatory in order to adequately select and treat these patients by minimizing the risk of additional morbidity.

Risk factors for postoperative recurrence of cesarean scar endometriosis.

BACKGROUND: The increasing global prevalence of cesarean scar endometriosis necessitates a thorough understanding of the risk factors for postoperative recurrence, as this is crucial for developing preventive strategies and informed decision-making. OBJECTIVE: To obtain insight into the clinical risk factors for postoperative recurrence of cesarean scar endometriosis following open lesion resection. STUDY DESIGN: The cohort for this study comprised 272 women, including 26 patients with postoperative recurrence and 246 without recurrence. Various parameters, including baseline characteristics, preoperative, intraoperative, and postoperative conditions, and follow-up information, were analyzed. A comparison of these parameters was made between patients with and without postoperative recurrence. Time-to-recurrence analyses were conducted using Cox's univariate and multivariate proportional hazard analyses, the Kaplan-Meier method, and the log-rank test. RESULTS: The results revealed significant differences between patients with and without postoperative recurrence in terms of visual analog scale for abdominal pain (P=.008), method of surgery (P<.001), and incision length (P=.002). The Cox proportional hazard model identified the visual analog scale for abdominal pain ≥4 as a significant risk factor for postoperative recurrence (hazard ratio, 3.72 [95% confidence interval, 1.65-8.43]; P=.002). In addition, patients who received removal of scar, excision of mass, and exploration underneath the scar (named as integrated excision) had a lower risk of recurrence than those who received local excision of mass (hazard ratio, 0.14 [95% confidence interval, 0.04-0.48]; P=.002). Furthermore, older patients (aged ≥35 years) were found to have a lower risk of postoperative recurrence than those <35 years (hazard ratio, 0.35 [95% confidence interval, 0.12-1.04]; P=.058). In addition, the depth of involvement was identified as a meaningful factor in postoperative recurrence for patients with local excision of mass, as determined by the log-rank test (P=.018). CONCLUSION: The study highlights that the visual analog scale for abdominal pain ≥4 is a risk factor for the recurrence of cesarean scar endometriosis after open lesion resection. Furthermore, the surgical method of integrated excision was identified as a protective factor.

First-line surgery versus first-line assisted reproductive technology for women with deep infiltrating endometriosis: a systematic review and meta-analysis.

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

Long noncoding RNA BMPR1B-AS1 stability regulated by IGF2BP2 affects the decidualization in endometriosis patients through the SMAD1/5/9 pathway.

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