Search Results (88)

Background/Objectives: As the population of women with endometriosis increases, approximately 10% of those of reproductive age experience symptoms such as pelvic pain, painful menstruation, and infertility. Individuals with endometriosis usually undergo multiple surgeries due to the high recurrence rate of the condition. However, ovarian surgery tends to reduce the ovarian reserve, presenting a dilemma when deciding whether to recommend surgery or medical treatment for women of reproductive age. The impact of endometriomas on the residual volume of ovarian tissue remains controversial, and it is unclear whether endometriosis itself or endometriomas are the primary problem. In this study, we aimed to investigate whether women with endometriosis have lower levels of anti-Müllerian hormone than women with healthy ovaries before treatment initiation. Methods: A total of 298 participants enrolled in the endometriosis cohort at Severance Hospital, Korea, from 1 October 2020 to 1 July 2024 were included in this study. Of these, 63 participants were from a retrospective study, and 235 were from a prospective study. Due to the use of different assay methods between the reference values and anti-Müllerian hormone measurements from Severance Hospital, a correction was applied using the regression equation. The mean anti-Müllerian hormone levels for individuals with endometriosis were corrected with the regression equation and compared to those of the reference group for each age group using a one-sample t-test. Results: Anti-Müllerian hormone levels decreased with age in the endometriosis group. When comparing mean anti-Müllerian hormone concentrations between the endometriosis group and reference values, among 168 participants aged 20–31 years, the corrected mean anti-Müllerian hormone concentration was 5.96 ± 3.22 ng/mL, higher than the reference value of 4.94 ± 0.17 ng/mL (p < 0.01). Among 31 participants aged 35–37 years, the corrected average anti-Müllerian hormone value was 4.33 ± 3.06 ng/mL, compared to the reference anti-Müllerian hormone level of 3.22 ± 0.15 ng/mL (p = 0.05). There were no significant differences in corrected anti-Müllerian hormone levels between the 32–34-, 38–40-, 41–43-, and ≥44 years age groups. Conclusions: Patients with endometriosis, especially those aged 20–31 years, tended to have higher anti-Müllerian hormone levels than did individuals with healthy ovaries. In other age groups, there were no differences. Given that these levels do not differ significantly across age groups, it is difficult to conclude that patients with endometriosis have a reduced ovarian reserve. Full article

The assessment of the ovarian reserve is important in patients with fertility intent. The anti-Müllerian hormone (AMH) serum level is a useful ovarian reserve marker. Endometriosis is a benign disease with three phenotypes: superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA), and deep endometriosis (DE). Endometriosis is linked with infertility; however, the exact impact of endometriosis and endometriosis surgery on AMH levels is less clear. This narrative review examines how different endometriosis phenotypes and related surgeries affect AMH levels as well as explores whether pre- and post-surgical AMH can predict the reproductive outcomes in women seeking pregnancy. The evidence suggests that OMA is linked to reduced AMH values and a higher AMH decline rate over time. OMA cystectomy causes further a reduction in AMH, which, however, tends to recover postoperatively. Non-excisional surgery for OMA spares the ovarian parenchyma; however, an at least temporary decline in AMH is observed. The effect is likely smaller than that of cystectomy. Non-thermal methods of hemostasis following cystectomy are likely superior in terms of AMH. The AMH levels before OMA cystectomy appear to be positively correlated with the postoperative probability of pregnancy, particularly spontaneous conception, but not livebirth rates. Preoperative AMH levels are also predictive of the risk of diminished ovarian reserve (DOR). Similarly, postoperative AMH levels and the rate of AMH decline at 1 year after OMA cystectomy appear to be predictive of fertility outcomes. SUP likely has little (if any) impact on AMH levels. DE reduces AMH levels, and a further reduction following surgery is anticipated. However, a reduction in AMH values should not be interpreted as a decline in the patient’s reproductive potential. Further research should focus on the extra-ovarian locations of endometriosis and their impact on AMH values. Full article

Some studies indicate the role of TNF-α, IL-6, and IL-8 in the development of endometriosis. However, a comprehensive assessment of plasma, peritoneal, and endometrioma fluids of proinflammatory cytokine concentrations in women with ovarian endometriosis has not yet been performed. Therefore, this study aimed to analyze plasma, peritoneal, and endometrioma fluids for selected proinflammatory cytokine concentrations in women operated on for ovarian endometriosis. A retrospective study was conducted with 56 women who underwent surgery for ovarian endometriosis. Body mass, height, and waist circumference were measured, as well as BMI being calculated. Plasma, peritoneal, and endometrioma fluids’ interleukin-6 (IL-6), IL-8, and tumor necrosis factor-alpha (TNF-α) were determined by ELISA. Levels of IL-6 and TNF-α were significantly higher in endometrioma fluid compared to plasma and peritoneal fluid. In addition, levels of IL-6 and TNF-α were significantly higher in peritoneal fluid than found in plasma. Levels of IL-8 did not significantly differ between plasma and both peritoneal and endometrioma fluids, or between peritoneal and endometrioma fluids. There were also positive correlations among IL-6, IL-8, and TNF-α levels in endometrioma and peritoneal fluids (ρ = 0.29; p < 0.05; ρ = 0.51; p < 0.001; ρ = 0.52; p < 0.001, respectively). There were no associations between cytokine levels in plasma, peritoneal, and endometrioma fluids and endometriosis stage. Plasma IL-8 levels can be considered an emerging biomarker of severity of local inflammation related to endometrioma. Further studies are needed for understanding the role of IL-6 and TNF-α as the markers of local inflammation in endometrioma. Full article

Background/Objectives: Endometriosis can present as ovarian endometriosis in 15–25% of the cases. While chronic pelvic pain and dysmenorrhea dominate its clinical presentation, acute complications, such as spontaneous OMA rupture, are rare (<3%), often mimicking acute abdominal pain and necessitating emergency surgery. Diagnostic delays persist due to the condition’s rarity and overlapping symptoms with ovarian torsion or appendicitis. This study investigates the clinical features of ruptured OMAs to enhance preoperative suspicion and optimize management. Methods: From February 2011 to August 2023, 14 patients with spontaneous rupture of histologically confirmed endometriomas underwent emergency laparoscopy for acute abdominal pain in the University Hospital of Bern, Switzerland. The clinical data of these patients were analyzed to find common patterns of spontaneous endometrioma ruptures. We also conducted a literature search in PubMed, Scopus, ScienceDirect, Cochrane, and Embase databases from inception to December 2023 in order to identify other possible confounding factors. The search was based on the keywords “ruptured endometrioma”. All English full-text prospective and retrospective observational and interventional studies with at least five patients that described the clinical features and findings of women diagnosed with ruptured endometrioma and treated surgically were included. Results: The median age at operation was 37.4 (23–49) years old, and all cases presented with acute abdominal pain, with/without peritonitis. Only 3/14 patients presented with fever, while the most common laboratory finding was an elevated CRP level of 45.6 mg/L (3–100 mg/L), while leukocytosis was less pronounced, with a median of 12.2 G/L (6.04–21.4 G/L). Notably, 64.3% (9 out of 14) of the patients reported experiencing dysmenorrhea, while for the remaining 5 individuals, the presence or absence of dysmenorrhea could not be obtained. Interestingly, only one patient had undergone hormonal treatment, with a combined oral contraceptive (COC) of Ethinylestradiol (0.02 mg) and Desogestrel (0.15 mg), while the other patients either lacked awareness of their endometriosis or expressed reluctance towards hormonal downregulation therapy. The median endometrioma size was 7 cm (3.5–18 cm), and 78.57% of the cases (11 out of 14 patients) had only ovarian endometriosis, while only 3 patients had involvement of compartment A, B, or C according to the # ENZIAN classification. Conclusions: Though rare, spontaneous OMA rupture should be considered in acute abdomen cases, especially with cysts > 5 cm. Hormonal therapy may reduce rupture risk, but more research is needed to confirm this and refine diagnostic strategies. Full article

Background: Endometriosis is a benign gynecologic condition that has the risk of malignant transformation in approximately 0.5–1% of cases, most of which develop into endometriosis-associated ovarian cancers (EAOCs), such as clear cell and endometrioid adenocarcinomas. The current systematic review aims to condense recent information on the genetic and molecular mechanisms, clinical risk factors, and possible therapeutic targets of the malignant transformation of endometriosis. Methods: A systematic literature search of PubMed, Europe PMC, and Google Scholar was carried out according to PRISMA guidelines for articles published until December 2024. Following a screening of 44,629 titles, 43 full articles were included after meeting inclusion criteria. No case reports or reviews were included, and articles had to mention a malignant transformation of endometriosis and not just a diagnosis of cancer. The quality and risk of bias of studies were evaluated using ROBINS-I. Results: Malignant transformation of endometriosis is associated with genetic alterations, including ARID1A mutations, microsatellite instability, and abnormal PI3K/Akt and mTOR pathway activation. Increased oxidative stress, inflammation-driven mismatch repair deficiency, and epigenetic alterations like RUNX3 and RASSF2 hypermethylation are implicated in carcinogenesis. Clinical risk factors are advanced age (40–60 years), large ovarian endometriomas (>9 cm), postmenopausal status, and prolonged estrogen exposure. Imaging techniques like MR relaxometry and risk models based on machine learning are highly predictive for early detection. Conclusions: Endometriosis carcinogenesis is a multifactorial process driven by genetic changes, oxidative stress, and inflammatory mechanisms. Identification of high-risk individuals through molecular and imaging biomarkers may result in early detection and personalized therapy. Further research should aim at the development of more precise predictive models and exploration of precision medicine approaches to inhibit the emergence of EAOC. Full article

Background/Objectives: Endometriosis is commonly associated with infertility due to multiple factors. In this paper, we investigated the histopathological factors underlying these effects by comparing microscopic samples obtained during laparoscopic stripping. Methods: Morpho-functional examination through the follicular Score (FS) of ovarian tissue adjacent to the cystic wall (Specimen 1) was compared with the FS of ovarian tissue inadvertently harvested during cystectomy (Specimen 2). The follicular score was compared with clinical factors such as age, parity, BMI, and CA-125 levels. Results: Cohen’s kappa analysis revealed a 77.8% concordance between the follicular score of the ovarian tissue alongside the endometrioma (S1) and the ovarian tissue inadvertently removed (S2), reflecting a moderate level of concordance between the two samples. A statistically significant positive correlation was observed between the FS of Specimen 1 and the preoperative CA-125 value (p = 0.01); in contrast, a negative correlation was found between the FS and both the patient’s age (p = 0.006) and parity (p = 0.03). Additionally, a statistically significant negative correlation was demonstrated between the FS of Specimen 2 and patient age (p = 0.04). Conclusions: The functional quality of the remaining ovary after endometrioma stripping may be assessed by evaluating the follicular score of the pericystic ovarian tissue. Full article

Ovarian endometriomas (OEMs), cystic formations within the ovaries, are a significant manifestation of endometriosis and present in 20–40% of affected women. Despite extensive research, the pathogenesis of endometriosis remains unclear, with retrograde menstruation, coelomic metaplasia, and lymphatic dissemination being proposed mechanisms. OEMs negatively impact ovarian function by reducing the ovarian reserve, disrupting folliculogenesis, and altering the ovarian microenvironment through oxidative stress, inflammation, and fibrosis. Elevated reactive oxygen species (ROS) accelerate follicular atresia, and extracellular matrix remodeling contributes to ovarian damage, while immune dysregulation and cytokine imbalances further exacerbate the condition. The presence of OEMs does not significantly affect live birth rates in in vitro fertilization (IVF) treatments, despite potential reductions in the quality and quantity of oocytes. However, their surgical excision compromises the ovarian reserve. This review highlights the complex mechanisms by which OEMs impair ovarian function and emphasizes the need for further research to develop strategies that mitigate these effects, ultimately improving reproductive outcomes for women with endometriomas. Full article

Background and Clinical Significance: Paratubal Leydig cell nodules are rare incidental findings that present diagnostic challenges. Case Presentation: A 45-year-old female with a history of hypertension and diabetes mellitus presented with fever and chills following an episode of severe dysmenorrhea and menorrhagia. The patient reported heavy menstrual bleeding, persisting for 2–3 years. Physical examination revealed erythema of the perineum and whitish vaginal discharge, with no cervical lesions. Imaging revealed a 15 cm right ovarian cyst. Laboratory investigations showed elevated C-reactive protein (6.37 mg/L) and CA125 (88.82 U/mL) levels, whereas other tumor markers were within normal limits. A pelvic ultrasound revealed a retroverted uterus and a large ovarian mass suggestive of malignancy. The patient underwent a right salpingo-oophorectomy, during which a 15 cm ovarian tumor adherent to the right pelvic sidewall was excised. Histopathological examination revealed an endometriotic cyst with endometrial glandular epithelium positive for estrogen receptor and focal mucinous metaplasia. CD10-positive endometrial stromal cells and paratubal cysts were also observed. Additionally, a small Leydig cell tumor originated from the ovarian hilum was identified and confirmed by positive staining for inhibin, calretinin, and androgen receptors, as well as negative estrogen receptor staining. The postoperative recovery was uneventful, and at the five-week follow-up, the patient’s hormonal levels were normal, and there were no complications. Conclusions: This case highlights the importance of thorough histopathological evaluation in managing ovarian masses and the potential coexistence of benign and rare pathological entities, such as Leydig cell tumors. Full article

The molecular mechanisms through which endometriosis-related ovarian neoplasms (ERONs) develop from benign endometrioma remain unclear. It is especially a long-standing mystery why ovarian endometrioma has the potential to develop into two representative histological subtypes: endometrioid ovarian carcinoma or clear cell ovarian carcinoma. This study aimed to investigate the molecular carcinogenesis of ERONs using newly developed in vitro and in vivo carcinogenesis models. Epithelial cells were isolated and purified from surgically removed benign endometrioma samples, followed by immortalization by overexpressing cyclinD1/CDK4 in combination with the human TERT gene. Immortalized cells were subjected to various molecular manipulations by combining knockout or overexpression of several candidate drivers, including ARID1A, KRAS, PIK3CA, AKT, and MYC, based on previous comprehensive genome-wide studies of ERONs. These cells were then inoculated into immunocompromised mice and evaluated for malignant transformation. Inoculated cells harboring a combination of three genetic alterations successfully developed tumors with malignant features in mice, whereas those with two genetic manipulations failed to do so. Especially, ARID1A gene knockout, combined with overexpressing the KRAS oncogenic mutant allele (or overexpressing AKT) and c-Myc overexpression led to efficient tumor formation. Of note, these three combinations of genetic alterations produced tumors that histologically represented typical clear cell carcinoma in SCID mice, while the same combination led to tumors with endometrioid histology in nude mice. A combination of ARID1A mutation, KRAS mutation or AKT activation, and c-Myc overexpression were confirmed to be the main candidate drivers for the development of ERONs, as suggested by comprehensive genetic analyses of ERONs. A tumor immune microenvironment involving B-cell signaling may contribute to the diverse histological phenotypes. The present model may help to clarify the molecular mechanisms of ERON carcinogenesis and understand their histological diversity and novel molecular targets. Full article

Background/Objectives: Epithelial–Mesenchymal Transition (EMT) is the process by which epithelial cells acquire mesenchymal properties, which helps endometriotic cells migrate and invade. This study looks at the expression of E-CADHERIN, a critical epithelial marker, and miR-200b, an EMT regulator, in several types of endometriosis, including endometriomas and deep infiltrating endometriotic (DIE) nodules. Methods: We examined 19 individuals with endometriosis (9 with just endometriotic cysts and 10 with both DIE and endometriotic cysts) and 8 controls with benign gynecological abnormalities. Tissue samples were taken during laparoscopic surgery, and E-CADHERIN and miR-200b expression were measured using Real-Time PCR, with G6PD and U6 as controls. Results:E-CADHERIN expression was maintained in the eutopic endometrium of both ovarian and DIE types, but it was considerably reduced in endometriotic cysts, indicating heightened mesenchymal features. miR-200b was downregulated in the eutopic endometrium of ovarian endometriosis but upregulated in DIE. Endometriotic cysts in both groups had greater miR-200b expression than their corresponding eutopic endometrium. E-CADHERIN and miR-200b expression in DIE lesions was similar to that found in matched eutopic endometrium. Conclusions: The regulation of E-CADHERIN and miR-200b varies across ovarian and DIE lesions. The miR-200b-ZEB1 feedback loop is increased in DIE eutopic endometrium but downregulated in ovarian endometriosis. E-CADHERIN downregulation in endometriotic cysts indicates heightened mesenchymal dynamics, whereas DIE nodules have gene expression patterns similar to eutopic endometrium. These findings emphasize the distinct regulatory processes that govern endometriotic lesions. Full article

Background/Objectives: Endometriosis has a marked impact on fertility, although the mechanisms behind this relationship remain poorly understood, particularly in cases without significant anatomical distortions or in the context of ovarian endometriomas. This study aimed to investigate the effect of peritoneal endometriosis on ovarian function by assessing ovarian reserve and apoptosis. Methods: Peritoneal endometriosis was surgically induced in Sprague Dawley rats through the autotransplantation of uterine fragments onto the bowel mesothelium. One month post-surgery, ovarian structures were counted, follicle and corpora lutea apoptosis was evaluated by TUNEL, and apoptotic-related protein expression in ovaries was assessed by Western blot. Additionally, a co-culture system using 12Z endometriotic and KGN granulosa cell lines was utilized to evaluate gene expression by RT-qPCR. Results: Rats with peritoneal endometriosis exhibited a significant reduction in ovarian structures characterized by a low number of total follicles, particularly primordial, primary, preantral, and late-antral follicles. Consistently, AMH protein expression was decreased in ovaries in the presence of endometriosis. In addition, this disease led to a significant increase in late-antral follicles that were TUNEL-positive and in the number of apoptotic cells in corpora lutea, indicating higher apoptosis in endometriosis ovaries. Concomitantly, the altered expression of apoptosis-related proteins was observed, with increased procaspase 3 and decreased BCL-2 expression. In addition, KGN granulosa cells co-cultured with 12Z endometriotic cells displayed reduced KITLG mRNA expression and increased AMHR2 mRNA expression. Conclusions: Peritoneal endometriosis significantly impairs ovarian health by disrupting folliculogenesis, reducing ovarian reserve, and increasing apoptosis, potentially accelerating ovarian aging and contributing to infertility. These results underscore the need for further research to identify the molecular pathways involved and to develop targeted therapeutic strategies. Full article

Endometriosis is a multifaceted gynecological disorder defined by endometrium-like tissue outside the uterine cavity. It is mainly localized in the pelvis and creates a local inflammatory environment responsible for its manifestations and complications. In 30–50% of cases, endometriosis is associated with infertility. In 17–44% of cases, the ovaries are affected in the form of ovarian endometriomas (OEs). The symptoms of OEs are not very pronounced. The development is slow. Diagnosis is difficult because OEs resemble cystic ovarian pathology, which is so diverse. The actual diagnosis is possible through direct visualization or laparoscopy. Surgical treatment by cystectomy is common for OEs. Recently, other therapeutic modalities have emerged that have less impact on ovarian reserves and pregnancy rates. In this context, the review attempts to shed light on the best diagnostic and treatment methods for an insidious pathology with a major impact on fertility. Full article

Background: Endometriosis is characterized by the presence of endometrial tissue outside the uterus. Beyond medical treatment, surgical intervention is also a viable consideration. However, current guidelines do not clearly indicate whether laparoscopic cystectomy, ablative methods (CO₂ laser vaporization, plasma energy), or sclerotherapy is the preferred option. Methods: We conducted searches in two databases (PubMed and Europe PMC) to retrieve articles containing the keywords ‘surgical intervention for Endometrioma, ovarian reserve, pregnancy rates, fertility’, published between 1 January 2000 and 31 December 2023. We included articles presenting information on surgical intervention for endometrioma and its correlation with infertility parameters. Articles describing conservative treatment were excluded. Data were extracted by two authors using predefined criteria. Results: The initial database search produced 1376 articles, which were narrowed down to 41 relevant articles meeting the eligibility criteria. Conclusions: Laparoscopic cystectomy appears to impact postoperative anti-mullerian hormone levels, showing a stronger correlation with larger cysts and individual factors. CO₂ laser vaporization demonstrates favorable results compared to traditional cystectomy. Combining GnRH agonist treatment with assisted reproduction treatment after cystectomy could be considered an alternative method. Plasma energy causes less damage to ovarian function, with pregnancy outcomes comparable to cystectomy. Sclerotherapy shows promising results for ovarian reserve preservation, recurrence rates, and safety. Further studies comparing these techniques are necessary to provide guidance to clinicians. Full article

Ethanol sclerotherapy (EST) has gained attention as a minimally invasive treatment option for ovarian endometriomas, particularly in infertile women with endometrioma undergoing in vitro fertilization (IVF). Endometriomas are associated with decreased ovarian reserve and impaired fertility outcomes, and traditional surgical approaches, such as cystectomy, often lead to further reductions in ovarian reserve. Ethanol sclerotherapy offers a potential alternative that preserves ovarian function while effectively managing endometriomas. This review examines the safety, efficacy, and impact of EST on ovarian reserve, IVF outcomes, and recurrence rates. Comparative studies suggest that pregnancy rates following EST are similar to or better than those after cystectomy, with the added benefit of more oocytes retrieved, which may lead to higher cumulative live birth rates. Despite these promising results, challenges such as recurrence and complications, particularly with prolonged ethanol exposure, remain. The use of transvaginal versus laparoscopic approaches and optimal ethanol exposure protocols are areas of ongoing research. The need for further large-scale, prospective studies is highlighted to refine the EST protocol and better understand the long-term outcomes. Sclerotherapy presents a feasible option for preserving fertility in women with endometriomas, with positive implications for IVF success and ovarian reserve preservation. Full article

This study aimed to identify unique characteristics in the peripheral blood mononuclear cells (PBMCs) of endometriosis patients and develop a non-invasive early diagnostic tool. Using single-cell RNA sequencing (scRNA-seq), we constructed the first single-cell atlas of PBMCs from endometriosis patients based on 107,964 cells and 25,847 genes. Within CD16⁺ monocytes, we discovered JUP as a dysregulated gene. To assess its diagnostic potential, we measured peritoneal fluid (PF) and serum JUP levels in a large cohort of 199 patients including 20 women with ovarian cancer (OC). JUP was barely detectable in PF but was significantly elevated in the serum of patients with endometriosis and OC, with levels 1.33 and 2.34 times higher than controls, respectively. Additionally, JUP was found in conditioned culture media of CD14⁺/CD16⁺ monocytes aligning with our scRNA-seq data. Serum JUP levels correlated with endometriosis severity and endometrioma presence but were unaffected by dysmenorrhea, menstrual cycle, or adenomyosis. When combined with CA125 (cancer antigen 125) JUP enhanced the specificity of endometriosis diagnosis from 89.13% (CA125 measured alone) to 100%. While sensitivity remains a challenge at 19%, our results suggest that JUP’s potential to enhance diagnostic accuracy warrants additional investigation. Furthermore, employing serum JUP as a stratification marker unlocked the potential to identify additional endometriosis-related genes, offering novel insights into disease pathogenesis. Full article