Search Results (1,420)

Melatonin has evolved from its classical role as a pineal-derived circadian regulator to a molecule increasingly recognized for its mitochondrial and cytoprotective functions. This review examines the molecular mechanisms and translational implications of melatonin within a mitochondria-centered framework, with particular emphasis on reproductive medicine. Available evidence suggests that melatonin may influence mitochondrial quality control (MQC) through multiple interconnected processes, including ROS regulation, mitochondrial dynamics, mitophagy, biogenesis, and mitochondrial inflammatory signaling. In mitochondria, melatonin can attenuate electron transport chain-derived oxidative stress through direct radical-scavenging reactions, antioxidant metabolite formation, and indirect activation of endogenous antioxidant systems. Experimental studies further suggest that melatonin may modulate Drp1-mediated fission, OPA1- and Mfn1/2-associated fusion, PINK1/Parkin-mediated mitophagy, and SIRT1/PGC-1α-related mitochondrial biogenesis. In reproductive medicine, melatonin has been investigated as a potential adjunctive strategy in assisted reproductive technology, endometriosis, and polycystic ovary syndrome. However, clinical evidence remains heterogeneous, and most human studies have evaluated reproductive or biochemical outcomes rather than direct MQC-related biomarkers. Therefore, although melatonin represents a promising mitochondria-targeted adjunct, standardized dosing strategies, tissue-level pharmacodynamic assessment, and validated mitochondrial biomarkers are needed to determine whether these mechanisms translate into reproducible clinical benefit. Full article

Endometriosis is a chronic gynecological disease affecting about 10% of reproductive age women, with a significant impact on socio-economic sphere and quality of life. It is a multifactorial phenomenon, in which genetic predisposition, immunologic malfunction, hormone imbalance, and environmental insult play an important role in disease development and progression. The aim of this review is to report the current evidence from the literature related to the association between endometriosis and endocrine disruptors. This study was designed as a systematic review and meta-analysis investigating the association between exposure to endocrine disruptors and the risk of endometriosis. The review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The systematic search identified 428 records from national and international scientific databases. The included studies were published between 2001 and 2020, with most studies classified as fair-to-good quality. The overall random-effects meta-analysis demonstrated a statistically significant association between exposure to endocrine-disrupting chemicals and endometriosis. This systematic review and meta-analysis provides evidence of a significant association between exposure to endocrine-disrupting chemicals and endometriosis, with the strongest and most consistent association observed for polychlorinated biphenyls. Full article

Background/Objectives: Endometriosis manifests as ectopic endometrial tissue outside the uterine cavity. This lesion can sometimes appear at unusual anatomical sites or within the intestinal tract, growing and mimicking cancer. Such tumor-like endometriosis lesions are relatively uncommon and biologically intriguing. Methods: This study is a retrospective case series of 14 patients presenting with tumor-like endometriosis at a single institution between 2007 and 2023. Laser capture microdissection was used to isolate epithelial cells from endometriotic glands in tissue sections from formalin-fixed, paraffin-embedded blocks, and the microdissected epithelium was analyzed for cancer driver mutations. Results: Unlike conventional endometriosis, these tumor-like lesions were generally sizable and clinically presented in the groin area, aortic wall, omentum, bowel wall, or lymph nodes, all of which raised suspicion for malignancy, despite 11 (78.6%) of the 14 cases having a history of or clinical signs of endometriosis. A total of 11 cancer-driver mutations were identified in 6 of the 14 patients, with four patients harboring multiple mutations. Recurrent mutations included KRAS-activating mutations in four cases and ARID1A-inactivating mutations in two cases. Additional mutations involved PIK3CA, CTNNB1, CHD4, MYD88, and STAG2. Conclusions: This study detected mutations in KRAS, ARID1A, PIK3CA, CTNNB1, and MYD88 in endometriotic lesions, consistent with previous literature, and identified newly reported mutations in CHD4 and STAG2. Not every tumor-like lesion harbored cancer driver mutations. Full article

Background: Abdominal wall endometriosis (AWE) following cesarean section (CS) is an increasingly recognized complication. Intramuscular involvement of the rectus abdominis and the management of associated fascial defects remain underreported. Methods: We retrospectively analyzed 14 consecutive women with histopathologically confirmed AWE following CS. Clinical presentation, imaging, operative technique, and follow-up outcomes were analyzed. Results: Mean age was 35.4 years (range 29–45). Three cases (21.4%) showed intramuscular rectus abdominis invasion; 11 (78.6%) were subcutaneous. Mean nodule size was 24.1 mm (range 9–45 mm). Cross-sectional imaging (MRI or CT) was obtained selectively in four patients with the largest lesions. Wide local excision with free margins was achieved in all cases. Two intramuscular cases required primary fascial repair (defects ~2 cm) without prosthetic mesh. No recurrences were detected at 12–24 months of follow-up. Conclusions: AWE following CS may involve both subcutaneous and intramuscular planes. Wide local excision with primary fascial repair is effective for small defects. Preoperative sonographic evaluation and individualized operative planning are essential for optimal outcomes. Full article

Background: Endometriosis is a chronic inflammatory disease affecting approximately 10% of women of reproductive age and is commonly associated with pelvic pain and infertility. Increasing evidence indicates that lower urinary tract symptoms (LUTS) are more common in women with endometriosis, even in the absence of direct urinary tract involvement; however, the underlying mechanisms remain poorly understood. This study aimed to compare LUTS in women with surgically confirmed endometriosis and symptomatic women in whom endometriosis was surgically excluded, and to investigate their association with urethral ultrasonographic parameters and lesion localization. Methods: This prospective case–control study included 163 women: 81 with surgically confirmed endometriosis and 82 symptomatic controls in whom endometriosis was surgically excluded. Urinary symptoms were assessed using the validated Urogenital Distress Inventory Short Form (UDI-6). Urethral length and mobility were evaluated by transvaginal pelvic floor ultrasonography at rest, during pelvic floor muscle contraction, and during the Valsalva maneuver. Associations between urinary symptoms, ultrasonographic findings, lesion localization, and selected clinical variables were analyzed using appropriate non-parametric tests and multivariable linear regression. Results: Women with endometriosis demonstrated significantly higher total UDI-6 scores than symptomatic controls (p = 0.002), indicating a greater burden of lower urinary tract symptoms. Significant differences were observed only for pain/discomfort and post-void urine leakage, whereas the remaining UDI-6 domains did not differ between groups. Overall urethral ultrasonographic parameters were comparable between groups. However, among symptomatic women (UDI-6 ≥ 1), urethral mobility during the Valsalva maneuver was significantly lower in women with endometriosis than in controls (p = 0.041). Endometriosis localization was not associated with urinary symptom severity or urethral ultrasonographic findings. In multivariable analysis, previous cesarean section, but not endometriosis itself, was independently associated with higher UDI-6 scores. Conclusions: Women with surgically confirmed endometriosis experienced a greater burden of lower urinary tract symptoms than symptomatic women without endometriosis, particularly pain/discomfort and post-void urine leakage. These symptoms were not associated with lesion localization or major differences in urethral morphology, indicating that structural urethral abnormalities alone do not explain urinary symptom severity in this population. Routine assessment of urinary symptoms using validated questionnaires may facilitate comprehensive evaluation of women with endometriosis. Further prospective multicenter studies incorporating standardized pain assessment, urodynamic evaluation, and longitudinal follow-up are warranted to better elucidate the mechanisms underlying lower urinary tract symptoms in this population. Full article

Background: Endometriosis is a chronic inflammatory and estrogen-dependent disease in which oxidative stress, immune dysregulation, and lesion-supportive microenvironmental signaling contribute to lesion development. N-acetylcysteine (NAC), a glutathione-replenishing and redox-modulating agent, has been studied as a possible non-hormonal intervention. Methods: Following preregistration in the Open Science Framework (OSF), we performed a PRISMA-compliant systematic review of studies evaluating NAC in endometriosis-related clinical, in vivo, ex vivo, or in vitro settings. We searched PubMed/MEDLINE, EBSCOhost, and the Bielefeld Academic Search Engine (BASE) from inception to 24 May 2026. Risk of bias was assessed with design-specific instruments. Results: Twenty-two studies were included. Clinical evidence comprised six studies and suggested that the findings vary by clinical context. In non-postoperative settings, NAC was associated with reduced pain, decreased NSAID use, and endometrioma shrinkage or stabilization. In contrast, the only postoperative randomized comparison found no added benefit of NAC over continuous oral contraceptive therapy for recurrence or pain. Fertility-related clinical findings were suggestive but preliminary. Across nonclinical models, NAC reduced proliferation, lesion burden, oxidative stress, inflammatory mediators, and, in selected systems, migration-related behavior. Mechanistic studies linked NAC to modulation of ROS-dependent proliferation, TNF-α, COX-2, MMP-2/-9, autophagy-related signaling, oxidation-sensitive nociception, and partial protection of oocyte and embryo competence under endometriosis-associated oxidative conditions. Conclusions: NAC shows biological plausibility and preclinical activity in endometriosis, but clinical evidence is heterogeneous and methodologically limited. Full article

Purpose: We aim to elucidate the impact of endometriomas on oocyte developmental competence and identify genetic alterations that may influence ICSI success rates in women of different ages. Methods: In this retrospective study, two groups of patients have been analyzed: 108 women with a history of severe endometriosis (stages III and IV), who underwent OPU and ICSI after endometriosis surgery, and a control group, built out of 108 women with no endometriosis history. The Turku Endometriosis Database was used for differential gene expression analysis. Results: The number of aspirated oocytes (endometrioma group: 2.75 ± 0.32 vs. control 10.32 ± 0.54) was significantly (p < 0.0001) lower in patients with endometrioma excision, and the number of generated blastocysts was significantly (p < 0.0001) lower when compared to patients without endometriosis (endometrioma group: 1.09 ± 0.13 vs. control group: 3.76 ± 0.23). Additionally, AMH levels were significantly lower (p < 0.001) in the endometriosis-affected group below the age of 35 years (1.65 ± 0.15) than in the unaffected control group (2.99 ± 0.27) within the same age group. The mRNA expression of the following genes related to oxidative stress was significantly (p < 0.05) upregulated in the endometriosis group compared with healthy controls: DES, P2RX1, FOS, SRF, RASD2, SLITRK3, and TEAD3. Gene Ontology and pathway enrichment analyses demonstrated a significant (p < 0.0001) enrichment of oxidative stress–associated biological processes and signaling pathways, including responses to reactive oxygen species and hypoxia, HIF-1, MAPK, PI3K–Akt, NF-κB, and apoptotic signaling, supporting oxidative stress as a central molecular mechanism underlying the observed transcriptomic alterations. Conclusions: In conclusion, this retrospective study provides a holistic perspective on the impact of endometrioma and its oxidative stress effect on oocyte developmental rates and ICSI outcomes across different age groups. Full article

Background: The introduction of the Morphological Uterus Sonographic Assessment (MUSA) 2022 criteria for diagnosing adenomyosis has reduced diagnoses compared with previous criteria. However, the impact of each ultrasonographic sign on diagnosis and symptom management remains unexplored. Methods: We retrospectively re-evaluated data from our 2015 study, which used criteria available before the first MUSA consensus. Nulligravid women aged 18–30 years without endometriosis were included to determine whether MUSA 2022 criteria result in fewer diagnoses than previous criteria. Sonographic images were reviewed and MUSA 2022 criteria applied. The primary outcome was to estimate previous overdiagnosis; the secondary outcome was to identify correlations between ultrasound features and symptoms. Results: Among 156 patients, at least one direct MUSA 2022 sign was present in 36 women; 17 had only indirect signs; and 103 had no ultrasound signs. MUSA 2022 criteria reduced adenomyosis prevalence from 34% to 23.1%. Direct signs were associated with greater dyspareunia (44.4% vs. 11.8%) and higher VAS scores. Hypermenorrhoea was associated with asymmetrical thickness (Odds Ratio 2.84) and a globular uterus (Odds Ratio 4.03). Conclusions: Applying MUSA 2022 criteria reduces adenomyosis diagnoses, suggesting that previous criteria may have overestimated prevalence. Nevertheless, ultrasound remains an adjunct to clinical assessment, and symptoms should guide management when direct signs are absent. Full article

The first trimester (FT) of pregnancy is characterized by rapid placental growth and differentiation, rendering this period sensitive to maternal metabolic influences. Maternal obesity is associated with chronic low-grade inflammation and altered redox homeostasis with implications in later cardiometabolic risk in offspring, yet its impact on early placental oxidative stress remains unclear. Here, we investigated whether maternal overweight and obesity are associated with oxidative lipid and protein damage and altered expression of antioxidant enzymes and stress signaling pathways. Placental tissue from lean (BMI < 25 kg/m²), overweight (BMI ≥ 25 kg/m²) and obese (BMI ≥ 30 kg/m²) non-smoking women (5–12 weeks’ gestation) was analyzed. Oxidative damage was assessed by immunoblotting for 4-hydroxynonenal and 3-nitrotyrosine, and antioxidant and stress-related transcripts were quantified using targeted mRNA arrays. Explants were exposed to increased oxygen tension or TNF-α to evaluate transcriptional responsiveness. No differences in oxidative lipid or protein modifications were detected between groups. In contrast, overweight and obesity were associated with reduced expression of selected antioxidant enzymes and transcriptional remodeling of MAPK-related genes. These changes correlated with IL6 expression but not with oxidative damage markers. Collectively, maternal overweight and obesity are linked to inflammation-associated transcriptional adaptation in FT placenta without detectable oxidative injury. Full article

Background: Endometriosis of the cervix is a rare, non-cancerous disease that can look or behave like cancerous cervical tissue, causing challenges regarding diagnosis and management. Discrimination between benign and malignant lesions can be difficult when utilizing cytological, colposcopic, and histopathological data if the findings do not agree with each other. Case Presentation: We report the case of an asymptomatic 45-year-old woman who was initially diagnosed with FIGO stage IA1 microinvasive cervical carcinoma based on cytological, colposcopic, and conization findings. Further evaluation yielded persistent uncertainty in diagnostic imaging and, in addition, a concern for invasive cervical disease. Therefore, the patient underwent a total hysterectomy with bilateral salpingo-oophorectomy, and the result of the postoperative evaluation was cervical endometriosis without evidence of invasive malignancy. This example demonstrates the diagnostic challenges associated with rare benign cervical lesions, which may resemble cervical carcinoma, and emphasizes the high-risk for overtreatment due to the vagueness of these types of cases. Conclusions: When there is a discrepancy among clinical findings, cytology, and histopathology in suspicious cervical lesions, cervical endometriosis must be considered in the differential diagnosis. To increase accuracy in diagnosis and minimize the possibility of unnecessary radical treatment, careful histopathologic reevaluation and multidisciplinary assessment are necessary. Full article

Endometriosis is a chronic inflammatory disease characterized by the ectopic growth of endometrial-like tissue and is closely associated with pain and infertility. This review summarizes current evidence on immune dysregulation and emerging immunomodulatory therapies in endometriosis. Relevant clinical and mechanistic studies were identified through a structured literature review and qualitatively synthesized. Increasing evidence suggests that immune dysregulation plays a critical role in disease pathogenesis. Within the immune microenvironment, innate and adaptive immune cells—including macrophages, dendritic cells, neutrophils, mast cells, T cells, and B cells—collectively promote inflammation, angiogenesis, fibrosis, and immune evasion. Emerging immunotherapeutic strategies, including macrophage repolarization, NK cell restoration, dendritic cell modulation, neutrophil extracellular traps inhibition, immune checkpoint blockade, and cytokine/chemokine targeting, have shown promising preclinical and early clinical potential. However, disease heterogeneity, reproductive safety concerns, and the lack of validated biomarkers remain major barriers to clinical translation, highlighting the potential of immunomodulatory therapies as future non-hormonal treatment strategies. Full article

Endometriosis is a chronic estrogen-dependent condition affecting women of reproductive age and commonly presents with dysmenorrhea, chronic pelvic pain, dyspareunia, and infertility. In a substantial proportion of patients, pain persists despite first-line hormonal treatment, making alternative pharmacologic strategies necessary. GnRH agonists and antagonists act primarily by suppressing ovarian estrogen production and thereby reduce an important hormonal driver of disease activity. Although both classes are effective for pain relief, they differ in onset of action, reversibility, tolerability, and suitability for prolonged use. This narrative review summarizes the current evidence on GnRH-based therapies for endometriosis-associated pain, with particular attention to biological rationale, clinical efficacy, safety, and the role of add-back therapy. Overall, both agonists and antagonists appear to provide clinically significant symptom improvement, especially in women who do not respond adequately to oral contraceptives or progestins. Their clinical use, however, is limited by hypoestrogenic adverse effects such as vasomotor symptoms and bone mineral density loss, which often require monitoring and adjunctive add-back therapy. Oral GnRH antagonists may offer practical advantages in selected patients through rapid action, the absence of a flare effect, and dose-adjustable hormonal suppression, although treatment choice must also consider long-term safety, cost, access, and individual patient characteristics. In summary, GnRH analogues remain useful second-line options, but treatment should be individualized according to symptom severity, previous treatment response, reproductive goals, tolerability, bone health, cost, and availability. Full article

Objective: To evaluate reproductive outcomes following fertility-sparing surgery for deep endometriosis (DE), specifically assessing the impact of bowel resection on spontaneous conception rates and the predictive value of the Endometriosis Fertility Index (EFI). Design: Retrospective observational cohort study. Setting: High-volume tertiary referral center for endometriosis. Patients: A total of 507 women with histologically confirmed endometriosis and documented infertility or active desire for pregnancy, managed between 2018 and 2025. Patients undergoing hysterectomy were excluded. Interventions: Laparoscopic complete excision of endometriotic lesions using a nerve-sparing technique. The surgical strategy for bowel involvement was tailored to nodule characteristics: 194 patients (38.3%) underwent segmental colorectal resection, 38 (7.5%) underwent rectal shaving, and 9 (1.8%) were treated with advanced organ-sparing techniques (lateral rectal resection or extra-mucosal excision—EMEB). Main Outcome Measures: Postoperative pregnancy rate (PR), mode of conception (spontaneous vs. ART), and factors influencing fertility. Results: The cohort presented with severe disease (mean rASRM stage 3.4) and a high prevalence of primary infertility (79.3%). During the follow-up period, 310 patients achieved pregnancy, resulting in an overall pregnancy rate of 61.1%. Notably, 70.3% of these pregnancies were achieved spontaneously. Radicality did not compromise fertility: the segmental resection group achieved a pregnancy rate of 91.2% (177/194), while patients treated with rectal shaving achieved 100%. The EFI score was identified as a robust predictor of success (mean score 5.5 in pregnant vs. 4.9 in non-pregnant patients, p < 0.05). Conclusions: Comprehensive nerve-sparing excision of DE, including segmental bowel resection, is associated with high pregnancy rates and a predominant restoration of natural fertility. Surgery should be considered a first-line strategy to reduce dependency on assisted reproductive technologies. Full article

The anion exchanger 1 (AE1), traditionally known for its role in erythrocyte anion transport and acid–base homeostasis, has recently been identified in non-erythroid tissues, suggesting broader physiological functions. In the present study, we investigated for the first time the expression and potential role of AE1 in human ovarian granulosa cells (GCs) obtained from women with endometriosis (ENDO-GCs) or male factor infertility controls (MF-GCs). Cells were cultured in the presence of follicular fluid derived from control (FF-MF) or endometriosis patients (FF-ENDO), and DIDS-sensitive anion exchange activity was pharmacologically inhibited using 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS). AE1 expression was evaluated at both protein and transcript levels together with markers of proliferation, inflammation, and steroidogenesis. The results demonstrate that AE1 is constitutively expressed in GCs and may contribute to granulosa cell homeostasis. Inhibition of DIDS-sensitive anion exchange activity inhibited cell proliferation, shifted cell morphology toward a fibroblast-like phenotype, and reduced estradiol and progesterone secretion and inflammatory (IL-6) gene transcription. Notably, MF-GCs cultured in FF-MF exhibited compensatory upregulation of AE1, whereas ENDO-GCs and cells exposed to FF-ENDO showed impaired adaptive responses and generalized transcriptional suppression. These findings provide preliminary evidence supporting a role for DIDS-sensitive anion exchange activity in granulosa cell physiology and warrant further studies to clarify the specific contribution of AE1 to follicular dysfunction associated with endometriosis. However, the specific mechanistic contribution of AE1 could not be established and will require further functional and genetic investigations. Full article

Background and Clinical Significance: Abdominal wall endometriosis (AWE) is an ectopic endometrial tissue embedded into the anterior abdominal wall, mainly infiltrating the rectus abdominis or oblique muscles and subcutaneous tissue. In most cases, AWE is associated with surgical scars after obstetrical and gynecological, as well as non-gynecological surgeries. Case Presentation: A 51-year-old female patient presented to the ultrasound outpatient clinic with a non-cyclic painful, palpable nodular mass located in the postoperative scar in the right lower abdominal quadrant. She underwent an appendectomy at the age of 9 (premenarchal period). The patient had regular menstrual cycles, one cesarean section and two vaginal deliveries, denied any trauma to that abdominal region, and had no history of pelvic endometriosis. Her past medical history was also remarkable for left-sided breast cancer, and she was worried it could be metastasis. Following imaging evaluation, a preliminary diagnosis was a benign lesion in the post-appendectomy scar, most likely a suture granuloma, also known as Schloffer’s tumor. Fine-needle aspiration was performed, and findings were primarily suspicious for AWE. The patient was then referred to an abdominal surgeon for excision of the affected area, and subsequent histopathological analysis confirmed that the mass was AWE. Conclusions: Imaging findings of a mass in the abdominal wall are not pathognomonic for AWE; only histopathological examination can confirm the diagnosis. If a painful nodular mass is located adjacent to a surgical scar in a female patient, AWE should be a leading consideration in the differential diagnosis, along with suture granuloma in cases of old surgical scars. Full article