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Keywords = early ovarian aging

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15 pages, 1055 KB  
Article
Intraoperative Ex Vivo Shear-Wave Elastography of Sentinel Lymph Nodes in Endometrial Cancer and Other Gynaecological Malignancies
by Walid Shaalan, Mohamed Eldesouky, Theresa Mokry, Arved Bischoff, Peter Sinn, Nourhan Hassan, Riku Togawa, Dina Batarseh, Kathrin Haßdenteufel, Lara Meike Tretschock, Maryna Hlamazda, Christina Schmidt, Cecilie Torkildsen, Axel Gerhardt, Andre Hennigs, Lisa Katharina Nees, Oliver Zivanovic and Fabian Riedel
Cancers 2026, 18(2), 183; https://doi.org/10.3390/cancers18020183 - 6 Jan 2026
Viewed by 161
Abstract
Background: Accurate intraoperative assessment of sentinel lymph node (SLN) status is critical for staging and guiding surgical management in gynaecological malignancies. Frozen-section histopathology remains the gold standard, but it is time-consuming and resource-intensive. Shear-wave elastography (SWE) quantifies tissue stiffness in real time and [...] Read more.
Background: Accurate intraoperative assessment of sentinel lymph node (SLN) status is critical for staging and guiding surgical management in gynaecological malignancies. Frozen-section histopathology remains the gold standard, but it is time-consuming and resource-intensive. Shear-wave elastography (SWE) quantifies tissue stiffness in real time and may offer a rapid alternative. Methods: In this prospective single-centre study, 63 women (median age 62 years) undergoing primary surgery with sentinel lymph node biopsy (SLNB) for endometrial, cervical, vulvar, or early ovarian carcinoma were enrolled. A total of 172 SLNs were excised, submerged in coupling gel, and scanned ex vivo using a 9 MHz linear probe. Results: A total of 172 SLNs underwent SWE (mean 2.7 nodes/patient). Endometrial primaries accounted for 58% of nodes, mostly retrieved by robotic-assisted surgery (71.8%). Node dimensions were significantly larger in malignant lesions for sonographic (long-axis: 13.02 ± 3.31 mm vs. 10.80 ± 3.28 mm; p = 0.002) and pathological long-axis measurements (11.45 ± 2.83 mm vs. 9.75 ± 2.61 mm; p = 0.004). Mean SWE velocities were similar between groups (1.381 ± 0.307 vs. 1.343 ± 0.236 m/s; p = 0.541). Histopathology identified metastases in 18% of SLNs, comprising macrometastases (7%), micrometastases (5%), and isolated tumour cells (6%). Conclusions: Although ex vivo SWE is rapid, reproducible, and integrates seamlessly into the sterile field, stiffness measurements alone lack sufficient discriminatory power for SLN staging in gynaecological cancers. Future research should focus on three-dimensional SWE, advanced radiomic analyses, and machine-learning algorithms to improve the detection of low-volume metastatic disease. Full article
(This article belongs to the Special Issue Gynecologic Cancer: From Diagnosis to Treatment: 2nd Edition)
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11 pages, 731 KB  
Case Report
Polymicrobial PID Presenting as Primary Peritonitis in a Young Immunocompetent Patient—Case Report and Disease Perspectives
by Georgiana Nemeti, Maria Adriana Neag, Iulian Gabriel Goidescu, Mihai Surcel, Cerasela Mihaela Goidescu, Ioana Cristina Rotar and Daniel Muresan
Diagnostics 2026, 16(1), 134; https://doi.org/10.3390/diagnostics16010134 - 1 Jan 2026
Viewed by 186
Abstract
Background and Clinical Significance: Pelvic inflammatory disease represents a multifaceted sexually transmitted disease affecting women of reproductive age, beginning in adolescence. Clinical presentation ranges from asymptomatic patients to acute abdominal pain in the setting of tubo-ovarian abscesses; however, presentation as primary peritonitis [...] Read more.
Background and Clinical Significance: Pelvic inflammatory disease represents a multifaceted sexually transmitted disease affecting women of reproductive age, beginning in adolescence. Clinical presentation ranges from asymptomatic patients to acute abdominal pain in the setting of tubo-ovarian abscesses; however, presentation as primary peritonitis with seemingly intact fallopian tubes is exceptional. Primary peritonitis in the absence of other comorbid conditions (e.g., liver cirrhosis and nephrotic syndrome) in healthy, immunocompetent women is rare and typically occurs without an identifiable intra-abdominal source. The diagnosis can be challenging due to its mild-to-moderate, nonspecific symptoms. Case Presentation: We report the case of a 21-year-old immunocompetent woman who presented with lower abdominal and left iliac fossa pain with hyperleukocytosis. Laparoscopic exploration confirmed the diagnosis of primary peritonitis. Following diagnosis, she underwent peritoneal lavage and was started on empiric broad-spectrum parenteral antibiotic therapy. Cervico-vaginal cultures established the diagnosis of PID following identification of Chlamydia trachomatis, Mycoplasma hominis, and Ureaplasma parvum. The clinical course was favorable. Conclusions: An early multidisciplinary approach, including consultation with an infectious disease specialist and clinical pharmacologist, is recommended in cases of peritonitis with an unclear source. PID may present as primary peritonitis and this clinical scenario should be considered in sexually active young women with unexplained peritoneal infection when no gastrointestinal or gynecologic source is evident intraoperatively. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Gynecological Infections)
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14 pages, 652 KB  
Article
From Biobank to Bedside: A Pilot Study on Returning Medically Actionable BRCA1/2 Results in Qatar’s Precision Medicine Landscape
by Salha Bujassoum Al Bader, Hind Habish, Hajer Almulla, Fatemeh Abbaszadeh, Mariem Sidenna, Tasnim Fadl, Mohamed Alvi, Marwa Eldeeb, Huda Farah, Amal Elfatih, Radja Messai Badji, Lotfi Chouchane, Nahla Afifi, Said Ismail, Reem Alsulaiman and Wadha Al-Muftah
Biomedicines 2025, 13(12), 3047; https://doi.org/10.3390/biomedicines13123047 - 11 Dec 2025
Viewed by 526
Abstract
Background: Hereditary breast and ovarian cancer is an inherited condition caused by pathogenic (P) or likely pathogenic (LP) variants in the BRCA1 and BRCA2 genes. Population-level sequencing allows for the identification of asymptomatic genotype-positive participants (GPPs) before disease onset. This study assessed the [...] Read more.
Background: Hereditary breast and ovarian cancer is an inherited condition caused by pathogenic (P) or likely pathogenic (LP) variants in the BRCA1 and BRCA2 genes. Population-level sequencing allows for the identification of asymptomatic genotype-positive participants (GPPs) before disease onset. This study assessed the feasibility and impact of returning clinically relevant BRCA results to participants at the Qatar Precision Health Institute (QPHI). Methods: We established a structured framework to identify and refer asymptomatic individuals who were found to carry P/LP variants in BRCA among 6142 QPHI participants. The process integrated genomic analysis, participant recontact, counseling, referral, variants validation, and personalized risk-reducing strategies. Results: Six variants (four BRCA1, two BRCA2) were validated in ten GPPs with a median age of 48 years (IQR: 40.5–56). Eight variants were confirmed through Sanger sequencing in a CAP-accredited laboratory at Hamad Medical Corporation. All eligible participants were referred for counseling and personalized clinical management. Four men initiated breast and prostate cancer surveillance, while four women pursued breast and ovarian surveillance. One asymptomatic GPP underwent prophylactic salpingo-oophorectomy, revealing early-stage ovarian cancer. Cascade testing identified 20 additional GPPs and, in one asymptomatic relative, facilitated the detection of early-stage uterine cancer. The genetic testing acceptability rate was 0.77 (95% CI: 0.46–0.94), with a 100% adherence to surveillance at 12- and 24-month follow-ups. Conclusions: This pilot demonstrates the feasibility and clinical utility of returning actionable BRCA1/2 findings and represents the first initiative in an Arabic population to implement the return of medically actionable BRCA results from a population-based biobank. Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
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17 pages, 1440 KB  
Article
Experimental Galactose-1-Phosphate Uridylyltransferase (GALT) mRNA Therapy Improves Motor-Related Phenotypes in a Mouse Model of Classic Galactosemia—A Pilot Study
by Olivia Bellagamba, Aaron J. Guo, Xinhua Yan, Joe Sarkis, Bijina Balakrishnan and Kent Lai
Biomedicines 2025, 13(12), 2848; https://doi.org/10.3390/biomedicines13122848 - 21 Nov 2025
Viewed by 641
Abstract
Background: Despite life-saving newborn screening programs and a life-long galactose-restricted diet, many patients with classic galactosemia continue to develop long-term debilitating neurological deficits, speech dyspraxia, and primary ovarian insufficiency (POI). In an earlier study, we showed that administration of an experimental human GALT [...] Read more.
Background: Despite life-saving newborn screening programs and a life-long galactose-restricted diet, many patients with classic galactosemia continue to develop long-term debilitating neurological deficits, speech dyspraxia, and primary ovarian insufficiency (POI). In an earlier study, we showed that administration of an experimental human GALT mRNA predominantly expressed in the liver of the GalT gene-trapped mouse model augmented the expression of hepatic GALT activity, which reduced build-up of galactose and its toxic metabolites not only in the liver but also in the peripheral tissues. Moreover, we showed that the administration of GALT mRNA in the mutant mice restored whole-body galactose oxidation (WBGO), which is a functional biomarker. Methods: In this pilot study, we extended our proof-of-concept efficacy studies to a disease-relevant phenotype: motor impairment. GalT-KO mice aged 3 and 6 weeks old administered biweekly intravenous injections of 100 µL GALT mRNA at a dose of 2 mg/kg for 2 months. Motor performance was assessed using rotarod testing and composite phenotype scoring, 3 and 9 weeks following the dosing regimen. Results: Preliminary results showed that a biweekly dosing at 2 mg/kg for 2 months improved the motor performance of the animals in rotarod and composite phenotype scoring tests in a short-term experiment. Conclusions: Despite being a small-scale study, our findings suggest that when treated early in life, the experimental GALT mRNA is effective in improving the motor-related phenotypes in GalT-KO mice using the specified dosing regimen. These findings highlight the potential of mRNA-based therapies for mitigating neurological symptoms in Classic galactosemia. Full article
(This article belongs to the Section Molecular Genetics and Genetic Diseases)
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15 pages, 1537 KB  
Article
Effectiveness of Controlled Ovarian Stimulation for Oocyte Preservation in Oncologic Patients: Insights from DuoStim Protocol
by Andrea Panattoni, Maria Magdalena Montt Guevara, Ilaria Marzi, Koray Görkem Saçıntı, Francesca Papini, Chiara Maggiorano, Sara Macaluso, Elena Casarosa, Tommaso Simoncini, Paolo Giovanni Artini and Vito Cela
J. Clin. Med. 2025, 14(22), 8062; https://doi.org/10.3390/jcm14228062 - 14 Nov 2025
Viewed by 991
Abstract
Background/Objectives: Fertility preservation is a key component of oncological care. This study evaluated the effectiveness of different controlled ovarian stimulation (COS) protocols, including dual stimulation (DuoStim), for oocyte preservation, with a specific focus on breast cancer patients, and aimed to identify predictors [...] Read more.
Background/Objectives: Fertility preservation is a key component of oncological care. This study evaluated the effectiveness of different controlled ovarian stimulation (COS) protocols, including dual stimulation (DuoStim), for oocyte preservation, with a specific focus on breast cancer patients, and aimed to identify predictors of mature oocyte yield. Methods: A retrospective single-center study was conducted on 203 women under 40 years undergoing fertility preservation before cancer treatment between August 2013 and May 2024 at the Fertility Unit of the University Hospital of Pisa. COS protocols were stratified by menstrual cycle phase: early follicular (EFP), late follicular (LFP), luteal (LP), and DuoStim. The primary outcome was fertility preservation, assessed by the number of mature oocytes retrieved (MII). Independent predictors of oocyte yield were assessed using multivariable Poisson regression. Results: A total of 244 COS cycles were analyzed. The DuoStim group showed a lower median number of MII oocytes collected during the second stimulation compared to EFP, LFP, and LP (all adjusted p-value < 0.05, FDR); however, cumulative MII counts across both stimulations were comparable to other protocols. Oocyte maturity rates were similar across groups. Multivariable analysis identified AMH and AFC, but not age, basal FSH, hormonal parameters, and year of cryopreservation, as independent predictors of MII oocyte yield. Conclusions: COS is effective for fertility preservation across different cycle phases without delaying cancer treatment. DuoStim is not inferior but rather a valuable strategy for poor responders with insufficient oocyte yield after an initial cycle, thereby broadening opportunities for cryopreservation in time-sensitive oncological settings. Full article
(This article belongs to the Section Reproductive Medicine & Andrology)
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22 pages, 6496 KB  
Article
Fluoxetine Disrupts Ovarian Serotonin Signaling and Oocyte Competence in Mice
by Nina M. Alyoshina, Maria V. Beketova, Maria D. Tkachenko, Yulia O. Nikishina, Veronika S. Frolova, Lyudmila A. Malchenko, Maria L. Semenova, Maria P. Rubtsova and Denis A. Nikishin
Pharmaceuticals 2025, 18(11), 1647; https://doi.org/10.3390/ph18111647 - 31 Oct 2025
Viewed by 911
Abstract
Background: Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed, yet their direct impact on ovarian function remains poorly understood. While serotonin signaling is known to occur within the ovarian follicle, the specific molecular consequences of its disruption by SSRIs are unclear. This study [...] Read more.
Background: Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed, yet their direct impact on ovarian function remains poorly understood. While serotonin signaling is known to occur within the ovarian follicle, the specific molecular consequences of its disruption by SSRIs are unclear. This study aimed to elucidate the direct, intra-ovarian mechanisms by which fluoxetine, a common SSRI, affects follicular development and oocyte competence. Methods: We administered fluoxetine (20 mg/kg) or vehicle daily for seven days to both prepubertal and adult female mice to model short-term therapeutic exposure. Results: Fluoxetine treatment successfully blocked peripheral serotonin uptake, reducing serum levels by over 90%. Crucially, this occurred without altering circulating levels of estradiol, FSH, or LH and without disrupting the estrous cycle, indicating a mechanism independent of the central hypothalamic–pituitary–gonadal axis. Instead, we pinpoint a direct ovarian effect: fluoxetine inhibited serotonin transport activity in oocytes and significantly downregulated the expression of the pivotal oocyte-derived growth factor Gdf9. This was accompanied by reduced expression of genes crucial for granulosa cell function (Lhr, Fshr) and steroidogenesis (Cyp19a1). Functionally, these molecular changes manifested as a decline in oocyte quality and a significant reduction in ovulation rates in adult mice. Notably, these detrimental effects were more pronounced in prepubertal mice, indicating a heightened vulnerability during early follicular development. Conclusions: Our findings reveal a direct, intra-ovarian mechanism of fluoxetine-induced disruption. By inhibiting oocyte serotonin transport and downregulating GDF9, fluoxetine impairs critical oocyte–granulosa cell communication, thereby compromising oocyte competence and reducing fertility outcomes. This work identifies follicular development as a critical window of susceptibility to SSRI exposure, holding significant clinical implications for reproductive-aged and adolescent populations. Full article
(This article belongs to the Special Issue Pharmacology of Antidepressants: Recent Advances)
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21 pages, 2727 KB  
Article
Explainable Artificial Intelligence for Ovarian Cancer: Biomarker Contributions in Ensemble Models
by Hasan Ucuzal and Mehmet Kıvrak
Biology 2025, 14(11), 1487; https://doi.org/10.3390/biology14111487 - 24 Oct 2025
Viewed by 879
Abstract
Ovarian cancer’s high mortality is primarily due to late-stage diagnosis, underscoring the critical need for improved early detection tools. This study develops and validates explainable artificial intelligence (XAI) models to discriminate malignant from benign ovarian masses using readily available demographic and laboratory data. [...] Read more.
Ovarian cancer’s high mortality is primarily due to late-stage diagnosis, underscoring the critical need for improved early detection tools. This study develops and validates explainable artificial intelligence (XAI) models to discriminate malignant from benign ovarian masses using readily available demographic and laboratory data. A dataset of 309 patients (140 malignant, 169 benign) with 47 clinical parameters was analyzed. The Boruta algorithm selected 19 significant features, including tumor markers (CA125, HE4, CEA, CA19-9, AFP), hematological indices, liver function tests, and electrolytes. Five ensemble machine learning algorithms were optimized and evaluated using repeated stratified 5-fold cross-validation. The Gradient Boosting model achieved the highest performance with 88.99% (±3.2%) accuracy, 0.934 AUC-ROC, and 0.782 Matthews correlation coefficient. SHAP analysis identified HE4, CEA, globulin, CA125, and age as the most globally important features. Unlike black-box approaches, our XAI framework provides clinically interpretable decision pathways through LIME and SHAP visualizations, revealing how feature values push predictions toward malignancy or benignity. Partial dependence plots illustrated non-linear risk relationships, such as a sharp increase in malignancy probability with CA125 > 35 U/mL. This explainable approach demonstrates that ensemble models can achieve high diagnostic accuracy using routine lab data alone, performing comparably to established clinical indices while ensuring transparency and clinical plausibility. The integration of state-of-the-art XAI techniques highlights established biomarkers and reveals potential novel contributors like inflammatory and hepatic indices, offering a pragmatic, scalable triage tool to augment existing diagnostic pathways, particularly in resource-constrained settings. Full article
(This article belongs to the Special Issue AI Deep Learning Approach to Study Biological Questions (2nd Edition))
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21 pages, 1802 KB  
Review
The Relationship Between the Vaginal Microbiota and the Ovarian Cancer Microenvironment: A Journey from Ideas to Insights
by Stefano Restaino, Giulia Pellecchia, Martina Arcieri, Eva Pericolini, Giorgio Bogani, Alice Poli, Federico Paparcura, Sara Pregnolato, Doriana Armenise, Barbara Frossi, Gianluca Tell, Carlo Tascini, Lorenza Driul, Anna Biasioli, Vito Andrea Capozzi, Carlo Ronsini, Luigi Della Corte, Canio Martinelli, Alfredo Ercoli, Francesco De Seta and Giuseppe Vizzielliadd Show full author list remove Hide full author list
Cells 2025, 14(20), 1590; https://doi.org/10.3390/cells14201590 - 13 Oct 2025
Cited by 1 | Viewed by 1615
Abstract
Background: The tumor microenvironment offers a new perspective in gynecologic oncology. In ovarian cancer, numerous preclinical studies, especially organoid models, have highlighted cellular, immune, and biochemical mechanisms. Beyond these sophisticated findings, more practical aspects require attention, such as the role of vaginal microbiota, [...] Read more.
Background: The tumor microenvironment offers a new perspective in gynecologic oncology. In ovarian cancer, numerous preclinical studies, especially organoid models, have highlighted cellular, immune, and biochemical mechanisms. Beyond these sophisticated findings, more practical aspects require attention, such as the role of vaginal microbiota, which represents an interplay between external agents and internal genitalia, and its potential profiling role in early detection beyond the promise of microbiota-targeted therapies. Objectives: This review aims to assess whether such a correlation is speculative or scientifically grounded. Methods: A focused literature search was conducted on vaginal microbiota and its correlation with ovarian cancer to define the current state of knowledge. Results: Mixed outcomes have been reported, yet there is a rational and scientific basis supporting further investigation. Clinical approaches increasingly consider vaginal microbiota as relevant. However, we have to say that most available evidence is still preliminary and largely preclinical to set realistic expectations for readers. Although additional studies are needed, emerging insights highlight its importance and practical implications. We present a diagnostic–therapeutic management flowchart summarizing current evidence). Discussion: Most links between the vaginal microbiota and ovarian cancer are correlational rather than causal. The idea that microbes ascend from the vagina to the ovaries is proposed but still definitely not demonstrated. Confounding factors like age, hormones, and BRCA status complicate interpretation, and ovarian cancer itself could secondarily alter the microbiota. Mechanistic studies and longitudinal data are still needed to clarify whether dysbiosis contributes to carcinogenesis or is merely a consequence. As gynecologists, we summarize key aspects and emphasize to colleagues the importance of incorporating these findings into daily clinical practice. Vaginal dysbiosis should be considered not only a local imbalance but also a potential strategy for primary cancer prevention. Conclusions: Future research on the tumor microenvironment and vaginal microbiota will expand scientific knowledge and guide innovative preventive and therapeutic strategies. Full article
(This article belongs to the Section Cellular Pathology)
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17 pages, 2779 KB  
Article
Self-Reported Outcomes of Endocrine Therapy with or Without Ovarian Suppression in Premenopausal Breast Cancer Patients: A Brazilian Quality-of-Life Prospective Cohort
by Natália Nunes, Giselle Carvalho, Bernardo Ramos, Juliana Pecoraro, Lilian Lerner, Debora Azevedo, Thamirez Ferreira, Larissa Santiago de Moura, Carolina Galvão and Mariana Monteiro
Cancers 2025, 17(19), 3229; https://doi.org/10.3390/cancers17193229 - 4 Oct 2025
Viewed by 1073
Abstract
Background: Endocrine therapy (ET) with or without ovarian function suppression (OFS) is a cornerstone treatment for estrogen receptor-positive (ER+) breast cancer (BC) in premenopausal women, but its impact on quality of life (QoL) and sexual health remains a concern. Methods: We conducted a [...] Read more.
Background: Endocrine therapy (ET) with or without ovarian function suppression (OFS) is a cornerstone treatment for estrogen receptor-positive (ER+) breast cancer (BC) in premenopausal women, but its impact on quality of life (QoL) and sexual health remains a concern. Methods: We conducted a multicenter, prospective, observational study including premenopausal women (≤50 years) diagnosed with stage I–III ER+ BC and treated in private healthcare facilities in Brazil between 2013 and 2023. Patients received ET alone (ET-only) or combined with OFS (OFS-ET). QoL was assessed at baseline and 3, 6, 9, 12, and 24 months using the EORTC QLQ-BR23. Sexual functioning and sexual enjoyment were prespecified primary outcomes. Logistic regression identified factors associated with OFS use, and Fisher’s exact test was applied for categorical comparisons at 24 months. Results: Among 363 patients (80% ET-only, 20% ET + OFS), younger age, advanced stage, and chemotherapy were independently associated with OFS use. Both groups reported early declines in sexual functioning and enjoyment. By 24 months, ET-only patients had returned to baseline, whereas OFS patients remained below baseline. At the item level, no significant differences were observed in sexual desire (51.5% vs. 42.0%; p = 0.33) or enjoyment (26.0% vs. 13.5%; p = 0.20). Lack of sexual activity was more frequent in the OFS group (60.6% vs. 41.2%; p = 0.05). Body image was significantly more impaired with OFS, with a higher proportion of patients reporting feeling less attractive (38.2% vs. 19.9%; p = 0.04) and less feminine (26.5% vs. 11.7%; p = 0.05). Conclusions: ET impairs sexual health in young BC survivors, particularly when combined with OFS. These findings underscore the need for routine sexual health assessments and supportive interventions in survivorship care. Full article
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15 pages, 618 KB  
Article
Clinicopathological Characteristics and Oncologic Outcomes of Endometrioid Ovarian Carcinoma: A Retrospective Study from a Tertiary Cancer Centre
by Christina Pappa, Aakriti Aggarwal, Sally El Tawab, Sabina Nistor, Jennifer Thorne, Negin Sadeghi, Sanjiv Manek, Kezia Gaitskell, Sunanda Dhar, Jacopo Conforti, Federico Ferrari and Hooman Soleymani majd
Biomedicines 2025, 13(10), 2381; https://doi.org/10.3390/biomedicines13102381 - 28 Sep 2025
Viewed by 1366
Abstract
Background/Objectives: To evaluate the clinicopathological features, treatment, and survival outcomes and to identify independent prognosticators for recurrence and mortality in patients with endometrioid ovarian cancer. Methods: The medical records of patients diagnosed with endometrioid ovarian carcinoma between January 2010 and December [...] Read more.
Background/Objectives: To evaluate the clinicopathological features, treatment, and survival outcomes and to identify independent prognosticators for recurrence and mortality in patients with endometrioid ovarian cancer. Methods: The medical records of patients diagnosed with endometrioid ovarian carcinoma between January 2010 and December 2022 were reviewed retrospectively. Demographic and disease-related data were evaluated. Kaplan–Meier survival analysis using log rank test and Cox regression was performed. Results: Seventy-six patients were included in the study. The median age at diagnosis was 54 years (range 31–86). A total of 85.5% of the patients were diagnosed with early-stage disease and 88.1% of the tumours represented low-grade carcinomas. Synchronous endometrioid endometrial cancer was confirmed in 19.7% of the cases. All patients underwent surgical management and 65.8% received adjuvant chemotherapy. Median follow-up time was 67.5 months. The 5-year disease-free survival and overall survival were 92.1% and 93.4%, respectively. The risk of cancer-related death was higher in advanced stages (HR = 13.86; 95% CI 2.16–57.17; p < 0.001) and in the presence of residual disease (HR = 15.18; 95% CI 2.36–87.17; p < 0.002). Residual disease and advanced stages were also identified as independent risk factors for disease relapse with HR = 16.04 (95% CI 2.61–93.7; p < 0.002) and HR = 11.73 (95% CI 1.92–41.6; p < 0.001), respectively. Conclusions: Endometrioid ovarian carcinoma usually affects younger patients with the majority of the cases representing low-grade carcinomas diagnosed at early stages. Residual disease and advanced stages are independently associated with inferior survival outcomes. There was no significance of lymph node dissection and adjuvant chemotherapy in the overall and recurrence-free survival rates. Further research focusing on molecular profiling should aim to define the prevalence and the prognostic value of major molecular alterations and develop precise stratification models to plan personalised treatment for optimal care. Full article
(This article belongs to the Special Issue New Advances in Ovarian Cancer)
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24 pages, 808 KB  
Review
Cervical Cancer Treatment and Fertility: What We Know and What We Do
by Nassir Habib, Salwa Idoubba, Francoise Futcher, Emilio Pieri, Giorgia Schettini, Matteo Giorgi, Ramon Rovira Negre and Centini Gabriele
Cancers 2025, 17(18), 3057; https://doi.org/10.3390/cancers17183057 - 18 Sep 2025
Viewed by 2684
Abstract
Cervical cancer is a major health issue worldwide, with approximately 660,000 new cases a year, particularly in women of reproductive age (47.4 ± 12.8 years at diagnosis). Current advances in screening and immunization have shifted cervical cancer diagnoses to earlier stages; as a [...] Read more.
Cervical cancer is a major health issue worldwide, with approximately 660,000 new cases a year, particularly in women of reproductive age (47.4 ± 12.8 years at diagnosis). Current advances in screening and immunization have shifted cervical cancer diagnoses to earlier stages; as a result, fertility preservation is an essential component of building a treatment plan. Objectives: This systematic review aims to synthesize the existing techniques for fertility preservation with a focus on early-stage cervical cancer (cancer stage IA1-IB1). We will describe the different surgical and medical approaches for the treatment of cervical cancer, followed by an analysis of their oncologic safety and the associated reproductive risks and outcomes. Methods: A descriptive synthesis of the strategies for surgical management, including conization, radical trachelectomy, neoadjuvant chemotherapy (NACT), and radiotherapy, was completed. Fertility and successful pregnancy rely on patient selection, prognostic variables, and obstetric outcomes. The use of transposition of the ovaries and cryopreservation in the context of gonadotoxic treatment plans also requires investigation. Results: For patients meeting conservative eligibility criteria, conservative surgery for tumors up to 2 cm has been considered a safe oncological management strategy, although evidence remains limited. Pregnancy rate after conization ranged from 36 to 55% and 10 to 38% after radical trachelectomy. Ovarian function can be successfully preserved in >60% of laparoscopic transposition cases but resulted in a less than 15% chance of natural conception; the need for assistive reproductive techniques was often required. Conclusions: Fertility-preserving management of cervical cancer is safe and feasible in carefully selected patients, with oncologic outcomes comparable to more radical management. Continued innovation and randomized control trials in treatment paths and oncologic and fertility outcomes will benefit the field. Full article
(This article belongs to the Section Cancer Therapy)
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48 pages, 557 KB  
Review
Molecular Signatures of Obesity-Associated Infertility in Polycystic Ovary Syndrome: The Emerging Role of Exosomal microRNAs and Non-Coding RNAs
by Charalampos Voros, Georgios Papadimas, Despoina Mavrogianni, Aristotelis-Marios Koulakmanidis, Diamantis Athanasiou, Kyriakos Bananis, Antonia Athanasiou, Aikaterini Athanasiou, Ioannis Papapanagiotou, Dimitrios Vaitsis, Charalampos Tsimpoukelis, Maria Anastasia Daskalaki, Vasileios Topalis, Marianna Theodora, Nikolaos Thomakos, Fotios Chatzinikolaou, Panagiotis Antsaklis, Dimitrios Loutradis, Evangelos Menenakos and Georgios Daskalakis
Genes 2025, 16(9), 1101; https://doi.org/10.3390/genes16091101 - 17 Sep 2025
Cited by 1 | Viewed by 1566
Abstract
Polycystic ovarian syndrome (PCOS) is one of the most common endocrine and metabolic conditions affecting women of reproductive age. This condition affects around 20% of this demographic and is characterized by polycystic ovarian morphology, hyperandrogenism, and chronic anovulation. Obesity, impacting 40–85% of women [...] Read more.
Polycystic ovarian syndrome (PCOS) is one of the most common endocrine and metabolic conditions affecting women of reproductive age. This condition affects around 20% of this demographic and is characterized by polycystic ovarian morphology, hyperandrogenism, and chronic anovulation. Obesity, impacting 40–85% of women with PCOS, exacerbates insulin resistance, increases insulin levels, and intensifies low-grade inflammation. This exacerbates the reproductive and metabolic complications associated with the condition. Recent advancements in molecular biology have underscored the significance of non-coding RNAs, including as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), as crucial regulators of gene expression and prospective biomarkers for PCOS. Exosome-derived microRNAs (ex-miRNAs) have emerged as compelling candidates due to their stability in body fluids and their capacity to promote intercellular communication among adipose tissue, the ovary, and the endometrium. Research, encompassing both experimental and clinical studies, has shown that ex-miRNAs display differing expression levels in women with obesity-related PCOS. Several of these ex-miRNAs are associated with networks that govern inflammation, glucose metabolism, steroidogenesis, and folliculogenesis. Moreover, the encapsulation of these chemicals within exosomes safeguards them from enzymatic breakdown, hence augmenting their potential as non-invasive biomarkers for diagnosis, prognosis, and treatment monitoring. Despite the initial results being encouraging, challenges remain in standardising exosome separation, quantifying miRNA, and analyzing functional data within the complex pathophysiology of PCOS. This narrative review consolidates existing evidence regarding the molecular signatures of obesity-related infertility in PCOS, emphasising the growing significance of exosomal miRNAs and other non-coding RNAs, while examining their translational potential for early diagnosis and personalised therapeutic approaches. Full article
(This article belongs to the Section Genetic Diagnosis)
22 pages, 1881 KB  
Article
Explainable Machine Learning for the Early Clinical Detection of Ovarian Cancer Using Contrastive Explanations
by Zeynep Kucukakcali, Ipek Balikci Cicek and Sami Akbulut
J. Clin. Med. 2025, 14(17), 6201; https://doi.org/10.3390/jcm14176201 - 2 Sep 2025
Viewed by 1333
Abstract
Background: Ovarian cancer is often diagnosed at advanced stages due to the absence of specific early symptoms, resulting in high mortality rates. This study aims to develop a robust and interpretable machine learning (ML) model for the early detection of ovarian cancer, [...] Read more.
Background: Ovarian cancer is often diagnosed at advanced stages due to the absence of specific early symptoms, resulting in high mortality rates. This study aims to develop a robust and interpretable machine learning (ML) model for the early detection of ovarian cancer, enhancing its transparency through the use of the Contrastive Explanation Method (CEM), an advanced technique within the field of explainable artificial intelligence (XAI). Methods: An open-access dataset of 349 patients with ovarian cancer or benign ovarian tumors was used. To improve reliability, the dataset was augmented via bootstrap resampling. A three-layer deep neural network was trained on normalized demographic, biochemical, and tumor marker features. Model performance was measured using accuracy, sensitivity, specificity, F1-score, and the Matthews correlation coefficient. CEM was used to explain the model’s classification results, showing which factors push the model toward “Cancer” or “No Cancer” decisions. Results: The model achieved high diagnostic performance, with an accuracy of 95%, sensitivity of 96.2%, and specificity of 93.5%. CEM analysis identified lymphocyte count (CEM value: 1.36), red blood cell count (1.18), plateletcrit (0.036), and platelet count (0.384) as the strongest positive contributors to the “Cancer” classification, with lymphocyte count demonstrating the highest positive relevance, underscoring its critical role in cancer detection. In contrast, age (change from −0.13 to +0.23) and HE4 (change from −0.43 to −0.05) emerged as key factors in reversing classifications, requiring substantial hypothetical increases to shift classification toward the “No Cancer” class. Among benign cases, a significant reduction in RBC count emerged as the strongest determinant driving a shift in classification. Overall, CEM effectively explained both the primary features influencing the model’s classification results and the magnitude of changes necessary to alter its outputs. Conclusions: Using CEM with ML allowed clear and trustworthy detection of early ovarian cancer. This combined approach shows the promise of XAI in assisting clinicians in making decisions in gynecologic oncology. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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16 pages, 1404 KB  
Review
The Final Phases of Ovarian Aging: A Tale of Diverging Functional Trajectories
by Stefania Bochynska, Miguel Ángel García-Pérez, Juan J. Tarín, Anna Szeliga, Blazej Meczekalski and Antonio Cano
J. Clin. Med. 2025, 14(16), 5834; https://doi.org/10.3390/jcm14165834 - 18 Aug 2025
Cited by 4 | Viewed by 3896
Abstract
Ovarian aging is characterized by a gradual decline in both reproductive and endocrine functions, ultimately culminating in the cessation of ovarian activity around the age of 50, when most women experience natural menopause. The decline begins early, as follicular attrition is initiated in [...] Read more.
Ovarian aging is characterized by a gradual decline in both reproductive and endocrine functions, ultimately culminating in the cessation of ovarian activity around the age of 50, when most women experience natural menopause. The decline begins early, as follicular attrition is initiated in utero and continues throughout childhood and reproductive life. Most follicles undergo atresia without progressing through substantial stages of growth. With increasing age, a pronounced reduction occurs in the population of resting follicles within the ovarian reserve, accompanied by a decline in the size of growing follicular cohorts. Around the age of 38, the rate of follicular depletion accelerates, sometimes resulting in diminished ovarian reserve (DOR). The subsequent menopausal transition involves complex, irregular hormonal dynamics, manifesting as increasingly erratic menstrual patterns, primarily driven by fluctuations in circulating estrogens and a rising incidence of anovulatory cycles. In parallel with the progressive depletion of the follicular pool, the serum concentrations of anti-Müllerian hormone (AMH) decline gradually, while reductions in inhibin B levels become more apparent during the late reproductive years. The concomitant decline in both inhibin B and estrogen levels leads to a compensatory rise in circulating follicle-stimulating hormone (FSH) concentrations. Together, these endocrine changes, alongside the eventual exhaustion of the follicular reserve, converge in the onset of menopause, which is defined by the absence of menstruation for twelve consecutive months. The mechanisms contributing to ovarian aging are complex and multifactorial, involving both the oocyte and the somatic cells within the follicular microenvironment. Oxidative stress is thought to play a central role in the age-related decline in oocyte quality, primarily through its harmful effects on mitochondrial DNA integrity and broader aspects of cellular function. Although granulosa cells appear to be relatively more resilient, they are not exempt from age-associated damage, which may impair their hormonal activity and, given their close functional relationship with the oocyte, negatively influence oocyte competence. In addition, histological changes in the ovarian stroma, such as fibrosis and heightened inflammatory responses, are believed to further contribute to the progressive deterioration of ovarian function. A deeper understanding of the biological processes driving ovarian aging has facilitated the development of experimental interventions aimed at extending ovarian functionality. Among these are the autologous transfer of mitochondria and stem cell-based therapies, including the use of exosome-producing cells. Additional approaches involve targeting longevity pathways, such as those modulated by caloric restriction, or employing pharmacological agents with geroprotective properties. While these strategies are supported by compelling experimental data, robust clinical evidence in humans remains limited. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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15 pages, 701 KB  
Article
Fertility Preservation in Pediatric Oncology: A 10-Year Single-Center Experience in Northern Spain
by Anabel Carmona-Nunez, Maria Begoña Prieto Molano, Alba Gonzalez Lopez, Itziar Astigarraga and Ricardo Lopez-Almaraz
J. Clin. Med. 2025, 14(16), 5762; https://doi.org/10.3390/jcm14165762 - 14 Aug 2025
Viewed by 864
Abstract
Background/Objectives: The aim of this study is to describe fertility preservation (FP) techniques performed over the last 10 years at a tertiary hospital in northern Spain in patients under 18 diagnosed with cancer. Methods: A retrospective medical record review was conducted [...] Read more.
Background/Objectives: The aim of this study is to describe fertility preservation (FP) techniques performed over the last 10 years at a tertiary hospital in northern Spain in patients under 18 diagnosed with cancer. Methods: A retrospective medical record review was conducted for patients aged 0 to 18 years diagnosed between January 2014 and December 2023 in the Pediatric Oncology Unit at a university hospital. We evaluated patient characteristics, the timing of FP procedures, and potential risk factors for ovarian insufficiency and early azoospermia. Additionally, we assessed the agreement between two gonadotoxicity risk classifications. Results: In our center, FP is more frequently offered to pubertal patients (12 to 16 years old), prior to treatment in those at high risk of subsequent gonadotoxicity (>80%), and after treatment in those at low risk (<20%). Additionally, the increased provision of FP over the last five years of the study suggests improved clinician uptake of this long-term effect of cancer treatment. Our study found weak agreement between available gonadotoxicity risk classifications, complicating the identification of FP candidates. Long-term follow-up of survivors allowed for the detection of ovarian insufficiency (1.2%) and early azoospermia (0.7%), enabling hormone replacement therapy when necessary. Hematopoietic stem cell transplantation (HSCT) emerged as a predictor of early infertility. Conclusions: Our study highlights the prevalence of gonadotoxicity in pediatric cancer patients at our center and the increasing access to FP techniques. The findings emphasize the importance of personalized medicine, tailored FP strategies based on individual risk, and long-term follow-up to assess fertility status. Full article
(This article belongs to the Section Oncology)
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