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Keywords = ovarian ageing

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11 pages, 624 KiB  
Article
The Role of Asprosin in Females in the Context of Fertility—An Exploratory Study
by Magdalena Skowrońska, Michał Pawłowski, Aleksandra Dyszkiewicz, Angelika Buczyńska and Robert Milewski
J. Clin. Med. 2025, 14(15), 5527; https://doi.org/10.3390/jcm14155527 - 6 Aug 2025
Abstract
Background: Asprosin is a relatively recently discovered glucogenic adipokine secreted during fasting that plays an important role in various biochemical processes in the body, including those connected with obesity and insulin resistance. The aim of this exploratory study was to investigate the associations [...] Read more.
Background: Asprosin is a relatively recently discovered glucogenic adipokine secreted during fasting that plays an important role in various biochemical processes in the body, including those connected with obesity and insulin resistance. The aim of this exploratory study was to investigate the associations between selected hormonal, anthropometric, and lifestyle-related parameters and serum asprosin concentration. As studies concerning fertility and asprosin have so far been limited to men or women with PCOS, its role in the general female population remains largely unexplored. The direction of this exploration was thus pointed toward possible connections with female fertility. Methods: The case-control study group included 56 women of reproductive age (25–42 years), who were patients of the Reproductive Health Clinic and the Clinic of Endocrinology, Diabetology, and Internal Medicine of the Medical University of Białystok, Poland. The levels of selected hormones, including anti-Müllerian hormone (AMH), estradiol, sex hormone-binding globulin (SHBG), and testosterone, body composition parameters, and a lifestyle parameter—night fasting duration—were assessed to test their associations with serum asprosin concentration. Results: A weak negative correlation was found between AMH level and serum asprosin concentration, suggesting a potential link between asprosin and ovarian reserve. Furthermore, a moderate positive correlation was found between the percentage of total body water (TBW) and serum asprosin concentration. No significant associations were observed between the levels of the other tested hormones and serum asprosin concentration, or between body composition parameters or night fasting duration and serum asprosin concentration. The multivariate model designed in the study shows that AMH, TBW, and night fasting duration explain 23.4% of asprosin variability. Conclusions: Although the nature of the study is exploratory, the findings indicate that the role of asprosin in the female population—particularly its role in fertility—requires further research. Not only is the number of available studies on asprosin insufficient, but the results of this study partly contradict what is known about the hormone from previous studies, which were largely performed with male cohorts. In addition, the results of this study suggest that asprosin may indeed be involved in mechanisms related to female fertility, particularly those connected with ovarian reserve. Nevertheless, studies performed in larger, more homogeneous populations are necessary to confirm the role of asprosin in women, including its association with female fertility. Full article
(This article belongs to the Section Reproductive Medicine & Andrology)
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18 pages, 1241 KiB  
Review
PCOS and the Genome: Is the Genetic Puzzle Still Worth Solving?
by Mario Palumbo, Luigi Della Corte, Dario Colacurci, Mario Ascione, Giuseppe D’Angelo, Giorgio Maria Baldini, Pierluigi Giampaolino and Giuseppe Bifulco
Biomedicines 2025, 13(8), 1912; https://doi.org/10.3390/biomedicines13081912 - 5 Aug 2025
Abstract
Background: Polycystic ovary syndrome (PCOS) is a complex and multifactorial disorder affecting reproductive, endocrine, and metabolic functions in women of reproductive age. While environmental and lifestyle factors play a role, increasing evidence highlights the contribution of genetic and epigenetic mechanisms to its pathogenesis. [...] Read more.
Background: Polycystic ovary syndrome (PCOS) is a complex and multifactorial disorder affecting reproductive, endocrine, and metabolic functions in women of reproductive age. While environmental and lifestyle factors play a role, increasing evidence highlights the contribution of genetic and epigenetic mechanisms to its pathogenesis. Objective: This narrative review aims to provide an updated overview of the current evidence regarding the role of genetic variants, gene expression patterns, and epigenetic modifications in the etiopathogenesis of PCOS, with a focus on their impact on ovarian function, fertility, and systemic alterations. Methods: A comprehensive search was conducted across MEDLINE, EMBASE, PubMed, Web of Science, and the Cochrane Library using MeSH terms including “PCOS”, “Genes involved in PCOS”, and “Etiopathogenesis of PCOS” from January 2015 to June 2025. The selection process followed the SANRA quality criteria for narrative reviews. Seventeen studies published in English were included, focusing on original data regarding gene expression, polymorphisms, and epigenetic changes associated with PCOS. Results: The studies analyzed revealed a wide array of molecular alterations in PCOS, including the dysregulation of SIRT and estrogen receptor genes, altered transcriptome profiles in cumulus cells, and the involvement of long non-coding RNAs and circular RNAs in granulosa cell function and endometrial receptivity. Epigenetic mechanisms such as the DNA methylation of TGF-β1 and inflammation-related signaling pathways (e.g., TLR4/NF-κB/NLRP3) were also implicated. Some genetic variants—particularly in DENND1A, THADA, and MTNR1B—exhibit signs of positive evolutionary selection, suggesting possible ancestral adaptive roles. Conclusions: PCOS is increasingly recognized as a syndrome with a strong genetic and epigenetic background. The identification of specific molecular signatures holds promise for the development of personalized diagnostic markers and therapeutic targets. Future research should focus on large-scale genomic studies and functional validation to better understand gene–environment interactions and their influence on phenotypic variability in PCOS. Full article
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36 pages, 6047 KiB  
Review
Prevalence and Levels of Thyroid Autoantibodies in Polycystic Ovary Syndrome—Impact of TSH- and BMI-Matched Comparisons: A Systematic Review and Meta-Analysis
by Jakub Kwiatkowski, Nicole Akpang, Lucja Zaborowska and Artur Ludwin
Int. J. Mol. Sci. 2025, 26(15), 7525; https://doi.org/10.3390/ijms26157525 - 4 Aug 2025
Abstract
Polycystic ovary syndrome (PCOS) is a complex condition affecting women of reproductive age, characterized by menstrual irregularities, hyperandrogenism, polycystic ovarian morphology, and low-grade inflammation accompanied by oxidative stress and increased autoimmune risk, particularly Hashimoto’s thyroiditis. Many studies have examined thyroid autoantibodies—anti-thyroid peroxidase antibodies [...] Read more.
Polycystic ovary syndrome (PCOS) is a complex condition affecting women of reproductive age, characterized by menstrual irregularities, hyperandrogenism, polycystic ovarian morphology, and low-grade inflammation accompanied by oxidative stress and increased autoimmune risk, particularly Hashimoto’s thyroiditis. Many studies have examined thyroid autoantibodies—anti-thyroid peroxidase antibodies (anti-TPO) and anti-thyroglobulin antibodies (anti-TG)—in PCOS; however, observed differences in baseline thyroid-stimulating hormone (TSH) levels and body mass indices (BMIs) impede a direct interpretation of the results. This systematic review and meta-analysis aimed to summarize the available evidence on the prevalence and levels of anti-TPO and anti-TG in women with PCOS. We conducted a systematic search of PubMed, Scopus, and Embase, which yielded 40 eligible, observational studies including 6045 women with PCOS and 4527 controls. Subgroup analyses were conducted separately for TSH- and BMI-matched populations. Anti-TPO prevalence (odds ratio [OR] = 2.03; 95% confidence interval [CI]: 1.35–3.04; p = 0.0006) and levels (standardized mean difference [SMD] = 0.63; 95% CI: 0.37–0.88; p < 0.00001) were significantly higher in PCOS patients. Anti-TG prevalence (OR = 1.92; 95% CI: 1.23–3.01; p = 0.004) and levels (SMD = 0.41; 95% CI: 0.18–0.64; p = 0.0004) were also significantly elevated. In matched subgroups, prevalence differences were no longer significant, though anti-TPO levels remained significantly elevated and anti-TG levels were borderline significant in the TSH-matched subgroup of PCOS women. Although differences in thyroid autoantibody prevalence in women with PCOS appear to be driven by elevated TSH levels and BMIs, the persistently increased antibody levels in the majority of matched subgroups suggest that PCOS itself may contribute independently to heightened autoimmune activation. Full article
(This article belongs to the Section Molecular Oncology)
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14 pages, 397 KiB  
Article
Combination of Continuous Use of Oral Clomiphene Citrate with Injectable Gonadotropins for Ovarian Stimulation: A Single-Center Study
by Adamantia Kontogeorgi, Gkalia Tsangkalova, Panagiota Ambatzi, Ioannis Boutas, Eleftherios Meridis, Ioannis Gryparis, Dimitrios Kalaitzis, Angeliki Fenga, Melpomeni Peppa, Sophia Kalantaridou, Antonios Makrigiannakis and Minas Paschopoulos
Life 2025, 15(8), 1235; https://doi.org/10.3390/life15081235 - 4 Aug 2025
Viewed by 76
Abstract
Objective: This retrospective observational study evaluated the efficacy and safety of an ovarian stimulation protocol for embryo banking that involves continuous administration of clomiphene citrate (CC) in combination with gonadotropins, without the use of GnRH antagonists. Methods: Conducted at the Serum [...] Read more.
Objective: This retrospective observational study evaluated the efficacy and safety of an ovarian stimulation protocol for embryo banking that involves continuous administration of clomiphene citrate (CC) in combination with gonadotropins, without the use of GnRH antagonists. Methods: Conducted at the Serum IVF Clinic in Athens, Greece, the study included 250 women aged 25–45 who underwent IVF for embryo banking. The protocol involved administering 150 mg of CC daily from day 2 of the menstrual cycle until the day before hCG trigger, alongside 150 IU/day of Meriofert. Outcomes assessed included oocyte yield, fertilization rates, incidence of ovarian hyperstimulation syndrome (OHSS), and hormonal correlations. Comparative and regression analyses explored differences between age groups and predictors of success. Results: The protocol demonstrated a favorable safety profile with no cases of OHSS and yielded a mean of 10.25 oocytes per patient. Group analysis showed significantly more oocytes retrieved in women under 40 (mean: 12.5) versus those over 40 (mean: 8.43), while fertilization rates were paradoxically higher in the older cohort (59.16% vs. 30.68%, p < 0.0001). Regression models revealed basal FSH to be a significant inverse predictor of oocyte yield, but it was positively associated with fertilization rate. Continuous CC use effectively suppressed premature LH surges without compromising oocyte or embryo quality, allowing flexible and cost-effective stimulation with minimal monitoring. Conclusions: Continuous administration of clomiphene citrate in combination with gonadotropins presents a promising, antagonist-free ovarian stimulation protocol for embryo banking. The approach is economically efficient, reduces monitoring requirements, and maintains safety and effectiveness and is particularly notable in women over 40. Further studies are warranted to validate these findings and refine protocol mechanisms. Full article
(This article belongs to the Section Reproductive and Developmental Biology)
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16 pages, 948 KiB  
Review
Oxytocin: From Biomarker to Therapy for Postmenopausal Osteoporosis
by Tiago Franca, Joana Fonseca Ferreira, Melissa Mariana and Elisa Cairrao
Women 2025, 5(3), 27; https://doi.org/10.3390/women5030027 - 1 Aug 2025
Viewed by 126
Abstract
Postmenopausal osteoporosis is estrogen-dependent and results in an imbalance between bone formation and resorption. The approved therapy is intended to reduce the risk and consequences of fractures, but still has a number of contraindications and associated adverse effects. Recently, oxytocin has been shown [...] Read more.
Postmenopausal osteoporosis is estrogen-dependent and results in an imbalance between bone formation and resorption. The approved therapy is intended to reduce the risk and consequences of fractures, but still has a number of contraindications and associated adverse effects. Recently, oxytocin has been shown to have an anabolic effect on bone tissue, increasing the production of osteoblasts and inhibiting the activity of osteoclasts. Thus, this study aimed to examine the potential of oxytocin as a biomarker and therapeutic agent for postmenopausal osteoporosis. A PubMed search yielded 16 articles upon analysis of the inclusion and exclusion criteria. The results showed that, compared to women in the same age group without bone loss, those diagnosed with osteoporosis exhibited lower blood oxytocin levels, possibly related to a greater tendency towards fractures. The administration of oxytocin could be a promising strategy to enhance bone quality and, consequently, to reduce the incidence of fragility fractures; however, no human studies have been conducted regarding its use as a possible treatment. Thus, it is essential to increase the number of clinical trials in women with ovarian dysfunction and bone loss, in which oxytocin could become a viable therapeutic alternative. Full article
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12 pages, 1095 KiB  
Article
Barriers and Breakthroughs in Precision Oncology: A National Registry Study of BRCA Testing and PARP Inhibitor Uptake in Women from the National Gynae-Oncology Registry (NGOR)
by Mahendra Naidoo, Clare L Scott, Mike Lloyd, Orla McNally, Robert Rome, Sharnel Perera and John R Zalcberg
Cancers 2025, 17(15), 2541; https://doi.org/10.3390/cancers17152541 - 31 Jul 2025
Viewed by 171
Abstract
Background: The identification of pathogenic variants in the Breast Cancer Genes 1 and 2 (BRCA1/2) is a critical predictive biomarker for poly (ADP-ribose) polymerase inhibitor (PARPi) therapy in epithelial ovarian cancer (EOC). The aim of this study is to define real-world [...] Read more.
Background: The identification of pathogenic variants in the Breast Cancer Genes 1 and 2 (BRCA1/2) is a critical predictive biomarker for poly (ADP-ribose) polymerase inhibitor (PARPi) therapy in epithelial ovarian cancer (EOC). The aim of this study is to define real-world rates and determinants of germline and somatic BRCA1/2 testing and subsequent PARPi utilisation in Australia using a national clinical quality registry. Methods: This multi-centre cohort study analysed data from 1503 women with non-mucinous EOC diagnosed between May 2017 and July 2022, captured by the Australian National Gynae-Oncology Registry (NGOR). We evaluated rates of germline and somatic testing and PARPi use, using multivariate logistic regression to identify associated clinical and demographic factors. Results: Overall germline and somatic testing rates were 68% and 32%, respectively. For the high-grade serous ovarian cancer (HGSOC) cohort, rates were higher, at 78% and 39%, respectively. Germline testing was significantly less likely for women aged >80 years (OR 0.49), those in regional areas (OR 0.61), and those receiving single-modality treatment. Somatic testing uptake increased significantly following public reimbursement for PARPi (p = 0.004). Among eligible women with a newly diagnosed BRCA pathogenic variant and advanced disease (n = 110), 52% commenced first-line maintenance PARPi. Conclusions: This national study offers valuable insights into Australian ovarian cancer care, highlighting opportunities to enhance testing equity for older women (aged >80) and regional patients. Furthermore, it identifies the translation of a positive test into PARPi therapy as a complex area that warrants further collaborative investigation to optimise patient outcomes. Full article
(This article belongs to the Special Issue Gynecologic Oncology: Clinical and Translational Research)
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18 pages, 305 KiB  
Review
Causes of Childhood Cancer: A Review of Literature (2014–2021): Part 2—Pregnancy and Birth-Related Factors
by Rebecca T. Emeny, Angela M. Ricci, Linda Titus, Alexandra Morgan, Pamela J. Bagley, Heather B. Blunt, Mary E. Butow, Jennifer A. Alford-Teaster, Raymond R. Walston III and Judy R. Rees
Cancers 2025, 17(15), 2499; https://doi.org/10.3390/cancers17152499 - 29 Jul 2025
Viewed by 572
Abstract
Purpose: To review parental pre-pregnancy and pregnancy exposures in relation to pediatric cancer (diagnosis before age 20). Methods: We conducted literature searches using Ovid Medline and Scopus to find primary research studies, review articles, and meta-analyses published from 2014 to 17 March 2021. [...] Read more.
Purpose: To review parental pre-pregnancy and pregnancy exposures in relation to pediatric cancer (diagnosis before age 20). Methods: We conducted literature searches using Ovid Medline and Scopus to find primary research studies, review articles, and meta-analyses published from 2014 to 17 March 2021. Results: Strong evidence links increased risk of childhood cancer with maternal diabetes, age, and alcohol and coffee consumption during pregnancy. Both paternal and maternal cigarette smoking before and during pregnancy are associated with childhood cancers. Diethylstilbestrol (DES) exposure in utero has long been known to be causally associated with increased risk of vaginal/cervical cancers in adolescent girls. More recent evidence implicates in utero DES exposure to testicular cancer in young men and possible intergenerational effects on ovarian cancer in the granddaughters of women exposed to DES during pregnancy. There is strong evidence that childhood cancer risk is also associated with both high and very low birth weight and with gestational age. Evidence is also strong for the protective effects of maternal vitamin consumption and a healthy diet during pregnancy. Unlike early studies, those reviewed here show no association between in utero exposure to medical ionizing radiation, which may be explained by reductions over time in radiation doses, avoidance of radiation during pregnancy, and/or by inadequate statistical power to detect small increases in risk, rather than a lack of causal association. Evidence is mixed or conflicting for an association between childhood cancer and maternal obesity, birth order, cesarean/instrumental delivery, and prenatal exposure to diagnostic medical radiation. Evidence is weak or absent for associations between childhood cancer and multiple gestations or assisted reproductive therapies, as well as prenatal exposure to hormones other than DES, and medications. Full article
21 pages, 2004 KiB  
Review
Interplay of Oxidative Stress, Autophagy, and Rubicon in Ovarian Follicle Dynamics: Orchestrating Ovarian Aging
by Kiyotaka Yamada, Masami Ito, Haruka Nunomura, Takashi Nishigori, Atsushi Furuta, Mihoko Yoshida, Akemi Yamaki, Kanto Shozu, Ippei Yasuda, Sayaka Tsuda, Tomoko Shima and Akitoshi Nakashima
Antioxidants 2025, 14(8), 919; https://doi.org/10.3390/antiox14080919 - 27 Jul 2025
Viewed by 477
Abstract
Organ functions generally decline with age, but the ovary is a prototypical organ that undergoes functional loss over time. Autophagy plays a crucial role in maintaining organ homeostasis, and age-related upregulation of the autophagy inhibitor protein, Rubicon, has been linked to cellular and [...] Read more.
Organ functions generally decline with age, but the ovary is a prototypical organ that undergoes functional loss over time. Autophagy plays a crucial role in maintaining organ homeostasis, and age-related upregulation of the autophagy inhibitor protein, Rubicon, has been linked to cellular and tissue dysfunction. This review describes how granulosa cell autophagy supports follicular growth and oocyte selection and maturation by regulating cellular energy metabolism and protein quality control. We then introduce the role of selective autophagy, including mitophagy or lipophagy, in steroidogenesis and cellular remodeling during luteinization. In aged ovaries, Rubicon accumulation suppresses autophagic flux, leading to diminished oxidative-stress resilience and enhanced DNA damage. Moreover, impaired autophagy drives the accumulation of ATP citrate lyase, which correlates with poor oocyte quality and reduced ovarian reserve. Following fertilization, oocytes further upregulate autophagy to provide the energy required for blastocyst transition. Conversely, in infertility-related disorders, such as premature ovarian insufficiency, endometriosis, and polycystic ovary syndrome, either deficient or excessive autophagy contributes to disease pathogenesis. Both autophagy inhibitors (e.g., Rubicon) and activators (e.g., Beclin1) could be emerging as promising biomarkers for assessing ovarian autophagy status. Therapeutically, Rubicon inhibition by trehalose in aged ovaries and autophagy suppression by agents such as hydroxychloroquine in polycystic ovary syndrome and endometriosis hold potential. Establishing robust methods to evaluate ovarian autophagy will be essential for translating these insights into targeted treatments. Full article
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12 pages, 1442 KiB  
Article
Does BRCA Mutation Status Influence Ovarian Cancer Onset Timing and Patients’ Treatment Outcomes?
by Kaja Michalczyk, Agata Mokrzycka, Marianna Rudzińska, Barbara Michalczyk, Janusz Menkiszak and Anita Chudecka-Głaz
Genes 2025, 16(8), 883; https://doi.org/10.3390/genes16080883 - 27 Jul 2025
Viewed by 432
Abstract
Background/Objectives: Mutations in the BRCA1 and BRCA2 genes are well-known risk factors for ovarian cancer. They are also associated with response to platinum-based chemotherapy; however, their definitive impact on patient prognosis remains not fully understood. This study aimed to investigate the influence of [...] Read more.
Background/Objectives: Mutations in the BRCA1 and BRCA2 genes are well-known risk factors for ovarian cancer. They are also associated with response to platinum-based chemotherapy; however, their definitive impact on patient prognosis remains not fully understood. This study aimed to investigate the influence of BRCA mutation status on the age of ovarian cancer onset and on treatment outcomes in patients with high-grade serous ovarian cancer. Methods: This single-center retrospective analysis included newly diagnosed FIGO stage III and IV HGSOC patients treated between June 2018 and April 2023. Patients’ age, tumor histology, CA125 levels, BRCA mutation status, type of treatment (neoadjuvant or adjuvant chemotherapy), and surgical outcomes were collected and analyzed. Survival analyses were performed using the Kaplan–Meier method and log-rank test. Results: Pathogenic mutations were identified in 25 patients (15 in BRCA1, 10 in BRCA2). Patients with a BRCA mutation were diagnosed at a significantly younger age (median 58.78 years) compared to non-carriers (66.81 years; p < 0.001), with BRCA1 carriers being diagnosed the youngest (median 46.52 years). The study found no statistically significant difference in progression-free survival (PFS) between BRCA carriers and non-carriers. However, a significant improvement in overall survival (OS) was observed for patients with a BRCA1 mutation (p = 0.036). No significant OS difference was found for BRCA2 carriers. Conclusions: BRCA mutations, particularly in the BRCA1 gene, are associated with an earlier onset ovarian cancer. BRCA1 mutation appears to be a favorable prognostic factor for overall survival in patients with HGSOC. Our findings demonstrate the clinical implications of different BRCA mutations and support the need for further research in larger cohorts to confirm their influence on prognostic effects. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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21 pages, 2483 KiB  
Article
Relations of Insulin Resistance, Body Weight, Vitamin D Deficiency, SHBG and Androgen Levels in PCOS Patients
by Zsófi Balogh, Szilvia Csehely, Mónika Orosz, Harjit Pal Bhattoa, Zoárd Tibor Krasznai, Tamás Deli and Attila Jakab
Biomedicines 2025, 13(8), 1803; https://doi.org/10.3390/biomedicines13081803 - 23 Jul 2025
Viewed by 371
Abstract
Background: The most common female endocrinopathy is polycystic ovary syndrome (PCOS), affecting 10–20% of women of reproductive age. It is associated with a wide range of hormonal and biochemical abnormalities and long-term metabolic and cardiovascular risks. It is characterized by infertility due to [...] Read more.
Background: The most common female endocrinopathy is polycystic ovary syndrome (PCOS), affecting 10–20% of women of reproductive age. It is associated with a wide range of hormonal and biochemical abnormalities and long-term metabolic and cardiovascular risks. It is characterized by infertility due to chronic anovulation, hyperandrogenism, polycystic ovarian morphology, and is often associated with insulin resistance (IR) and obesity. Hyperinsulinemia further increases androgen production and reduces sex hormone-binding globulin (SHBG) levels, thereby aggravating symptoms. In addition, vitamin D deficiency is often present in PCOS patients, and increasing evidence suggests that it may also be associated with insulin resistance and hyperandrogenism. Objective: This study aimed to evaluate the relationships between insulin resistance, vitamin D deficiency, body mass index (BMI), and androgen levels in women with PCOS. Method: A cross-sectional study was conducted in which data from 195 women diagnosed with PCOS and not yet receiving therapy at a gynecologic endocrinology unit of a university-based tertiary clinical center, between 2019 and 2024, were analyzed. The parameters recorded were age, body mass index (BMI), 25(OH) vitamin D levels, androgen hormone levels (testosterone, androstenedione), glucose-insulin responses during a 3-point oral glucose tolerance test (OGTT). Statistical analyses, including linear regression, Pearson, and Spearman correlation tests were used to assess associations between variables. Results: The mean age of the patients was 24.8 years (18–42), and the mean BMI was 30.6 kg/m2 (17–51). Vitamin D deficiency was observed in 84.1% of patients, hyperandrogenism in 45.8%, and insulin resistance in 44.5%. A significant inverse correlation was found between BMI and vitamin D levels (r = −0.31, p =< 0.01) indicating that higher BMI is associated with lower vitamin D status. Similarly, BMI also showed a significant negative correlation with SHBG levels (r = –0.45, p < 0.01), suggesting that increasing body weight is linked to reduced SHBG concentrations. In addition, BMI was significantly positively correlated with 2 h insulin levels (r = 0.43, p =< 0.01) and with testosterone levels (r = 0.21, p = 0.01). These findings suggest that increased adiposity intensifies insulin resistance and is linked to both vitamin D deficiency and elevated androgen levels. Moreover, the combination of hyperinsulinemia and low vitamin D further disrupts hormonal balance by promoting ovarian androgen production and decreasing SHBG levels, thereby increasing the bioavailability of testosterone. A significant inverse correlation was found between vitamin D levels and 2 h insulin levels (r = −0.28, p =< 0.01), indicating that lower vitamin D status is associated with increased insulin resistance. Furthermore, 2 h insulin levels showed a significant positive correlation with testosterone levels (r = 0.32, p =< 0.01), suggesting that greater insulin resistance is linked to higher androgen production. Additionally, vitamin D levels were inversely correlated with testosterone (r = −0.18, p = 0.02), demonstrating that a lower vitamin D status may further contribute to the hyperandrogenic environment. Vitamin D levels also showed a significant positive correlation with SHBG concentrations (r = 0.29, p < 0.01), indicating that a higher vitamin D status may be associated with increased SHBG levels. In contrast, 2 h insulin levels were inversely correlated with SHBG (r = −0.43, p < 0.01), reflecting the suppressive effect of hyperinsulinemia on SHBG production. Conclusions: Insulin resistance, BMI, and vitamin D deficiency are closely related to each other and to the severity of PCOS, which is confirmed by the correlations with androgen levels. The revealed relationships draw attention to the special importance of vitamin D supplementation and the correction of carbohydrate metabolism in alleviating the symptoms of the disease and reducing long-term health risks. Full article
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16 pages, 10508 KiB  
Article
Pharmacological Evaluation of Polygoni Multiflori Radix Praeparata Extract: Inhibition of PANoptosis in Alleviating Premature Ovarian Insufficiency
by Can Zhu, Jinhong Li, Yaofeng Li, Daiyong Chen and Chang Lin
Curr. Issues Mol. Biol. 2025, 47(7), 569; https://doi.org/10.3390/cimb47070569 - 19 Jul 2025
Viewed by 385
Abstract
Polygoni Multiflori Radix Praeparata (PMRP), a processed root of Polygonum multiflorum Thunb. (known as Zhiheshouwu in Chinese medicine), exhibits anti-aging properties and is used to improve ovarian aging. However, its therapeutic mechanism against premature ovarian insufficiency (POI) remains unclear. This study investigates whether [...] Read more.
Polygoni Multiflori Radix Praeparata (PMRP), a processed root of Polygonum multiflorum Thunb. (known as Zhiheshouwu in Chinese medicine), exhibits anti-aging properties and is used to improve ovarian aging. However, its therapeutic mechanism against premature ovarian insufficiency (POI) remains unclear. This study investigates whether PMRP alleviates POI by inhibiting PANoptosis—a cell death pathway characterized by the concurrent occurrence and interplay of pyroptosis, apoptosis, and necroptosis. POI was induced in rats using tripterygium glycosides. We evaluated the estrous cycle, serum hormone levels (follicle-stimulating hormone [FSH], estrogen [E2], anti-Müllerian hormone [AMH]), follicular development, and the ultrastructure of granulosa cells. PANoptosome assembly (apoptosis-associated speck-like protein containing a CARD [ASC]/caspase-8/receptor-interacting protein kinase 3 [RIPK3] co-localization) and key effectors of PANoptosis (caspase 3, cleaved caspase 3, gasdermin D [GSDMD], cleaved GSDMD, GSDME, RIPK1, mixed-lineage kinase domain-like protein [MLKL], and p-MLKL) were analyzed. PMRP restored the estrous cycle, lowered FSH levels, and increased E2 and AMH levels in POI rats. It reduced follicular atresia, preserved primordial follicles, and suppressed PANoptosis-like death in granulosa cells. Mechanistically, PMRP disrupted PANoptosome assembly and downregulated key effectors of PANoptosis. PMRP alleviates POI by inhibiting PANoptosis in granulosa cells, overcoming the previous limitations of targeting single death pathways and providing novel insights into the pathogenesis and treatment strategies for POI. Full article
(This article belongs to the Section Molecular Pharmacology)
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14 pages, 912 KiB  
Article
Physical, Emotional, and Stress-Related Dynamics over Six Months in Newly Diagnosed Epithelial Ovarian Cancer Survivors
by Camelia Budisan, Razvan Betea, Maria Cezara Muresan, Zoran Laurentiu Popa, Cosmin Citu, Ioan Sas and Veronica Daniela Chiriac
J. Clin. Med. 2025, 14(14), 5087; https://doi.org/10.3390/jcm14145087 - 17 Jul 2025
Viewed by 252
Abstract
Background and Objectives: Epithelial ovarian cancer (EOC) remains the deadliest gynecologic malignancy, yet the psychosocial dynamics of early survivorship are inadequately described. We prospectively quantified six-month trajectories in the quality of life in a consecutive cohort of 88 women newly diagnosed with EOC [...] Read more.
Background and Objectives: Epithelial ovarian cancer (EOC) remains the deadliest gynecologic malignancy, yet the psychosocial dynamics of early survivorship are inadequately described. We prospectively quantified six-month trajectories in the quality of life in a consecutive cohort of 88 women newly diagnosed with EOC and explored clinical moderators of change. Methods: Eighty-eight consecutive patients (mean age 59.1 ± 10.7 years) completed the SF-36, WHOQOL-BREF, EORTC QLQ-C30, and 10-item Perceived Stress Scale (PSS-10) at baseline (pre-therapy) and six months after cytoreductive surgery ± platinum-based chemotherapy. Stage (FIGO I–II vs. III–IV) and treatment pathway (primary debulking surgery, neoadjuvant chemotherapy plus interval debulking, chemotherapy only) data were recorded. Results: Global QoL improved significantly (EORTC Global Health +5.9 ± 7.7 points; p < 0.001) while perceived stress declined (ΔPSS −3.6 ± 5.1; p < 0.001). SF-36 Physical Functioning rose 4.7 ± 7.9 points (p < 0.001) and Mental Health 4.4 ± 7.9 points (p = 0.004). The WHOQOL Physical and Psychological domains gained 4.7 ± 7.1 and 4.3 ± 7.4 points, respectively (both p < 0.01). Advanced-stage patients experienced larger stress reductions than early-stage patients (−4.1 ± 2.7 vs. −2.9 ± 2.2; p = 0.028) but comparable QoL gains. Greater stress relief correlated with greater mental-health improvement (r = −0.51) and global-health gains (r = −0.45) (all p < 0.001). Treatment pathway did not significantly influence trajectories. Conclusions: Early survivorship after first-line ovarian-cancer therapy was characterized by the clinically meaningful recovery of physical and emotional functioning together with the moderate alleviation of perceived stress. Improvements were observed irrespective of stage and treatment strategy, suggesting that contemporary multimodal regimens do not inevitably compromise patient-reported outcomes. Our estimates provide preliminary effect sizes that should be validated in multi-center cohorts with longer follow-up. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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14 pages, 2345 KiB  
Article
Clinical Experience in the Management of a Series of Fetal–Neonatal Ovarian Cysts
by Constantin-Cristian Văduva, Laurentiu Dira, Dominic Iliescu, Dan Ruican, Anișoara-Mirela Siminel, George Alin Stoica, Mircea-Sebastian Şerbănescu and Andreea Carp-Velișcu
Children 2025, 12(7), 934; https://doi.org/10.3390/children12070934 - 16 Jul 2025
Viewed by 257
Abstract
Introduction: Fetal ovarian cysts are known to be a common form of fetal abdominal masses in female fetuses, often resulting from hormonal stimulation in utero. Although many resolve spontaneously without sequelae, others can develop into more complex pathologies, such as intracystic hemorrhage or [...] Read more.
Introduction: Fetal ovarian cysts are known to be a common form of fetal abdominal masses in female fetuses, often resulting from hormonal stimulation in utero. Although many resolve spontaneously without sequelae, others can develop into more complex pathologies, such as intracystic hemorrhage or torsion, which can compromise ovarian integrity and long-term reproductive outcomes. Early detection and appropriate follow-up evaluation are therefore crucial for optimal perinatal management. Materials and Methods: We conducted a retrospective study of 12 cases of fetal ovarian cysts diagnosed by routine prenatal ultrasound examinations over a two-year period at our institution. Inclusion criteria were the presence of a cystic adnexal lesion detected in utero, detailed prenatal ultrasound documentation, and a comprehensive postnatal examination. Sonographic features such as cyst size, internal echogenicity, and signs of vascular compromise were recorded. The mother’s clinical variables, including gestational age at diagnosis and relevant medical conditions, were noted. Postnatal follow-up evaluation consisted of ultrasound examinations and, if indicated, pediatric surgical consultation. Results: Of the 12 cases, 9 were characterized by a simple cystic morphology. All spontaneously regressed postnatally and did not require surgical intervention. Three were defined as complex cysts showing septations or echogenic deposits; one of these cysts required immediate surgical exploration for suspected torsion. No cases with a malignant background were identified. All infants showed a favorable course with normal growth and development until follow-up evaluation. Conclusions: This series emphasizes that most fetal ovarian cysts are benign and often resolve without intervention, highlighting the benefit of systematic prenatal imaging. Nevertheless, complex or large cysts require close prenatal and neonatal monitoring to diagnose complications such as torsion. Full article
(This article belongs to the Special Issue Advances in Prenatal Diagnosis and Their Impact on Neonatal Outcomes)
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11 pages, 2247 KiB  
Case Report
Extremely Rare Case of a Giant Paratubal Cyst, Coexisting with a Mucinous Cystadenoma, Surgically Treated Through Laparoscopy—A Case Report and Review of the Literature
by Tudor Andrei Butureanu, Ana-Maria Apetrei, Ioana Pavaleanu, Ana-Maria Haliciu, Razvan Socolov and Raluca Balan
Reports 2025, 8(3), 106; https://doi.org/10.3390/reports8030106 - 14 Jul 2025
Viewed by 269
Abstract
Background and Clinical Significance: A paratubal cyst, which makes up about 10% of all adnexal masses, is a specific type of adnexal cyst that develops from the mesothelium in the broad ligament located between the fallopian tube and the ovary. Interestingly, the [...] Read more.
Background and Clinical Significance: A paratubal cyst, which makes up about 10% of all adnexal masses, is a specific type of adnexal cyst that develops from the mesothelium in the broad ligament located between the fallopian tube and the ovary. Interestingly, the majority of paratubal cyst cases are initially misidentified as ovarian cysts, with suspicion arising in only 1 out of every 15 patients before undergoing surgery. Case Presentation: We report a case of a giant paratubal cyst mimicking an ovarian cyst in a 21-year-old woman supported by some representative images along with a literature review. The cyst’s therapeutic management was surgical removal of the adnexa and the final postoperative histopathological diagnosis was that of a benign paratubal cyst. Conclusions: This case highlights the need to include a paratubal cyst in the differential diagnosis of pelvic masses, especially in women of reproductive age. To the best of our knowledge, this represents the largest paratubal cyst reported in the literature to date, based on overall dimensions and the highest recorded volume of aspirated fluid, successfully managed via laparoscopy. A further notable aspect of this case is the coexistence of the giant paratubal cyst with an ovarian mucinous cystadenoma. Full article
(This article belongs to the Section Obstetrics/Gynaecology)
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13 pages, 815 KiB  
Article
An Artificial Intelligence-Based Model to Predict Pregnancy After Intrauterine Insemination: A Retrospective Analysis of 9501 Cycles
by Jaume Minano Masip, Camille Grysole, Penelope Borduas, Isaac-Jacques Kadoch, Simon Phillips, Doina Precup and Daniel Dufort
J. Pers. Med. 2025, 15(7), 308; https://doi.org/10.3390/jpm15070308 - 12 Jul 2025
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Abstract
Background/Objectives: Intrauterine insemination (IUI) is a common first-line approach in the treatment of numerous infertile couples, especially in cases of unexplained infertility. Its relatively low success rate, however, could benefit from the development of AI-based support tools to predict its outcome, thus helping [...] Read more.
Background/Objectives: Intrauterine insemination (IUI) is a common first-line approach in the treatment of numerous infertile couples, especially in cases of unexplained infertility. Its relatively low success rate, however, could benefit from the development of AI-based support tools to predict its outcome, thus helping the clinical management of patients undergoing IUI cycles. Our objective was to develop a robust and accurate machine learning model that predicts pregnancy outcomes following IUI. Methods: A retrospective, observational, and single-center study was conducted. In total, 3535 couples (aged 18–43 years) that underwent IUI between January 2011 and December 2015 were recruited. Twenty-one clinical and laboratory parameters of 9501 IUI cycles were used to train different machine learning algorithms. Accuracy of pregnancy outcome was evaluated by an area under the curve (AUC) analysis. Results: The linear SVM outperformed AdaBoost, Kernel SVM, Random Forest, Extreme Forest, Bagging, and Voting classifiers. Pre-wash sperm concentration, the ovarian stimulation protocol, cycle length, and maternal age were strong predictors of a positive pregnancy test following IUI (AUC = 0.78). Paternal age was found to be the worst predictor. Conclusions: Our Linear SVM model predicts a positive pregnancy outcome following IUI. Although this model shows value for the clinical management of infertile patients and informed decision-making by the patients, further validation using independent datasets is required prior to clinical implementation. Full article
(This article belongs to the Section Omics/Informatics)
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