Search Results (201)

Background/Objectives: Volatile organic compounds (VOCs) have emerged as promising non-invasive biomarkers for assessing metabolic and reproductive health. In the context of assisted reproductive techniques (ARTs), the volatilomic composition of follicular fluid (FF) may reflect the biochemical environment surrounding the oocyte, influencing fertilization success and embryo development. This study aimed to characterize the volatilomic profile of FF in women undergoing ARTs and to explore associations between specific VOCs and female fertilization-related parameters (FFRPs). Methods: A total of 54 Caucasian women aged 19–39 years, enrolled between October 2015 and July 2019, were recruited at the Assisted Reproduction Laboratory of the Local Health Unit of Cova da Beira, Covilhã. FF samples were analyzed via gas chromatography–mass spectrometry (GC–MS) in scan mode, identifying 136 VOCs, of which 72 were selected based on prevalence. Sixteen FFRPs were evaluated, including age, body mass index (BMI), smoking habits, infertility factor, oocyte yield, embryo quality, β-hCG levels, country of birth, and reproductive history. Associations between VOCs and FFRPs were assessed using the Chi-square (χ²) test. Results: Significant correlations (p ≤ 0.05) were identified between 45 VOCs and 11 FFRPs. The detected compounds comprised alkanes, siloxanes, aromatics, alcohols, ketones, aldehydes, carboxylic acids and esters, fatty acid derivatives, epoxides, acrylates, nitriles, and sterols. Several VOCs were associated with more than one FFRP, indicating overlapping metabolic pathways that may influence reproductive performance. Conclusions: The volatilomic profile of FF demonstrates significant variability linked to individual reproductive and metabolic factors. VOC analysis may provide novel insights into follicular physiology, representing a promising approach for identifying potential biomarkers of infertility and ART outcomes. Full article

Background/Objectives: Endocrine therapy (ET) is a common treatment for hormone-dependent breast cancer and is associated with a significant reduction in recurrence and mortality rates. However, the decision to initiate endocrine therapy is a critical and often distressing juncture for patients. The need to weigh its survival benefits against the potential burden of side effects, including mood changes, pain, muscle stiffness, and fatigue, can render this decision-making phase a source of significant distress. The present systematic review aimed to identify and synthesize the sociodemographic and psychosocial predictors of the decision-making process related to ET adherence among women with breast cancer. Methods: A systematic literature search was conducted in three electronic databases—PubMed Central, ProQuest, and Scopus—to identify studies examining the association between sociodemographic and psychosocial factors and the decision-making process regarding ET among women with breast cancer. Inclusion criteria encompassed cross-sectional studies published between 2000 and 2025. Data were extracted and analyzed to identify recurring predictors across studies. The findings were synthesized through a narrative synthesis. Results: Twelve cross-sectional studies met the inclusion criteria, comprising a total of 8510 women diagnosed with breast cancer and undergoing ET. Ten studies (83%) identified sociodemographic variables—such as age, marital status, educational level, and ethnicity—as significant predictors of decision-making. Moreover, nine studies (75%) reported psychosocial factors, including quality of life (QoL), fear of progression, infertility concerns, and social support, as influential in the decision to initiate or continue ET. Specifically, the decision to adhere to ET is generally supported by younger age, higher education, better perceived quality of life, and greater social support. Conversely, it is hindered by lower income, lower education, fertility concerns related to marital status, and diminished quality of life. Conclusions: The findings of this review indicate that both sociodemographic and psychosocial factors play key roles in shaping women’s decisions regarding adherence to ET. Understanding these predictors can facilitate decision-making and inform the development of targeted interventions aimed at improving treatment adherence and supporting patient-centered care in breast cancer treatment. The focus on decision-making processes, rather than on adherence rates, is what distinguishes this review from other systematic reviews. Full article

Background/Objectives: Infertility is a multifactorial condition with an etiopathology that remains largely unclear. Although substantial evidence implicates oxidative stress (OS) as a key contributor to both male and female infertility, targeted strategies for OS-mediated reproductive dysfunction are still not well defined and require further investigation. Ubiquinol is the reduced form of Coenzyme Q10 involved in mitochondrial bioenergetics. It can be synthesized by humans endogenously or provided by dietary sources—typically egg yolks, oily fish, organ meats, and in smaller amounts in nuts and seeds and leafy green vegetables. The present article reviews possible mechanisms through which Ubiquinol plays a role in the regulation of fertility and reproduction, discussing why it could be positioned as a conditionally essential nutrient. Several questions and areas for further inquiry are also proposed. Methods: The present position paper narratively summarizes evidence related to Ubiquinol fertility and reproduction, focusing on the literature from PubMed, Science Direct, and Semantic Scholar. Results: Research advancements suggest that when physiological demands rise during certain life stages, e.g., the reproductive years, the amount of Ubiquinol produced internally may not be enough to meet heightened needs, particularly with advanced maternal/paternal age. This places a heavier reliance on obtaining Ubiquinol from the diet, thus presenting itself as a conditionally essential nutrient during certain life stages. Conclusions: Overall, Ubiquinol appears to enhance mitochondrial energy production and antioxidant defense in gametes, a process that appears to aid sperm function, oocyte quality, and early embryo development. Collectively, these data indicate a key physiological role for Ubiquinol in male and female fertility, especially given its age-related decline. Full article

Background and Objectives: The Mediterranean diet is traditionally linked to metabolic balance and improved reproductive health. However, dietary patterns in Mediterranean regions have progressively shifted toward more Westernized models, particularly among women of reproductive age, raising concerns about declining adherence to this historically protective diet. Objective: To assess adherence to the Mediterranean diet among women undergoing assisted reproductive technology (ART) and to explore possible associations with ovarian response and clinical outcomes. Materials and Methods: This prospective observational cohort study was conducted at a reproductive clinic in Sicily between 1 June and 31 July 2022. One hundred women aged 18–40 years undergoing infertility assessment and scheduled for controlled ovarian stimulation were enrolled. Mediterranean diet adherence was evaluated using the validated 14-item MEDAS questionnaire during the first clinical visit. ART-related outcomes, including ovarian response and pregnancy rates, were extracted from medical records. Results: The mean MEDAS score was 7.6 ± 1.2: 93% of women showed moderate adherence, 3% high adherence, and 4% low adherence. No significant associations were found between MEDAS score, and total oocytes retrieved, MII oocytes, or clinical pregnancy. Conclusions: Despite living in a traditionally Mediterranean area, participants demonstrated only moderate adherence to the Mediterranean diet. Although no associations with single-cycle ART outcomes emerged, the findings underscore the need for structured nutritional counseling to reinforce sustained adherence and support long-term reproductive health. Full article

Background: Despite significant advances in assisted reproductive technology (ART), disparities in clinical outcomes persist. While patient-related factors are well-studied, the role of partner ethnicity remains understudied. We hypothesized that partner ethnicity affects ART outcomes. This study examined the association between partner ethnicity and ART outcomes. Methods: We conducted a retrospective cohort study among patients and their partners undergoing IVF treatment in the United Kingdom between 2017 and 2018. The exposure was partner ethnicity. Outcomes included biochemical pregnancy, clinical pregnancy, pregnancy loss, and live birth. We calculated risk ratios (RR) and 95% confidence intervals (CI) using multivariable regression models to estimate the association between partner ethnicity and IVF outcomes, adjusting for female patient age, partner age, patient ethnicity, gravidity, infertility diagnosis, treatment type, preimplantation genetic testing for aneuploidy, and number of prior in vitro fertilization (IVF) cycles. Results: Among 158,813 IVF cycles, live birth rates per cycle were 26.3% for couples with White partners and 23.1% for those with non-White partners. Non-White partners were associated with a 5% lower clinical pregnancy rate (RR 0.95, 95% CI 0.92–0.97) and a 6% lower live birth rate (RR 0.94, 95% CI 0.92–0.97). Specifically, Black (RR 0.82, 95% CI 0.77–0.87) and Asian (RR 0.67, 95% CI 0.59–0.76) partners had significantly reduced live birth rates, though these associations were attenuated after adjusting for patient ethnicity. Couples in which both the partner and patient were Black or Asian had 24–42% lower live birth rates compared with White couples (Black: RR 0.76, 95% CI 0.70–0.82; Asian: RR 0.58, 95% CI 0.49–0.68). Conclusions: Partner ethnicity is independently associated with IVF outcomes, with non-White partners showing lower rates of these outcomes. These findings suggest the clinical relevance of partner ethnicity in reproductive outcomes. Further research is warranted to elucidate the mechanisms underlying these associations. Full article

Background: Adequate folate intake before and during early pregnancy is essential for neural tube defect (NTD) prevention. In 2023, the Polish Society of Gynecologists and Obstetricians updated national recommendations, emphasizing the use of L-5-methyltetrahydrofolate (5-MTHF). Evidence on women’s awareness of these guidelines is limited. Methods: This cross-sectional online survey (2025) included 188 Polish women aged 18–45 years who were currently pregnant or had been pregnant within the previous 12 months. Knowledge, attitudes, and supplementation practices were compared between women with (n = 94) and without infertility (n = 94). Group differences were assessed using χ² tests, and predictors of 5-MTHF use were examined with multivariable logistic regression. Results: General awareness of folate recommendations was high (98.9%). However, detailed knowledge varied substantially. Women with infertility more frequently recognized different folate forms (87.2% vs. 72.3%; p = 0.018), knew the role of the MTHFR gene (77.7% vs. 39.4%; p < 0.001), and initiated supplementation ≥3 months before conception (88.3% vs. 47.9%; p < 0.001). Overall, 66% reported using 5-MTHF. Independent predictors of choosing 5-MTHF included awareness of folate forms, MTHFR knowledge, and awareness of emerging considerations related to folic acid metabolism. Infertility status was not an independent predictor. Conclusions: Although folate supplementation was nearly universal in this selective sample, more advanced knowledge—particularly regarding folate forms and genetic aspects of folate metabolism—remained limited. Higher awareness among women with infertility likely reflects greater exposure to medical supervision rather than inherent differences between groups. These findings may represent early signals of how the 2023 Polish recommendations are disseminating among women who are more engaged with health information, highlighting the need for continued public and professional education to support informed use of folate supplements. Full article

Background/Objectives: Endometriosis (EM) is a chronic gynecological condition associated with infertility, oxidative stress, and altered metabolic regulation. Follicular fluid (FF) reflects the microenvironment of the developing oocyte, and changes in its amino acid composition may affect reproductive outcomes. This study aimed to characterize alterations in the amino acid composition of the FF in EM and to identify potential reproductive outcomes. Methods: Targeted metabolomic analysis of 20 amino acids was performed on FF samples from 56 women undergoing in vitro fertilization (17 with endometriosis, 39 controls). Amino acid concentrations were quantified and compared between groups, adjusting for age and body mass index. Pathway, biomarker, and multivariate analyses were conducted to explore metabolic alterations and potential diagnostic markers. Results: Asparagine, histidine, and glycine concentrations were significantly higher in the EM group after adjustment for age and BMI. Pathway analysis indicated perturbations in glycine/serine metabolism, glutathione metabolism, and porphyrin metabolism, consistent with oxidative stress and mitochondrial dysfunction. Multivariate modeling demonstrated partial separation between groups, while biomarker analysis identified asparagine (AUC = 0.76), along with glycine and histidine, as potential discriminators. Additional enrichment of bile acid and methylation-related pathways suggested broader systemic metabolic changes in EM. Conclusions: EM is associated with distinct amino acid alterations in the FF, particularly elevated asparagine, histidine, and glycine, reflecting oxidative and mitochondrial imbalance in the follicular environment. These metabolites emerged as candidate biomarkers requiring validation for EM-related oocyte quality changes and may help individualize in vitro fertilization approaches. Full article

Male infertility affects nearly 15% of couples worldwide, with chromosomal abnormalities representing a major underlying cause. This review explores how numerical and structural chromosomal anomalies, along with environmental exposures, lifestyle factors, and age-related genetic changes, disrupt spermatogenesis and contribute to infertility. It synthesizes findings from cytogenetic, molecular, and clinical studies, with particular focus on mechanisms such as meiotic nondisjunction, spindle assembly checkpoint dysfunction, and alterations in cohesin and synaptonemal complex proteins. Chromosomal abnormalities, both numerical and structural, emerge as key contributors to male infertility by impairing chromosomal segregation and recombination, often leading to azoospermia or oligospermia. Meiotic checkpoint failures and recombination errors further exacerbate the production of aneuploid sperm. Environmental toxins, oxidative stress, and poor nutrition disrupt hormonal balance and chromatin integrity, while advancing paternal age is associated with increased sperm aneuploidy and impaired meiotic control, with implications for assisted reproduction. Specific syndromes, including AZF deletions, Kallmann syndrome, and 46,XX testicular DSD, exemplify the direct genetic impact on male fertility. Overall, chromosomal abnormalities are central to the pathophysiology of male infertility, arising from intrinsic meiotic errors as well as extrinsic environmental and lifestyle factors. Integrating cytogenetic diagnostics, genetic counseling, and lifestyle interventions is essential for comprehensive fertility assessment and management. Further research into molecular biomarkers and targeted therapies could enhance diagnosis, improve treatment strategies, and lead to better reproductive outcomes. Full article

Background: Endometriosis is a chronic, estrogen-dependent inflammatory disease affecting up to 10% of women of reproductive age. It substantially impacts quality of life (QoL) through pelvic pain, infertility, and psychological distress. Increasing attention has been directed toward patient-reported outcomes and validated QoL instruments, which are essential for understanding the burden of disease and guiding individualized management. Materials and Methods: We performed a narrative review of the literature published in the last five years in PubMed, Scopus, Web of Science, and Cochrane Library, focusing on validated QoL instruments, fertility indices, and clinical outcomes after minimally invasive surgery (MIS) for deep infiltrating endometriosis (DIE). Discussions: The most widely used QoL instruments are the Endometriosis Health Profile-30 (EHP-30), Short Form-36 (SF-36), and EQ-5D, each providing multidimensional evaluation across physical, psychological, and social domains. Fertility-related prognosis is assessed with the Endometriosis Fertility Index (EFI), while staging of disease severity relies on rASRM and #ENZIAN classifications. Evidence from comparative and cohort studies suggests that both laparoscopic and robotic MIS can improve QoL and reproductive outcomes; however, the magnitude of benefit varies across studies, patient phenotypes, and follow-up periods. Conclusions: MIS is an increasingly used therapeutic option for DIE, with growing evidence of improvement in pain and QoL, but current data remain heterogeneous and do not uniformly support superiority over other approaches. Routine incorporation of validated QoL instruments and fertility indices into both clinical practice and research is essential to better stratify patients, support shared decision-making, and optimize long-term outcomes. Full article

Background: In vitro fertilization (IVF) has become a widely used method of assisted reproduction. However, concerns remain regarding the potential genotoxic effects of ovarian stimulation protocols used during IVF, especially in relation to cervical epithelial cells. The micronucleus (MN) assay is a validated cytogenetic biomarker of chromosomal damage and genome instability, increasingly utilized in cancer risk assessment. This study aimed to evaluate the genotoxic effect of IVF treatment on cervical epithelial cells in infertile women by comparing MN frequency before and after IVF cycles and with matched healthy controls. Methods: This prospective observational study included 15 women undergoing IVF and 15 age-matched healthy controls. All IVF participants had primary infertility and were undergoing their first IVF/ICSI cycle. Cervical smear samples were collected from the IVF group before and three months after treatment failure. MN assay was applied, and cytogenetic parameters (MN, binucleated cells, broken egg cells, and budding cells) were evaluated under light microscopy. Non-parametric statistical tests were used for analysis. Results: A statistically significant increase in MN frequency was found in the IVF group following treatment compared to pre-treatment samples and the control group (p = 0.001). HPV status was not assessed during the study period and is acknowledged as a key limitation. However, no significant differences were observed in other nuclear anomalies. Pre-treatment MN frequencies were not significantly different from those in controls. Conclusions: The findings suggest a potential cytogenetic impact of IVF-related hormonal stimulation on cervical epithelial cells, as evidenced by increased MN frequency. While no direct clinical implications were identified, these changes warrant further investigation into the long-term genomic safety of assisted reproductive technologies. Full article

Male infertility is a global health concern, and many cases are idiopathic in nature. The development and differentiation of germ cells (Gcs) are supported by Sertoli cells (Scs). Differentiated Scs support the development of Gcs into sperm, and hence, male fertility. We previously reported on a developmental switch in Scs around 12 days of age onwards in rats. During the process of the differentiation of Scs, the differential expression of mitophagy-related genes and its role in male fertility are poorly understood. To address this gap, we evaluated the microarray dataset GSE48795 to identify 12 mitophagy-related hub genes, including B-Cell Leukemia/Lymphoma 2 (Bcl2) and FBJ murine osteosarcoma viral oncogene homolog (Fos). We identify Neuron-derived orphan receptor 1 (Nor1) as a potential mitophagy-related gene of interest due to its strong regulatory association with two hub genes, Bcl2 and Fos, which were differentially expressed during Sc maturation. To validate this finding, we generated a transgenic rat model with the Sc-specific knockdown of Nor1 during puberty. A functional analysis showed impaired spermatogenesis with reduced fertility in these transgenic rats. Our findings suggest that Nor1 may be an important mitophagy-related gene regulating the function of Scs and thereby regulating male fertility. Full article

Background/Objectives: Infertility imposes substantial psychosocial burdens on affected individuals, often resulting in a decline in quality of life comparable to that experienced in chronic diseases. Exploring lifestyle and health awareness-related factors is essential to develop complex, multidisciplinary approaches. This study investigated the associations between the components of 24-h movement behaviour (physical activity, sedentary lifestyle, sleep), health literacy, fertility awareness, and general and infertility-specific quality of life. Additionally, the study assessed whether these factors could predict quality of life outcomes in women living with infertility. Methods: A cross-sectional study was conducted using questionnaire-based data collection in four fertility centres in Hungary. The convenience sample included 361 women aged 18–45 years with a documented infertility diagnosis. Validated questionnaires were used to assess health literacy (BRIEF), fertility awareness (FAS), physical activity (GPAQ-H), sleep quality (AIS), and quality of life (WHOQOL-BREF and FertiQoL). Data analysis included Kolmogorov–Smirnov tests, Spearman correlations, and generalised linear modelling (GLM), with statistical significance set at p < 0.05. Results: Based on the FAS, 77.8% of participants (n = 274) self-reported being adequately informed; however, objective knowledge scores accounted for only 48.5% of the possible total, indicating limited knowledge. Fertility awareness positively correlated with recreational physical activity (ρ = 0.156; p = 0.003). Recreational physical activity showed low but significant positive associations with all quality-of-life dimensions (e.g., psychological well-being: r = 0.177; p ≤ 0.002), whereas sedentary time was negatively associated with psychological well-being (r = −0.109) and social relationships (r = −0.118). Sleep duration correlated positively while sleep quality problems correlated negatively with FertiQoL scores (r = −0.339; p ≤ 0.001). Better sleep quality, lower sedentary time, and higher health literacy were positive predictors of infertility-specific quality of life, whereas higher fertility awareness showed a paradoxical adverse effect. Conclusions: These findings highlight the role of 24-h movement behaviour and health awareness in improving quality of life among women with infertility. The study supports the need for tailored, multi-component lifestyle interventions to promote physical, mental, and psycho-social well-being. Full article

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

Background: Female infertility represents a significant global public health concern, yet its evolving trends and data-driven risk prediction remain under examined in nationally representative cohorts. This study investigates temporal changes in infertility prevalence and evaluates Machine Learning (ML) models for infertility risk prediction using harmonized clinical features from NHANES cycles (2015, 2016, 2017, 2018, 2021, 2022, and 2023). Methods: Women aged 19 to 45 with complete data on infertility-related variables (including reproductive history, menstrual irregularity, Pelvic Infection Disease (PID), hysterectomy, and bilateral oophorectomy) were analyzed. Descriptive statistics and cohort comparisons employed ANOVA and Chi-square tests, while multivariate Logistic Regression (LR) estimated Adjusted Odds Ratios (OR) and informed feature importance. Predictive models (LR, Random Forest, XGBoost, Naive Bayes, SVM, and a Stacking Classifier ensemble) were trained and tuned via GridSearchCV with five-fold cross-validation. Model performance was evaluated using accuracy, precision, recall, F1-score, specificity, and AUC-ROC. Results: We observed a notable increase in infertility prevalence from 14.8% in 2017–2018 to 27.8% in 2021–2023, suggesting potential post-pandemic impacts on reproductive health. In multivariate analysis, prior childbirth emerged as the strongest protective factor (Adjusted OR $\approx 0.00$), while menstrual irregularity showed a significant positive association with infertility (OR $=0.55$, 95% CI $0.40$ to $0.77$, $p<0.001$). Unexpectedly, PID, hysterectomy, and bilateral oophorectomy were not significantly associated with infertility after adjustment ($p>0.05$), which may partly reflect the inherent definition of self-reported infertility used in this study. All six ML models demonstrated excellent and comparable predictive ability (AUC $>0.96$), reinforcing the effectiveness of even a minimal common predictor set for infertility risk stratification. Conclusions: The rising prevalence of self-reported infertility among U.S. women underscores emerging public health challenges. Despite relying on a streamlined feature set, interpretable and ensemble ML models successfully predicted infertility risk, showcasing their potential applicability in broader surveillance and personalized care strategies. Future models should integrate additional sociodemographic and behavioral factors to enhance precision and support tailored interventions. Full article

Background and Objectives: Currently, infertility is one of the major problems affecting up to 12% of couples worldwide, with more than a quarter of cases being male-related. It is assumed that Leukocyte-poor platelet-rich plasma (LP-PRP) can improve the function of germ cells and serve as a regenerative substrate as a source of biologically active substances that play an important role in the process of spermatogenesis in infertile men. We aimed to evaluate the proliferation, apoptosis, and growth factors of germ cells after the administration of LP-PRP in patients with non-obstructive azoospermia. Materials and Methods: The study used archival material (paraffin blocks of testicular biopsies) of patients with non-obstructive azoospermia aged 21–34 years (n = 41; associated diagnosis: varicocele). We confirm that no interventions or biopsies were performed as part of the study itself. They were injected bilaterally into the spermatic cord and in the region of the lower pole of the testis under ultrasound control were injected with PRP once a week for 6 weeks. Biopsies were immunohistochemical reactions with antibodies to Ki-67, Bcl-2, caspase 3 and p53, IGF-1, TGF-β, and VEGF-A. Results: Immunohistochemical study of testicular biopsies after LP-PRP injection revealed an increase in the number of cells stained for proliferation proteins (Ki-67) and anti-apoptosis (Bcl-2), IGF-1, TGF-β, VEGF-A; decrease caspase-3- and p53-positive cells. Conclusions: In LP-PRP, platelet α-granule growth factors, which are key regulators of the cell cycle of germ cells, demonstrate restoration of the proliferative-apoptotic balance, confirmed by the expression levels of Ki-67, Bcl-2, caspase 3, and p53 in patients with non-obstructive azoospermia. In human testicular biopsies, the administration of LP-PRP led to an exponential release of numerous growth factors from platelet α-granules, which, based on their regenerative properties, improved the morphological and immunohistochemical picture of the germinal epithelium in non-obstructive azoospermia. Full article