Search Results (1,271)

Bisphenols and phthalates are ubiquitous endocrine-disrupting chemicals with potential effects on reproductive neuroendocrine regulation, particularly during sensitive developmental windows. This review summarizes current evidence on their exposure profile, mechanisms of reproductive disruption, and female- and male-specific reproductive adversities. A structured narrative review was conducted using PubMed/MEDLINE, Scopus, and Web of Science, including experimental, epidemiological, biomonitoring, systematic review, and meta-analytic studies addressing bisphenols, phthalates, fertility, hormonal regulation, gametogenesis, pregnancy outcomes, and reproductive toxicity mechanisms. Bisphenols and phthalates interfere with estrogenic and androgenic signaling, hypothalamic–pituitary–gonadal axis regulation, steroidogenesis, oxidative stress, inflammation, apoptosis, mitochondrial function, and epigenetic regulation. Reported outcomes include impaired ovarian function, altered oocyte development, hormonal imbalance, reduced semen quality, defective spermatogenesis, sperm DNA damage, infertility, and adverse developmental or pregnancy-related effects. However, human evidence remains heterogeneous and limited by observational designs, exposure misclassification, residual confounding, and insufficient mixture assessment. Current evidence supports biological plausibility for bisphenol- and phthalate-related reproductive toxicity, but causal inference remains limited. Prospective studies with repeated biomonitoring, standardized reproductive endpoints, sex- and age-specific analyses, and improved mixture modeling are needed. A precautionary reduction in avoidable exposure appears reasonable, particularly during sensitive reproductive and developmental periods. Full article

Spinal cord injury is strongly associated with male infertility, traditionally attributed to erectile and ejaculatory dysfunction. However, accumulating evidence demonstrates that infertility in this population extends beyond neurogenic impairment and involves profound biochemical and molecular alterations within the male reproductive system. The objective of this review is to synthesize current evidence on the role of oxidative stress, inflammation, and sperm DNA damage as central mechanisms driving impaired fertility in men with spinal cord injury. A comprehensive evaluation of clinical and experimental studies indicates that seminal plasma in affected individuals is characterized by elevated reactive oxygen species, reduced antioxidant capacity, and a pro-inflammatory cytokine profile, including increased levels of tumor necrosis factor alpha, interleukin 6, and interleukin 1 beta. These alterations are closely linked to leukocytospermia, mitochondrial dysfunction, and disruption of the blood–testis barrier, creating a toxic microenvironment that compromises sperm function. As a consequence, spermatozoa exhibit reduced motility, impaired membrane integrity, and significantly increased DNA fragmentation and chromatin abnormalities. Elevated sperm DNA damage has been consistently associated with poor fertilization outcomes, reduced embryo quality, and increased risk of pregnancy loss in assisted reproductive settings. Importantly, these molecular defects persist even when sperm are retrieved using advanced techniques such as electroejaculation or surgical extraction, highlighting the need for targeted therapeutic strategies. Interventions aimed at reducing oxidative stress and modulating inflammation, including antioxidant supplementation and advanced sperm selection methods, show promise but remain insufficiently standardized. Future research should focus on the development of personalized approaches integrating molecular diagnostics and targeted therapies to improve reproductive outcomes in this population. Collectively, this review reframes spinal cord injury-related infertility as a complex inflammatory and oxidative disorder and underscores the importance of addressing sperm DNA integrity in clinical management. Full article

Background/Objectives: This study aims to assess changes in seminal parameters and sperm DNA fragmentation (SDF) index after empirical oral antibiotic therapy in infertile men with baseline SDF index > 15%. Methods: This retrospective, paired, uncontrolled pre- and post-intervention study included 98 infertile men with elevated baseline SDF index. Semen samples were obtained before treatment and at least two months after simultaneous oral treatment with ciprofloxacin 1000 mg/day for 21 days and doxycycline 100 mg/day for 10 days. Semen volume, sperm concentration, total sperm count, progressive motility, sperm morphology, round cell concentration, and SDF index were assessed before and after treatment. Results: After treatment, conventional semen parameters did not change significantly. Round cell concentration decreased from 0.3 to 0.2 × 10⁶/mL (p = 0.003), and median SDF index decreased from 30% to 20% (p < 0.0001). Conclusions: Empirical oral antibiotic therapy was associated with reductions in the SDF index and round cell concentration in this cohort. Because microbiological confirmation and an untreated control group were lacking, causality cannot be established, and controlled studies are required before routine clinical adoption. Full article

Background: Male infertility, largely driven by declining sperm quality, is a growing global concern. Radix Bupleuri Chinensis (Chaihu, CH)—a key component of traditional formulas such as Chaihu Shengjing Tang and Chaihu Shugan San—has been clinically used to enhance sperm quality. However, the specific role and mechanism of CH as a single entity in ameliorating spermatogenic dysfunction remain unclear. This study aimed to determine whether CH extract ameliorates spermatogenic dysfunction and whether GnRH/GnRHR signaling and taurine biosynthesis are involved. Methods: Male Kunming (KM) mice and GC-1 spermatogonial cells were used to establish experimental models. Histopathological and cellular changes were examined via hematoxylin and eosin (H&E) staining and immunofluorescence. Enzyme and hormone levels were quantified, while gene and protein expression were analyzed using quantitative real-time polymerase chain reaction, Western blotting, and high-content imaging. Results: CH extract mitigated DOX-induced spermatogenic dysfunction by activating the GnRHR signaling pathway, enhancing taurine biosynthesis, and reducing oxidative stress. In vitro, saikosaponin D alleviated DOX-induced injury in GC-1 cells and was associated with changes in GnRHR-related signaling and taurine-biosynthesis-related proteins, supporting its potential role as a candidate bioactive constituent of CH. Conclusions: CH extract alleviated DOX-induced spermatogenic impairment in mice. The in vivo cetrorelix experiments support the involvement of the GnRHR signaling pathway, whereas the concurrent changes in taurine, CDO1, and FMO1 are consistent with enhanced taurine biosynthesis. These findings provide experimental support for further investigation of CH as a potential intervention for chemotherapy-related reproductive injury. Full article

Background/Objectives: Infertility is associated with considerable psychological distress and impaired quality of life; however, gender-related differences in these outcomes remain unclear. This study aimed to compare anxiety, depression, and fertility-related quality of life between women and men in infertile couples and to examine the relationships between psychological distress and fertility-specific quality of life. Methods: This cross-sectional study included 75 infertile women and their male partners attending the Reproductive Health and Infertility Outpatient Clinic. Anxiety and depressive symptoms were assessed using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory-II (BDI-II), respectively. Fertility-related quality of life was evaluated using the Fertility Quality of Life (FertiQoL) questionnaire. Group comparisons and correlation analyses were performed using appropriate statistical tests. Results: Females had significantly higher total anxiety scores than males (10.44 ± 10.04 vs. 6.18 ± 7.86, p = 0.004). Females also showed higher affective depressive symptom scores (3.21 ± 3.05 vs. 2.20 ± 2.70, p = 0.033). Males reported significantly higher overall FertiQoL scores than females (54.61 ± 4.79 vs. 52.42 ± 6.39, p = 0.019). Increased depression were significantly associated with poorer fertility-related quality of life in males (r = −0.463, p < 0.001). Cronbach’s alpha coefficients demonstrated excellent internal consistency for BDI-II (0.905), BAI (0.922), and FertiQoL (0.879). Conclusions: Infertile females experience greater anxiety and poorer fertility-related quality of life than males. Psychological distress is strongly associated with reduced fertility-specific quality of life, highlighting the importance of routine psychosocial assessment in infertility care. Full article

More than 70% of non-obstructive azoospermia (NOA) cases remain idiopathic, and the underlying genetic causes need to be investigated. In this study, we aimed to identify genes and variants associated with the etiology of NOA. Two NOA patients from consanguineous families, with normal karyotypes and no Y-chromosome microdeletions, were selected for whole-genome sequencing (WGS). Candidate variants were validated by Sanger sequencing. Structural protein modeling and assessment of mutation-induced changes in molecular interactions were performed using SWISS-MODEL and AlphaFold. We identified a candidate homozygous missense variant (c.899C>T, p.(Ser300Phe); rs375931805) in SOX30 in one patient; this transcription factor is highly expressed in the testis. In the second patient, a homozygous missense variant (c.1472C>T, p.(Thr491Met); rs746902232) in RNF220 and a hemizygous missense variant (c.2354A>G, p.(Gln785Arg) in the X-linked AKAP4 gene were simultaneously detected. Previous studies have shown that SOX30 knockout in mice leads to meiosis I arrest and impaired spermiogenesis. AKAP4 is exclusively expressed in the testis, and missense variants have been reported in different forms of male infertility. The co-occurrence of variants in AKAP4 and RNF220 may suggest an oligogenic etiology of NOA and contribute to the phenotypic variability associated with AKAP4 variants. Full article

Background: The aim of this study was to evaluate the diagnostic performance of combined testicular function indices in patients with non-obstructive azoospermia and to investigate the clinical value of these indices in predicting the diagnosis of non-obstructive azoospermia and the success of testicular sperm extraction. Methods: This retrospective observational study included 224 male patients who underwent infertility assessment. The patients were classified into a normospermic group (n = 165) and a non-obstructive azoospermia group (n = 59). Serum anti-Müllerian hormone, follicle-stimulating hormone, luteinising hormone and total testosterone levels were assessed. The Testicular Function Index, the modified Testicular Function Index and the logarithmically transformed index were calculated. Patients in the non-obstructive azoospermia group underwent micro-TESE and were classified according to sperm retrieval status. Diagnostic performance was assessed using ROC analysis. Results: Among the 59 patients with non-obstructive azoospermia who underwent micro-TESE, sperm retrieval was successful in 26 patients and unsuccessful in 33 patients. In the non-obstructive azoospermia group, anti-Müllerian hormone and testosterone levels were lower, whilst follicle-stimulating hormone and luteinising hormone levels were higher (all p < 0.001). All combined indices were found to be significantly lower in the non-obstructive azoospermia group (all p < 0.001). In the ROC analysis, follicle-stimulating hormone demonstrated the highest discriminatory performance (AUC = 0.978). In the testicular sperm extraction analysis, anti-Müllerian hormone was found to be the marker with the highest performance (AUC = 0.930). Conclusions: (Follicle-stimulating hormone demonstrated the highest diagnostic performance for distinguishing non-obstructive azoospermia, whereas anti-Müllerian hormone was the strongest predictor of TESE success. Although the combined testicular function indices showed good diagnostic performance, they did not outperform these established hormonal markers and should therefore be regarded as complementary tools for the integrated assessment of testicular function. These findings should be considered exploratory and require further validation. Full article

Background and Objectives: Male factors account for approximately 30–50% of subfertile couples. Teratozoospermia is one of the major causes of male infertility; however, the genetic factors underlying many cases remain incompletely understood. This study aimed to identify potential genetic variants associated with teratozoospermia and to investigate the possible involvement of Caudal-Type Homeobox 4 (CDX4) in sperm morphogenesis. Materials and Methods: Whole-exome sequencing was performed in 44 individuals with teratozoospermia. A rare CDX4 variant (NM_005193.2, c.103G>T; NP_005184.1, Gly35Cys) was identified and confirmed by Sanger sequencing. Because CDX4 is located on the X chromosome, this variant was interpreted as hemizygous in the male patient. Sperm morphology, CDX4 localization, public GEO transcriptomic data (GSE6969), and CDX4 expression during murine spermiogenesis were analyzed. Results: The CDX4 p.Gly35Cys variant is located within the Caudal-like transactivation domain, a conserved region involved in transcriptional regulation. Spermatozoa from the patient carrying this variant exhibited severe morphological abnormalities, predominantly involving sperm-head defects, together with aberrant CDX4 localization along the midpiece and tail, in contrast to the neck- and annulus-enriched distribution observed in control spermatozoa. Reanalysis of the GEO dataset showed increased CDX4 transcript levels in teratozoospermic samples compared with normozoospermic controls. During murine spermiogenesis, CDX4 was detected in the nuclei of spermatogonia and spermatocytes and subsequently localized to the sperm head and neck/tail regions during sperm morphogenesis. Conclusions: CDX4 c.103G>T (p.Gly35Cys) is a rare hemizygous X-linked candidate variant associated with severe teratozoospermia in a single patient. Further cohort-based, segregation, and functional studies are required to clarify its role in sperm morphogenesis. Full article

Background/Objectives: Varicocele is usually clinically left-sided, but imaging and mechanistic studies suggest that contralateral venous reflux or bilateral testicular effects may be more common than physical examination indicates. This narrative review critically examines whether varicocele-associated infertility is better conceptualized as an asymmetric disorder with potential bilateral anatomical or functional involvement and considers the implications for diagnosis and treatment. Methods: PubMed/MEDLINE and Scopus were searched from inception to 21 June 2026 for studies on varicocele laterality, bilateral and subclinical disease, color Doppler ultrasonography, venography, and unilateral versus bilateral repair. Reference lists and contemporary clinical guidelines were also reviewed. Because the included studies differed substantially in patient selection, age, operator technique, diagnostic criteria, and reference standards, reported bilateral rates were not interpreted as head-to-head estimates of diagnostic sensitivity or as pooled prevalence estimates. Results: Physical examination identifies predominantly left-sided clinical disease. Bilateral involvement is reported more frequently when both sides are assessed using Doppler ultrasonography or venography, but estimates vary widely across referral-enriched and highly selected cohorts. Human and experimental evidence supports several mechanisms by which a clinically unilateral lesion may have bilateral functional effects, including shared scrotal hyperthermia, oxidative stress, endocrine disturbance, and venous cross-communication. Bilateral repair is consistent with standard treatment criteria when both varicoceles are clinically palpable. In men with a clinical left varicocele and non-palpable right-sided reflux, comparative evidence is mixed, and current guidelines do not support routine treatment of imaging-only disease. Conclusions: Varicocele is best viewed as an asymmetric disorder that may be anatomically or functionally bilateral in selected men, rather than as a universally bilateral disease. Deliberate bilateral clinical assessment and standardized bilateral ultrasonography when imaging is clinically indicated may improve phenotyping and operative planning. However, contralateral imaging abnormalities should not automatically be converted into a surgical indication. Full article

The widespread adoption of in vitro fertilization (IVF) has profoundly transformed the management of infertility and established IVF as the most effective assisted reproductive technology for many clinical indications. Nevertheless, intrauterine insemination (IUI) remains widely used because of its lower invasiveness, reduced treatment burden, lower costs, and broader accessibility. The contemporary role of IUI in an IVF-dominated era remains a subject of ongoing debate. This narrative review aims to critically evaluate the current role of IUI in modern reproductive medicine by examining its clinical indications, effectiveness, limitations, cost-effectiveness, and patient-centered implications in comparison with IVF. A narrative review of the literature was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Relevant studies, systematic reviews, meta-analyses, randomized controlled trials, and international guidelines published primarily between 2010 and 2025 were identified and synthesized. Particular attention was given to recommendations from the European Society of Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM). Current evidence supports the use of IUI, particularly when combined with ovarian stimulation, as an appropriate first-line treatment in selected couples with unexplained infertility, mild male-factor infertility, and minimal-to-mild endometriosis. Although IVF generally provides higher live birth rates per treatment cycle and remains the preferred option for several infertility diagnoses, IUI continues to offer meaningful clinical benefits in appropriately selected patients. Beyond effectiveness, treatment decisions should also consider cost-effectiveness, accessibility, treatment burden, safety, and patient preferences. Recent evidence increasingly supports individualized and prognosis-based approaches to fertility treatment selection. Evidence also highlights the importance of female age, infertility duration, and ovarian reserve in determining the relative benefit of IUI versus IVF. Despite the clinical dominance of IVF, IUI remains an evidence-based and clinically relevant component of contemporary fertility care. Rather than being viewed as competing interventions, IUI and IVF should be considered complementary treatment options within a personalized infertility management strategy. Appropriate patient selection, particularly considering female reproductive prognosis, remains essential to maximize reproductive outcomes while minimizing treatment burden and healthcare costs. Full article

Metabolic syndrome (MetS) is a complex metabolic disorder that includes central fat accumulation and insulin resistance, abnormal lipid levels, high blood pressure, and ongoing mild inflammation as its main symptoms. The global rise in metabolic syndrome parallels the increasing prevalence of male infertility, suggesting a potential association between metabolic health and reproductive function. Male fertility suffers from obesity, which represents a major element of metabolic syndrome because it disrupts hormonal balance, raises scrotal temperatures, and causes oxidative damage and HPG axis malfunction. Excess body fat functions as an endocrine system that induces the body to produce pro-inflammatory cytokines, which include tumor necrosis factor-α and interleukin-6, and various other inflammatory substances that result in ongoing body-wide inflammation. The state of inflammation leads to damaged spermatogenesis, which results in lower testosterone production and impaired semen quality that includes changes in sperm concentration, motility, morphology, and DNA integrity. The combination of insulin resistance and metabolic disturbances that occur in MetS leads to oxidative stress and mitochondrial dysfunction, which harms male reproductive abilities in testicular tissue. Recent research shows that adipokines and endocrine disruptors, together with epigenetic modifications, function as mediators that establish the connection between metabolic syndrome and male infertility. The development of targeted therapeutic strategies and lifestyle interventions requires researchers to study how obesity and chronic inflammation interact with each other to create reproductive dysfunction. This review defines the pathophysiological mechanisms that connect metabolic syndrome to male infertility by focusing on how obesity-related inflammation affects male reproductive health. Full article

Background: Infertility is a global public health problem among males, with asthenozoospermia representing the most common cause. Since flagellar activity is vital for proper fertilization, identification of the mechanisms controlling this process is crucial. Microtubules are necessary for sperm functionality; however, their regulatory proteins in humans require further research. DCDC2C belongs to the doublecortin domain-containing family and has a role in microtubule stabilization; therefore, DCDC2C could affect the sperm flagellar structure. Objectives: The goal of the present study was to examine the presence and possible relationship between DCDC2C expression and sperm motility in asthenozoospermia. Materials and Methods: This study involved sixty men from December 2024 to December 2025. The sperm samples were processed according to the WHO criteria (6th ed.). Conventional sperm characteristics, biochemical indicators of seminal plasma, DNA fragmentation, and chromatin condensation were evaluated. Immunofluorescence staining for DCDC2C was performed, especially with respect to flagellar localization. Results: DCDC2C-positive spermatozoa were significantly more common in the normozoospermic group (78.93 ± 1.67%) than in the asthenozoospermic group (17.27 ± 2.23%; p < 0.0001). No significant differences were found for seminal biochemical markers, sperm DNA fragmentation, or chromatin condensation. Discussion: Reduced detectable distal flagellar DCDC2C immunoreactivity was associated with asthenozoospermia. Conclusions: DCDC2C protein expression is highly correlated with sperm movement, indicating that DCDC2C is a potential molecular marker for the diagnosis of asthenozoospermia. Full article

Introduction: Leukemia is the most common childhood malignancy. Treatment requires urgent polychemotherapy and may escalate to hematopoietic stem cell transplantation (HSCT) with or without total body irradiation (TBI). Due to the frequently young age at diagnosis, time limitations and unpredictable course, fertility preservation (FP) is especially challenging and may not be feasible prior to treatment, particularly in females. Methods: We conducted a systematic review and meta-analysis of fertility outcomes in leukemia survivors using MEDLINE, Embase, and Cochrane databases (search date: 13 June 2024). Results: Forty-two studies with 2048 patients were included. Overall infertility was 37% (95% CI 23–54%) with substantial heterogeneity. The highest infertility rates were observed after HSCT (68%) and after testicular irradiation (92%) or TBI ≥ 10–12 Gy (66%). Chemotherapy alone was associated with lower infertility (4%). Sex-specific differences were noted, with higher infertility in males following chemotherapy-only regimens (18% vs. 6% in females), while females were more affected after HSCT (70% vs. 59% in males). Subfertility affected about one-fifth of survivors. Conclusions: While standard chemotherapy is associated with relatively low gonadotoxicity, HSCT and irradiation confer substantial risk. These findings support individualized fertility counseling and long-term reproductive follow-up based on treatment exposure. Full article

Background: Sperm DNA fragmentation (SDF) is increasingly recognized as a clinically relevant marker of male reproductive potential and has been associated with impaired embryo development, miscarriage, and suboptimal assisted reproductive technology outcomes, particularly in selected infertile populations. Because conventional sperm-preparation methods do not directly target molecular sperm damage, combined selection strategies such as density gradient centrifugation (DGC) and annexin V-based magnetic-activated cell sorting (MACS) have been proposed to enrich spermatozoa with improved DNA integrity before intracytoplasmic sperm injection (ICSI). Regardless of their more favorable functional characteristics, the optimal sequence for combining these methods remains uncertain. Methods: This study presents a hybrid analysis combining a structured review of 25 published studies with original prospective observational laboratory data. The review examined the effects of DGC, MACS, and sequential combined protocols on SDF, conventional semen parameters, and reported assisted reproduction outcomes, with particular attention to the unresolved question of sequencing order. In parallel, a blinded observational cohort of 67 infertile men with baseline SDF of at least 30% underwent sequential DGC followed by MACS, with SDF measured before and after processing using the sperm chromatin dispersion test (Halosperm ^® assay). Results: Across the reviewed literature, combined DGC/MACS approaches generally reduced SDF more than single-step preparation, although the magnitude of benefit varied across assays, patient populations, and laboratory protocols. Some studies also reported improvements in embryo quality and pregnancy-related outcomes, but these data were derived mainly from retrospective or small comparative cohorts, and no large randomized head-to-head trials were identified comparing DGC→MACS with MACS→DGC for fertilization, miscarriage, or live-birth outcomes. In the observational cohort, DGC→MACS was associated with a significant mean absolute SDF reduction of 19.42% +/− 9.4% (p < 0.0001). Most patients (85.1%) achieved post-treatment SDF values below the 30% threshold. Conclusions: Combined DGC/MACS sperm preparation, supported by the data in our study sequence, appears promising for reducing SDF in selected infertile men, particularly those with elevated baseline SDF. However, the optimal sequencing strategy and its impact on major reproductive endpoints remain uncertain and require better standardized comparative clinical studies. Full article

Testicular adrenal rest tumors (TARTs) are a frequent and clinically relevant complication of congenital adrenal hyperplasia (CAH), particularly its classic forms due to 21-hydroxylase deficiency. Although histologically benign, these masses develop within the rete testis and can progressively compress the seminiferous tubules, leading to fibrosis and, when longstanding, permanent gonadal injury and obstructive azoospermia; they are the foremost cause of impaired fertility in men with classic CAH. Their frequency increases with age, from approximately 25% in childhood to 46% in adulthood. This narrative review summarizes current evidence on the pathogenesis, predisposing factors and diagnostic work-up of TARTs, focusing on two practical questions: the appropriate age to begin monitoring and the imaging tools best suited to it. Sustained ACTH excess is regarded as the dominant growth-promoting signal, while the salt-wasting phenotype, severe CYP21A2 variants and inadequate disease control emerge as the principal predisposing factors. Although current guidelines advise ultrasound monitoring from adolescence, a growing body of pediatric data shows that TARTs can be detected well before puberty in patients at greatest risk. Scrotal ultrasonography remains the first-line technique, complemented by CEUS, elastography and MRI in selected cases. We outline a pragmatic, risk-adapted monitoring scheme and argue that earlier, childhood assessment in the highest-risk patients may help to safeguard future fertility, an approach that still awaits prospective confirmation. Full article