Letrozole, a third-generation aromatase inhibitor initially developed for breast cancer, has become the preferred first-line agent for ovulation induction (OI), particularly in women with polycystic ovary syndrome (PCOS). This narrative review critically evaluates the efficacy, safety, and clinical applications of letrozole across diverse infertility contexts. Compared to clomiphene citrate, letrozole is associated with higher ovulation and live birth rates, a lower risk of multiple gestation, and a more favorable endometrial environment. Its pharmacokinetics—marked by transient estrogen suppression and a short half-life—limit embryonic exposure, supporting its favorable safety profile. Emerging data from large, randomized trials and meta-analyses demonstrate no increase in congenital anomalies, miscarriage, or adverse perinatal outcomes in letrozole-conceived pregnancies. Moreover, maternal side effects are generally mild, and the risk of ovarian hyperstimulation syndrome is low. Letrozole has also shown utility in mild stimulation protocols, fertility preservation for estrogen-sensitive malignancies, and clomiphene-resistant PCOS. Key clinical strategies—such as early-cycle initiation, lowest effective dosing, and individualized monitoring—optimize therapeutic outcomes while minimizing potential risks. While long-term offspring data remain limited and mechanistic concerns persist, current evidence robustly supports letrozole as a safe and effective option for OI, balancing reproductive success with maternal–fetal safety across a range of infertility indications.

Urolithiasis represents one of the most common urologic diseases, and its incidence demonstrates, globally, an increasing trend. The application of preventive measures is an established strategy to reduce urolithiasis-related morbidity, and it is based mostly on the adaptation of lifestyle factors and pharmacotherapy. Furthermore, other research areas demonstrate promising results, such as the research on the microbiome. In the current review, we searched for the latest data on lifestyle–based prevention and microbiome alterations in urolithiasis patients. The majority of the proposed lifestyle measures are already included in the urological guidelines, while additional factors, such as vitamin D supplementation, seem to have a putative positive effect. From the microbiome studies, several microbial composition patterns and metabolic pathways demonstrated an inhibiting or promoting role in lithogenesis. Up to the present, stone prevention has not shown satisfying results, which suggests that lifestyle measures are not adequate. Moreover, microbiome studies are prone to bias, since microbes are strongly affected by numerous clinical factors, while the analysis procedures are not standardized yet. Analysis standardization and data pooling from extensive registration of clinical and microbiome data are essential steps in order to improve the existing prevention strategy with targeted microbiome manipulations.

Prostatitis includes infectious and noninfectious inflammatory phenotypes that can impair male reproductive potential and may influence couple-level reproduction via seminal inflammatory and microbial exposure. This review summarizes mechanisms linking prostatic inflammation and dysbiosis to semen dysfunction and sperm DNA damage and proposes an infertility-oriented diagnostic and management framework. This is a narrative review of clinical and translational evidence addressing semen inflammation, oxidative stress, sperm DNA fragmentation (SDF), microbiome signatures, and reproductive outcomes in prostatitis (National Institutes of Health (NIH) categories I-IV). Across prostatitis phenotypes, leukocytospermia and elevated seminal cytokines (especially interleukin-8) are associated with impaired motility, altered viscosity and liquefaction, oxidative stress, and higher SDF. Persistent infection or dysbiosis may sustain immune activation and redox injury, while ductal remodeling and pain-related sexual dysfunction can further reduce natural conception. Seminal cytokines and microbes may affect female reproductive tract biology, although clinical outcome data remain limited. Prostatitis-related infertility requires evaluation beyond routine semen analysis. A biomarker-guided workup integrating inflammatory markers, oxidative stress testing, targeted microbiology (culture plus nucleic acid amplification tests when indicated), SDF testing in selected men, and imaging when obstruction is suspected can identify treatable drivers and guide timing and selection of assisted reproduction strategies. Future studies should standardize fertility endpoints and validate biomarker-guided and microbiome-directed interventions.

Background/Objectives: Beta-thalassemia (BTH), a genetic disorder resulting from beta-globin gene mutations, affects over 1.5 million people globally. The disorder’s multifactorial impact on male fertility, particularly through oxidative stress (OS), warrants focused study. This review examines the mechanisms of OS in TM, its implications for male infertility, and the potential of antioxidant therapies to mitigate fertility challenges. Methods: A non-systematic review was conducted using the PubMed, Cochrane, and Medscape databases, focusing on studies on beta-thalassemia (BTH), erectile dysfunction (ED), hormonal alterations, and OS. Studies were screened based on relevance, language, and topic, with 71 articles meeting the inclusion criteria after removing duplicates. Results: The findings reveal that OS, exacerbated by iron overload from regular blood transfusions, is significantly associated with impaired sperm quality and fertility in patients with TM. Iron toxicity affects gonadotropin levels, reduces sperm quality, and contributes to hypogonadism. Additionally, antioxidant therapies show promise in reducing OS-induced sperm damage, though efficacy is limited by a lack of robust clinical trials. Conclusions: OS plays a considerable role in male infertility among patients with TM, primarily through iron-induced sperm damage and hormonal disruptions. While antioxidant therapies may offer a partial remedy, further research is necessary to understand OS’s mechanisms in TM and develop effective fertility treatments. This review highlights the need for personalized antioxidant approaches to improve reproductive outcomes in this population.

Background: Radiation Therapy (RT) is an established treatment option for benign intracranial lesions. The aim of this study is to display an update on the role of RT concerning the most frequent benign brain lesions and tumors.Methods: Published articles about RT and meningiomas, Vestibular Schwannomas (VSs), Pituitary Adenomas (PAs), Arteriovenous Malformations (AVMs) and craniopharyngiomas were reviewed and extracted data were used.Results: In meningiomas RT is applied as an adjuvant therapy, in case of patientrefusing surgery or in unresectable tumors. The available techniques are External Beam RT (EBRT) and stereotactic ones such as Stereotactic Radiosurgery (SRS), Fractionated Stereotactic RT (FSRT), Intensity Modulated RT (IMRT) and proton-beam therapy. The same indications are considered in PAs, in which SRS and FSRT achieve excellent tumor control rate (92-100%), acceptable hormone remission rates (>50%) and decreased Adverse Radiation Effects (AREs). Upon tumor growth or neurological deterioration, RT emerges as alone or adjuvant treatment against VSs, with SRS, FSRT, EBRT or protonbeam therapy presenting excellent tumor control growth (>90%), facial nerve (84-100%), trigeminal nerve (74-99%) and hearing (>50%) preservation. SRS poses an effective treatment modality of certain AVMs, demonstrating a 3-year obliteration rate of 80%. Lastly, a combination of microsurgery and RT presents equal local control and 5-year survival rate (>90%) but improved toxicity profile compared to total resection in case of craniopharyngiomas.Conclusion: RT comprises an effective treatment modality of benign brain and intracranial lesions. By minimizing its AREs with optimal use, RT projects as a potent tool against such diseases.

Sickle cell disease (SCD) is an inherited hemoglobinopathy in which hemoglobin S polymerization drives hemolysis and vaso-occlusion with progressive organ morbidity. Male reproductive impairment is increasingly recognized but remains underreported. This narrative review summarizes mechanistic pathways, clinical manifestations, and fertility preservation options relevant to men with SCD. PubMed, the Cochrane Library, and Medscape were searched through 31 December 2025 for human studies addressing endocrine changes, semen quality, priapism and erectile dysfunction, oxidative stress, and treatment-related gonadotoxicity. Evidence supports converging mechanisms: recurrent vaso-occlusion and chronic hypoxia may injure the seminiferous epithelium and impair Leydig cell steroidogenesis; oxidative stress and inflammation contribute to sperm DNA and membrane damage; and disease-modifying or curative therapies such as hydroxyurea and hematopoietic stem cell transplantation can further compromise spermatogenesis. Clinically, men with SCD may present with oligozoospermia, azoospermia, hypogonadism, and sexual dysfunction, particularly after recurrent ischemic priapism. Fertility preservation should be discussed early, ideally before prolonged hydroxyurea exposure or transplantation, and may include semen cryopreservation and testicular sperm extraction (TESE) with assisted reproduction when needed. Prospective longitudinal studies are required to define reproductive trajectories and optimize counseling and management.