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.

Prostate cancer (PCa) is a common malignancy in men and is among the leading causes of cancer-related death worldwide. Genomic tests assess disease aggressiveness and guide treatment, particularly in low- and intermediate-risk PCa. We reviewed the literature on the use of four genomic tests (Prolaris^®, Promark^®, Oncotype DX^®, and Decipher^®) in assessing the prognosis of PCa and their use in treatment decision-making. Most of the studies showed that Prolaris^® has a strong correlation with biochemical recurrence, metastasis risk, PCa-specific mortality (PCSM), and pathological features. Similarly, three studies on Promark^® indicated a connection between results and pathological features in the subsequent prostatectomy, time to metastasis, and biochemical recurrence. Fourteen studies on Oncotype DX^® showed a clear correlation between high scores, death, and PCSM. One study found that routine biopsy pathology reports, combined with serum PSA levels, provide a risk assessment comparable to Oncotype DX^® testing. Results from 22 studies on Decipher^® were controversial. The test was associated with conservative management, suggesting that patients with a high GC score are more likely to need radiation after surgery. Comparative studies indicated that Oncotype DX^® is preferable for assessing PCSM, Decipher^® for predicting metastasis, and Prolaris^® for predicting recurrence. With the incidence rate of PCa dramatically increasing, genomic tests appear to be useful adjunctive precision medicine tools with significant potential in improving prognostic discrimination, facilitating better risk stratification, and guiding personalized treatment, especially in the intermediate-risk patient group. Large-scale, prospective, multi-sectional studies are required to validate the utility of these tests prior to their integration into clinical practice.

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.

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.

Background and Objectives: Benign prostatic hyperplasia (BPH) is a progressive, androgen-dependent condition driven by dihydrotestosterone (DHT). 5α-reductase inhibitors (5-ARIs), including finasteride and dutasteride, target this pathway and provide disease-modifying effects. Materials and Methods: This narrative review summarizes evidence from randomized trials, meta-analyses, and observational studies evaluating the efficacy, timing, and safety of 5-ARIs in the management of LUTS due to BPH. Results: 5-ARI therapy reduces prostate volume by 18–28% and serum PSA by approximately 50% within 6–12 months. Landmark trials (MTOPS, CombAT) demonstrate significant reductions in acute urinary retention (AUR) and BPH-related surgery (>50% RR reduction). Combination therapy with α-blockers provides superior symptom control and greater prevention of clinical progression, particularly in men with prostate volume ≥ 30–40 mL or PSA ≥ 1.5 ng/mL. Early initiation of combination therapy improves long-term outcomes, while α-blocker withdrawal may be feasible in selected patients. Adverse events are mainly sexual, with emerging data suggesting a possible association with depression. Conclusions: 5-ARIs are central to BPH management, offering sustained clinical benefits and prevention of progression. Optimal outcomes depend on appropriate patient selection, early treatment in high-risk individuals, and individualized long-term strategies.