Grigorios Daligkaros

Primary carcinoma of the seminal vesicle is an exceptionally rare genitourinary malignancy, with evidence limited largely to case reports and small retrospective series. Diagnosis requires exclusion of more common secondary involvement from prostate, bladder, or rectal carcinoma through integration of clinical findings, imaging, histomorphology, and immunohistochemistry. Patients typically present with nonspecific symptoms and often have locally advanced disease. Computed tomography identifies retrovesical masses, while magnetic resonance imaging provides superior local staging. Core biopsy may establish the diagnosis, although definitive classification may require resection. The typical immunophenotype is CK7-positive, often with CA-125 expression, and negative for PSA, PAP, and NKX3.1; however, no marker profile is invariable. A contemporary panel including GATA3, p63/p40, uroplakin markers, CK20, p53, CD44, CDX2, and SATB2 is important for excluding urothelial and intestinal primaries. Conventional papillary adenocarcinoma is the predominant histological type, with mucinous, clear cell, squamous, and neuroendocrine variants also reported. Non-carcinomatous primary seminal vesicle neoplasms, including germ-cell tumours, sarcomas, solitary fibrous tumour, and mixed epithelial and stromal tumour, form an important differential diagnosis. Complete surgical excision with negative margins is the treatment most consistently associated with prolonged survival in the reported cases and is generally regarded as the only potentially curative option, whereas radiotherapy, chemotherapy, and hormonal therapy are selectively used for advanced or recurrent disease. International registries and collaborative molecular studies are needed to improve diagnosis, treatment, and follow-up.

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.

Background/Objectives: Hypogonadotropic hypogonadism (HH) is an uncommon but treatable cause of non-obstructive azoospermia (NOA). Fertility can often be restored with gonadotropin therapy. This study evaluated spermatogenic and reproductive outcomes in men with HH-related NOA managed by stepwise gonadotropin therapy, microdissection testicular sperm extraction (microTESE) for persistent azoospermia, and assisted reproduction when indicated. Methods: A retrospective cohort study included 35 men treated between 2010 and 2022. Human chorionic gonadotropin (hCG), with or without follicle-stimulating hormone (FSH), was administered to induce spermatogenesis. Outcomes included sperm appearance in the ejaculate, microTESE sperm retrieval rate in persistent azoospermia, and pregnancy and live birth outcomes after natural conception or in vitro fertilization with intracytoplasmic sperm injection (IVF-ICSI) when required. Results: Mean gonadotropin therapy duration was 12.0 months (range 6–24). Sperm appeared in the ejaculate in 27/35 men (77%). The remaining 8/35 (23%) underwent microTESE, with sperm retrieved in 7/8 (88%). Seven couples proceeded to IVF-ICSI, undergoing 11 cycles that yielded 6 clinical pregnancies (55% per cycle) and 5 live birth deliveries, including 2 twin pregnancies. Among responders, 13 natural pregnancies occurred, resulting in 13 live birth deliveries, including 2 twin pregnancies. Overall, 18/35 men (51%) achieved biological fatherhood, corresponding to 18 live birth delivery events (4 twin and 14 singleton deliveries) and 22 newborns. Conclusions: In men with HH-related NOA, exogenous gonadotropin therapy is expected to induce spermatogenesis in most patients. MicroTESE provides high sperm retrieval rates for those without ejaculatory sperm. Through an integrated approach of hormonal induction, microsurgical sperm retrieval, and assisted reproduction, approximately half of patients may ultimately achieve biological fatherhood in longer-term follow-up, depending on baseline severity and partner factors.