Michela Cuccorese

Background/Objectives: Fertility preservation (FP) has become an integral component of multidisciplinary care for patients at risk of treatment- or disease-related infertility. Although several established and emerging fertility preservation strategies are currently available, important challenges remain regarding patient selection, timing of intervention, long-term reproductive outcomes, and the translation of experimental approaches into routine clinical practice. This review critically appraises the current evidence on female and male fertility preservation, highlighting established techniques, emerging technologies, unresolved clinical challenges, and future research priorities. Oocyte vitrification remains the preferred strategy for postpubertal women when ovarian stimulation is feasible, whereas ovarian tissue cryopreservation has become an established option for selected patients requiring urgent treatment or for prepubertal girls. In men, sperm cryopreservation remains the standard of care, while fertility preservation in prepubertal boys is still investigational. Despite excellent laboratory outcomes, the real-world utilization of cryopreserved reproductive material remains unexpectedly low, highlighting persistent barriers in patient referral, counselling, and long-term follow-up. Methods: A structured narrative review was conducted using PubMed/MEDLINE and Embase to identify international guidelines, systematic reviews, meta-analyses, multicentre cohorts, registry-based studies, and original clinical investigations published between January 2015 and June 2025. Evidence was synthesized according to sex, age, fertility preservation indication, and clinical applicability. Interventions reviewed include oocyte and embryo cryopreservation, ovarian tissue cryopreservation (OTC), GnRH agonist co-treatment, ovarian transposition, in vitro maturation (IVM), sperm banking, surgical sperm retrieval (SSR), testicular tissue cryopreservation (TTC), and spermatogonial stem-cell (SSC) approaches. Results: Oocyte vitrification remains the preferred strategy for postpubertal women when ovarian stimulation is feasible, whereas ovarian tissue cryopreservation has become an established option for selected patients requiring urgent treatment or for prepubertal girls. In men, sperm cryopreservation prior to therapy is standard; SSR provides sperm for selected azoospermic cases. Paediatric FP strategies are asymmetric: OTC is clinically established, while TTC remains investigational. Random-start COS and aromatase inhibitor or tamoxifen protocols minimise treatment delay and hormonal exposure, and GnRHa co-treatment can serve as an adjunctive ovarian-protective measure. Despite high laboratory success, utilisation of banked gametes and tissue is modest, underscoring the need for structured referral pathways, patient counselling, and longitudinal follow-up. Conclusions: FP should be systematically integrated into both oncological and non-oncologic care pathways, with timely referral, age- and sex-specific counselling on live-birth probabilities, and long-term follow-up. Future priorities include harmonization of clinical protocols, standardized outcome reporting, registry-based long-term follow-up, and validation of emerging technologies to improve both reproductive outcomes and equitable access to fertility preservation.

Background/Objectives: Golgi protein 73 (GP73) is a transmembrane protein expressed by epithelial cells of the bile duct in the normal liver. High serum levels of GP73 have been detected in patients with acute or chronic liver diseases, MASLD, and its measurement has been suggested as a potential biomarker for liver fibrosis staging. We evaluated the utility of GP73 in the diagnosis of MASLD, MASH, and for liver fibrosis staging. Methods: We performed a literature scoping review to map the current evidence about the accuracy of GP73 in patients with MASLD. We searched in Medline and EMBASE for English studies reporting an AUC value of GP73 in diagnosing MASLD and MASH and evaluating GP73 for fibrosis staging. A narrative synthesis of the evidence was conducted. Moreover, we performed an observational study including 84 patients with MASLD, of which 60 were biopsy-confirmed MASH, and different liver fibrosis stages, and 15 healthy controls. Serum GP73 levels were determined using a chemiluminescent assay and reported as mean and standard deviation (SD). Sensitivity (SE), specificity (SP), the area under the receiver operating characteristic (AUROC) curve, and the optimal cut-off value were calculated. Data were considered statistically significant when p < 0.05. Results: Available studies evaluating GP73 in MASLD reported the ability to discriminate MASH from simple steatosis and distinguish patients at different fibrotic stages, but the evidence is still scarce. Our experimental study showed that the serum levels of GP73 were 30 ± 12 ng/mL in MASLD and 32 ± 12 ng/mL in MASH patients and were statistically higher than those of the control group (19 ± 30 ng/mL), increasing from liver fibrosis stage F0 to F4. GP73 levels were significantly higher in patients with significant and advanced fibrosis than controls and no significant fibrosis (p > 0.05). ROC analysis demonstrated that serum GP73 had a good diagnostic potential for MASLD (AUROC 0.85; SE 90%; SP 73%), MASH (AUROC 0.75; SE 82%; SP64%), and significant fibrosis (AUROC 0.7; SE 56%; SP 79%) and was better than other biomarkers for chronic liver diseases. Conclusions: Serum GP73 could support clinicians in the evaluation of patients with MASH and significant fibrosis.

The formation of a robust long-term antigen (Ag)-specific memory, both humoral and cell-mediated, is created following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination. Here, by using polychromatic flow cytometry and complex data analyses, we deeply investigated the magnitude, phenotype, and functionality of SARS-CoV-2-specific immune memory in two groups of healthy subjects after heterologous vaccination compared to a group of subjects who recovered from SARS-CoV-2 infection. We find that coronavirus disease 2019 (COVID-19) recovered patients show different long-term immunological profiles compared to those of donors who had been vaccinated with three doses. Vaccinated individuals display a skewed T helper (Th)1 Ag-specific T cell polarization and a higher percentage of Ag-specific and activated memory B cells expressing immunoglobulin (Ig)G compared to those of patients who recovered from severe COVID-19. Different polyfunctional properties characterize the two groups: recovered individuals show higher percentages of CD4⁺ T cells producing one or two cytokines simultaneously, while the vaccinated are distinguished by highly polyfunctional populations able to release four molecules, namely, CD107a, interferon (IFN)-γ, tumor necrosis factor (TNF), and interleukin (IL)-2. These data suggest that functional and phenotypic properties of SARS-CoV-2 adaptive immunity differ in recovered COVID-19 individuals and vaccinated ones.