The evaluation of morpho-functional sperm characteristics alone is not enough to explain infertility or to predict the outcome of Assisted Reproductive Technologies (ART): more sensitive diagnostic tools are needed in clinical practice. The aim of the present study was to analyze Sperm DNA Fragmentation (SDF) and sperm-borne miR-34c-5p and miR-449b-5p levels in men of couples undergoing ART, in order to investigate any correlations with fertilization rate, embryo quality and development. Male partners (n = 106) were recruited. Semen analysis, SDF evaluation and molecular profiling analysis of miR-34c-5p and miR-449b-5p (in 38 subjects) were performed. Sperm DNA Fragmentation evaluation- a positive correlation between SDF post sperm selection and the percentage of low-quality embryos and a negative correlation with viable embryo were found. SDF > 2.9% increased the risk of obtaining a non-viable embryo by almost 4-fold. Sperm miRNAs profile—we found an association with both miRNAs and sperm concentration, while miR-449b-5p is positively associated with SDF. Moreover, the two miRNAs are positively correlated. Higher levels of miR-34c-5p compared to miR-449b-5p increases by 14-fold the probability of obtaining viable embryos. This study shows that SDF, sperm miR-34c-5p, and miR-449b-5p have a promising role as biomarkers of semen quality and ART outcome.

During the COVID-19 pandemic, the most severe form of the disease was most often seen in male patients. The aim of this study was to identify any male predispositions that could be used to predict the outcome of the disease and enable early intervention. We investigated CAG polymorphism in the androgen receptor gene and serum levels of testosterone and LH, which were considered as probably responsible for this predisposition. The study involved 142 patients who had recovered from COVID-19 at least three months previously and were classified according to their disease severity using the World Health Organization (WHO) classification. We observed a significant increase in the number of CAG repeats with increasing disease severity: the percentage of patients with more than 23 repeats increased two-fold from Grade I to Grade IV. Furthermore, testosterone levels were significantly lower in patients with severe disease. Reduced androgenic signaling could predispose men to a more severe form: low testosterone levels and a reduced androgen receptor activity (CAG > 23) expose the host to an excessive inflammatory response, leading downstream to the multi-organ damage seen in severe COVID-19.

Primary Bladder Neck Obstruction (PBNO) management provides medical and surgical treatment, such as transurethral incisions that can lead to retrograde ejaculation. The aim of this study was to investigate the maintenance of anterograde ejaculation and semen quality before and after this surgical procedure. A retrospective evaluation was carried out between 2011 and 2020. A total of 73 patients diagnosed with PBNO were recruited. Ejaculatory function, semen quality, and the fertility of recruited subjects were evaluated. Semen parameters—Baseline, 8.2% of patients were oligozoospermic and 12.3% had a semen volume below the WHO 2010 fifth percentile. Post-surgery, 20% of patients were oligozoospermic. We detected a significant decrease in total sperm number, a significant increase in the number of abnormal forms, and a reduction in the leukocyte concentration. Ejaculatory function—A total of 7.7% of patients reported anejaculation after transurethral incision of the bladder neck. Fertility—9.2% of the patients already had children before surgery; 13.8% had naturally conceived children in the years following surgery; 76.9% had no desire for paternity at the time. Our data have important implications for sperm bank management. The alterations in semen parameters and the risk of anejaculation suggest that the use of sperm cryopreservation before surgery for PBNO should be encouraged.

Background/Objectives: Aberrant DNA methylation of imprinted genes and increased sperm DNA fragmentation (SDF) have been implicated in male infertility. However, their impact on assisted reproductive technology (ART) outcomes remains unclear. This pilot study aimed to investigate SDF and methylation status of H19, IGF2, and PEG1/MEST in relation to fertilisation and embryo development following intracytoplasmic sperm injection (ICSI). Methods: Twenty male partners of women undergoing ICSI were recruited and classified according to ART outcome into viable embryos (VEs, n = 7), non-viable embryos (NVEs, n = 7), and no fertilisation (NF, n = 6). Before sperm selection, an aliquot of each seminal sample was used for semen analysis according to WHO, 2021, SDF assessment (TUNEL assay), and sperm DNA methylation analysis of H19, IGF2, and PEG1/MEST (pyrosequencing). Results: Semen parameters were above the fifth percentile. SDF was significantly lower in the VE group compared with the other groups. H19 CpG1 methylation correlated positively with viable embryos (p = 0.016), while H19 CpG2 island showed a positive correlation with sperm concentration (p = 0.028). In male/couple infertility cases, total H19 methylation correlated negatively with SDF (p = 0.050). IGF2 CpG3 island methylation correlated positively with viable embryos (p = 0.027). Total PEG1/MEST methylation was positively correlated with fertilisation events (p = 0.002) and viable embryos (p = 0.011). PEG1/MEST CpG2 island also positively correlated with sperm motility (p = 0.034), while CpG3 and CpG4 showed significant correlations with fertilisation (p < 0.001; p = 0.004). Conclusions: This pilot study shows that SDF and sperm methylation levels of H19, IGF2, and PEG1/MEST are related to ICSI outcomes, supporting that sperm molecular and epigenetic features may influence fertilisation and embryo development.