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Background: Hyaluronan (HA) sperm selection, utilizing the affinity of mature sperm for HA, has emerged as a technique to enhance the selection of sperm for intracytoplasmic sperm injection (ICSI). However, conflicting evidence exists regarding the impact of HA-ICSI on clinical outcomes including fertilization, embryo utilization, and pregnancy rates. The study aimed to compare clinical outcomes including fertilization, utilization, and pregnancy rates between paired ICSI and HA-ICSI cycles within patients, particularly for male factor and low utilization subgroups. Methods: A retrospective study from 3,988 ICSI treatment cycles was conducted between January 2018 and March 2022. A HA-ICSI cycle was paired with the preceding ICSI cycle from the same patient. Fertilization, utilization, and clinical pregnancy rates were compared based on infertility diagnosis and utilization rate (UR) from the initial ICSI cycle. Results: There were no differences in fertilization, utilization, embryo quality, euploidy, or pregnancy rates between ICSI and HA-ICSI in all paired cycles. However, for patients with male factor infertility UR increased from 25.0% to 38.5% in their HA-ICSI cycle ([Formula: see text]). There was no difference observed for female factor infertility patients. HA-ICSI use was of particular benefit for male factor infertility patients with low ([Formula: see text]) embryo utilization in their initial ICSI cycle, evident by an increased utilization from 14.3% to 25.0% in their HA cycle ([Formula: see text]). Conclusions: This is the first study to focus on the impact of HA-ICSI on embryo utilization, particularly in patients with male factor infertility. The efficacy of HA-ICSI as a sperm selection tool appears to be limited to improving UR in patients with male factor infertility, particularly those with low utilization in a previous ICSI cycle, with no significant effect on fertilization or pregnancy rates. Conclusion: HA-ICSI may be useful for sperm selection

Non-obstructive azoospermia (NOA) is the most severe form of male infertility and typically incurable. Defining the genetic basis of NOA has proven challenging, and the most advanced classification of NOA subforms is not based on genetics, but simple description of testis histology. In this study, we exome-sequenced over 1000 clinically diagnosed NOA cases and identified a plausible recessive Mendelian cause in 20%. We find further support for 21 genes in a 2-stage burden test with 2072 cases and 11,587 fertile controls. The disrupted genes are primarily on the autosomes, enriched for undescribed human "knockouts", and, for the most part, have yet to be linked to a Mendelian trait. Integration with single-cell RNA sequencing data shows that azoospermia genes can be grouped into molecular subforms with synchronized expression patterns, and analogs of these subforms exist in mice. This analysis framework identifies groups of genes with known roles in spermatogenesis but also reveals unrecognized subforms, such as a set of genes expressed across mitotic divisions of differentiating spermatogonia. Our findings highlight NOA as an understudied Mendelian disorder and provide a conceptual structure for organizing the complex genetics of male infertility, which may provide a rational basis for disease classification.

Healthy Male [formerly Andrology Australia] was created in 2000 to improve community and professional awareness and education in male reproductive health [MRH]. Supported by the Federal Government, this national 'virtual centre' brings together experts to implement a collaborative strategy. Initially focussing on MRH issues [androgen use/ abuse, infertility, ED, testis cancer, prostate disease] HM recognised the linkages to chronic disease [cardiovascular disease, diabetes, mental health] and expanded its focus. The overall approach has been to first understand consumer needs, then assess the evidence, educate and upskill health professionals and finally "close the loop" through community education of what and how help can be accessed. Although not resourced as a research organisation the longitudinal "Men in Australia telephone survey" [MATeS, Lancet 2006] identified knowledge gaps for future attention. Core material was generated by expert advisory groups and collaborative programs developed with primary health practitioners and disadvantaged groups, such as indigenous people. Strong demand from grassroots organisations for evidence-based information has occurred for local and national use. Rebranding to "Healthy Male" in 2018, a new website and social media engagement expanded its profile. Most effort has been given to the primary care workforce, but specialist issues are being addressed e.g. IVF gynaecologists in male fertility care, the Endocrine Society re androgen guidelines, and HM trainee fellowships. A close relationship has been forged with the Federal Health Department with HM as a trusted resource for policy development, notably overseeing National Men's Health Strategy 2020-2030. Recognizing the need to better support young men from preconception though their first year of fatherhood, the "Plus Paternal Project" is currently developing a roadmap for action. HM is now well-recognized as a trusted resource in all sectors: its innovative, responsive and f

Sperm develop from puberty in the seminiferous tubules, inside the blood-testis barrier to prevent their recognition as "non-self" by the immune system, and it is widely assumed that human sperm-specific proteins cannot access the circulatory or immune systems. Sperm-specific proteins aberrantly expressed in cancer, known as cancer-testis antigens (CTAs), are often pursued as cancer biomarkers and therapeutic targets based on the assumption they are neoantigens absent from the circulation in healthy men. Here, we identify a wide range of germ cell-derived and sperm-specific proteins, including multiple CTAs, that are selectively deposited by the Sertoli cells of the adult mouse and human seminiferous tubules into testicular interstitial fluid (TIF) that is "outside" the blood-testis barrier. From TIF, the proteins can access the circulatory- and immune systems. Disruption of spermatogenesis decreases the abundance of these proteins in mouse TIF, and a sperm-specific CTA is significantly decreased in TIF from infertile men, suggesting that exposure of certain CTAs to the immune system could depend on fertility status. The results provide a rationale for the development of blood-based tests useful in the management of male infertility and indicate CTA candidates for cancer immunotherapy and biomarker development that could show sex-specific and male-fertility-related responses.

STUDY QUESTION: What are the causative genetic variants in patients with male infertility due to severe sperm motility disorders? SUMMARY ANSWER: We identified high confidence disease-causing variants in multiple genes previously associated with severe sperm motility disorders in 10 out of 21 patients (48%) and variants in novel candidate genes in seven additional patients (33%). WHAT IS KNOWN ALREADY: Severe sperm motility disorders are a form of male infertility characterised by immotile sperm often in combination with a spectrum of structural abnormalities of the sperm flagellum that do not affect viability. Currently, depending on the clinical sub-categorisation, up to 50% of causality in patients with severe sperm motility disorders can be explained by pathogenic variants in at least 22 genes. STUDY DESIGN, SIZE, DURATION: We performed exome sequencing in 21 patients with severe sperm motility disorders from two different clinics. PARTICIPANTS/MATERIALS, SETTING, METHOD: Two groups of infertile men, one from Argentina (n = 9) and one from Australia (n = 12), with clinically defined severe sperm motility disorders (motility <5%) and normal morphology values of 0-4%, were included. All patients in the Argentine cohort were diagnosed with DFS-MMAF, based on light and transmission electron microscopy. Sperm ultrastructural information was not available for the Australian cohort. Exome sequencing was performed in all 21 patients and variants with an allele frequency of <1% in the gnomAD population were prioritised and interpreted. MAIN RESULTS AND ROLE OF CHANCE: In 10 of 21 patients (48%), we identified pathogenic variants in known sperm assembly genes: CFAP43 (3 patients); CFAP44 (2 patients), CFAP58 (1 patient), QRICH2 (2 patients), DNAH1 (1 patient) and DNAH6 (1 patient). The diagnostic rate did not differ markedly between the Argentinian and the Australian cohort (55% and 42%, respectively). Furthermore, we identified patients with variants in the novel human c