Andrology最新文献

Background: Current guidelines indicate that patients with extreme oligozoospermia or azoospermia should be tested for chromosomal imbalances, azoospermia factor (AZF) deletions and/or CFTR variants. For other sperm abnormalities, no genetic diagnostics are recommended.

Objectives: To determine whether exome sequencing (ES) with combined copy number variant (CNV) and single nucleotide variant (SNV) analysis is a reliable first-tier method to replace current methods (validation study), and to evaluate the diagnostic yield after 10 months of implementation (evaluation study).

Materials and methods: In the validation study, ES was performed on DNA of patients already diagnosed with AZF deletions (n = 17), (non-)mosaic sex chromosomal aneuploidies or structural chromosomal anomalies (n = 37), CFTR variants (n = 26), or variants in known infertility genes (n = 4), and 90 controls. The data were analyzed using our standard diagnostic pipeline, with a bioinformatic filter for 130 male infertility genes. In the evaluation study, results of 292 clinical exomes were included.

Results: All previously reported variants in the validation cohort, including clinically relevant Y-chromosomal microdeletions, were correctly identified and reliably detected. In the evaluation study, we identified one or more clinically relevant genetic anomalies in 67 of 292 of all cases (22.9%): these included aberrations that could have been detected with current methods in 30 of 67 patients (10.2% of total), (possible) (mono)genetic causes in the male infertility gene panel in 28 of 67 patients (9.6%), and carriership of cystic fibrosis in nine of 67 patients (3.1%).

Conclusion: ES is a reliable first-tier method to detect the most common genetic causes of male infertility and, as additional genetic causes can be detected, in our evaluation cohort the diagnostic yield almost doubled (10.2%-19.8%, excluding CF carriers). A genetic diagnosis provides answers on the cause of infertility and helps the professionals in the counseling for treatment, possible co-morbidities and risk for offspring and/or family members. Karyotyping will still remain necessary for detecting balanced translocations or low-grade chromosomal mosaicism.

Background: Genetic testing serves as a valuable element of reproductive care, applicable at various stages of the reproductive journey: (i) before pregnancy, when a couple's genetic reproductive risk can be evaluated; (ii) before embryo implantation, as part of in vitro fertilization (IVF) treatment, to ascertain several inherited or de novo genetic/chromosomal diseases of the embryo before transfer; (iii) during the prenatal period, to assess the genetic costitution of the fetus. Preconception carrier screening (CS) is a genetic test typically performed on couples planning a pregnancy. The primary purpose of CS is to identify couples at-risk of conceiving a child affected by a severe genetic disorder with autosomal recessive or X-linked inheritance. Detection of high reproductive risk through CS allows prospective parents to be informed of their predisposition and improve reproductive decision-making. These include undergoing IVF with preimplantation genetic testing (PGT) or donor gametes, prenatal diagnosis, adoption, remaining childless, taking no actions. Both the presence of the affected gene (PGT-M) and chromosomal status (PGT-A) of the embryo can be comprehensively assessed through modern approaches.

Objectives: We provide a review of CS and PGT applications to equip healthcare providers with up-to-date information regarding their opportunities and complexities.

Results and discussion: The use of CS and PGT is currently considered the most effective intervention for avoiding both an affected pregnancy whilst using autologous gametes in couples with known increased risk, and chromosomal abnormalities. As our understanding in the genetic component in pathological conditions increases, the number of tested disorders will expand, offering a more thorough assessment of one's genetic inheritance. Nevertheless, implementation and development in this field must be accompanied by scientific and ethical considerations to ensure this approach serves the best long-term interests of individuals and society, promoting justice and autonomy and preserving parenthood and the healthcare system.

Conclusion: The combination of CS and PGT aligns with principles of personalized medicine by offering reproductive care tailored to the individual's genetic makeup.

Introduction: Several robust epidemiological studies suggest that men are often engaged in sexual relationships with younger women with a variable, age-dependent age difference. However, the ageing process determines a significant worsening of the andrological status, which favors the onset of erectile dysfunction and hypogonadism.

Objectives: To analyze the effects of differences in age between the partners [delta (Δ) age (M - F)] on patients referring to the Andrology Unit of Careggi University Hospital for male sexual dysfunction.

Materials and methods: A monocentre cohort of 4055 male subjects was evaluated by SIEDY structured interview. The cross-sectional analysis assessed the psychobiological and relational correlates. The rate of forthcoming major cardiovascular events (MACE) was investigated in the longitudinal analysis. All the models have been adjusted for age, education, lifestyle, and chronic disease score.

Results: ∆ age (M-F) shows a stepwise increase, according to the increasing age bands of the male partner. ∆ age (M-F) was associated with a greater number of children, at the cost of more conflictual relationships within the family. The phenotype of these relationships is characterized by the report of a partner with a higher sexual desire and a higher ability to reach climax. Men seeking a younger partner show more often a histrionic personality (p = 0.023) and higher testosterone levels (p = 0.032). However, having a younger partner doesn't improve the ability to obtain a full erection. Kaplan-Maier analysis of a longitudinal subgroup of patients followed longitudinally (N = 1402) for 4.3 ± 2,59 years, showed that patients in the fourth quartile had a higher rate of forthcoming MACE versus those in the first quartile (p = 0.005).

Discussion and conclusion: In subjects with sexual dysfunctions (as in the general population) age-different relationships increase as a function of male ageing. A greater Δ age (M-F) is associated with specific men and relationship features and a higher risk of MACE.

Background: Priapism is a urological condition characterized by a persistent erection. The management varies based on its subclassifications. Despite established clinical guidelines for ischemic priapism, there is a lack of large-scale research focused on patient characteristics and management strategies.

Objectives: To analyze the contemporary management of ischemic priapism in the US, exploring patient demographics and clinical characteristics, as well as predictors of erectile dysfunction (ED) and penile prosthesis implantation (PPI).

Materials and methods: We performed a retrospective analysis of the PearlDiver Mariner database, reviewing records from 2010-2021. Adult males diagnosed with ischemic priapism were included. Data analysis covered demographic, clinical variables, and management strategies. Predictors of de novo ED and PPI were evaluated using multivariable logistic regression analysis.

Results: Of 36,120 patients, most (93%) received only medical management, and a minority underwent surgical interventions (penile shunt surgery [PSS], PPI or both). Medical management was typically effective, as 67.08% of the patients in this group experienced only one episode of priapism. However, de novo ED occurred in 16.57% of these patients. The majority of patients undergoing PPI had an inflatable prosthesis (81%). Older age (odds ratio, OR 1.02), the presence of metabolic diseases (OR 1.39), neurogenic disorders (OR 1.72), solid pelvic malignancies (OR 1.09), and multiple episodes of priapism were identified as significant predictors of de novo ED (all p < 0.05). Similarly, age (OR 1.03), the presence of metabolic diseases (OR 1.23), solid pelvic malignancies (OR 1.99), and multiple episodes of priapism were associated with higher likelihood of PPI (all p < 0.05).

Conclusion: Most cases of ischemic priapism are managed with the medical therapy. Less than 3% of patients with ischemic priapism receive PPI, and when this occurs an inflatable prosthesis is favored. Age, specific comorbidities, and multiple episodes of priapism appear to be significant predictors of ED and PPI.

Background: The current cutoff values of intravaginal ejaculation latency time for diagnosing lifelong premature ejaculation do not always match clinical practice, and the inconsistency in the cutoff values of intravaginal ejaculation latency time among different definitions has also posed challenges to both clinical management and research of premature ejaculation.

Objectives: To re-evaluate the intravaginal ejaculation latency time and to find evidence-based cut-off values for diagnosing lifelong premature ejaculation that can be widely accepted and match clinical practice.

Materials and methods: We addressed the flaws of previous studies. Lifelong premature ejaculation was diagnosed based on both patient self-report of premature ejaculation status and scores on the Premature Ejaculation Diagnostic Tool, with a control group consisting of non-premature ejaculation individuals included for comparison. Utilizing receiver operating characteristic curve analysis, the optimal self-estimated cutoff value for intravaginal ejaculation latency time in diagnosing lifelong premature ejaculation was determined.

Results: A total of 307 heterosexual participants (mean age = 30.7 ± 6.4) were included, comprising 187 lifelong premature ejaculation patients (mean age = 28.0 ± 4.6) and 120 non-premature ejaculation individuals (mean age = 35.0 ± 6.5). 2.7% of lifelong premature ejaculation patients experienced anteportal ejaculation. 59.9%, 92%, and 97.9% of lifelong premature ejaculation patients displayed intravaginal ejaculation latency times within 1, 2, and 3 min, respectively. The receiver-operating characteristic curve's area under the curve was 0.996 with a 95% confidence interval of 0.991-1.000 (p < 0.0001). The perceived intravaginal ejaculation latency time cut-off at 3.5 (sensitivity = 97.9%, specificity = 99.2%) showed the highest Youden index compared with other options.

Discussion: Although we found that 92.0% of lifelong premature ejaculation patients had a perceived intravaginal ejaculation latency time within 2 min, a perceived intravaginal ejaculation latency time cutoff value of less than 3.5 min for diagnosing lifelong premature ejaculation could encompass a larger proportion (97.9%) of patients seeking medical help for complaints of PE, and increasing the perceived intravaginal ejaculation latency time cutoff value to 3.5 min would not significantly increase the false-positive rate.

Conclusion: The perceived intravaginal ejaculation latency time cutoff value for diagnosing lifelong premature ejaculation within a clinical practice context is 3.5 min.

Objective: Elevated sperm DNA fragmentation has potential implications for semen quality and fertility. The commonly used sperm chromatin dispersion test offers an indirect estimation but has limitations in terms of bias and variability. This study aimed to assess the reliability of the sperm chromatin dispersion assay for predicting assisted reproductive technology outcomes.

Materials and methods: This systematic review included studies published until December 2023 that adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed/MEDLINE, Scopus, and Google Scholar databases were searched. Various assisted reproductive technology outcomes in patients with high (≥ 30%) versus low (< 30%) sperm DNA fragmentation were compared using a sperm chromatin dispersion assay and including a sub-analysis of intracytoplasmic sperm injection versus in vitro fertilization. A comprehensive meta-analysis software facilitated quantitative analysis with statistical comparisons between cases and controls. Interstudy heterogeneity was assessed, and sensitivity and publication bias tests were performed.

Results: Of the 199 abstracts assessed, 64 full-text articles were screened, and 44 articles were qualitatively synthesized. Fourteen articles representing 5346 participants were quantitatively analyzed. Using the sperm chromatin dispersion assay, elevated sperm DNA fragmentation was associated with lower fertilization and embryo cleavage rates. Notably, high sperm DNA fragmentation levels did not affect the clinical pregnancy, implantation, miscarriage, or live birth outcomes. Sub-analysis revealed lower fertilization, embryo cleavage, clinical pregnancy, live birth rates, and higher miscarriage rates in the intracytoplasmic sperm injection subgroup only.

Conclusions: The sperm chromatin dispersion assay did not show significant differences in pregnancy or live birth rates between the high- and low-sperm DNA fragmentation groups. Noteworthy, high sperm DNA fragmentation was associated with worse assisted reproductive technology outcomes in the intracytoplasmic sperm injection group. Given the current quality of the evidence, affected by the experimental design and the absence of correction for female factors of infertility, clinicians should be wary of the assay's limited predictive power for pregnancy and live birth outcomes.

Background: Physical, chemical, and biological factors in the environment constantly influence in vivo and in vitro biological processes, including diverse histone modifications involved in cancer and metabolism. However, the intricate mechanisms of acetylation regulation remain poorly elucidated. In mammalian spermatogenesis, acetylation plays a crucial role in repairing double-strand DNA breaks, regulating gene transcription, and modulating various signaling pathways.

Results: This review summarizes the histone acetylation sites in the mouse testis and provides a comprehensive overview of how histone acetylation is involved in different stages of spermatogenesis under the regulation by histone deacetylases. The regulatory functions of various class histone deacetylases during spermatogenesis and the crossroad between histone acetylation and other histone modifications are highlighted. It is imperative to understand the mechanisms of histone acetylation regulated by histone deacetylases in spermatogenesis, which facilitates to prevent and treat infertility-related diseases.