New perspectives in the genetic diagnosis of male infertility

The current issue of the Croatian Medical Journal features two interesting articles on reproductive health. Sengun et al (1) present their findings of novel mutations in the gene coding for FK506 binding protein-like (FKBPL) associated with male infertility, while Bilić et al (2) discuss the benefits of ovarian tissue cryopreservation. In spite of tremendous advances in the field, various aspects of reproductive health, particularly infertility, still necessitate further study and development of novel diagnostic and therapeutic approaches

Impact of Varicocele Repair on Semen Parameters in Infertile Men: A Systematic Review and Meta-Analysis

Purpose: Despite the significant role of varicocele in the pathogenesis of male infertility, the impact of varicocele repair (VR) on conventional semen parameters remains controversial. Only a few systematic reviews and meta-analyses (SRMAs) have evaluated the impact of VR on sperm concentration, total motility, and progressive motility, mostly using a before-after analytic approach. No SRMA to date has evaluated the change in conventional semen parameters after VR compared to untreated controls. This study aimed to evaluate the effect of VR on conventional semen parameters in infertile patients with clinical varicocele compared to untreated controls. Materials and Methods: A literature search was performed using Scopus, PubMed, Embase, and Cochrane databases following the Population Intervention Comparison Outcome (PICOS) model (Population: infertile patients with clinical varicocele; Intervention: VR [any technique]; Comparison: infertile patients with clinical varicocele that were untreated; Outcome: sperm concentration, sperm total count, progressive sperm motility, total sperm motility, sperm morphology, and semen volume; Study type: randomized controlled trials and observational studies). Results: A total of 1,632 abstracts were initially assessed for eligibility. Sixteen studies were finally included with a total of 2,420 infertile men with clinical varicocele (1,424 patients treated with VR vs. 996 untreated controls). The analysis showed significantly improved post-operative semen parameters in patients compared to controls with regards to sperm concentration (standardized mean difference [SMD] 1.739; 95% CI 1.129 to 2.349; p<0.001; I2=97.6%), total sperm count (SMD 1.894; 95% CI 0.566 to 3.222; p<0.05; I2=97.8%), progressive sperm motility (SMD 3.301; 95% CI 2.164 to 4.437; p<0.01; I2=98.5%), total sperm motility (SMD 0.887; 95% CI 0.036 to 1.738; p=0.04; I2=97.3%) and normal sperm morphology (SMD 1.673; 95% CI 0.876 to 2.470; p<0.05; I2=98.5%). All the outcomes showed a high inter-study heterogeneity, but the sensitivity analysis showed that no study was sensitive enough to change these results. Publication bias was present only in the analysis of the sperm concentration and progressive motility. No significant difference was found for the semen volume (SMD 0.313; 95% CI -0.242 to 0.868; I2=89.7%). Conclusions: This study provides a high level of evidence in favor of a positive effect of VR to improve conventional semen parameters in infertile men with clinical varicocele. To the best of our knowledge, this is the first SRMA to compare changes in conventional semen parameters after VR with changes in parameters of a control group over the same period. This is in contrast to other SRMAs which have compared semen parameters before and after VR, without reference to a control group. Our findings strengthen the available evidence and have a potential to upgrade professional societies’ practice recommendations favoring VR to improve conventional semen parameters in infertile men. Copyright © 2022 Korean Society for Sexual Medicine and Andrology

Obstructive Sleep Apnea and Testosterone Replacement Therapy

The evidence on the role of obstructive sleep apnea (OSA) in the pathogenesis of hypogonadism and the impact of testosterone replacement therapy (TRT) in OSA patients are still contradictory. OSA i..

IGF2 and IGF1R mRNAs Are Detectable in Human Spermatozoa.

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Impact of antioxidant therapy on natural pregnancy outcomes and semen parameters in infertile men: A systematic review and meta-analysis of randomized controlled trials

Purpose: Seminal oxidative stress (OS) is a recognized factor potentially associated with male infertility, but the efficacy of antioxidant (AOX) therapy is controversial and there is no consensus on its utility. Primary outcomes of this study were to investigate the effect of AOX on spontaneous clinical pregnancy, live birth and miscarriage rates in male infertile patients. Secondary outcomes were conventional semen parameters, sperm DNA fragmentation (SDF) and seminal OS.Materials and Methods: Literature search was performed using Scopus, PubMed, Ovid, Embase, and Cochrane databases. Only randomized controlled trials (RCTs) were included and the meta-analysis was conducted according to PRISMA guidelines.Results: We assessed for eligibility 1,307 abstracts, and 45 RCTs were finally included, for a total of 4,332 infertile patients. We found a significantly higher pregnancy rate in patients treated with AOX compared to placebo-treated or untreated controls, without significant inter-study heterogeneity. No effects on live-birth or miscarriage rates were observed in four studies. A significantly higher sperm concentration, sperm progressive motility, sperm total motility, and normal sperm morphology was found in patients compared to controls. We found no effect on SDF in analysis of three eligible studies. Seminal levels of total antioxidant capacity were significantly higher, while seminal malondialdehyde acid was significantly lower in patients than controls. These results did not change after exclusion of studies performed following varicocele repair.Conclusions: The present analysis upgrades the level of evidence favoring a recommendation for using AOX in male infertility to improve the spontaneous pregnancy rate and the conventional sperm parameters. The failure to demonstrate an increase in live-birth rate, despite an increase in pregnancy rates, is due to the very few RCTs specifically assessing the impact of AOX on live-birth rate. Therefore, further RCTs assessing the impact of AOX on live-birth rate and miscarriage rate, and SDF will be helpful

Ruolo del volume piastrinico medio nella disfunzione erettile a patogenesi arteriosa

SommarioIl volume piastrinico medio (VPM) è un parametro che sta acquisendo sempre maggiore importanza nella stratificazione del rischio vascolare sistemico dal momento che è in grado di predire il grado di attività piastrinica. Piastrine più attive sono infatti più trombogeniche e contribuiscono al processo di aterosclerosi che, a sua volta, è la principale causa della disfunzione vascolare. La disfunzione erettile (DE) è una condizione che impatta notevolmente sulla qualità della vita di un uomo e, tra le varie cause, la DE su base vascolare arteriosa è quella che ha la prevalenza maggiore. Per questo motivo, alcuni studi hanno cercato di valutare la relazione tra i valori di VPM nei pazienti con DE, suggerendo che questo parametro può essere considerato uno strumento per la diagnosi precoce della DE oltre che un possibile nuovo bersaglio terapeutico, facilmente valutabile

Cerebellar degeneration-related protein 1 expression in fibroblasts of patients affected by down syndrome

Down syndrome (DS) is the most common genetic cause of intellectual disability, resulting from lack of disjunction of sister chromatids of human chromosome 21 or not partial disjunction of chromoso..

Contraccezione ormonale e funzione tiroidea.

SommarioLe disfunzioni della ghiandola tiroidea rappresentano un gruppo di patologie rilevanti sotto il profilo epidemiologico, specie nel sesso femminile. La terapia ormonale contraccettiva è capace di influenzare la funzione tiroidea modulando i livelli di TBG e SHBG e, sebbene frequentemente prescritta, esistono poche evidenze riassuntive circa i limiti prescrittivi nelle donne con disfunzione tiroidea. Lo scopo di questo articolo è quello di rivedere gli effetti del trattamento con levo-tiroxina (LT4) nelle donne in terapia ormonale contraccettiva e come quest'ultima influenzi la funzione tiroidea. La componente estrogenica è responsabile dell'aumento di TBG, SHBG e dei fattori di coagulazione. Per contro, la componente progestinica, attraverso l'azione anti-androgenica, è utile per mantenere basso il rischio tromboembolico e cardiovascolare. Ciò assume particolare rilevanza nelle donne affette da ipotiroidismo subclinico e in quelle trattate con LT4. Infatti, l'ipotiroidismo subclinico è associato a un aumentato volume piastrinico medio, il quale aumenta, a sua volta, il rischio cardiovascolare a causa dell'iperattività piastrinica dovuta alla incompleta maturazione megacariocitica

Clinical Evaluation of a Custom Gene Panel as a Tool for Precision Male Infertility Diagnosis by Next-Generation Sequencing

Background: Up to 15% of couples are infertile and male factor infertility accounts for approximately 50% of these cases. Male infertility is a multifactorial pathological condition. The genetic of male infertility is very complex and at least 2000 genes are involved in its etiology. Genetic testing by next-generation sequencing (NGS) technologies can be relevant for its diagnostic value in male infertile patients. Therefore, the aim of this study was to implement the diagnostic offer with the use of an NGS panel for the identification of genetic variants. Methods: We developed an NGS gene panel that we used in 22 male infertile patients. The panel consisted of 110 genes exploring the genetic causes of male infertility; namely spermatogenesis failure due to single-gene mutations, central hypogonadism, androgen insensitivity syndrome, congenital hypopituitarism, and primary ciliary dyskinesia. Results: NGS and a subsequent sequencing of the positive pathogenic or likely pathogenic variants, 5 patients (23%) were found to have a molecular defect. In particular, pathogenic variants were identified in TEX11, CCDC39, CHD7, and NR5A1 genes. Moreover, 14 variants of unknown significance and 7 novel variants were found that require further functional studies and family segregation. Conclusion: This extended NGS-based diagnostic approach may represent a useful tool for the diagnosis of male infertility. The development of a custom-made gene panel by NGS seems capable of reducing the proportion of male idiopathic infertility