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.

Consensus and Diversity in the Management of Varicocele for Male Infertility: Results of a Global Practice Survey and Comparison with Guidelines and Recommendations.

Purpose: Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes.

Clinical impact of parental consanguineous marriage in idiopathic nonobstructive azoospermia.

Objective: To determine the frequency of parental consanguineous marriages (PCMs) in men with diagnosed idiopathic nonobstructive azoospermia (INOA) and to compare clinical and pathological parameters between azoospermic men with and without PCM.

Design: Retrospective.

Setting: A private clinic.

Efficacy of the second micro-testicular sperm extraction after failed first micro-testicular sperm extraction in men with nonobstructive azoospermia.

Objective: To evaluate the efficacy of the second micro-testicular sperm extraction (TESE)in men with nonobstructive azoospermia in whom the first micro-TESE failed.

Design: Retrospective.

Setting: Private clinic.

Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility.

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo.

Evaluation of the morphokinetic parameters and development of pre-implantation embryos obtained by testicular, epididymal and ejaculate spermatozoa using time-lapse imaging system.

Low sperm quality has negative effects on fertilisation and embryo development. The males with azoospermia apply for testicular sperm extraction (TESE) or microsurgical epididymal sperm aspiration (MESA) in order to retrieve sperm. To date, there have not been any reports investigating morphokinetic parameters of pre-implantation embryos using testicular and epididymal spermatozoa.

Longitudinal analysis of treatment-induced genomic alterations in gliomas.

Background: Glioblastoma multiforme (GBM) constitutes nearly half of all malignant brain tumors and has a median survival of 15 months. The standard treatment for these lesions includes maximal resection, radiotherapy, and chemotherapy; however, individual tumors display immense variability in their response to these approaches. Genomic techniques such as whole-exome sequencing (WES) provide an opportunity to understand the molecular basis of this variability.

Whole-exome sequencing identifies novel homozygous mutation in NPAS2 in family with nonobstructive azoospermia.

Objective: To investigate the genetic cause of nonobstructive azoospermia (NOA) in a consanguineous Turkish family through homozygosity mapping followed by targeted exon/whole-exome sequencing to identify genetic variations.

Design: Whole-exome sequencing (WES).

Setting: Research laboratory.

Somatic POLE mutations cause an ultramutated giant cell high-grade glioma subtype with better prognosis.

Background: Malignant high-grade gliomas (HGGs), including the most aggressive form, glioblastoma multiforme, show significant clinical and genomic heterogeneity. Despite recent advances, the overall survival of HGGs and their response to treatment remain poor. In order to gain further insight into disease pathophysiology by correlating genomic landscape with clinical behavior, thereby identifying distinct HGG molecular subgroups associated with improved prognosis, we performed a comprehensive genomic analysis.

Brain malformations associated with Knobloch syndrome--review of literature, expanding clinical spectrum, and identification of novel mutations.

Background: Knobloch syndrome is a rare, autosomal recessive, developmental disorder characterized by stereotyped ocular abnormalities with or without occipital skull deformities (encephalocele, bone defects, and cutis aplasia). Although there is clear heterogeneity in clinical presentation, central nervous system malformations, aside from the characteristic encephalocele, have not typically been considered a component of the disease phenotype.

Methods: Four patients originally presented for genetic evaluation of symptomatic structural brain malformations.

Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads to early-onset progressive neurodegeneration.

Ubiquitin C-terminal hydrolase-L1 (UCHL1), a neuron-specific de-ubiquitinating enzyme, is one of the most abundant proteins in the brain. We describe three siblings from a consanguineous union with a previously unreported early-onset progressive neurodegenerative syndrome featuring childhood onset blindness, cerebellar ataxia, nystagmus, dorsal column dysfuction, and spasticity with upper motor neuron dysfunction. Through homozygosity mapping of the affected individuals followed by whole-exome sequencing of the index case, we identified a previously undescribed homozygous missense mutation within the ubiquitin binding domain of UCHL1 (UCHL1(GLU7ALA)), shared by all affected subjects.

Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO.

We report genomic analysis of 300 meningiomas, the most common primary brain tumors, leading to the discovery of mutations in TRAF7, a proapoptotic E3 ubiquitin ligase, in nearly one-fourth of all meningiomas. Mutations in TRAF7 commonly occurred with a recurrent mutation (K409Q) in KLF4, a transcription factor known for its role in inducing pluripotency, or with AKT1(E17K), a mutation known to activate the PI3K pathway. SMO mutations, which activate Hedgehog signaling, were identified in ~5% of non-NF2 mutant meningiomas.

Common variant near the endothelin receptor type A (EDNRA) gene is associated with intracranial aneurysm risk.

The pathogenesis of intracranial aneurysm (IA) formation and rupture is complex, with significant contribution from genetic factors. We previously reported genome-wide association studies based on European discovery and Japanese replication cohorts of 5,891 cases and 14,181 controls that identified five disease-related loci. These studies were based on testing replication of genomic regions that contained SNPs with posterior probability of association (PPA) greater than 0.

Recessive LAMC3 mutations cause malformations of occipital cortical development.

The biological basis for regional and inter-species differences in cerebral cortical morphology is poorly understood. We focused on consanguineous Turkish families with a single affected member with complex bilateral occipital cortical gyration abnormalities. By using whole-exome sequencing, we initially identified a homozygous 2-bp deletion in LAMC3, the laminin γ3 gene, leading to an immediate premature termination codon.

The essential role of centrosomal NDE1 in human cerebral cortex neurogenesis.

We investigated three families whose offspring had extreme microcephaly at birth and profound mental retardation. Brain scans and postmortem data showed that affected individuals had brains less than 10% of expected size (≤10 standard deviation) and that in addition to a massive reduction in neuron production they displayed partially deficient cortical lamination (microlissencephaly). Other body systems were apparently unaffected and overall growth was normal.

Klinefelter syndrome: does it confer a bad prognosis in treatment of nonobstructive azoospermia?

Objective: To determine the effectiveness of microsurgical testicular sperm extraction (micro-TESE) and intracytoplasmic sperm injection (ICSI) for men with Klinefelter syndrome (KS).

Design: Retrospective clinical study.

Setting: Private IVF center.

Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations.

The development of the human cerebral cortex is an orchestrated process involving the generation of neural progenitors in the periventricular germinal zones, cell proliferation characterized by symmetric and asymmetric mitoses, followed by migration of post-mitotic neurons to their final destinations in six highly ordered, functionally specialized layers. An understanding of the molecular mechanisms guiding these intricate processes is in its infancy, substantially driven by the discovery of rare mutations that cause malformations of cortical development. Mapping of disease loci in putative Mendelian forms of malformations of cortical development has been hindered by marked locus heterogeneity, small kindred sizes and diagnostic classifications that may not reflect molecular pathogenesis.

Gonadotrophin therapy in combination with ICSI in men with hypogonadotrophic hypogonadism.

The aim of this study was to evaluate the impact of gonadotrophin therapy in combination with intracytoplasmic sperm injection (ICSI) in men with hypogonadotrophic hypogonadism (HH). Twenty-five azoospermic men were diagnosed with HH due to low FSH, LH and total testosterone concentrations. These patients were treated with human chorionic gonadotrophin for 1 month plus recombinant FSH the following month.

The effect of labor and/or ovariectomy on rodent continence mechanism--the neuronal changes.

Many women develop stress urinary incontinence (SUI) after childbirth, but the exact neuronal changes are largely unknown. This study is designed to identify the neuronal changes associated with pregnancy, delivery and ovariectomy. A total of 10 virgin and 48 pregnant rats were used.

Tunica albuginea acellular matrix graft for penile reconstruction in the rabbit: a model for treating Peyronie's disease.

Objective: To evaluate the use of an acellular matrix graft of the tunica albuginea for functional penile reconstruction in severe cases of Peyronie's disease.

Materials And Methods: In 18 rabbits, an acellular matrix graft of the tunica albuginea was used to cover a 4 x 8 mm tunical defect, and six animals each were killed 1, 3 and 6 months later; four unoperated animals served as histological controls. Before death an erection was induced by papaverine, with the quality classified on a scale of 0-5, and cavernosography performed.