Actionable secondary findings following exome sequencing of 836 non-obstructive azoospermia cases and their value in patient management.

Study Question: What is the load, distribution and added clinical value of secondary findings (SFs) identified in exome sequencing (ES) of patients with non-obstructive azoospermia (NOA)?

Summary Answer: One in 28 NOA cases carried an identifiable, medically actionable SF.

What Is Known Already: In addition to molecular diagnostics, ES allows assessment of clinically actionable disease-related gene variants that are not connected to the patient's primary diagnosis, but the knowledge of which may allow the prevention, delay or amelioration of late-onset monogenic conditions. Data on SFs in specific clinical patient groups, including reproductive failure, are currently limited.

[Effect of tadalafil 5mg daily treatment on penile haemodynamics in patients with erectile dysfunction].

Introduction And Objective: Phosphodiesterase-5 inhibitors (PDE-5) are the first-line treatment. ED diagnostic and evaluation methods are clinical: erection self-perception and evaluation questionnaires. It is necessary to identify predictive markers to choose the best drug and the best dose for each individual patient.

Correction: gr/gr deletion predisposes to testicular germ cell tumour independently from altered spermatogenesis: results from the largest European study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genetic dissection of spermatogenic arrest through exome analysis: clinical implications for the management of azoospermic men.

Purpose: Azoospermia affects 1% of men and it can be the consequence of spermatogenic maturation arrest (MA). Although the etiology of MA is likely to be of genetic origin, only 13 genes have been reported as recurrent potential causes of MA.

Methods: Exome sequencing in 147 selected MA patients (discovery cohort and two validation cohorts).

Short anogenital distance is associated with testicular germ cell tumour development.

Background: Testicular germ cell tumour is a multifactorial disease in which various genetic and environmental factors play a role. Testicular germ cell tumour is part of the testicular dysgenesis syndrome which includes also cryptorchidism, hypospadias, oligo/azoospermia and short anogenital distance.

Objectives: The primary objective was to examine anogenital distance in testicular germ cell tumour cases and healthy fertile controls.

Clinical factors affecting semen improvement after microsurgical subinguinal varicocelectomy: which subfertile patients benefit from surgery?

Background: The exact mechanism of varicocele-related infertility is still elusive, therefore, the current challenges for its management lie in determining which patients stand to benefit most from surgical correction. The authors aimed to assess the clinical factors affecting semen improvement after left microsurgical subinguinal varicocelectomy (MSV) in relation to patient age, ultrasound varicocele grading (USVG), and presence of a right subclinical varicocele (RSV).

Methods: From 2010 to 2017 a total of 228 infertile patients underwent left MSV for clinical varicocele.

Sequencing of a 'mouse azoospermia' gene panel in azoospermic men: identification of RNF212 and STAG3 mutations as novel genetic causes of meiotic arrest.

Study Question: What is the diagnostic potential of next generation sequencing (NGS) based on a 'mouse azoospermia' gene panel in human non-obstructive azoospermia (NOA)?

Summary Answer: The diagnostic performance of sequencing a gene panel based on genes associated with mouse azoospermia was relatively successful in idiopathic NOA patients and allowed the discovery of two novel genes involved in NOA due to meiotic arrest.

What Is Known Already: NOA is a largely heterogeneous clinical entity, which includes different histological pictures. In a large proportion of NOA, the aetiology remains unknown (idiopathic NOA) and yet, unknown genetic factors are likely to play be involved.

gr/gr deletion predisposes to testicular germ cell tumour independently from altered spermatogenesis: results from the largest European study.

The association between impaired spermatogenesis and TGCT has stimulated research on shared genetic factors. Y chromosome-linked partial AZFc deletions predispose to oligozoospermia and were also studied in TGCT patients with controversial results. In the largest study reporting the association between gr/gr deletion and TGCT, sperm parameters were unknown.

From exome analysis in idiopathic azoospermia to the identification of a high-risk subgroup for occult Fanconi anemia.

Purpose: In about 10% of patients affected by Fanconi anemia (FA) the diagnosis is delayed until adulthood, and the presenting symptom in these "occult" FA cases is often a solid cancer and cancer treatment-related toxicity. Highly predictive clinical parameter(s) for diagnosing such an adult-onset cases are missing.

Methods: (1) Exome sequencing (ES), (2) Sanger sequencing of FANCA, (3) diepoxybutane (DEB)-induced chromosome breakage test.