Identification of differentially expressed genes in human testis biopsies with defective spermatogenesis.

Purpose: Sperm morphology and motility are major contributors to male-factor infertility, with many genes predicted to be involved. This study aimed to elucidate differentially expressed transcripts in human testis tissues of normal and abnormal spermatogenesis that could reveal new genes that may regulate sperm morphology and function.

Methods: Human testis biopsies were collected from men with well-characterized phenotypes of normal spermatogenesis, spermatid arrest, and Sertoli cell-only phenotype, and transcriptional differences were quantified by RNA-sequencing (RNA-Seq).

[Cryopreservation of human spermatozoa or testicular tissue for fertility preservation].

Loss of reproductive capacity due to treatments for malignant or non-malignant diseases or even as a result of diseases themselves significantly impacts patients' quality of life. Cryopreservation of sperm from ejaculate is a well-established procedure for preserving the fertility of these patients and thus improving their quality of life in the long term. If cryopreservation of sperm from ejaculate is not possible, either because ejaculation cannot occur or no sperm can be found in the ejaculate, the preferred treatment option is (microsurgical) testicular sperm extraction (mTESE).

[Desire to have children after vasectomy : Vasectomy reversal or assisted reproductive technology?].

The vasectomy is a safe and effective method of contraception for men. Up to 6% of men who underwent vasectomy have a renewed child wish. Microsurgical vasectomy reversal (VR) in men, microsurgical epididymal sperm aspiration (MESA), or testicular sperm extraction (TESE) in men plus assisted reproductive technology (ART) in the female partner as well as the combination of VR and MESA/TESE plus ART represent established therapeutic strategies.

Genital gender-affirming surgery trends in Germany: Total population data with 19,600 cases from 2006 to 2022.

Purpose: To delineate the current trends regarding gender-affirming surgeries (GAS) in Germany.

Methods: Analysis of German hospital quality reports from 2006 to 2022 was conducted using the reimbursement.info tool.

Investigations into the Concentrations and Metabolite Profiles of Doping Agents and Antidepressants in Human Seminal Fluid Using Liquid Chromatography-Mass Spectrometry.

Exogenous substances, including drugs and chemicals, can transfer into human seminal fluid and influence male fertility and reproduction. In addition, substances relevant in the context of sports drug testing programs, can be transferred into the urine of a female athlete (after unprotected sexual intercourse) and trigger a so-called adverse analytical finding. Here, the question arises as to whether it is possible to distinguish analytically between intentional doping offenses and unintentional contamination of urine by seminal fluid.

[Digital health applications in urology].

Background: Digital health applications (DiGA) were included in the German healthcare system in 2020. They are available for prescription and reimbursed by public and private insurance companies. For the specialty of urology, there are currently two DiGA available: for the treatment of erectile dysfunction and benign prostatic hyperplasia/overactive bladder (BPH/OAB).

Inherited defects of piRNA biogenesis cause transposon de-repression, impaired spermatogenesis, and human male infertility.

piRNAs are crucial for transposon silencing, germ cell maturation, and fertility in male mice. Here, we report on the genetic landscape of piRNA dysfunction in humans and present 39 infertile men carrying biallelic variants in 14 different piRNA pathway genes, including PIWIL1, GTSF1, GPAT2, MAEL, TDRD1, and DDX4. In some affected men, the testicular phenotypes differ from those of the respective knockout mice and range from complete germ cell loss to the production of a few morphologically abnormal sperm.

AXDND1 is required to balance spermatogonial commitment and for sperm tail formation in mice and humans.

Dynein complexes are large, multi-unit assemblies involved in many biological processes via their critical roles in protein transport and axoneme motility. Using next-generation sequencing of infertile men presenting with low or no sperm in their ejaculates, we identified damaging variants in the dynein-related gene AXDND1. We thus hypothesised that AXDND1 is a critical regulator of male fertility.

App-based Therapy of Erectile Dysfunction Using a Digital Health Application (EDDIG Study): A Randomized, Single-blind, Controlled Trial.

Background And Objective: While international guidelines advocate for a multifaceted approach to treating erectile dysfunction (ED) involving physical activities, psychological support, and education, structured programs are infrequent. To address this gap, an app-based therapy was developed, offering a systematic approach. This randomized, single-blind controlled trial aimed to assess the effectiveness of an app-based therapeutic in improving ED.

Decreased spermatogonial numbers in boys with severe haematological diseases.

This study examines spermatogonial numbers in testicular samples from 43 prepubertal patients undergoing haematopoietic stem cell transplantation (HSCT). High-dose chemotherapy and/or radiation during HSCT can impact spermatogenesis requiring fertility preservation. Results show that 49% of patients have decreased and 19% severely depleted spermatogonial pool prior to HSCT.

Complementary information concerning the suspected interindividual transmission of GW1516, a substance prohibited in sport, through intimate contact: a case report.

Purpose: Inadvertent and/or unknowing exposure to drugs and drug residues has been frequently debated in situations of so-called adverse analytical finding (AAF) in the context of sports drug testing programs. Transfer of drug residues via unprotected intercourse is a conceivable scenario but scientific data and authentic case reports are scarce. Herein, investigations into two AAFs with the peroxisome proliferator-activated receptor delta (PPARδ) agonist GW1516 are reported and discussed.

T cells in testicular germ cell tumors: new evidence of fundamental contributions by rare subsets.

Background: Immune cell infiltration is heterogeneous but common in testicular germ cell tumors (TGCT) and pre-invasive germ cell neoplasia in situ (GCNIS). Tumor-infiltrating T cells including regulatory T (Treg) and follicular helper T (Tfh) cells are found in other cancer entities, but their contributions to TGCT are unknown.

Methods: Human testis specimens from independent patient cohorts were analyzed using immunohistochemistry, flow cytometry and single-cell RNA sequencing (scRNA-seq) with special emphasis on delineating T cell subtypes.

Recessively Inherited Deficiency of Secreted WFDC2 (HE4) Causes Nasal Polyposis and Bronchiectasis.

Bronchiectasis is a pathological dilatation of the bronchi in the respiratory airways associated with environmental or genetic causes (e.g., cystic fibrosis, primary ciliary dyskinesia, and primary immunodeficiency disorders), but most cases remain idiopathic.

Online decision aid for patients with prostate cancer evaluated by 11 290 patients and 91 urologists in Germany.

Objective: To evaluate the nationwide online decision aid 'Entscheidungshilfe Prostatakrebs' (established in 2016, >11.000 users and 60 new users/week) for patients with non-metastatic prostate cancer (PCa), from the perspective of patients and urologists.

Patients And Methods: To provide personalised information, the tool collects most of the International Consortium for Health Outcomes Measurement standard set, personal preferences, psychological features, and a validated rating of the tool.

TRACK_9: Testosterone replacement assessment: Classical vs. functional hypogonadism-knowledge from a 9-year study.

Background And Objective: The longitudinal efficacy and clinical utility of Testosterone Therapy (TTh) in ameliorating functional hypogonadism (FH) remain contentious, with long-term data being scarce. To address this lacuna, a comprehensive long-term registry study, stratifying patients across a spectrum of hypogonadal etiologies, offers a robust investigative paradigm.

Materials And Methods: This 9-year registry, encompassing 650 patients (equivalent to 4,362 cumulative years of treatment), included 188 patients diagnosed with FH (mean age 42.

A 20-year overview of fertility preservation in boys: new insights gained through a comprehensive international survey.

Study Question: Twenty years after the inception of the first fertility preservation programme for pre-pubertal boys, what are the current international practices with regard to cryopreservation of immature testicular tissue?

Summary Answer: Worldwide, testicular tissue has been cryopreserved from over 3000 boys under the age of 18 years for a variety of malignant and non-malignant indications; there is variability in practices related to eligibility, clinical assessment, storage, and funding.

What Is Known Already: For male patients receiving gonadotoxic treatment prior to puberty, testicular tissue cryopreservation may provide a method of fertility preservation. While this technique remains experimental, an increasing number of centres worldwide are cryopreserving immature testicular tissue and are approaching clinical application of methods to use this stored tissue to restore fertility.

Identification of two hidden clinical subgroups among men with idiopathic cryptozoospermia.

Study Question: Are there subgroups among patients with cryptozoospermia pointing to distinct etiologies?

Summary Answer: We reveal two distinct subgroups of cryptozoospermic (Crypto) patients based on testicular tissue composition, testicular volume, and FSH levels.

What Is Known Already: Cryptozoospermic patients present with a sperm concentration below 0.1 million/ml.

C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germ line.

In the male mouse germ line, PIWI-interacting RNAs (piRNAs), bound by the PIWI protein MIWI2 (PIWIL4), guide DNA methylation of young active transposons through SPOCD1. However, the underlying mechanisms of SPOCD1-mediated piRNA-directed transposon methylation and whether this pathway functions to protect the human germ line remain unknown. We identified loss-of-function variants in human SPOCD1 that cause defective transposon silencing and male infertility.

Heterozygous loss-of-function SMC3 variants are associated with variable growth and developmental features.

Heterozygous missense variants and in-frame indels in SMC3 are a cause of Cornelia de Lange syndrome (CdLS), marked by intellectual disability, growth deficiency, and dysmorphism, via an apparent dominant-negative mechanism. However, the spectrum of manifestations associated with SMC3 loss-of-function variants has not been reported, leading to hypotheses of alternative phenotypes or even developmental lethality. We used matchmaking servers, patient registries, and other resources to identify individuals with heterozygous, predicted loss-of-function (pLoF) variants in SMC3, and analyzed population databases to characterize mutational intolerance in this gene.

Human fertilization in vivo and in vitro requires the CatSper channel to initiate sperm hyperactivation.

The infertility of many couples rests on an enigmatic dysfunction of the man's sperm. To gain insight into the underlying pathomechanisms, we assessed the function of the sperm-specific multisubunit CatSper-channel complex in the sperm of almost 2,300 men undergoing a fertility workup, using a simple motility-based test. We identified a group of men with normal semen parameters but defective CatSper function.

AXDND1 is required to balance spermatogonial commitment and for sperm tail formation in mice and humans.

Dynein complexes are large, multi-unit assemblies involved in many biological processes including male fertility via their critical roles in protein transport and axoneme motility. Previously we identified a pathogenic variant in the dynein gene in an infertile man. Subsequently we identified an additional four potentially compound heterozygous variants of unknown significance in in two additional infertile men.