Sabine Kliesch

University Hospital Münster

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Frank Tüttelmann

Institute of Reproductive Medicine

122

Eberhard Nieschlag

University Hospital Münster

Stefan Schlatt

University Hospital Münster

Hermann M. Behre

University Hospital in Halle

Michael Zitzmann

University Hospital Münster

Nina Neuhaus

University of Münster

Jörg Gromoll

University of Münster

Joachim Wistuba

University of Münster

W. Weidner

University of Giessen

Peter Albers

Heinrich Heine University Düsseldorf

Cooperative Institutions

University of Münster

293

University Hospital Münster

262

Heidelberg University

147

Klinik und Poliklinik für Urologie

138

University of Giessen

132

Charité - Universitätsmedizin Berlin

113

Universität Hamburg

108

University Hospital Heidelberg

107

Heinrich Heine University Düsseldorf

Ludwig-Maximilians-Universität München

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Testicular Biopsy and Histology

Andrology (2010)

Martin Bergmann Sabine Kliesch

Indications for testicular biopsy are summarized in Table 11.1. According to the European Association of Urology (EAU) guidelines, a therapeutic testicular biopsy (for testicular sperm extraction, TESE) is indicated (1) in the case of obstructive aszoospermia (OA), indicated by normal testicular volume, normal FSH (<7 IU/l), and low levels of epididymal (α-glucosidase, L-carnitine) or seminal vesicle (fructose) markers with no chance for surgical reconstruction (e.g., congenital bilateral aplasia of the vas deferens). Alternatively, microsurgical epididymal sperm aspiration (MESA) can be applied. However, sperm obtained by TESE show better fertilization rates. In the case of microsur-gical refertilization (vasovasostomy, vasotubulostomy), after vasectomy a diagnostic biopsy helps to exclude impairment of seminiferous epithelium. In both cases, cryopreservation allows the use of extracted sperm (TESE, MESA) in combination with intracytoplasmic sperm injection (ICSI), if microsurgical refertilization techniques are not applicable or fail.

Testicular sperm extraction

Vasovasostomy

Vasectomy

Sperm Retrieval

Vas deferens

Vasectomy reversal

10.1007/978-3-540-78355-8_11

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Citations (56)

Randomized Phase III Trial Comparing Retroperitoneal Lymph Node Dissection With One Course of Bleomycin and Etoposide Plus Cisplatin Chemotherapy in the Adjuvant Treatment of Clinical Stage I Nonseminomatous Testicular Germ Cell Tumors: AUO Trial AH 01/94 by the German Testicular Cancer Study Group

Journal of Clinical Oncology (2008)

Peter Albers Roswitha Siener S. Krege Hans-Uwe Schmelz Klaus‐Peter Dieckmann

Retroperitoneal lymph node dissection (RPLND) and adjuvant chemotherapy are two adjuvant treatment options for patients with clinical stage I nonseminomatous germ cell tumors of the testis (NSGCT). Aim of this trial was to prove the advantage of one cycle of bleomycin, etoposide, and cisplatin (BEP) chemotherapy compared with RPLND in terms of recurrence.Between 1996 and 2005, 382 patients were randomly assigned to receive either RPLND (n = 191) or one course of BEP (n = 191) after orchidectomy. The primary study end point was the rate of recurrence. The trial was powered to detect a 7% reduction (from 10% to 3%) of recurrence with chemotherapy compared with surgery.After a median follow-up of 4.7 years, two and 15 recurrences were observed in the intention-to-treat population with chemotherapy and surgery, respectively (P = .0011). The difference in the 2-year recurrence-free survival rate between chemotherapy (99.46%; 95% CI, 96.20% to 99.92%) and surgery (91.87%; 95% CI, 86.87% to 95.02%) was 7.59% (95% CI, 3.13% to 12.05%). The hazard ratio to experience a tumor recurrence with surgery as opposed to chemotherapy was 7.937 (95% CI, 1.808 to 34.48).To our knowledge, this is the largest randomized trial investigating adjuvant treatment strategies in clinical stage I NSGCT, which showed the superiority of one course BEP over RPLND performed according to community standards to prevent recurrence. Although not standard treatment, one course of BEP is active in an unselected group of patients with clinical stage I disease and merits further investigation.

Induction chemotherapy

10.1200/jco.2007.12.0899

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Citations (325)

Improved phenotypic classification of male infertility to promote discovery of genetic causes

Nature Reviews Urology (2023)

Margot J. Wyrwoll Godfried W. van der Heijden Csilla Krausz Kenneth I. Aston Sabine Kliesch

10.1038/s41585-023-00816-0

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Citations (17)

Gynäkomastie: Diagnostik und Therapie

DMW - Deutsche Medizinische Wochenschrift (2008)

Jens Jacobeit Sabine Kliesch

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

10.1055/s-0028-1105855

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Citations (10)

„Praktisches Spermiogramm“ – Ejakulatdiagnostik gemäß WHO

Der Urologe (2021)

Sabine Kliesch

10.1007/s00120-021-01537-1

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Citations (2)

Cryopreservation of Human Sperm and Testicular Germ Cell Tissue for Fertility Reserve

Andrology (2023)

Sabine Kliesch Nina Neuhaus Stefan Schlatt

Cryopreservation of human sperm can be offered as fertility reserve to adolescents and adults in oncological and non-oncological diseases, as a preventive measure before vasectomy and securing sperm availability in ART procedures. The methods of cryopreservation differ with regard to fresh ejaculate and surgically (epididymal or testicular) retrieved tissue. Current cryopreservation methods allow sperm to survive for at least 30 years, probably indefinitely. Cryopreserved sperm can be used as part of ICSI therapy with pregnancy and birth rates comparable to fresh sperm. Since 2012, cryopreservation of immature testicular tissue has been available to cryopreserve spermatogonial stem cells for pre- and early pubertal boys in Germany. This currently experimental procedure is on the cusp of clinical application, and intensive research will hopefully increase the chances of refertilization for affected individuals in coming years.

Sperm bank

Ovarian Reserve

10.1007/978-3-031-31574-9_42

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Citations (1)

Diverse Monogenic Subforms of Human Spermatogenic Failure

medRxiv (Cold Spring Harbor Laboratory) (2022)

Liina Nagirnaja Alexandra M. Lopes Wu‐Lin Charng Brian Miller Rytis Stakaitis

Abstract Non-obstructive azoospermia (NOA) is the most severe form of male infertility and typically incurable with current medicine. Due to the biological complexity of sperm production, defining the genetic basis of NOA has proven challenging, and to date, the most advanced classification of NOA subforms is based on simple description of testis histology. In this study, we exome-sequenced over 1,000 clinically diagnosed NOA cases and identified a plausible recessive Mendelian cause in 20%. Population-based testing against fertile controls identified 27 genes as significantly associated with azoospermia. The disrupted genes are primarily on the autosomes, enriched for undescribed human “knockouts”, and, for the most part, have yet to be linked to a Mendelian trait. Integration with single-cell RNA sequencing of adult testes shows that, rather than affecting a single cell type or pathway, azoospermia genes can be grouped into molecular subforms with highly synchronized expression patterns, and analogs of these subforms exist in mice. This analysis framework identifies groups of genes with known roles in spermatogenesis but also reveals unrecognized subforms, such as a set of genes expressed specifically in mitotic divisions of type B spermatogonia. Our findings highlight NOA as an understudied Mendelian disorder and provide a conceptual structure for organizing the complex genetics of male infertility, which may serve as a basis for disease classification more advanced than histology.

Mendelian inheritance

10.1101/2022.07.19.22271581

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Citations (2)

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

bioRxiv (Cold Spring Harbor Laboratory) (2023)

Brendan J. Houston Joseph Nguyen D. Jo Merriner Anne E. O′Connor Alexandra M. Lopes

Abstract 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 AXDND1 in an infertile man. Subsequently we identified an additional four potentially compound heterozygous variants of unknown significance in AXDND1 in two additional infertile men. We thus tested the role of AXDND1 in mammalian male fertility by generating a knockout mouse model. Axdnd1 -/- males were sterile at all ages but could undergo one round of histologically complete spermatogenesis. Subsequently, a progressive imbalance of spermatogonial commitment to spermatogenesis over self-renewal occurred, ultimately leading to catastrophic germ cell loss, loss of blood-testis barrier patency and immune cell infiltration. Sperm produced during the first wave of spermatogenesis were immotile due to abnormal axoneme structure, including the presence of ectopic vesicles and abnormalities in outer dense fibres and microtubule doublet structures. Sperm output was additionally compromised by a severe spermiation defect and abnormal sperm individualisation. Collectively, our data highlight the essential roles of AXDND1 as a regulator of spermatogonial commitment to spermatogenesis and during the processes of spermiogenesis where it is essential for sperm tail development, release and motility.

Axoneme

Capacitation

Spermiogenesis

10.1101/2023.11.02.565050

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Citations (2)

Varicocele

Endocrinology (2017)

Mohamed Ragab Sabine Kliesch

Etiology

10.1007/978-3-319-44441-3_38

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Citations (7)

Cylicins are a structural component of the sperm calyx being indispensable for male fertility in mice and human

Simon Schneider Andjela Kovacevic Michelle Mayer Ann‐Kristin Dicke Lena Arévalo

Cylicins are testis specific proteins which are exclusively expressed during spermiogenesis. In mice and humans, two Cylicins, the gonosomal X-linked Cylicin 1 ( Cylc1/CYLC1 ) and the autosomal Cylicin 2 ( Cylc2/CYLC2) genes have been identified. Cylicins are cytoskeletal proteins with an overall positive charge due to lysine-rich repeats. While Cylicins have been localized in the acrosomal region of round spermatids, they resemble a major component of the calyx within the perinuclear theca at the posterior part of mature sperm nuclei. However, the role of Cylicins during spermiogenesis has not yet been investigated. Here, we applied CRISPR/Cas9 mediated gene-editing in zygotes to establish Cylc1- and Cylc2 -deficient mouse lines as a model to study the function of these proteins. Cylc1 -deficiency resulted in male subfertility whereas Cylc2 −/- , Cylc1 −/y Cylc2 +/- , and Cylc1 −/y Cylc2 −/- males were infertile. Phenotypical characterization revealed that loss of Cylicins prevents proper calyx assembly during spermiogenesis. This results in decreased epididymal sperm counts, impaired shedding of excess cytoplasm, and severe structural malformations, ultimately resulting in impaired sperm motility. Furthermore, exome sequencing identified an infertile man with a hemizygous variant in CYLC1 and a heterozygous variant in CYLC2 , displaying morphological abnormalities of the sperm including the absence of the acrosome. Thus, our study highlights the relevance and importance of Cylicins for spermiogenic remodeling and male fertility in human and mouse, and provides the basis for further studies on unraveling the complex molecular interactions between perinuclear theca proteins required during spermiogenesis.

Calyx

Component (thermodynamics)

Human fertility

Male fertility

10.7554/elife.86100.1

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Citations (0)