Professor Eric Chung ( left ) Consultant urological surgeon at the AndroUrology Centre for Sexual , Urinary and Reproductive Excellence ; professorial academic appointments at the University of Queensland in Brisbane and Macquarie University Hospital in Sydney ; chair of the male lower urinary tract symptoms section and past chair of the andrology section within the Urological Society of Australia and New Zealand ; and serves as an adviser on the Panel of Clinical Experts for the federal Department of Health and Aged Care .

Dr Jason Kim ( right ) Senior urology registrar at the Princess Alexandra Hospital , Brisbane , Queensland .

Copyright © 2024 Australian Doctor All rights reserved . No part of this publication may be reproduced , distributed , or transmitted in any form or by any means without the prior written permission of the publisher . For permission requests , email : howtotreat @ adg . com . au .

This information was correct at the time of publication : 13 September 2024

INTRODUCTION

IT is estimated that male infertility

contributes to 30-50 % of causes in the 15 % of couples who are unable to conceive over a 12-month period . 1 Male infertility may be attributed to a variety of causes related to abnormal reproductive anatomy or genetic , hormonal or environmental factors . 2 Genetic abnormalities associated with male infertility are responsible for 15-30 % of cases , with molecular defects and genetic alterations causing disruption to various physiological processes that adversely impact hormonal homeostasis , spermatogenesis and sperm quality . 3 Chromosomal abnormalities such as single-gene point mutations , polygenic and / or multifactorial genetic defects as well as endocrine disorders of genetic origin are the most frequently reported genetic causes of male infertility . 4 , 5 In addition , mutations and polymorphisms of various genes involved in spermatogenesis ( see figure 1 ) and other aspects of male reproduction have been found to be associated with male infertility . 6

Given that genetic conditions can pose problems , including the risk

of transmission to future offspring , genetic testing has taken a prominent role in the evaluation of male infertility and assisted reproductive technology ( ART ). Up to 70 % of diagnoses can be identified through comprehensive history taking and physical examination in conjunction with specific laboratory tests . 1 , 7 While genetic testing is not clinically indicated for all infertile patients , it should be considered in males with non-obstructive azoospermia ( see figure 2 ), severe oligospermia or non-palpable vasa . 1 , 5

Some genetic conditions related to male infertility may be transmissible to offspring so genetic testing plays a prominent role in male infertility evaluation and should be undertaken after proper informed discussion with couples about the role of testing as well as prognostic and psychological consequences that may follow . 8

Genetic testing serves three major purposes in the setting of male infertility ; first , to provide an answer about potential genetic causes ; second , to define potential heritable conditions that may be passed to offspring ; and third , to evaluate for conditions that may

impact on the success of ART . However , many of these genetic tests are not widely available in clinical practice , especially outside of expert male reproductive units . This may be because of limited availability of specific genomic kits , lack of technical expertise , high diagnostic cost , and actual clinical application in the setting of ART .

This How to Treat provides an overview of the current clinical practice in the genetic evaluation of male infertility and briefly explores other novel genetic tests in this field . It aims to ensure that GPs have basic knowledge of the current genetic tests performed in male infertility and understand the relevance of these genetic tests to the different causes of male infertility .

WHO AND WHEN TO TEST

Genetic testing is not indicated for

all infertile male patients . Consider genetic testing ( figure 3 ) in males with non-obstructive azoospermia , severe oligospermia or non-palpable vasa , to clarify potential aetiology of male infertility prior to treatment . 1 , 5

Genetic testing can be performed by the GP or reproductive specialist with the male patient at the initial workup stage , after an informed discussion given the potential prognostic and psychological consequences .

CURRENT EVIDENCE ON GENETIC TESTING IN MALE INFERTILITY

GENETIC testing in male infertility

involves a complex evaluation across a wide array of genes , proteins and metabolites . Despite advances in our understanding of sperm physiology and genomic testing , considerable challenges remain with relatively poor translation from bench science to meaningful clinical diagnostic tools that significantly alter the practice of ART . An aetiology for male infertility remains elusive in up to 80 % of cases . Current established genetic testing in clinical practice can be broadly divided into three main categories ( see box 1 ).

Genetic karyotyping with chromosomal analysis

Genetic karyotypes , Y chromosome