Overview
Male factor infertility contributes to approximately 50% of cases where couples experience difficulty conceiving. Of these, about 30% of cases are solely attributable to male infertility, and 20% are a combination of male and female factors.[1]
Infertility is defined as the inability to achieve pregnancy after 12 months of regular, unprotected sexual intercourse. It can lead to significant stress, both to the individual and in the relationship.[1]
Male infertility diagnosis
The causes of male infertility are numerous, but in up to 40% of cases, the aetiology is undetermined. Male infertility may be due to:[1]
pre-testicular causes: hypogonadotropic hypogonadism (eg, Kallman syndrome, for which symptoms include delayed puberty and an impaired sense of smell), hyperprolactinaemia (eg from a prolactinoma)
testicular causes (eg, testicular cancer, genetic sperm abnormalities, infection, and injury)
antisperm antibodies (ASA) result from a breakdown of the blood-testis barrier from injury or illness[2]
ASA may impair sperm function, but not all ASA will cause subfertility[2]
sperm agglutination on laboratory testing may indicate ASA[2]
post-testicular (eg, coital problems, retrograde ejaculation, injury or congenital absence of the vas deferens, Young’s syndrome (triad of bronchiectasis, chronic rhinosinusitis, and vas deferens obstruction))
When couples present with infertility, a comprehensive evaluation of male infertility is essential, and should be conducted concurrently with the female partner's assessment. This evaluation includes a detailed history, physical examination, and laboratory investigations as necessary.
1. History
Key aspects to cover in the history include:[1,3]
reproductive history: age of both partners, previous pregnancies, duration of attempts to conceive, and sexual practices, such as frequency, use of fertility-safe lubrication, and timing of intercourse with ovulation.
medical history: childhood illnesses (eg, mumps), undescended testes, testicular torsion, systemic diseases (eg, diabetes), infections (eg, sexually transmissible infections), trauma, surgery to the reproductive organs or nearby structures, and exposure to gonadotoxins (eg, chemotherapy)
potentially modifiable factors: use of tobacco, alcohol, recreational drugs, and exposure to environmental toxins (eg, pesticides)
2. Physical examination
The physical examination should assess:[3]
general appearance: secondary sexual characteristics, virilisation, and body habitus
genital examination: testicular size as measured with an orchidometer, position, and assessment of the scrotum and penis
3. Additional investigations[3]
semen analysis is the primary investigation for assessing male infertility. Instruct sexual abstinence for 2–7 days prior to sample collection
if the initial analysis is abnormal, repeat the test six weeks later, to ensure that the abnormality was not transitory. Abnormal results warrant referral to a male reproductive specialist
hormonal assessment is recommended for all men with atrophic testes, sperm concentration and/or total sperm count below the normal limit, or who have indications of androgen deficiency:
serum testosterone
serum hormone binding globulin
follicle-stimulating hormone (FSH)
luteinising hormone (LH)
prolactin
normal ranges for semen analysis and reference ranges for endocrine assessment can be found here
scrotal ultrasound is not recommended for the initial stage of investigations
if specialist referral is indicated, further testing may be performed, including testicular biopsy, post-ejaculatory urine analysis, genetic testing, and anti-sperm antibodies[1]
Management of male infertility
Management strategies depend on the identified cause of infertility and may include lifestyle modifications, medical treatments, surgical interventions, or assisted reproductive technologies (ART).
1. Behavioural modifications
General practitioners play a pivotal role in educating patients about modifiable factors that can impact fertility. Recommendations include:
cessation of smoking: smoking, including e-cigarettes, is associated with reduced sperm quality[1,4]
cessation of certain drugs: medicinal and recreational drugs can reduce fertility, including cannabis and opioids[1]
limiting alcohol consumption: excessive alcohol intake can impair spermatogenesis
weight management: obesity is linked to decreased testosterone levels, sexual dysfunction, and comorbidities such as diabetes, increasing the risk of infertility[1,5]
avoiding exposure to environmental hazards: heat (particularly to the scrotal area), pesticides, heavy metals, vibration, and ionising radiation can impact male fertility[1]
Male patients should be counselled against using testosterone supplements; as although they may promote sexual function, excessive testosterone has negative effects on fertility.[6]
2. Medical Treatments
Consider referral either immediately or after performing basic infertility testing as specific medical treatments may be available for certain cases of male factor infertility, such as:[1]
hypogonadotropic hypogonadism: may be managed with dopamine agonists, cessation of medications that interfere with normal prolactin production, or administration of gonadotropins
varicocele: surgical ligation or embolisation in patients with clinically evident variocele and semen parameters outside normal limits may improve conception rates
retrograde ejaculation: pseudoephedrine may help to close the bladder neck
anejaculation: may require neurostimulation
ejaculatory duct obstruction: transurethral resection of the duct to promote normal sperm transport and ejaculation
Where treatment or reversal of male factor infertility is unsuccessful or not feasible, referral for assisted reproductive technologies may be considered:[3]
intrauterine insemination (IUI): sperm is directly inserted into the uterus to facilitate fertilisation
in vitro fertilisation (IVF): eggs are fertilised with sperm in a laboratory setting, and resulting embryos are transferred to the uterus
intracytoplasmic sperm injection (ICSI): a single sperm is injected directly into an egg, often used in cases of severe male infertility
complete azoospermia will require donor insemination
For couples suffering from significant distress or relationship tension due to infertility, consider referring for psychologist or counsellor support.[3]
References
Katz DJ, Teloken P, Shoshany O. Male infertility - The other side of the equation. AFP. 2018;46(9):641-646.
Gupta S, Sharma R, Agarwal A, et al. Antisperm Antibody Testing: A Comprehensive Review of Its Role in the Management of Immunological Male Infertility and Results of a Global Survey of Clinical Practices. World J Mens Health. 2022;40(3):380-398. doi: 10.5534/wjmh.210164.
Healthy Male. Male infertility. 2024. (last accessed February 2025).
Montjean D, Godin Pagé MH, Bélanger MC, Benkhalifa M, Miron P. An Overview of E-Cigarette Impact on Reproductive Health. Life (Basel). 2023 Mar 18;13(3):827. doi: 10.3390/life13030827.
Patel AS, Leong JY, Ramos L, Ramasamy R. Testosterone Is a Contraceptive and Should Not Be Used in Men Who Desire Fertility. World J Mens Health. 2019 Jan;37(1):45-54. doi: 10.5534/wjmh.180036.
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