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Male infertility
Background
Overview
Definition
Male infertility is defined as the inability to achieve pregnancy in a fertile female partner after 12 months of regular unprotected sexual intercourse.
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Pathophysiology
The pathophysiology of male infertility involves several mechanisms: hormonal imbalances, such as hypogonadotropic hypogonadism ans androgen insensitivity; testicular dysfunction, usually due to varicocele or cryptorchidism; genital tract obstruction (obstructive azoospermia), such as epididymal, vas deferens, intratesticular, or ejaculatory duct obstruction; genetic abnormalities, such as Klinefelter syndrome, Y-chromosome microdeletions, and cystic fibrosis; and oxidative stress and DNA fragmentation in sperm.
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Epidemiology
The prevalence of male infertility in the US is estimated at 11.4% in men aged 15-49 years and 12.8% in men aged 25-49 years.
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Risk factors
Risk factors for male infertility can include older age, lifestyle factors (smoking, alcohol use, drug use), and environmental exposures (pesticides, heavy metals, radiation), comorbidities (diabetes, obesity, malignancy), and certain medications (such as anabolic steroid).
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Prognosis and risk of recurrence
The prognosis of male infertility can vary greatly. In some cases, infertility can be treated with lifestyle changes or medical treatment, while others may require assisted reproductive technologies.
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Guidelines
Key sources
The following summarized guidelines for the evaluation and management of male infertility are prepared by our editorial team based on guidelines from the European Association of Urology (EAU 2025), the American Urological Association (AUA/ASRM 2024,2021), the American Urological Association (AUA 2023,2014), the Canadian Urological Association (CUA 2023,2017), the European Reference Network on Rare Adult Solid Cancers (EURACAN/ESMO 2022), and the ...
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Screening and diagnosis
Indications for evaluation
As per EAU 2025 guidelines:
Evaluate all males seeking medical help for fertility issues, including patients with abnormal semen parameters for urogenital abnormalities.
A
Evaluate for infertility after 6 months of attempted conception if the female partner is aged > 35 years.
B
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Evaluation of female partner
Diagnostic investigations
History and physical examination: as per EAU 2025 guidelines, obtain a complete medical, reproductive, and family history, assessment of lifestyle and behavioral risk factors, and perform a physical examination and SA in the evaluation of male patients with infertility.
A
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SA
Hormone testing
Diagnostic imaging (scrotal ultrasound)
Diagnostic imaging (transrectal ultrasound)
Diagnostic imaging (renal and abdominal imaging)
Genetic testing (karyotyping)
Genetic testing (Y-chromosome microdeletion)
Genetic testing (CFTR mutation)
Genetic testing (sperm DNA fragmentation)
Antisperm antibodies
Reactive oxygen species testing
Diagnostic procedures
Testicular biopsy: as per EAU 2025 guidelines, consider obtaining a multidisciplinary team discussion concerning invasive diagnostic modalities (such as ultrasound-guided testicular biopsy with frozen section versus radical orchidectomy versus surveillance) in male patients with infertility with ultrasound-detected indeterminate testicular lesions, especially in the presence of additional risk factors for malignancy.
C
Medical management
Hormonal therapy, general principles
As per EAU 2025 guidelines:
Do not use selective estrogen receptor modulators or aromatase inhibitors routinely for the treatment of idiopathic infertility.
D
Do not initiate routine medical therapy (including recombinant FSH, highly purified FSH, human chorionic gonadotrophin, aromatase inhibitors, and selective estrogen receptor modulators) before testicular sperm extraction in patients with non-obstructive azoospermia.
D
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Hormonal therapy (FSH analogs)
Hormonal therapy (testosterone therapy)
Management of ejaculatory dysfunction
Management of erectile dysfunction
Treatment of active infections
Nonpharmacologic interventions
Lifestyle changes
As per EAU 2025 guidelines:
Consider advising lifestyle changes, including weight loss, increased physical activity, smoking cessation, and alcohol intake reduction, to improve sperm quality and the chances of conception in male patients with idiopathic oligoasthenoteratozoospermia.
C
Inform patients with infertility about the detrimental effects of obesity, low physical activity, smoking, and high alcohol intake on sperm quality and testosterone levels. Advise improving lifestyle factors to improve the chances of conception.
A
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Dietary supplements
Therapeutic procedures
Conservative sperm retrieval: as per ASRM/AUA 2021 guidelines, consider offering induced ejaculation in patients with aspermia, including using sympathomimetics, vibratory stimulations, and electroejaculation depending on the patient's condition and clinician's experience.
E
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Testicular sperm aspiration
Assisted reproductive technologies
Surgical interventions
Surgical sperm retrieval, indications
As per EAU 2025 guidelines:
Consider performing surgical sperm retrieval in male patients eligible for ART (intracytoplasmic sperm injection). Do not perform surgery in patients with complete AZFa and AZFb microdeletions.
B
Do not use preoperative biochemical and clinical variables to predict positive sperm retrieval at surgery in patients with non-obstructive azoospermia.
D
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Surgical sperm retrieval (choice of method)
Microsurgical vasoepididymostomy
Specific circumstances
Patients with hypogonadotropic hypogonadism
As per EAU 2025 guidelines:
Initiate combined hCG and FSH (recombinant FSH, highly purified FSH) or pulsed GnRH via pump therapy to stimulate spermatogenesis in patients with hypogonadotropic hypogonadism (secondary hypogonadism), including congenital causes. Induce spermatogenesis by effective medical therapy (hCG, human menopausal gonadotropins, recombinant FSH, highly purified FSH) in patients with hypogonadotropic hypogonadism.
A
Initiate testosterone therapy in symptomatic patients with primary or secondary hypogonadism not considering parenthood.
A
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Patients with hyperprolactinemia
Patients with varicocele
Patients with cryptorchidism
Patients with neurological disorders
Patients with testicular microcalcification
Patients with testicular cancer
Patients receiving gonadotoxic therapy
Patients after vasectomy