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Male infertility

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Updated 2024 AUA/ASRM guidelines for the diagnosis and management of 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 American Urological Association (AUA/ASRM 2024,2021), the European Association of Urology (EAU 2024), 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 ASRM/AUA 2024 guidelines:
Evaluate patients with abnormal semen parameters or presumed male infertility by male reproductive experts.
E
Evaluate the male partner of couples with failed ART cycles or recurrent (≥ 2) pregnancy losses.
B
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  • Evaluation of female partner

Diagnostic investigations

History and physical examination
As per ASRM/AUA 2024 guidelines:
Elicit a reproductive history in the initial evaluation of male fertility.
B
Perform a physical examination in the initial evaluation of male fertility to differentiate genital tract obstruction from impaired sperm production.
E
Elicit a complete history and perform a physical examination as well as other directed tests, when indicated by one or more abnormal semen parameters or presumed male infertility.
E
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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 2024 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
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Medical management

Hormonal therapy, general principles: as per ASRM/AUA 2024 guidelines, consider counseling patients with non-obstructive azoospermia about the limited data supporting pharmacologic treatment with selective estrogen receptor modulators, aromatase inhibitors, and gonadotropins before surgical intervention.
C
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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 ASRM/AUA 2024 guidelines, consider discussing risk factors (lifestyle, medication use, environmental and occupational exposures) associated with male infertility, and inform patients that the current data on most risk factors is limited.
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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 2024 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 ASRM/AUA 2024 guidelines, obtain evaluation for the etiology and treat accordingly in patients presenting with hypogonadotropic hypogonadism.
B
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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

Patient education

General counseling: as per EAU 2024 guidelines, counsel male patients with infertility or abnormal semen parameters of the associated health risks.
B
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  • Genetic counseling