What is the pathophysiology of male infertility?

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Last updated: June 23, 2025View editorial policy

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From the Guidelines

Male infertility is primarily caused by abnormal spermatogenesis, which can result from genetic factors, hormonal imbalances, or testicular damage, as well as obstructive causes, immunological factors, and environmental exposures, as outlined in the most recent guidelines 1. The pathophysiology of male infertility is complex and multifaceted, involving various factors that disrupt normal sperm production, function, or delivery.

  • Abnormal spermatogenesis can result from genetic factors, such as Y chromosome microdeletions or Klinefelter syndrome, which can lead to impaired sperm production or function.
  • Hormonal imbalances, such as hypogonadotropic hypogonadism, can also disrupt spermatogenesis, and can be treated with hormone therapy, such as human chorionic gonadotropin (hCG) or selective estrogen receptor modulators (SERMs) 1.
  • Testicular damage from trauma, infections, or varicoceles can also impair sperm production, and may require surgical correction.
  • Obstructive causes, such as blockages in the epididymis, vas deferens, or ejaculatory ducts, can prevent sperm transport despite normal production.
  • Immunological factors, such as anti-sperm antibodies, can impair sperm motility and function.
  • Environmental exposures to toxins, excessive heat, radiation, and lifestyle factors like smoking, alcohol consumption, and obesity can damage sperm DNA and reduce fertility.
  • Erectile dysfunction and ejaculatory disorders can directly impact sperm delivery.
  • Oxidative stress from excess reactive oxygen species can damage sperm membranes and DNA, while infections can cause inflammation that impairs sperm function. Treatment depends on the specific cause and may include hormone therapy, surgical correction of varicoceles or obstructions, lifestyle modifications, or assisted reproductive technologies when necessary, as recommended in the guidelines 1. It is essential to evaluate the male partner in cases of infertility, as some conditions may be medically important, and treatment can be directed accordingly, with the goal of improving morbidity, mortality, and quality of life outcomes 1.

From the Research

Pathophysiology of Male Infertility

The pathophysiology of male infertility is a complex and multifaceted issue, involving various factors that can affect sperm production, function, and transport.

  • The etiology of impaired sperm production and function can be related to factors acting at pre-testicular, post-testicular, or directly at the testicular level 2.
  • Primary testicular failure accounts for about 75% of all male factor infertility, with genetic factors identified in about 15% of cases, including congenital hypogonadotrophic hypogonadism, congenital absence of vas deferens, and primitive testicular failure 2.
  • Defective spermatogenesis can occur due to pituitary disorders, testicular cancer, germ cell aplasia, varicocele, and environmental factors, while defective sperm transport can be caused by congenital abnormalities, immunological, and neurogenic factors 3.

Genetic Factors

Genetic disorders can affect male infertility, interfering with germ cell generation and maturation or leading to the production of non-functional spermatozoa 3.

  • The identification of genetic causes of male infertility raises concerns about the transmission of defects to offspring, particularly with the increasing use of intracytoplasmic sperm injection (ICSI) 3.
  • Partial androgen insensitivity may account for a significant number of cases of severe oligozoospermia 4.

Other Factors

Other factors that can contribute to male infertility include:

  • Varicocele, which can affect seminal parameters through oxidative stress 5.
  • Chronic inflammatory processes, such as chronic chlamydial infections, which can be asymptomatic and difficult to demonstrate objectively 4.
  • Sexual dysfunction, including hypoactive sexual desire, erectile dysfunction, premature ejaculation, and orgasmic dysfunction, which can occur frequently in infertile men and may be related to infertility 6.
  • General health perturbations, such as cardiovascular disorders and cancerous conditions, which can lead to male infertility and/or sexual dysfunction 6.

Treatment and Diagnosis

The complete diagnostic workup is essential for identifying treatable or reversible conditions, selecting patients for assisted reproductive techniques, and providing genetic counseling 2.

  • Assisted fertilization techniques, such as IVF and GIFT, offer encouraging possibilities for the treatment of male-factor infertility 4.
  • Medications, such as recombinant human follicle-stimulating hormone (rhFSH), human chorionic gonadotropin (HCG), and human menopausal gonadotropin (HMG), can improve semen parameters and fertility after varicocelectomy 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Male infertility: pathogenesis and clinical diagnosis.

Best practice & research. Clinical endocrinology & metabolism, 2011

Research

Male infertility.

Best practice & research. Clinical obstetrics & gynaecology, 2003

Research

Male infertility: current concepts.

Annals of medicine, 1992

Research

Sexual dysfunction and male infertility.

Nature reviews. Urology, 2018

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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