What is the number one cause of infertility in males?

Number One Cause of Male Infertility

Varicocele is the most common correctable cause of male infertility, present in approximately 35-40% of men presenting with primary infertility and up to 80% of men with secondary infertility. 1, 2, 3

Understanding Varicocele as the Leading Cause

Prevalence and Clinical Significance

• Varicoceles occur in approximately 15% of the general male population but are found in 35-40% of infertile men with primary infertility, demonstrating a clear correlation between varicocele presence and fertility issues. 4, 2

• The prevalence increases dramatically to 80% in men with secondary infertility (those who previously achieved pregnancy but now cannot). 3

• Varicocele represents the single most common treatable cause of male infertility, distinguishing it from other etiologies that may be more difficult or impossible to correct. 2, 3, 5

Pathophysiologic Mechanisms

• Varicoceles impair spermatogenesis through multiple mechanisms including elevated scrotal temperature, testicular hypoxia, reflux of toxic metabolites from the renal and adrenal veins, and increased oxidative stress leading to sperm DNA damage. 4, 6

• Oxidative stress plays the major role in impairing both spermatogenesis and sperm function in men with varicoceles. 6

• Higher varicocele grades (particularly grade 3) are associated with progressively worse semen parameters and greater testicular dysfunction. 4

Clinical Identification and Diagnosis

Physical Examination Findings

• Varicoceles must be palpable (clinical varicoceles) to warrant treatment, as correction of palpable varicoceles results in improvement in both semen quality and fertility rates. 1

• Treatment of non-palpable (subclinical) varicoceles identified only by ultrasound is not associated with improvement in either semen parameters or fertility rates and should be discouraged. 1

• The physical examination should be performed in a warm room with the patient standing, as the dartos muscle contraction in cold environments can make varicoceles difficult to palpate. 1

When Imaging is Appropriate

• Scrotal ultrasound may be used before repair to confirm the presence of varicocele in difficult-to-examine patients (such as obese individuals) or following correction to determine procedural success, within the context of shared decision-making. 1

• Routine ultrasonography to identify non-palpable varicoceles should not be performed, as these do not benefit from treatment. 1

Treatment Outcomes and Fertility Impact

Evidence for Varicocele Repair

• Varicocele repair improves semen parameters, sperm DNA quality, and increases both pregnancy and live birth rates in natural conception and following assisted reproductive technology. 2

• Improvements in semen parameters typically require 3-6 months (two complete spermatogenic cycles) following varicocelectomy. 4, 3

• Microsurgical varicocelectomy (subinguinal or inguinal approach) appears to be the optimal treatment in most cases, with superior outcomes compared to conventional techniques. 3

Special Populations

• In men with non-obstructive azoospermia and palpable varicoceles, varicocelectomy may lead to the appearance of sperm in the ejaculate, particularly in those with hypospermatogenesis on testicular histology. 4, 7

• Studies show that 12-20% of azoospermic men with varicoceles recover sperm production following bilateral varicocelectomy. 7

• Treatment of clinical varicoceles improves surgical sperm retrieval rates among patients with non-obstructive azoospermia, especially those with hypospermatogenesis. 4

Important Clinical Caveats

What Does NOT Require Treatment

• Men with palpable varicoceles but normal semen parameters do not require treatment, as varicoceles occur in 12% of men with normal fertility. 3

• Only 20% of men with documented varicoceles actually experience fertility problems, indicating that varicocele presence alone does not mandate intervention. 3

• Right-sided varicoceles do not require routine abdominal imaging based solely on laterality, as retrospective data show no difference in cancer diagnoses regardless of varicocele side. 1

When to Consider Abdominal Imaging

• Abdominal imaging should be considered for men with new-onset or non-reducible varicoceles, especially if the varicocele is large, as these features may suggest retroperitoneal pathology. 1

Beyond Varicocele: Other Major Causes

While varicocele is the most common correctable cause, the complete picture of male infertility includes:

• Idiopathic infertility accounts for a substantial proportion of cases where no specific cause is identified despite thorough evaluation. 1

• Genetic causes including Klinefelter syndrome, Y-chromosome microdeletions, and other chromosomal abnormalities represent important non-correctable etiologies. 1, 8

• Obstructive causes such as congenital bilateral absence of the vas deferens (CBAVD) and ejaculatory duct obstruction affect sperm transport rather than production. 1

• Hormonal disorders including hypogonadism and hyperprolactinemia can impair spermatogenesis. 1

• Lifestyle and environmental factors such as anabolic steroid use, obesity, smoking, and occupational exposures contribute to reduced fertility. 1