What are the treatment options for a male patient of reproductive age with oligospermia (low sperm count)?

Treatment of Low Sperm Count (Oligospermia)

For men with oligospermia desiring fertility, assisted reproductive technology (ART), particularly IVF with ICSI, offers the highest pregnancy rates and should be discussed early as the primary treatment option, while medical therapies have limited benefits that are outweighed by ART advantages. 1

Initial Diagnostic Evaluation

Before initiating treatment, confirm the diagnosis and identify reversible causes:

• Perform at least two semen analyses separated by 2-3 months to establish baseline sperm parameters, as single analyses can be misleading due to natural variability 1
• Measure serum FSH, LH, and total testosterone to distinguish primary testicular dysfunction from secondary hypogonadism 1
• Obtain karyotype analysis and Y-chromosome microdeletion testing (AZFa, AZFb, AZFc regions) if sperm concentration is <5 million/mL, as genetic abnormalities are more common in severe oligospermia and have implications for offspring 1, 2
• Physical examination should assess testicular volume (normal >12 mL), consistency, presence of varicocele, and vas deferens patency 1, 3

Treatment Algorithm Based on Underlying Etiology

For Hypogonadotropic Hypogonadism (Low FSH, Low LH, Low Testosterone)

Use hCG injections to stimulate testosterone production, followed by FSH analogues if sperm counts remain low after testosterone normalizes. 1

• This approach successfully initiates spermatogenesis in 75% of men with hypogonadotropic hypogonadism 1
• Response correlates with baseline testicular size 1

For Normal or Elevated FSH with Low Testosterone

Clinicians may use aromatase inhibitors, hCG, selective estrogen receptor modulators (SERMs), or combinations thereof. 1

• This is a conditional recommendation with Grade C evidence 1
• Benefits are limited compared to ART outcomes 1

For Idiopathic Oligospermia with Normal Hormones

FSH analogue treatment may be considered to improve sperm concentration, pregnancy rate, and live birth rate. 1

• This represents a conditional recommendation with Grade B evidence 1
• However, benefits are measurable but limited, and FSH is not FDA-approved for this indication 1
• SERMs have limited benefits relative to ART results 1

For Clinical Varicocele with Abnormal Semen Parameters

Varicocele repair may be offered when there is a palpable varicocele, abnormal semen parameters, and minimal/no identified female factor. 1, 2

• Varicocelectomy can improve semen parameters including sperm concentration, motility, and morphology 1
• May halt progression of testicular atrophy and potentially reverse some damage 1
• IVF/ICSI should be considered the primary option when female factors require treatment, regardless of varicocele presence 1

Critical Contraindications

Never prescribe testosterone monotherapy to men desiring current or future fertility. 1

• Exogenous testosterone completely suppresses FSH and LH through negative feedback on the hypothalamus and pituitary 1
• This causes azoospermia that can take months to years to recover 1
• This is a Clinical Principle with the highest level of recommendation 1

Supplements and Antioxidants

Counsel patients that benefits of supplements (antioxidants, vitamins) are of questionable clinical utility in treating male infertility. 1

• Insufficient data exist to recommend supplemental antioxidant therapies for men with abnormal semen parameters 1
• Insufficient data exist to recommend herbal therapies 1
• This is a Conditional Recommendation with Grade B evidence 1

Assisted Reproductive Technology (ART)

For low total motile sperm count on repeated semen analysis, IUI success rates are reduced, and IVF/ICSI should be considered. 1

• ART does not correct the underlying condition but allows fertility when natural pregnancy has not occurred 1
• ICSI applied during IVF abrogates adverse effects of reduced sperm number and quality 1
• ART offers superior pregnancy rates compared to empiric hormonal therapy 1

Lifestyle Modifications

Counsel about weight-loss strategies when BMI and waist circumference demonstrate obesity, especially morbid obesity. 1

• Evidence supports a detrimental effect of obesity on health, with conflicting evidence about reproductive function specifically 1
• Recommend smoking cessation, as smoking has adverse effects on general health and wellbeing, though evidence on semen quality is mixed 1
• Maintain healthy body weight (BMI <25), as obesity and metabolic syndrome impair male fertility 4

Important Clinical Considerations

Men with low sperm counts have a 12-fold increased risk of hypogonadism and higher rates of metabolic syndrome, cardiovascular disease, and osteoporosis. 4

• Low sperm count is associated with higher BMI, waist circumference, systolic pressure, LDL cholesterol, triglycerides, and HOMA index 4
• 51% prevalence of osteoporosis/osteopenia in men with hypogonadism 4
• Fertility evaluation provides a unique opportunity for comprehensive health assessment and disease prevention 4

Sperm Cryopreservation

Men with reduced testicular reserve (small testicular volume, elevated FSH) should consider sperm cryopreservation. 1

• Bank at least 2-3 ejaculates when possible to provide backup samples and maximize future fertility options 1
• Once azoospermia develops, even microsurgical testicular sperm extraction only achieves 40-50% sperm retrieval rates 1

Common Pitfalls to Avoid

• Do not rely on single semen analysis - natural variability requires at least two analyses separated by 2-3 months 1
• Do not prescribe testosterone to men desiring fertility - this is the most critical error, causing potentially irreversible azoospermia 1
• Do not delay ART discussion - female partner age is the most critical factor determining conception success, and empiric medical therapies have limited benefits 1
• Do not assume elevated FSH precludes sperm production - up to 50% of men with non-obstructive azoospermia and elevated FSH have retrievable sperm with testicular sperm extraction 1