What is the risk of azoospermia (absence of sperm) in a patient with Grade 3 varicocele?

Risk of Azoospermia in Grade 3 Varicocele

While azoospermia can occur in patients with grade 3 varicocele, varicocelectomy may lead to the presence of sperm in the ejaculate for men with azoospermia, especially for those with a histological diagnosis of hypospermatogenesis. 1

Varicocele and Its Impact on Fertility

• Varicocele is present in approximately 15% of the normal male population, 25% of men with abnormal semen analysis, and 35-40% of men presenting with infertility, showing a clear correlation between varicocele and fertility issues 1, 2
• Higher varicocele grade (grade 3) is associated with worse semen parameters and greater testicular dysfunction 1, 3
• The pathophysiology involves multiple mechanisms affecting testicular function:
  • Higher scrotal temperature
  • Testicular hypoxia
  • Reflux of toxic metabolites
  • Increased DNA damage 1, 4

Risk of Azoospermia in Grade 3 Varicocele

• Grade 3 varicoceles are associated with poorer preoperative semen quality compared to lower grades 3, 5
• Men with grade 3 varicocele had significantly lower sperm counts compared to men with grades 1 and 2 varicocele 3
• Left-sided grade 3 varicocele may affect both testicular and epididymal function, potentially contributing to severe sperm abnormalities 6

Treatment Outcomes for Azoospermia in Varicocele

• Varicocelectomy may lead to the presence of sperm in the ejaculate for men with azoospermia 1, 7
• In patients with non-obstructive azoospermia (NOA) and varicocele:
  • Approximately 12% recovered sperm count four months after varicocelectomy 7
  • Up to 20% recovered sperm production one year after the procedure 7
• Timing of varicocelectomy is important:
  • Performing varicocelectomy before testicular sperm extraction (TESE) results in significantly higher sperm retrieval rates (57.8%) compared to varicocelectomy during TESE (27%) 8
• Treatment of clinical varicoceles improved surgical sperm retrieval rates among patients with NOA, especially for those with a histological diagnosis of hypospermatogenesis 1

Response to Treatment by Varicocele Grade

• Improvements in semen parameters after varicocelectomy are directly related to varicocele grade 5
• Mean sperm concentration improvement after treatment:
  • Grade 1: 5.5 million sperm/ml
  • Grade 2: 8.9 million sperm/ml
  • Grade 3: 16.0 million sperm/ml 5
• Mean improvement in sperm motility after treatment:
  • Grade 1: 9.6%
  • Grade 2: 10.6%
  • Grade 3: 17.7% 5
• Men with grade 3 varicocele showed greater improvement in fertility index (128%) compared to men with grade 1 (27%) or grade 2 (21%) varicocele after surgical correction 3

Clinical Approach for Patients with Grade 3 Varicocele and Azoospermia

• Perform thorough evaluation to confirm non-obstructive azoospermia and rule out genetic causes 7
• Consider varicocelectomy as it may lead to recovery of sperm production in approximately 20% of cases 7, 8
• Perform varicocelectomy before considering testicular sperm extraction for better sperm retrieval rates 8
• Monitor semen parameters after varicocelectomy, as improvements typically take up to two spermatogenic cycles (3-6 months) 1
• If sperm recovery is insufficient for natural conception, the presence of even minimal sperm may enable in-vitro fertilization without requiring donor sperm 7

Important Considerations and Caveats

• The quality of evidence regarding varicocele treatment in azoospermia is generally low 1
• The risks and benefits of varicocele repair must be discussed fully with patients with NOA and a clinically significant varicocele before treatment 1
• Special consideration should be given to couples with a female partner with limited ovarian reserve, as time spent waiting for sperm recovery may impact overall fertility outcomes 1
• Treatment of subclinical (non-palpable) varicocele is not effective at increasing chances of spontaneous pregnancy 1, 4