Can a Grade 3 varicocele (varicose vein in the scrotum) cause infertility?

Grade 3 Varicocele and Infertility

Grade 3 varicocele is strongly associated with infertility and significantly impairs semen parameters, with evidence showing that higher varicocele grades correlate with worse sperm quality and fertility outcomes. 1, 2

Relationship Between Grade 3 Varicocele and Fertility

• Grade 3 varicoceles (large varicoceles) are associated with lower sperm counts and poorer fertility indexes compared to men with grade 1 and 2 varicoceles 3
• Varicoceles are present in approximately 15% of the normal male population, but this percentage increases to 25% in men with abnormal semen analysis and 35-40% in men presenting with infertility, demonstrating a clear correlation between varicocele and fertility issues 1, 2
• Men with grade 3 varicocele have been shown to have higher levels of seminal reactive oxygen species than those with lower grade varicoceles, even in fertile men, suggesting potential for future fertility problems 4

Mechanisms of Fertility Impairment

• The exact mechanism linking varicocele to reduced fertility is not fully understood, but several pathways have been identified 1, 2:
  • Higher scrotal temperature affecting spermatogenesis 1, 2
  • Testicular hypoxia impairing sperm production 1, 2
  • Reflux of toxic metabolites causing testicular dysfunction 1, 2
  • Increased sperm DNA damage affecting sperm quality 1, 2
• Grade 3 varicoceles may also affect epididymal function, not just testicular function, further impairing fertility 5

Treatment Outcomes for Grade 3 Varicocele

• Men with grade 3 varicocele show the greatest improvement in fertility parameters after varicocele repair compared to those with grade 1 or 2 varicoceles 3
• After varicocele repair, sperm concentration in men with grade 3 varicocele has been shown to improve from 18 ± 5 million preoperatively to 32 ± 7 million postoperatively 3
• Fertility index (sperm count times percent motility) improved by 128% in men with grade 3 varicocele after repair, compared to only 27% and 21% improvement in men with grade 1 and 2 varicoceles, respectively 3
• Varicocele repair can lead to improvements in semen parameters within two spermatogenic cycles (approximately 3-6 months) 1, 2

Clinical Implications and Recommendations

• Treatment of clinical varicocele (including grade 3) has been associated with improvements in semen parameters and rates of pregnancy and live births 1
• Microsurgical varicocelectomy is considered the optimal treatment in most cases 6
• After varicocele repair, spontaneous pregnancy typically occurs between 6 and 12 months post-procedure 1, 2
• Varicocelectomy can also reverse sperm DNA damage and improve oxidative stress levels 1

Important Caveats

• Not all men with varicoceles experience fertility problems, as only about 20% of men with documented varicoceles suffer fertility issues 6
• The presence of a varicocele should be confirmed by physical examination, not just ultrasound, as treatment of non-palpable (subclinical) varicoceles is not associated with improvement in either semen parameters or fertility rates 1, 2
• Even fertile men with grade 3 varicocele show higher levels of seminal reactive oxygen species, suggesting they may be at increased risk for future infertility despite current fertility 4
• Consider varicocele repair before pursuing assisted reproductive technologies, as varicocelectomy may improve outcomes following ART in oligozoospermic men 1, 2