What anti-epileptic drugs (AEDs) do not significantly decrease male sperm count?

Anti-Epileptic Drugs That Do Not Significantly Decrease Male Sperm Count

Levetiracetam (Keppra), lamotrigine (Lamictal), and oxcarbazepine are the preferred anti-epileptic drugs for men concerned about fertility, as they have minimal to no adverse effects on sperm parameters and may even improve certain sperm quality measures. 1, 2, 3

Recommended AEDs for Male Fertility Preservation

First-Line Options

Levetiracetam is the safest choice for male fertility:

• FDA labeling confirms no impairment of fertility in animal studies at doses up to 6 times the maximum human dose 2
• Clinical studies show possible trends toward improvement in all semen parameters, though not statistically significant 3
• Does not affect reproductive hormone levels (testosterone, FSH, LH) 3
• No documented effects on sexual function 3

Lamotrigine demonstrates favorable fertility profiles:

• Significantly higher testosterone levels compared to carbamazepine and valproate-treated patients 4
• Better testosterone/LH ratio (gonadal efficiency) than enzyme-inducing AEDs 4, 5
• Possible trend toward improvement in semen parameters after 6 months of treatment 3
• No significant effects on sexual function or sex hormone levels 3, 5
• Only 5.5% of men taking lamotrigine had abnormally low sexual function scores, compared to 33.3% on enzyme-inducing AEDs 5

Oxcarbazepine may actually improve sperm quality:

• Significantly increases sperm fast forward movement rate (FFMR) and survival rate after 6 months of treatment 3
• No adverse effects on sexual function or sex hormone levels 3

AEDs to Avoid for Male Fertility

Enzyme-Inducing AEDs (High Risk)

Carbamazepine causes multiple reproductive abnormalities:

• Significantly lower testosterone levels compared to controls 4
• Lowest DHEAS levels among all AED groups 4
• Reduced gonadal efficiency (testosterone/LH ratio) 4
• Increased sperm tail, neck, and head abnormalities 6
• 33.3% of men have abnormally low sexual function scores 5

Phenytoin and phenobarbital have similar enzyme-inducing effects:

• Significantly elevated SHBG levels, reducing bioactive testosterone 5
• Progressive decline in bioactive testosterone with age (3.75 ng/dl/year vs. 1.80 in controls) 5
• 89% of men aged 40-50 on enzyme-inducing AEDs have low bioactive testosterone 5

Valproate (Moderate to High Risk)

Valproate has documented adverse effects on male fertility:

• Significantly lower testosterone levels than controls 4
• Higher androstenedione levels than all other groups 4
• Reduced gonadal efficiency 4
• Increased sperm tail abnormalities compared to controls 6
• Associated weight gain that may indirectly affect fertility through metabolic effects 7, 1

Clinical Management Algorithm

For Men Planning Conception

1. Obtain baseline semen analysis if the couple has been attempting conception for 12 months without success, or if there are clinical concerns 1

2. Do not discontinue or switch well-controlled AEDs solely based on theoretical fertility concerns, as seizure recurrence risk outweighs reversible sperm parameter changes 1

3. If switching is medically appropriate, transition to levetiracetam, lamotrigine, or oxcarbazepine as first-line alternatives 1, 3

4. If sperm abnormalities are documented, consider assisted reproductive technologies (ART) rather than medication changes that could compromise seizure control 7, 1

Counseling Points

Reassure patients about offspring safety: Despite adverse effects on sperm parameters, current evidence shows no increased risk of birth defects or adverse pregnancy outcomes when men father children while taking AEDs 1

Discuss reversibility: AED effects on sperm parameters are generally reversible, though this may take several months after medication changes 1

Address baseline fertility concerns: Men with epilepsy have reduced sperm quality even before treatment, with significantly lower percentages of rapidly progressive motile sperm, total sperm count, and normal sperm rates compared to healthy controls 3

Important Clinical Caveats

• Epilepsy itself contributes to reproductive dysfunction independent of medication effects 1
• Marriage and fertility rates are significantly lower in men with epilepsy compared to healthy controls, suggesting psychosocial factors beyond medication effects 3
• Age-related decline in testosterone is accelerated in men taking enzyme-inducing AEDs, with clinically significant hypogonadism developing earlier than in the general population 5
• Sexual dysfunction (86.7% of men with low sexual function scores have low bioactive testosterone) may be the first clinical manifestation of AED-induced reproductive hormone changes 5