# Analysis of ASMs and male infertility using the FDA adverse event reporting system (FAERS)

## TL;DR

This study uses FDA data to find that certain epilepsy drugs may be linked to male infertility, suggesting a need for reproductive health monitoring in patients.

## Contribution

This study is the first to analyze the association between antiseizure medications and male infertility using FAERS with a hybrid signal detection framework.

## Key findings

- Carbamazepine and valproic acid showed the highest risk for male infertility (ROR = 8.73 and 6.82 respectively).
- Oxcarbazepine, lamotrigine, and levetiracetam also showed positive signals for male infertility.
- Phenytoin sodium, topiramate, and clonazepam did not show significant risk for male infertility.

## Abstract

Antiseizure medications (ASMs) are the cornerstone of epilepsy treatment, but their potential reproductive toxicity may impact male fertility. Globally, approximately 15% of couples are affected by infertility, with male factors accounting for 50%. This study aimed to analyze the association between ASMs and male infertility using the FDA Adverse Event Reporting System (FAERS).

Data from January 1, 2004, to September 30, 2024, were extracted from FAERS. A hybrid signal detection framework combining non-Bayesian (Reporting Odds Ratio, ROR) and Bayesian (Bayesian Confidence Propagation Neural Network, BCPNN) methods was employed to evaluate the reporting frequency and risk of male infertility adverse events for different ASMs.

Among 81,618 deduplicated case reports involving specified ASMs, 60 were related to male infertility. Disproportionality analysis revealed that carbamazepine (ROR = 8.73; IC = 3.10) and valproic acid (ROR = 6.82; IC = 2.74) posed the highest risks. Oxcarbazepine, lamotrigine, and levetiracetam also showed positive signals. Phenytoin sodium, topiramate, and clonazepam showed no significant risk. Regarding overall ASM-related reports, the majority originated from the United States and involved patients aged 18–65.

Despite the limitations of the FAERS database, these findings emphasize the importance of monitoring reproductive health in male patients, particularly those of childbearing age, and highlight the need to balance ASM efficacy with potential reproductive toxicity in clinical practice. Further research is needed to validate these findings and explore underlying mechanisms.