Introduction: In endemic malarial nations, repeated use of antimalarial drugs has escalated owing to resistance, misuse, and unrestricted availability, which could contribute to infertility rates. Therefore, we investigated the effects of long-term repeated therapeutic treatment with two commonly prescribed artemisinin-based combination, artemether/lumefantrine (A/L) and artesunate-amodiaquine (A/A), on reproductive potential in mice.
Methods: Sixty male mice were divided into three groups: control, (A/L) and (A/A) treatment.  Mice underwent three consecutive days of therapeutic treatment per week, and this regimen was repeated every two weeks for a total of six cycles. Sperm parameters were evaluated after the 1^st, 2^nd, 3^rd, and 6^th exposure cycles, after which treated male mice were paired with female mice for mating.
Results: Sperm viability was significantly reduced by 21% (p < 0.001) following the 6th exposure to A/L, whereas the 2nd, 3rd, and 6th exposures to A/A resulted in significant decreases in sperm viability of 26% (p < 0.001), 12% (p < 0.01), and 31% (p < 0.001), respectively, compared to the control group. Treatment with A/A during the 3rd and 6th periods led to a significant decline (p < 0.001) in sperm mass activity by 20% and 28%, respectively, compared to the control group. However, long-term therapeutic exposure to A/L or A/A did not affect testosterone levels, epididymal content, or the ability to impregnate female mice.
Conclusion: Long-term therapeutic treatment with A/L or A/A did not affect testosterone levels or epididymal contents. However, a decrease in sperm viability was observed even though the mice remained fertile.