effects of long-term repeated treatment with artemisinin-based combination therapy on the reproductive potential of male mice

Introduction: in endemic malarial nations, repeated use of antimalarial drugs has increased due to resistance, misuse, and unrestricted availability, which could contribute to infertility rates. therefore, we investigated the effects of long-term repeated treatment with two commonly prescribed artemisinin-based combination therapies, 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 treatment for three consecutive days per week, and this regimen was repeated every two weeks for a total of six cycles. sperm parameters were evaluated after the 1st, 2nd, 3rd, and 6th 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 treatment with a/l or a/a did not affect testosterone levels or epididymal content. however, a decrease in sperm viability was observed, even though the mice remained fertile.