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2020 Translational Andrology and Urology. All rights reserved.Strategies exist that can mitigate the risk of causing iatrogenic infertility when men require testosterone replacement therapy (TRT). This article reviews the current medical therapies that preserve spermatogenesis when TRT is indicated. Furthermore, we highlight the re-emerging concept of hypothalamic-pituitary-gonadal (HPG) axis reset in hypergonadotrophic, hypogonadal infertile men who are planning sperm retrieval procedures. Finally, we present our hypothesis for a novel