From bench to babies – drug development for male subfertility

Infertility is estimated to affect more than 50 million couples around the world, with male factor accounting for half of these cases, yet there is a notable absence of effective treatment options for men, other than in-vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). This review considers unlicensed and empirical treatments used for male subfertility, including hormonal therapy, phosphodiesterase inhibitors, and antioxidants. Compounds generally demonstrate variable improvements in sperm function but benefits for fertility are less clear. There is a pressing need for effective treatment options for subfertile men, however, our knowledge of sperm function is limited, restricting the identification of precise treatment targets. The traditional drug discovery pathway is also notorious for its extensive resource and time requirements, often extending over decades and demanding significant financial investment. Unfortunately, a substantial number of potential therapies fail before reaching the marketplace. Furthermore, reliance on mammalian models is not possible in the drug development process for male subfertility, due to significant variability between animals and man. We review recent breakthroughs and highlight novel methods aimed at improving the effectiveness and efficiency of drug discovery for male subfertility. High-throughput screening, combinatorial chemistry, and the repurposing of established medications have great potential. These strategies offer the promise of accelerating the pace of drug development, curbing the extensive demand for resources, and, in the case of drug repurposing, diminish the demand for comprehensive pharmacokinetic and pharmacodynamic studies. As these innovative approaches are adopted, the feasibility of addressing male subfertility through scientific advancements appears to be increasingly attainable.