New Frontiers of Research and Therapy in Male Infertility

The advent of intracytoplasmic sperm injection (ICSI) in the late twentieth century revolutionized the management of the infertile couple. As a result, in the years that followed the introduction of this technology, the evaluation of the male partner and the male gamete was set aside. However, despite the success of this technology, there has been a growing concern regarding the safety of ICSI because it bypasses the barriers to natural selection, and we know that infertile men have measurable defects in sperm quality that can influence ICSI outcomes. As such, over the past 20 years, there has been a renewed interest in the management of the infertile male to improve overall health, male gamete integrity, and treatment outcomes both in natural and assisted reproduction. In this chapter, we discuss new and upcoming diagnostic and therapeutic approaches in the management of infertile males. We anticipate advances in semen testing including new-generation semen analyzers, introduction of reliable home testing kits, and incorporation of AI in the analysis and interpretation of results. We expect to see better studies on lifestyle modifications and their impact on male fertility potential. We will see ongoing work on markers of oxidative stress and sperm DNA fragmentation that should further define the clinical value of these tests. Advances in genetics and epigenetics together with the use AI will help integrate and analyze large databases of genetic abnormalities. The management of nonobstructive azoospermia remains challenging, and we will undoubtedly see studies on novel diagnostic and treatment modalities. We are witnessing an andrological renaissance, and a wide range of research opportunities and exciting frontiers await us.