This chapter reviews the short period between the exploration of male factor treatment using standard in vitro fertilization in small clinical series initiated in the early 1980s and subsequent development of micromanipulation technologies before ICSI. Instrumental fertilization was developed to improve the incidence of fertilization as well as apply the technology to patients with extreme male factor. A decade later, the Brussels team introduced ICSI, with fertilization rates that were at least twice as high compared to those of earlier micromanipulation approaches. A short history of male factor infertility and the biased views medical specialists showed in favor of solely treating the female partner is discussed in the context of discovery of gametes and the process of fertilization in the nineteenth century. The condition of infertility in men was basically considered untreatable until the 1970s, but as a clinical concept, it was also largely ignored. The possibility of using IVF for effectively treating less fertile men was considered experimental in 1980. The technical and physiological background as well as ambiguous animal models before clinical ICSI are evaluated particularly in the context of why early micromanipulation methods such as partial zona dissection and sub-zonal sperm insertion ultimately failed.