Still counting sperm? Why novel, truly informative measurements of testis function in male infertility are urgently needed

Couple infertility is estimated to affect between 13% and 18% of all couples of reproductive age, with male factors accounting for at least 50% of cases. Semen analysis is the first-line investigation for all male partners of couples referred for fertility evaluation. However, semen analysis is far from being a good predictor of the ultimate outcome: pregnancy. For instance, in approximately 25% of infertility cases, conventional semen parameters are considered ‘normal’, leading to a diagnosis of so-called ‘unexplained infertility’. Nonetheless, this tool is central in the assessment of male fertility potential. This review first provides a historical perspective on the evaluation of male infertility based on semen analysis, illustrating the evolution of diagnostic approaches over time. The second section explores major changes in the interpretation of semen analysis and highlights the need for alternative methodologies. Finally, the last section examines critically the limitations and pitfalls of semen analysis in the diagnostic workup of male infertility and suggests exploring radical new approaches. The aim of this work is to raise awareness of the clinical limitations of conventional semen analysis and, consequently, to emphasize the urgency of identifying new strategies for diagnosing male infertility and optimizing treatment decisions both a priori and during potential interventions.