Sperm selection in IVF: the long and winding road from bench to bedside

Spermatozoa wage battle to conquer fertilization but the traits needed to succeed remain elusive. The natural advantageous qualities that enable only a few selected sperm cells to reach the site of fertilization remain unknown. Although in vitro fertilization (IVF) facilitates the job of spermatozoa, a universally acceptable means of sperm selection is yet to be developed. No objective or reliable sperm quality indicators have been established and sperm selection is, to a great extent, based on subjective qualitative evaluation. The best method for sperm selection in IVF presents several challenges: intrinsic sperm qualities cannot be evaluated and the ideal endpoint for these studies is debatable. An ideal method for sperm selection in ART should be noninvasive and cost-effective, and allow the identification of high-quality spermatozoa and yield better outcomes in terms of pregnancy and live birth rates. This narrative review included 85 papers and focused on the new available methods and technologies that might shed some light on sperm selection in IVF. It discusses the available data on microfluidic devices, omics profiling, micronuclei studies, sperm plasma membrane markers, and other techniques, such as Magnetic Activated Cell Sorting (MACS), Raman micro-spectroscopy, and artificial intelligence systems. The new techniques herein reviewed offer fresh approaches to an old problem, for which a definite solution has yet to cross the bridge from bench to IVF clinics around the world, since clinical usefulness and application remain unproven.