Affiliation:
1. Clinical and Translational Science Institute The Lundquist Institute at Harbor‐UCLA Medical Center Torrance California USA
2. Division of Systems and Cellular Medicine Medical School Ninewells Hospital University of Dundee Dundee Scotland
3. Contraceptive Development Program Eunice Kennedy Shriver National Institute of Child Health and Human Development NIH Bethesda Maryland USA
Abstract
IntrodctionHuman spermatogenesis is a complex process that transforms spermatogonial stem cells through mitosis and meiosis to spermatozoa. Testosterone is the key regulator of the terminal stages of meiosis, adherence of spermatids to Sertoli cells, and spermiation. Follicle‐stimulating hormone (FSH) may be required for early spermatogenesis and is important for maintaining normal spermatogenesis in men. Hormonal contraception suppresses FSH, luteinizing hormone, and intratesticular testosterone concentration, resulting in marked suppression of sperm output.ResultsClinical trials using testosterone alone or testosterone plus progestin demonstrate that sustained suppression of sperm concentration to ≤1 million/mL is sufficient to prevent pregnancy in the female partner. New agents that target spermatogenesis could use this as a target for contraceptive efficacy while others that block sperm function or transport may require a lower threshold. When sperm concentrations are suppressed to such low levels, measurement of sperm motility and morphology is technically difficult and unnecessary. With current data from fertile and infertile men, it is not possible to establish a lower limit of sperm motility or percent normal morphology that equates to the prevention of conception. New compounds that decrease sperm motility or alter sperm morphology may need to demonstrate a complete absence of sperm motility or altered morphology in all spermatozoa in the ejaculate. Sperm function tests may be useful depending on the mechanism of action of each new compound.ConclusionMonitoring of sperm surrogate markers to ensure effective contraception relies on laboratories experienced in semen analyses. The development of at‐home tests to assess sperm parameters has progressed rapidly. Some tests have been assessed in clinical trials and approved by regulatory agencies for at‐home use for fertility assessment. However, caution must be exercised in using these tests as many have not been rigorously validated against semen parameters measured in laboratories by trained technologists using standardized tests defined in the World Health Organization Semen Manual.