Clinical and Translational Science Institute, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.
Division of Systems and Cellular Medicine, Medical School, Ninewells Hospital, University of Dundee, Dundee, Scotland.
Andrology. 2024 Oct;12(7):1574-1584. doi: 10.1111/andr.13701. Epub 2024 Jul 19.
Human 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.
Clinical 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.
Monitoring 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.
人类精子发生是一个复杂的过程，它通过有丝分裂和减数分裂将精原干细胞转化为精子。睾酮是减数分裂末期、精母细胞与支持细胞黏附以及精子释放的关键调节剂。卵泡刺激素（FSH）可能是早期精子发生所必需的，对维持男性正常精子发生也很重要。激素避孕抑制 FSH、黄体生成素和睾丸内睾酮浓度，导致精子输出明显抑制。
单独使用睾酮或睾酮加孕激素的临床试验表明，持续将精子浓度抑制到≤100 万/ml 足以防止女性伴侣怀孕。靶向精子发生的新药物可以将此作为避孕效果的靶标，而其他阻断精子功能或运输的药物可能需要更低的阈值。当精子浓度被抑制到如此低的水平时，精子运动和形态的测量在技术上是困难的，也是不必要的。根据有生育能力和无生育能力男性的现有数据，不可能确定与防止受孕相当的精子运动能力或正常形态百分比的下限。降低精子运动能力或改变精子形态的新化合物可能需要证明在射出精液中的所有精子中完全不存在精子运动能力或改变形态。精子功能测试可能取决于每种新化合物的作用机制而有用。
监测精子替代标志物以确保有效避孕依赖于有经验的精液分析实验室。评估精子参数的家庭测试已经迅速发展。一些测试已经在临床试验中进行了评估，并被监管机构批准在家中用于生育评估。然而，在使用这些测试时必须谨慎，因为许多测试尚未经过严格验证，无法与经过训练的技术人员使用标准化测试按照世界卫生组织精液手册在实验室中测量的精子参数相媲美。
