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Medical treatment for male infertility
Mehran Movassaghi, MD, Department of Urology, Stanford University School of Medicine, Stanford, CA, USA
Paul J. Turek, MD, Departments of Urology, Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco
The first consideration in the male-specific treatment of infertility is the response time to therapy. From an older kinetic analysis in 1963, the length of a human cycle of spermatogenesis had been estimated to be 64 days.[2] To arrive at this figure, sequential testis biopsies and radiography were taken from men who had undergone testicular injections of 3H-thymidine. From other studies, epididymal transit time has been estimated to be 5.5 days.[3] This forms the foundation for the general belief that human spermatogenesis requires 2-3 months to complete and has guided the care of infertile men for 40 years. More recent data, however, suggest that this timeline may in fact be shorter.[4] Using a noninvasive method to assess germ cell turnover time accurately in vivo with stable isotope labeling (2H20) and gas chromatography mass spectrometric analysis, we observed that a cycle of sperm production (from production to ejaculation) occurs in a mean 64 ± 8 days (range: 42-76 days).
Medical therapy for male infertility seeks to treat conditions with clearly defined (specific) or ill-defined (empirical) causes. These range from hormonal imbalances, which can alter testosterone, gonadotropins and spermatogenesis, to autoimmune disorders or infections that inhibit fertilization or implantation of an embryo. Much of medical therapy for male infertility is empirical in nature, and true efficacy requires further investigation.[5-9] The variety of current medical therapies for male infertility are reviewed here.
Hormonal Management
Our understanding of the hypothalamic-pituitary-gonadal (HPG) axis has benefited most from experiments performed in the 1950s in which hormones were purified from the brains of animals and used for bioassays. In the 1970s, the development of radioimmunoassays allowed hormone measurement without the need for living tissue and bioassays. It is now clear that HPG hormones play a critical role in the phenotypic development of the embryo, sexual maturation at puberty, endocrine testis function (testosterone production) and exocrine testis function (sperm production). These advances form the basis for the endocrine evaluation and management of the infertile male.
Sigman and Jarow published a large retrospective study of 1035 patients to define the prevalence of endocrine disorders among infertile men.[10] In general, 20% of men had an abnormal hormone level on initial testing, but only 9.6% harbored a hormone abnormality on repeat testing. If follicle-stimulating hormone (FSH) elevations are excluded, the incidence of clinically significant endocrinopathies in infertile men is 1.7%. Table 1 outlines the spectrum of endocrine abnormalities observed in infertile men from this study.
Testosterone
Exogenous testosterone replacement and withdrawal therapy was thought for years to improve semen quality after first reducing it and then letting it rebound on withdrawal of therapy. This technique has been abandoned as a form of therapy for male infertility. Testosterone must be endogenously made to be effective for male infertility. Endogenous testosterone can be increased in patients with secondary hypogonadism, such as diabetics, with the use of antiestrogens as described below.
Gonadotropins (Follicle Stimulating Hormone & Luteinizing Hormone)
In men with hypogonadotrophic hypogonadism (
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