Clinical evaluation of the infertile male: new options, new challenges.

M ale reproductive dysfunction is the sole or contributory cause of infertility in half of couples making the systematic clinical and laboratory evaluation of the male, and the application of costeffective management strategies tailored to the individual patient’s need, vital parts of fertility practice. Male infertility has a wide range of etiologies and effective approaches to initiate, restore or preserve natural fertility are available in some settings. But the most striking development in the past 20 years has been in the area of assisted reproductive technologies (ART), especially intracytoplasmic sperm injection (ICSI); the latter provides an extraordinarily effective bypass of the natural processes involved such that a single viable sperm, obtained from any part of the reproductive tract, will often successfully fertilize an oocyte and has allowed many previously sterile men to father healthy children. However, our understanding of the genetic and environmental factors causing male factor infertility has lagged behind these technological advances and still for a significant minority, no options exist other than adoption, donor sperm or abandonment of their aspirations for a family. It is important that these powerful ART approaches are not allowed to ‘corrupt’ good clinical practice by inducing: (i) a state of ‘diagnostic nihilism’ wherein effective, cheaper and less invasive alternative approaches are overlooked; and (ii) a mindset that male reproductive health can be defined by the availability of motile spermatozoa, thereby relieving the clinician of his/her obligation to evaluate and care for infertile men. For example, natural fertility may be restorable and even when specific treatment is not possible, providing the man with a reason for his infertility will assist him in coming to terms with his disability. Furthermore, some health issues are more prevalent in infertile men and must be actively sought (e.g., androgen or gonadotropin deficiency, testicular cancer) and the opportunity taken to assess and improve general and reproductive health. Finally, genetic causes for male infertility must be considered as they may have profound implications for the success of ART and for the health of offspring; in this regard, a close relationship with clinical geneticists is now an essential part of modern ART practice. All these biomedical considerations must be seen within the patients’ psychological and cultural context and the applicable health-care environment. Rigid prescriptive approaches cannot often be made (there may be more than one ‘correct answer’), but evidencebased guidelines assist the clinician in making his/her recommendations. A team approach to male infertility, as with broader fertile practice, involves the coordinated efforts of clinicians (andrology, urology, gynecology, endocrinology and primary care), scientific, laboratory, nursing and counseling staff. In broadly considering the clinical aspects of male infertility, we seek to emphasize a practical approach to evaluation and management, and also to provide the essential background on the pathophysiology of male infertility and emerging research that will translate into practice. At the laboratory interface, semen testing remains the cornerstone of evaluation and the World Health Organization guidelines have been recently revised and been the subject of recent extensive Reviews in a Special Edition 2010 of Asian Journal of Anrology (http://www. asiaandro.com/Current_Issue_v12_1.asp); implementation of these procedures in different regions is particularly challenging. Associations between sperm morphology and motility, egg interaction and reproductive outcome are evident but in the clinic, in vitro sperm function testing has not become widespread. The elaborate structure of sperm is best appreciated at the ultrastructural level; a wide variety of structural defects impact on motility, fertilization and embryonic developmental failure and their proper evaluation informs clinical decision making. Furthermore, disorders such as primary cilial dyskinesia, can present with a respiratory phenoptype (e.g., Kartageners syndrome), underscoring the need for full clinical evaluation. Sperm DNA is susceptible to damage, especially from reactive oxygen species; levels of sperm DNA damage levels rise as conventional sperm parameters decline, but are also evident in some men with normal parameters. Consistently high levels of sperm DNA damage is associated with poorer embryonic development, higher pregnancy loss and potentially adverse health effects in offspring. This area is complicated by the diversity of sperm DNA assessment methods, and controversy exists as to whether sperm DNA measures effectively inform or modify routine clinical practice, or are better directed to the evaluation of couples experiencing repetitive reproductive failure. Primary spermatogenic failure is a collective term for a heterogenous group of disorders featuring abnormal sperm number, motility, structure and/or and function. It represents by far the largest cohort of infertile men, indeed affecting ,5% of the general population. While damage from cancer treatments, vascular insult or trauma is readily understood, it is frustrating to both clinicians and patients that most cases are unexplained (idiopathic). Increasingly genetic factors are recognized and their identification is essential in informing couples about the prospect for normal pregnancy, transmission of infertility and/or non-gonadal disease in offspring. Karyotypic anomalies (numerical, autosomal translocations/inversions) are the commonest recognized cause and result in sterility or degrees of subfertility. The prevalence of abnormalities is high; ,7% of men with spermatogenic failure and ,14% of those with azoospermia, most of the latter having Klinefelter’s syndrome. An increased prevalence of aneuploidy in the Asian Journal of Andrology (2012) 14, 3–5 2012 AJA, SIMM & SJTU. All rights reserved 1008-682X/12 $32.00