Approach to the male with infertility
- Bradley D Anawalt, MD
Bradley D Anawalt, MD
- Chief of Medicine, University of Washington Medical Center
- Professor and Vice Chair of Medicine
- University of Washington
- Stephanie T Page, MD, PhD
Stephanie T Page, MD, PhD
- Professor of Medicine
- University of Washington School of Medicine
- Section Editors
- Peter J Snyder, MD
Peter J Snyder, MD
- Editor-in-Chief — Endocrinology
- Section Editor — Pituitary Disease; Male Reproductive Endocrinology
- Professor of Medicine
- University of Pennsylvania School of Medicine
- Alvin M Matsumoto, MD
Alvin M Matsumoto, MD
- Section Editor — Male Reproductive Endocrinology
- Professor of Medicine
- University of Washington School of Medicine
In the United States, infertility in a couple is defined as the inability to achieve conception despite one year of frequent, unprotected intercourse. However, up to 50 percent of young, healthy couples that fail to conceive in the first 12 months will conceive in the subsequent 12 months with no specific treatment . Therefore, in some circumstances, delay in extensive evaluation and treatment is reasonable. In approximately 35 percent of couples with infertility, a male factor is identified along with a female factor; in approximately 10 percent, a male factor is the only identifiable cause.
While many men with male infertility have oligozoospermia (a low number of sperm cells in the ejaculate compared with reference ranges) or azoospermia (no sperm cells in the ejaculate), some infertile men have normal sperm counts. Over 80 percent of infertile men have low sperm concentrations associated with a decrease in sperm motility (asthenozoospermia) and/or an increase in spermatozoa with abnormal morphology (teratozoospermia). A small percentage of infertile men have normal sperm concentrations but poor sperm quality, reflected by a decrease in sperm motility and/or abnormal sperm morphology, and another small percentage of infertile men have normal sperm concentrations and normal motility and morphology.
This topic will review the evaluation of male infertility. The causes and management of male infertility and an overview of infertility are reviewed separately. (See "Causes of male infertility" and "Treatments for male infertility" and "Overview of infertility".)
CATEGORIES OF MALE INFERTILITY
The causes of male infertility can be divided into four main areas (table 1):
●Endocrine and systemic disorders (usually related to secondary [hypogonadotropic] hypogonadism) – 2 to 5 percent.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Evers JL. Female subfertility. Lancet 2002; 360:151.
- Winters BR, Walsh TJ. The epidemiology of male infertility. Urol Clin North Am 2014; 41:195.
- Kruger TF, Acosta AA, Simmons KF, et al. Predictive value of abnormal sperm morphology in in vitro fertilization. Fertil Steril 1988; 49:112.
- Jungwirth A, Giwercman A, Tournaye H, et al. European Association of Urology guidelines on Male Infertility: the 2012 update. Eur Urol 2012; 62:324.
- Brugh VM 3rd, Lipshultz LI. Male factor infertility: evaluation and management. Med Clin North Am 2004; 88:367.
- Vogt PH. Azoospermia factor (AZF) in Yq11: towards a molecular understanding of its function for human male fertility and spermatogenesis. Reprod Biomed Online 2005; 10:81.
- Sakamoto H, Saito K, Oohta M, et al. Testicular volume measurement: comparison of ultrasonography, orchidometry, and water displacement. Urology 2007; 69:152.
- Rivkees SA, Hall DA, Boepple PA, Crawford JD. Accuracy and reproducibility of clinical measures of testicular volume. J Pediatr 1987; 110:914.
- Diamond DA, Paltiel HJ, DiCanzio J, et al. Comparative assessment of pediatric testicular volume: orchidometer versus ultrasound. J Urol 2000; 164:1111.
- Lotti F, Maggi M. Ultrasound of the male genital tract in relation to male reproductive health. Hum Reprod Update 2015; 21:56.
- World Health Organization Department of Reproductive Health and Research. World Health Organization Laboratory Manual for the Examination and Processing of Human Semen, 5th ed, World Health Organization, Geneva, Switzerland 2010.
- Cooper TG, Neuwinger J, Bahrs S, Nieschlag E. Internal quality control of semen analysis. Fertil Steril 1992; 58:172.
- Dunphy BC, Kay R, Barratt CL, Cooke ID. Quality control during the conventional analysis of semen, an essential exercise. J Androl 1989; 10:378.
- McLachlan RI, Baker HW, Clarke GN, et al. Semen analysis: its place in modern reproductive medical practice. Pathology 2003; 35:25.
- Cooper TG, Noonan E, von Eckardstein S, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update 2010; 16:231.
- McLachlan RI, O'Bryan MK. Clinical Review#: State of the art for genetic testing of infertile men. J Clin Endocrinol Metab 2010; 95:1013.
- Hofherr SE, Wiktor AE, Kipp BR, et al. Clinical diagnostic testing for the cytogenetic and molecular causes of male infertility: the Mayo Clinic experience. J Assist Reprod Genet 2011; 28:1091.
- Sokol RZ. Endocrinology of male infertility: evaluation and treatment. Semin Reprod Med 2009; 27:149.
- Anawalt BD. Approach to male infertility and induction of spermatogenesis. J Clin Endocrinol Metab 2013; 98:3532.
- Meacham RB, Hellerstein DK, Lipshultz LI. Evaluation and treatment of ejaculatory duct obstruction in the infertile male. Fertil Steril 1993; 59:393.
- Jarow JP. Transrectal ultrasonography in the diagnosis and management of ejaculatory duct obstruction. J Androl 1996; 17:467.
- Abdulwahed SR, Mohamed EE, Taha EA, et al. Sensitivity and specificity of ultrasonography in predicting etiology of azoospermia. Urology 2013; 81:967.
- Kroese AC, de Lange NM, Collins J, Evers JL. Surgery or embolization for varicoceles in subfertile men. Cochrane Database Syst Rev 2012; 10:CD000479.
- Bhasin S, Ma K, de Kretser DM. Y-chromosome microdeletions and male infertility. Ann Med 1997; 29:261.
- Chillón M, Casals T, Mercier B, et al. Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. N Engl J Med 1995; 332:1475.
- Testart J, Gautier E, Brami C, et al. Intracytoplasmic sperm injection in infertile patients with structural chromosome abnormalities. Hum Reprod 1996; 11:2609.
- Palermo GD, Schlegel PN, Sills ES, et al. Births after intracytoplasmic injection of sperm obtained by testicular extraction from men with nonmosaic Klinefelter's syndrome. N Engl J Med 1998; 338:588.
- Krausz C, Chianese C. Genetic testing and counselling for male infertility. Curr Opin Endocrinol Diabetes Obes 2014; 21:244.
- Hotaling J, Carrell DT. Clinical genetic testing for male factor infertility: current applications and future directions. Andrology 2014; 2:339.
- Martin RH. Cytogenetic determinants of male fertility. Hum Reprod Update 2008; 14:379.
- Krausz C, Quintana-Murci L, Barbaux S, et al. A high frequency of Y chromosome deletions in males with nonidiopathic infertility. J Clin Endocrinol Metab 1999; 84:3606.
- Page DC, Silber S, Brown LG. Men with infertility caused by AZFc deletion can produce sons by intracytoplasmic sperm injection, but are likely to transmit the deletion and infertility. Hum Reprod 1999; 14:1722.
- De Kretser DM, Baker HW. Infertility in men: recent advances and continuing controversies. J Clin Endocrinol Metab 1999; 84:3443.
- MACLEOD J, GOLD RZ. The male factor in fertility and infertility. II. Spermatozoon counts in 1000 men of known fertility and in 1000 cases of infertile marriage. J Urol 1951; 66:436.
- Bonde JP, Ernst E, Jensen TK, et al. Relation between semen quality and fertility: a population-based study of 430 first-pregnancy planners. Lancet 1998; 352:1172.
- Jørgensen N, Andersen AG, Eustache F, et al. Regional differences in semen quality in Europe. Hum Reprod 2001; 16:1012.
- Swan SH, Brazil C, Drobnis EZ, et al. Geographic differences in semen quality of fertile U.S. males. Environ Health Perspect 2003; 111:414.
- Guzick DS, Overstreet JW, Factor-Litvak P, et al. Sperm morphology, motility, and concentration in fertile and infertile men. N Engl J Med 2001; 345:1388.
- Cooper TG, Hellenkemper B, Jonckheere J, et al. Azoospermia: virtual reality or possible to quantify? J Androl 2006; 27:483.
- Menkveld R, Stander FS, Kotze TJ, et al. The evaluation of morphological characteristics of human spermatozoa according to stricter criteria. Hum Reprod 1990; 5:586.
- Kruger TF, du Toit TC, Franken DR, et al. Sperm morphology: assessing the agreement between the manual method (strict criteria) and the sperm morphology analyzer IVOS. Fertil Steril 1995; 63:134.
- Gatimel N, Moreau J, Parinaud J, Léandri RD. Sperm morphology: assessment, pathophysiology, clinical relevance, and state of the art in 2017. Andrology 2017; 5:845.
- Kruger TF, Menkveld R, Stander FS, et al. Sperm morphologic features as a prognostic factor in in vitro fertilization. Fertil Steril 1986; 46:1118.
- Wolff H. The biologic significance of white blood cells in semen. Fertil Steril 1995; 63:1143.
- Lackner J, Schatzl G, Horvath S, et al. Value of counting white blood cells (WBC) in semen samples to predict the presence of bacteria. Eur Urol 2006; 49:148.
- Wang C, Swerdloff RS. Limitations of semen analysis as a test of male fertility and anticipated needs from newer tests. Fertil Steril 2014; 102:1502.
- Björndahl L, Kirkman-Brown J, Hart G, et al. Development of a novel home sperm test. Hum Reprod 2006; 21:145.
- Klotz KL, Coppola MA, Labrecque M, et al. Clinical and consumer trial performance of a sensitive immunodiagnostic home test that qualitatively detects low concentrations of sperm following vasectomy. J Urol 2008; 180:2569.
- Dieudonné O, Godin PA, Van-Langendonckt A, et al. Biochemical analysis of the sperm and infertility. Clin Chem Lab Med 2001; 39:455.
- Zini A, Bach PV, Al-Malki AH, Schlegel PN. Use of testicular sperm for ICSI in oligozoospermic couples: how far should we go? Hum Reprod 2017; 32:7.
- Tomlinson M, Lewis S, Morroll D, British Fertility Society. Sperm quality and its relationship to natural and assisted conception: British Fertility Society guidelines for practice. Hum Fertil (Camb) 2013; 16:175.
- CATEGORIES OF MALE INFERTILITY
- DIAGNOSTIC APPROACH
- Initial visit
- - History and physical examination
- - Semen analysis
- Reference limits
- Additional evaluation
- - Men with a normal semen analysis
- - Men with an abnormal semen analysis
- Normal sperm concentration, abnormal morphology and/or motility
- Sperm concentration <10 million/mL
- Severe oligozoospermia or azoospermia
- - Endocrine testing
- - Scrotal and transrectal ultrasound
- - Genetic tests
- Chromosomal anomalies
- Y-chromosome microdeletions, X-chromosome defects, and epigenetics
- CFTR gene
- DESCRIPTION OF SEMEN ANALYSES
- Semen analysis interpretation
- - Low volume
- - Low concentration
- - Abnormal morphology
- - Poor motility
- - Prediction of fertility
- At-home test
- Specialized sperm and semen tests
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS