Table 1.
Comparison between the traditional and newly proposed, clinically based classification of male infertility etiology.
| Traditional Classification | Examples |
|---|---|
| Pre-testicular causes | Hypogonadotropic hypogonadism Pituitary diseases Coital disorders |
| Testicular causes | Varicocele Cryptorchidism Noonan Syndrome Vanishing Testis Syndrome Myotonic dystrophy 46,XX testicular disorders of sex development 47,XYY Syndrome Klinefelter’s Syndrome Y chromosome microdeletions Sertoli Cell-Only Syndrome (germ cell aplasia) Gonadotoxins Systemic diseases Testis injury Idiopathic infertility |
| Post-testicular causes | Male reproductive tract obstruction Disorders of sperm function or sperm motility Disorders of coitus |
| Clinically Based Classification | Examples (Top: Genetic Causes; Bottom: Non-Genetic or Mixed Causes) |
| Hypothalamic–pituitary axis | Kallmann’s Syndrome |
| Ablative treatments (e.g., surgery or radiation); pituitary adenomas; tumors of the CNS; infection; infiltrative disease; empty sella syndrome; autoimmune hypophysitis; abuse of anabolic steroids; testosterone-replacement therapy; use or abuse of opiates and their analogues | |
| Quantitative Spermatogenesis (i.e., affecting the production and numbers of sperm) |
Gross chromosomal/karyotype anomalies; submicroscopic deletions (such as AZF deletions); Klinefelter’s Syndrome (47,XXY); 46,XX male syndrome; isodicentric Y chromosome; structural aberrations of the autosomes; X-linked genetic anomalies (such as AR or TEX11 gene mutations) |
| Varicocele; previous cytotoxic chemotherapy or radiotherapy; mumps; viral orchitis; testicular torsion; gonadal malignancy; severe scrotal trauma; some common medications; severe systemic illness; cryptorchidism | |
| Qualitative Spermatogenesis (i.e., affecting the characteristics of sperm, such as motility, fertilization, and genetic competency) |
Globozoospermia (e.g., SPATA16, PICK1, DPY19L2 gene mutations); macrozoospermia (e.g., AURKC gene mutations); ageing |
| Oxidative stress; inflammation; infection; autoimmune reaction against the spermatozoa; phospholipase C ζ deficiencies | |
| Ductal obstruction or dysfunction | Congenital bilateral absence of the vas deferens (CBAVD) (e.g., CFTR gene mutations) |
| Vasectomy; epididymal occlusion; previous inguinal hernia repair with inadvertent interruption or scarring of the vasa; spinal cord injury affecting ejaculation; retrograde ejaculation; erectile dysfunction; Young’s Syndrome |