A. Noonan Syndrome
Also called male Turner syndrome, Noonan syndrome is associated with clinical features similar to Turner syndrome (45,X). However, the karyotype is either normal (46,XY) or mosaic (X/XY). Typically, patients have dysmorphic features like webbed neck, short stature, low-set ears, wide-set eyes, and cardiovascular abnormalities. At birth, 75% have cryptorchidism that limits fertility in adulthood. If testes are fully descended, then fertility is possible and likely. Associated FSH and LH levels depend on the degree of testicular function.
B. Myotonic Dystrophy
Myotonic dystrophy is the most common reason for adult-onset muscular dystrophy. In addition to having myotonia, or delayed relaxation after muscle contraction, patients usually present with cataracts, muscle atrophy, and various endocrinopathies. Most men have testis atrophy, but fertility has been reported. Infertile men may have elevated FSH and LH with low or normal testosterone, and testis biopsies show seminiferous tubule damage in 75% of cases. Pubertal development is normal; testis damage seems to occur later in life.
- Male reproductive physiology
- Diagnosis of Male Infertility
- Causes of Male infertility
- Chromosomal Causes
- Other Syndromes
- Systemic Disease
- Defective Androgen Activity
- Testis Injury
- Treatment of Male infertility
C. Vanishing Testis Syndrome
Also called bilateral anorchia, vanishing testis syndrome is rare, occurring in 1:20,000 males. Patients present with bilateral nonpalpable testes and sexual immaturity due to the lack of testicular androgens. The testes are lost due to fetal torsion, trauma, vascular injury, or infection. In general, functioning testis tissue must have been present during weeks 14-16 of fetal life, since wolffian duct growth and mullerian duct inhibition occur along with appropriate growth of male external genitalia. Patients have eunuchoid body proportions but no gynecomastia. The karyotype is normal. Serum LH and FSH levels are elevated, and serum testosterone levels are extremely low. There is no treatment for this form of infertility; patients receive lifelong testosterone for normal virilization and sexual function.
D. Sertoli-Cell-Only Syndrome
Also referred to as germ cell aplasia, the hallmarks of Sertoli-cell-only syndrome are an azoospermic male with testes biopsies that show the presence of all testis cell types except for germinal epithelium. Several causes have been proposed, including genetic defects, congenital absence of germ cells, and androgen resistance. Clinically, these men have normal virilization with small testes of normal consistency. There is no gynecomastia. Testosterone and LH levels are normal, but FSH levels are usually (90%) elevated. The use of the word “syndrome” implies that no recognized insult has occurred, since gonadotoxins like ionizing radiation, chemotherapy, and mumps orchitis can also render the testes aplastic of germ cells. There is no known treatment for this condition. In some patients, extensive testis sampling with fine-needle aspiration mapping or multiple biopsies can reveal sperm that can be used for pregnancy with assisted reproductive technologies.
E. Y Chromosome Microdeletions
Approximately 7% of men with low sperm counts and 13% with azoospermia have a structural alteration in the long arm of the Y chromosome (Yq). The testis-determining region genes that control testis differentiation are intact, but there may be gross deletions in other regions that may lead to defective spermatogenesis. The recent explosion in molecular genetics technology has allowed for sophisticated analysis of the Y chromosome. At present, 3 gene sites are being investigated as putative AZF (azoospermia factor) candidates: AZFa, b, and c. The most promising site is AZFc, which contains the DAZ gene region. The gene, of which there are at least 7 copies in this region, appears to encode an RNA-binding protein that regulates the meiotic pathway during germ cell production. Homologs of the DAZ gene are found in many other animals, including mouse and Drosophila. A quantitative polymerase chain reaction- based assay is used to test blood for these deletions. In the future, sperm DNA may also be tested as part of a semen analysis. Since men with these microdeletions can have sperm in the ejaculate, they are likely to pass them on to offspring if assisted reproductive technology is used.
Revision date: July 8, 2011
Last revised: by Sebastian Scheller, MD, ScD