Male factor infertility

The causes of male factor infertility include abnormal spermatogenesis; reproductive tract anomalies or obstruction; sexual and ejaculatory dysfunction; and impaired sperm motility.

Altered spermatogenesis is probably the most common reason for male infertility and is of unknown aetiology in most cases.[2] Factors that alter spermatogenesis through low testosterone levels include obesity, endocrinopathies, and exposure to medicine or environmental toxins.[6][8][9] Other factors that have a direct deleterious effect on spermatogenesis include varicocele, increased scrotal heat, systemic diseases, smoking, history of undescended testicles, and alcohol intake.[9][10][11][12][13][14] Y chromosome deletions and other chromosomal anomalies, such as Klinefelter syndrome (XXY), are less common causes.[15][16] Testicular torsion and trauma can also affect sperm production.[17]

Reproductive tract obstruction may be congenital, such as congenital bilateral absence of vas deferens, related frequently to a mutation in the cystic fibrosis transmembrane regulator gene, or acquired secondary to epididymal or prostatic infections, vasectomy, or complications of surgical procedures (e.g., inguinal hernia repair or orchiopexy for testicular non-descent).[2] Prostatic surgery and some pharmaceuticals may be associated with retrograde ejaculation.[2]

Erectile and ejaculatory dysfunction may be associated with psychological factors, hypogonadism, spinal cord disease, and diabetes mellitus.[2][18][19][20]

Sperm motility can be reduced in the immotile cilia syndrome (Kartagener syndrome) or in the presence of anti-sperm antibodies. Urogenital tract infections (e.g., prostatitis, orchitis, epididymitis) may result in an inflammatory response leading to obstruction or immunogenic spermatogenic dysfunction.[2][21]

Male fertility requires normal sperm production and transport and adequate sexual performance.

These functions require normal levels of testosterone. Testosterone is produced by the testicular Leydig cells under the influence of luteinising hormone (LH). Spermatogenesis is controlled directly by intratesticular testosterone and follicle-stimulating hormone (FSH). FSH is believed to act on the Sertoli cells, which support spermatogenesis in the seminiferous tubules. The pituitary production of FSH and LH is controlled by the hypothalamic gonadotrophin-releasing hormone (GnRH). GnRH and FSH production by the hypothalamus and pituitary is negatively controlled directly by testosterone levels and through its aromatisation to estradiol at the central or peripheral levels. Inhibin is produced by Sertoli cells and has a negative effect on FSH secretion. Circulating testosterone is bound mainly to the sex hormone-binding globulin (SHBG) and albumin. Levels of SHBG affect the active portion of circulating testosterone or free testosterone. Hyperprolactinaemia has a negative effect on GnRH secretion.

The presence of an intact Y and one copy of the X chromosome is essential for the differentiation of the embryonic gonads into testicles and for the later development of adequate spermatogenesis. Normal fertilisation of the oocyte requires many motile sperm with intact acrosome reaction.

Sperm production is negatively affected by endocrine effects of obesity, increased local testicular heat, and exposure to environmental toxins or endocrine disruptors.[9] Smoking, alcohol, and cannabis consumption also have a detrimental effect on semen production and sperm viability.[11][12][13][14][22] A variety of medications or metabolic conditions can alter testosterone production or have an anti-testosterone effect at the receptor level. Other medications or environmental exposures can directly alter spermatogenesis or sperm motility.

Causes of male infertility[2]

There is no formal classification of male infertility. It may be categorised as resulting from:

Congenital or acquired urogenital abnormalities (e.g., testicular dysgenesis, cryptorchidism, testicular torsion)

Malignancy (e.g., germ cell tumours)

Urogenital tract infections (e.g., prostatitis, orchitis, epididymitis)

Increased scrotal temperature (e.g., as a consequence of varicocele)

Endocrine disturbances (e.g., primary or secondary hypogonadism)

Genetic abnormalities (e.g., Klinefelter syndrome [47, XXY])

Immunological factors (e.g., sperm autoantibodies)
Iatrogenic (e.g., vasectomy, gonadotoxic therapies such as chemotherapy or radiation).

Pathophysiology

Classification

Causes of male infertility[2]