Causes of male factor infertility can be classified into pretesticular, testicular and post-testicular (Box 1). Conditions that act at the pretesticular level tend to be hormonal in nature and most of these can be treated with hormone manipulation. Causes at the testicular level are largely irreversible, but can be treated with assisted reproductive technology (ART), if sperm is retrievable. Post-testicular causes can be treated with microsurgery or with ART. It is estimated that in about 50% of men with poor semen quality, no cause for this will be identified.
Environmental, occupational and lifestyle factors
There is increasing evidence from epidemiological studies that occupational exposures to certain chemicals can affect semen quality.[20, 21] More than 104 000 such chemicals and physical agents have been identified. These include heat, X-rays, heavy metals (lead, mercury), glycol ethers (highly volatile compounds used as solvents) and pesticides; a well documented example being dibromochloropropane (DBCP), a nematocide used in certain crops. The exact mechanism by which these occupational substances affect male fertility remains unclear.
Despite earlier reports, the level of environmental estrogens would not appear to be a threat to male reproductive health. Recent observational studies support a dose-dependent decrease in semen parameters related to exposure to electromagnetic waves emitted from mobile phones.[24-26] The clinical significance of this, however, remains unclear. Testicular hyperthermia may affect semen quality. However, there is no clear evidence that wearing loose-fitting underwear improves fertility.[1, 28, 29] There is evidence that a sedentary lifestyle, most likely through elevated scrotal temperature, can affect sperm production.
Obesity is an important lifestyle factor that has been shown to be associated with poor semen quality.[31, 32] As the prevalence of obesity in Western countries is increasing, it is likely that it will have an increasing impact on male fertility. The mechanism by which obesity causes altered semen parameters is thought to be through an imbalance of reproductive hormone levels, as obese men have reduced sex hormone binding globulin and elevated estrogen levels. Altered metabolism of environmental toxins, sedentary lifestyle factors and increased risk of sexual dysfunction are also thought to contribute to reduced fertility in heavier men.
Anabolic-androgenic steroids may induce azoospermia by interfering with the hypothalamo-pituitary-gonadal (HPG) axis. They may also inhibit male reproductive function through loss of libido and erectile dysfunction secondary to low endogenous testosterone levels. Azoospermia may be reversed by conservative management when the drugs are discontinued, especially in non-heavy users,[33, 34] or by administration of human chorionic gonadotrophin and human menopausal gonadotrophin. Sperm quality tends to recover spontaneously within 4–12 months after discontinuation. However, persistent alterations in semen parameters can remain even after cessation of use. It is therefore important to encourage discontinuation of use immediately and to emphasise that even ‘steroid-free’ dietary supplements have been reported to be contaminated with traces of hormones.
Heavy alcohol consumption, but not moderate consumption, may affect sexual and reproductive performance in a reversible fashion.[1, 37] Tobacco smoking and cannabis consumption have been shown to reduce semen parameters, although the relationship between male smoking habits and fertility remains uncertain. Although smokers in general may not experience reduced fertility, men with suboptimal semen quality may benefit from quitting smoking and this should be strongly encouraged. Other recreational drugs such as cocaine, amphetamines and opiates may adversely affect reproductive performance due to decreased libido and erectile dysfunction.
According to some reports, sperm DNA damage secondary to oxidative stress may be the cause of between 30% and 80% of male subfertility cases. Recent evidence suggests that antioxidant supplementation in subfertile males, including carnitines, vitamin C, vitamin E, selenium, zinc and coenzyme Q10, improves semen quality and live birth rates in couples undergoing fertility treatment.[40, 41]
Hypogonadotrophic hypogonadism is rare and accounts for <1% of male factor fertility problems. It results from decreased production of FSH and LH secondary to hypothalamic or pituitary dysfunction, which leads to failure of spermatogenesis and testosterone secretion by the testes. It may be congenital or acquired. Causes include craniopharyngiomas, surgery for pituitary tumours, head trauma, haemochromatosis, Kallmann syndrome and other congenital genetic syndromes of reduced gonadotrophin releasing hormone (GnRH) secretion (Prader–Willi syndrome, Laurence–Moon–Biedl syndrome).
Obstruction, excluding vasectomy, accounts for up to 41% of causes of azoospermia. The diagnosis is based on normal serum FSH levels, normal testicular volume and evidence of complete spermatogenesis on biopsy. Causes include surgical trauma and vasectomy, infection (chlamydia, gonorrhoea, tuberculosis), and congenital bilateral absence of vas deferens (CBAVD).