There is increasing evidence that the harmful products of tobacco smoking may damage the testicles and kill sperm, but their effect on male fertility is not clear. Some governments require manufacturers to put warnings on packets. Smoking tobacco increases intake of cadmium, because the tobacco plant absorbs the metal. Cadmium, being chemically similar to zinc, may replace zinc in the DNA polymerase, which plays a critical role in sperm production. Zinc replaced by cadmium in DNA polymerase can be particularly damaging to the testes.

Pre-testicular factors refer to conditions that impede adequate support of the testes and include situations of poor hormonal support and poor general health including:

- Hypogonadotropic hypogonadism due to various causes

- Obesity increases the risk of hypogonadotropic hypogonadism. Animal models indicate that obesity causes leptin insensitivity in the hypothalamus, leading to decreased Kiss1 expression, which, in turn, alters the release of gonadotropin-releasing hormone (GnRH).

- Undiagnosed and untreated coeliac disease (CD). Coeliac men may have reversible infertility. Nevertheless, CD can present with several non-gastrointestinal symptoms that can involve nearly any organ system, even in the absence of gastrointestinal symptoms. Thus, the diagnosis may be missed, leading to a risk of long-term complications. In men, CD can reduce semen quality and cause immature secondary sex characteristics, hypogonadism and hyperprolactinaemia, which causes impotence and loss of libido. The giving of gluten free diet and correction of deficient dietary elements can lead to a return of fertility. It is likely that an effective evaluation for infertility would best include assessment for underlying celiac disease, both in men and women.

- Drugs, alcohol

- Strenuous riding (bicycle riding, horseback riding)

- Medications, including those that affect spermatogenesis such as chemotherapy, anabolic steroids, cimetidine, spironolactone; those that decrease FSH levels such as phenytoin; those that decrease sperm motility such as sulfasalazine and nitrofurantoin

- Genetic abnormalities such as a Robertsonian translocation

The presence of abnormally-shaped sperm can negatively affect fertility by preventing transport through the cervix and/or preventing sperm from adhering to the ovum. Achieving a pregnancy may be difficult.

In testing for teratozoospermia, sperm are collected, stained and analyzed under a microscope to detect abnormalities. These abnormalities may include heads that are large, small, tapered, or pyriform or tails that are abnormally shaped.

Antiestrogens have been shown to be effective in the treatment of teratozoospermia.

Teratozoospermia (including the "globozoospermia" type), may be treated by intracytoplasmic sperm injection (ICSI), injecting sperm directly into the egg. Once the egg is fertilized, abnormal sperm morphology does not appear to influence blastocyst development or blastocyst morphology. Even with severe teratozoospermia, microscopy can still detect the few sperm cells that have a "normal" morphology, allowing for optimal success rate.

The causes of teratozoospermia are unknown in most cases. However, Hodgkin's disease, coeliac disease, and Crohn's disease may contribute in some instances. Lifestyle and habits (smoking, toxin exposure, etc.) can also cause poor morphology. Varicocele is another condition that is often associated with decreased normal forms (morphology).

In cases of globozoospermia (sperm with round heads), the Golgi apparatus is not transformed into the acrosome that is needed for fertilization.