Males suspected to be infertile should have a detailed medical history and physical examination. Semen analysis is the main investigation. Unless the clinical picture is clear, several semen analyses need to be done because of the day-to-day variability. Measurement of gonadotrophin and Abstract of the 8th Royan International Twin Congress, Tehran, Iran, 5-7 September 2007 10 Yakhteh Medical Journal, Vol 9, Sup 1, Summer 2007 testosterone levels is helpful in distinguishing primary from secondary testicular failure. Testis biopsies are useful for confirming obstructive azoospermia and determining the type of spermatogenic defect with primary seminiferous tubule disorders. Other investigations: karyotype, genetic tests for Yq microdeletions, cystic fibrosis, imaging for pituitary tumour or ejaculatory duct obstruction, are performed where indicated. A number of conditions are untreatable and cause sterility, in particular primary spermatogenic disorders where no live sperm are produced. These patients need to consider other alternatives for having a family by donor insemination or adoption. Over the last 15 years it has become clear that sperm or elongated spermatids that can be used for intracytoplasmic sperm injection (ICSI) may be found in a proportion of patients with severe testicular disorders such as Klinefelter syndrome and Sertoli cell only syndrome, either in the semen or in testis biopsy specimens. Conditions that may be treatable to increase the chances of natural conception include: gonadotropin deficiency or suppression, sperm autoimmunity, genital tract obstruction and reversible toxin exposures or illness effects and some coital disorders. However ICSI is often a better alternative for conditions such as sperm autoimmunity and genital tract obstruction. The remaining patients have less severe abnormalities of the semen, ranging from oligospermia to normal standard semen analyses but defective sperm function. These patients may have varicoceles, features of low grade genital tract inflammation, increased abnormal DNA in the sperm and increased production of reactive oxygen species by their sperm. There are no good controlled trials which prove treatment of these problems will increase natural conception rates. These patients are subfertile rather than sterile and pregnancies may occur but at lower than normal rates. Infrequent or mistimed coitus and female factors such as ovulatory disorders may be contributing. Thus the male and female partners should be treated as a couple and reversible factors treated where possible. The estimation of prognosis for natural conception is also important. If this is low, ICSI is usually effective.