The etiology of infertility remains unexplained in a major proportion of couples presenting to fertility clinics. The proportion of couples with unexplained infertility is related to the extent of diagnostic tests performed to uncover the cause of childlessness. Semen analysis, noninvasive documentation of ovulation, and confirmation of tubal patency are the minimum set of diagnostic tests that should be performed. The value of a postcoital test and laparoscopy remains to be determined. A stepwise approach to unexplained infertility is prudent. Young couples with a short duration of infertility should be offered expectant management. Clomiphene citrate and gonadotropin treatment with or without intrauterine insemination should be tried next. As many studies indicate a gamete-or embryo-related etiology for unexplained infertility, assisted reproductive techniques are being used extensively. Whether standard in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) should be used for fertilization of the oocytes, however, is still debatable. Given the high incidence of unexpected total fertilization failure events with IVF, serious consideration should be given to ICSI. [ABSTRACT FROM AUTHOR]