Up to one in five couples experience infertility, as defined by lack of conception after 12 months of regular unprotected intercourse.  Many causes of infertility cannot be successfully overcome with specific medical and surgical treatment – especially where the cause of infertility is unexplained. In prolonged unresolved infertility, the preferred option is to use in-vitro fertilisation (IVF) which bypasses in-vivo reproductive processes and can overcome known as well as unknown barriers to conception. IVF was originally conceived as a treatment for women with absent or damaged tubes. The biological plausibility underpinning its effectiveness in this context is so strong that clinical trials are unethical and redundant.  In couples with unexplained infertility, recent evidence from randomised trials suggests that some of the first line treatments, such as clomifene citrate, are no more effective than no treatment and less effective than IVF. Thus IVF has emerged as the only viable option for prolonged infertility, regardless of etiology. Like any other treatment, it needs to be used judiciously in order to maximise clinical and cost effectiveness and minimise any potential risks.