Assisted reproductive techniques have become a routine treatment for infertility. The extended use of gonadotrophin-releasing hormone analogues in assisted reproductive techniques has made luteal phase support mandatory, as it has been clearly demonstrated that they alter luteal LH pulsatility. For luteal support, HCG administration, though effective, has a high risk of ovarian hyperstimulation syndrome. Progesterone continues to be the gold standard for supplementation. Vaginal progesterone represents a highly effective alternative to painful intramuscular injections. The vaginal route is mainly characterized by direct delivery of the progesterone to the endometrium, thus producing high levels at the target tissue and a very low incidence of side effects.