In the long history of controlled ovarian hyperstimulation (COH), two steps stand out as being the most important ones for providing the high efficacy of current treatments: the introduction of GnRH agonists for the prevention of premature ovulation and the widespread use of pretreatment with oral contraceptives before COH for in vitro fertilization. Interestingly, the benefits of both measures resulted largely from pure serendipity, as the discovery of these advantages was mostly fortuitous and/or unintended. Today, we believe that two areas of research have the highest potential for further improving the efficacy of COH: (1) switching the follicle-stimulating hormone stimulus to that of luteinizing hormone (or small amounts of hCG) in the last stages of COH; and (2) using the benefit of the new third-generation aromatase inhibitors that have recently become available. The effects of the latter products are to enhance the endogenous production of gonadotropins (mostly FSH). This article reviews the background data and rationale that justifies each of these two new developments and summarizes data currently available.