Integrating oral contraceptives (OCPs) into the down-regulation protocol had the benefit that stimulation was always commenced at a time of menstruation, and conceptions during treatment were avoided. Adding the OCP not only had the advantages of programming, avoiding conception during treatment, and decreasing the incidence of cyst formation, but it also saved on the amount of gonadotropin-releasing hormone (GnRH) agonist consumed, which was a cost-saving. Similar attempts at successfully programming cycles using progestogens were also reported. By 2008 GnRH antagonists were replacing the GnRH agonists in many protocols, as they were perceived to be more patient friendly being shorter, with fewer side-effects and a lower incidence of ovarian hyperstimulation syndrome (OHSS). This prompted the first systematic review of controlled trials using OCP, but was confined to controlled ovarian hyperstimulation (COH) cycles using GnRH antagonists.