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The aim of treatment with a gonadotropin-releasing hormone (GnRH) agonist is elimination of the luteinizing hormone (LH) surge and fluctuating LH concentrations, which compromise outcome in cycles of ovarian stimulation for in-vitro fertilization (IVF). This chapter addresses the characteristics of the standard long-course protocol. It is most common to initiate treatment in the luteal phase to minimize the consequences of the flare effect seen in the first few days of treatment with a GnRH agonist. The down-regulation effect of agonists can be established and maintained by multiple applications of nasal spray, single daily injection, or depo formulations lasting variable lengths of time. When the patient is down-regulated at the start of follicle stimulating hormone (FSH) treatment, subsequent follicular growth and recruitment is dictated by two elements: the ovarian reserve, which dictates the number of follicles available for recruitment, and the profile of circulating FSH concentrations.