Depot GnRH Agonists in COH for ART

Abstract

The ability of gonadotropin-releasing hormone (GnRH) agonists (GnRH-a), particularly when used in a long protocol, to fine-tune and conveniently program ovarian stimulation cycles with significant advantages in the prevention of premature luteinization and satisfactory clinical outcomes, has made them a preferred inclusion in stimulation protocols for assisted reproduction. GnRH-a may be administered as short-acting daily low-dose injections or as a single long-acting high-dose injection (depot). A remarkable improvement in clinical pregnancy rates has been reported following downregulation with GnRH-a depot formulation and gonadotropin stimulation compared to gonadotropins alone, particularly in hyperandrogenic patients. The higher duration of gonadotropin stimulation and gonadotropin requirement with the long-acting depot, owing to the suggested profound pituitary suppression, is controversial, and no significant differences in clinical outcomes, the levels of endogenous hormones, or time to pituitary desensitization have been reported in a majority of the studies compared with the short-acting daily preparations. Despite comparable pregnancy outcomes, the use of depot GnRH-a in controlled ovarian hyperstimulation (COH) protocols for assisted reproductive technology (ART) is controversial, with some favoring its use in terms of patient compliance and ease of administration, and results, especially with the reduced dose, while others favoring the short-acting daily GnRH-a in terms of cost-effectiveness, and ovarian response in poor responders. However, the GnRH antagonist single-dose protocol has proved to be superior to the depot GnRH-a for COH with advantages of a significantly reduced duration of gonadotropin stimulation and requirement, higher flexibility in treatment, economy, convenience, and safety despite comparable pregnancy outcomes. Poor responders, in contrast, are reported to benefit from a flare-up GnRH-a protocol with a depot formulation compared to the GnRH antagonist, with higher total pregnancy and implantation rates, possibly due to improved oocyte/embryo competence.