Use of Third Generation Gonadotropin-Releasing Hormone Antagonists in In Vitro Fertilization-Embryo Transfer: A Review

Before gonadotropin-releasing hormone agonists (GnRHa) became available, approximately 20% of stimulated cycles within an in vitro fertilization (IVF) program were cancelled due to premature LH surges. By using the GnRHa to prevent LH surges via gonadotrope GnRH receptor down-regulation and desensitization, this percentage decreased to about 2%, and concomitantly, the IVF and pregnancy rates per cycle initiated were increased. Several treatment schedules currently are in use, including the so-called “long protocol,” in which the GnRHa is begun in the luteal phase and down-regulation occurs before the start of the gonadotropin-stimulation treatment phase. This is generally the most effective regimen and is presently the most frequently used protocol. However, it has some disadvantages, such as hypoestrogenic side effects and an increase in the number of ampules of FSH or hMG required for adequate stimulation. There is a new generation of GnRH antagonists now clinically available, that has been able to minimize the potential side effects and provide reliable antagonism at the GnRH receptor. These agents seem better suited than GnRHa for assisted reproductive technology (ART) cycles inasmuch as they can prevent LH surges without requiring complete gonadotropin suppression. We have reviewed the current literature concerning their use in IVF cycles. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader will be able to summarize the data surrounding the use of GnRH antagonists in IVF cycles, to list the potential treatment protocols for using GnRH antagonists, and to outline the side effects of GnRH antagonists.