What is the Difference Between GnRH Agonist and GnRH Antagonist?

GnRH agonists and antagonists are both used in reproductive medicine, but they have different mechanisms of action and are applied in different protocols. Here are the main differences between GnRH agonists and antagonists:

1. Mechanism of action: GnRH agonists, such as leuprolide acetate, bind to and activate GnRH receptors, initially stimulating the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). However, after a few days of continuous administration, the GnRH receptors on the pituitary cells become desensitized, and the release of LH and FSH is suppressed, leading to a decrease in estradiol and progesterone levels. In contrast, GnRH antagonists, such as ganirelix, directly block the binding of endogenous GnRH to its receptor, rapidly and reversibly suppressing the release of LH and FSH.
2. Protocols: In the conventional long protocol, GnRH agonists are applied from 7 days before menstruation, while GnRH antagonists are applied on a fixed day of ovarian stimulation or when the size of the leading follicle is 14 mm. GnRH antagonists have also been used in mild protocols of controlled ovarian hyperstimulation, which involve administering lower doses of exogenous gonadotropins for a shorter duration.
3. Patient outcomes: A study found that the GnRH agonist protocol was better for women over 40 years or those with low ovarian reserve, while the GnRH antagonist protocol led to better outcomes for women with high ovarian reserve.
4. Pregnancy rates: A study comparing the GnRH agonist and antagonist mild protocols of controlled ovarian hyperstimulation found that the live birth rate (LBR) was significantly higher in the GnRH antagonist mild protocol (42.9%) compared to the GnRH agonist protocol.

In summary, GnRH agonists and antagonists have different mechanisms of action, protocols, and patient outcomes. The choice between the two depends on factors such as the patient's age, ovarian reserve, and the specific treatment being administered.

Comparative Table: GnRH Agonist vs GnRH Antagonist

In summary, GnRH agonists and GnRH antagonists are both used in controlled ovarian hyperstimulation for assisted reproductive treatments. However, they differ in their mechanisms of action, protocols, side effect profiles, and flexibility. GnRH antagonists have been developed as an alternative to GnRH agonists due to their more rapid and reversible suppression of gonadotropin release, as well as their potential to reduce the risk of OHSS and other complications.