What does it mean that GnRH agonists have a flare-up effect?

Gonadotropin-releasing hormone (GnRH) analogs are medications used during controlled ovarian stimulation in assisted reproduction. Their main function is to regulate the release of FSH and LH from the pituitary gland, allowing synchronization of follicle growth.

The so-called “flare-up effect” occurs at the beginning of treatment with GnRH agonists. During the first few days, instead of immediately suppressing gonadotropins, these drugs cause a temporary surge of FSH and LH, which leads to a short-term rise in estrogen and progesterone levels.

This effect can be:

1. Clinically useful: in long protocols, this temporary stimulation may help with early follicle recruitment.
2. Potentially undesirable: if uncontrolled, it can lead to premature ovulation or poor synchronization of follicle growth.

After several days, GnRH agonists induce pituitary desensitization, resulting in full suppression of FSH and LH—the intended effect of the treatment.

In contrast, GnRH antagonists—used in modern short protocols—do not produce a flare-up effect because they immediately block pituitary receptors. Therefore, in 2025, antagonist protocols are more common due to their safety, comfort, and lower risk of ovarian hyperstimulation syndrome (OHSS).

In summary, the flare-up effect is a transient physiological reaction that can be advantageous or inconvenient depending on the chosen protocol and the patient’s profile. The choice between an agonist or antagonist regimen must always be ,individualized.