Under normal physiological conditions, ovulation occurs when a pre-ovulatory follicle reaches a size of 16 to 22 mm in diameter. At this stage, the follicle produces enough estrogen to signal the brain, triggering a LH surge, which leads to the release of a mature egg ready for fertilization.  

However, during controlled ovarian stimulation, when multiple follicles are developing at the same time, the increased hormone production can cause an early ovulation signal, sometimes before the follicles have reached 16 mm. This increases the risk of releasing immature eggs, which cannot be fertilized and do not result in a viable pregnancy.  

To prevent premature ovulation, ovulation must be blocked in most multi-follicular stimulation protocols. There are two main ways to achieve this:  

1. GnRH Agonists (e.g., Decapeptyl, Gonadopeptyl, Zoladex, Synarel) – These are typically started before ovarian stimulation and continued throughout the process to suppress natural ovulation.  

2. GnRH Antagonists (e.g., Orgalutran, Cetrotide, Fyremadel) – These are administered a few days after stimulation begins to temporarily and daily block ovulation, allowing follicles to reach maturity before triggering ovulation.  

Once the follicles have reached the optimal size, ovulation is artificially triggered to ensure the eggs are mature and ready for retrieval or fertilization.