Birth of FSH Protocol and the HCG Trigger

In IVF a follicle stimulating hormone (FSH) is used to promote growth of multiple follicles for a controlled ovarian hyperstimulation (COH). Common known brand name COH drugs include Gonal F and Follistim, which mimic natural FSH. Follicle growth is monitored, and as follicles approach maturity an injectable Human Chorionic Gonadotropin (HCG) is used as a “trigger” to control the timing of ovulation.  Egg retrieval is generally scheduled for 34-36 hours after the trigger shot. 

Birth of FSH Protocol and the HCG Trigger

Prior to Louise Brown - the world’s first baby born from IVF – IVF pioneer Dr. Robert Edwards and his colleagues studied egg and embryo development of mice in a laboratory they called the “Mouse House” located on the grounds of Edinburgh University.  It was there that Edwards approached American academic Alan Gates who had developed a gonadotrophic hormone injection protocol effectively creating multiple eggs in immature mice. Gates had subscribed to the then conventional theory that adult female ovaries (post puberty) would not respond to gonadotrophic hormones, thus only immature mice were used as his test subjects.  Gates had previously injected his mice with serum from a pregnant mare then two days later injected them with a drop of serum from a pregnant woman, resulting in the creation and maturity (ripening) of multiple eggs.  At the Mouse House Edwards tested the serum solutions on adult mice of all sizes, and - to the surprise of Gates - discovered it worked just as well on them as it did on their immature counterparts.

March of the Chromosomes

Edwards observed that eggs matured in predictable intervals following both serums. He and Gates decided to examine the ripening process under a microscope. They witnessed an unexpected transformation two hours following the second serum (HCG trigger). The egg nucleus condensed and a set of chromosomes appeared at the center. The chromosomes then circulated the periphery wall in a fashion Edwards described as a military-like march. In the final stage of the march the chromosomes separated. One set remained in the egg and one set left the egg through the first polar body.  At that point the egg was ripened and ready for fertilization.

Human Egg Ripening

Although passionate to further his study of human embryology Edwards often lacked access to human eggs, reliant upon hospitals willing to donate ovarian tissue.  And for a lengthy period when he did have tissue he could not replicate the success on human eggs as he had achieved with mice.  Edwards’ efforts were modelled on the literature of Dr Gregory Pincus who claimed that human eggs, like many other mammals, ripened in 12 hours.  It would be a couple of years before Edwards discovered that the ripening phase in human eggs took approximately 36 hours.