Gonadotropin releasing hormone analogs as part of controlled ovarian stimulation

I describe how we identified the need to block the luteinizing hormone (LH) surge when trying to control the processes of luteinization and ovulation within the clinic. The first step, in fact, was using ovarian ultrasound evaluation of follicular development in the natural cycle (published in 1979) and then when the ovary was stimulated with exogenous follicle stimulating hormone. We observed that induced multiple follicular development often led to “premature” LH surges—which occurred before the leading follicle had achieved normal preovulatory dimensions. The work required both ovarian ultrasound and reliable radioimmunoassays, which were not always available. When early work with gonadotropin releasing hormone agonists showed that they could suppress LH activity, it was the logical step to try to use them to perform that task during the induction of multiple follicular development. High frequency administration of the gonadotropin releasing hormone-agonist successfully achieved sustained LH suppression through the follicular phase allowing clinical control of luteinization and ovulation.