GnRH analogues: applications in assisted reproductive techniques

Abstract

The ability to prevent an endogenous LH surge revolutionised the efficacy of assisted reproductive techniques (ART) such that GnRH agonists were rapidly adopted in the 1980s. Prior to this, premature luteinisation occurred in up to 25% of superovulated cycles leading to cycle cancellation and severely compromised outcomes. Analogues have been applied in a variety of drug protocols (long, short flare) but there has been little research to moderate the degree of pituitary suppression. There has also been ongoing and unresolved debate about the role of LH in supporting follicular development. By 2001, the first GnRH antagonists were registered for use in ART. Their ability to cause immediate suppression of gonadotrophin (particularly LH) secretion means that they can be given after exogenous stimulation has begun and thereby dramatically shorten the total duration of a treatment cycle. After initial enthusiasm and then scepticism that pregnancy rates may not be as high as the established agonist regimens, these preparations are now being increasingly adopted with at least comparable outcomes in large trials. They are certainly favoured by patients for their reduced side-effect profile and particularly for the shortening of the total cycle length. This shift in practice is occurring alongside gathering momentum in favour of milder stimulation protocols and a new perception of what constitutes successful treatment. The focus is moving away from surrogate outcomes such as oocyte numbers and conception rates towards long-term outcomes for women and their offspring, namely the achievement of a live singleton birth per treatment started.