Gonadotropin releasing hormone analogs in human reproduction

GnRH agonisti i antagonisti su skupine sintetskih spojeva, a nastali su zbog supstitucijskih promjena na različitim pozicijama u molekuli endogenog GnRH. Imaju veću biološku stabilnost i povećan afinitet za GnRH receptor u odnosu na prirodni GnRH. GnRH agonisti inicijalno povećavaju sekreciju gonadotropina iz hipofize („flare-up“ efekt) dok u drugoj fazi dovode do supresije hipofizne funkcije i gonadotropinske sekrecije. Antagonisti GnRH se kompetativno vežu na GnRH receptore i preveniraju stimulirajući učinak endogenog GnRH za stvaranje gonadotropina. Tim mehanizmom se izbjegava početni skok gonadotropina. Glavna zadaća GnRH analoga u stimulaciji ovulacije jest sprječavanje preranog skoka LH. GnRH agonisti koriste se u sklopu ultrakratkog, kratkog i dugog protokola stimulacije ovulacije u ciklusima za in vitro fertilizaciju (IVF). Njihova primjena je povezana sa značajnim smanjenjem neuspjelih ciklusa, povećanim brojem zrelih oocita i dobivenih embrija te većim brojem uspješno postignutih trudnoća. Nuspojava liječenja u dugom protokolu jest stvaranje folikularnih cista. Ovarijski hiperstimulacijski sindrom (OHSS) je najopasnija nuspojava stimulacije ovulacije. Rizik pojave OHSS-a se ne umanjuje primjenom agonista GnRH. Protokoli GnRH antagonistima imaju određene prednosti, kao što su kraći period stimulacije, trajanje liječenja i manje nuspojava te značajnije niži rizik OHSS-a. Na temelju dosadašnjih rezultata, broj postignutih trudnoća nakon IVF-a ne ovisi o vrsti primijenjenog analoga u protokolima stimulacije ovulacije. Ostale indikacije za primjenu GnRH analoga u humanoj reprodukciji su u sklopu liječenja endometrioze i mioma maternice.GnRH agonists and antagonists are a group of synthetic compounds resulting from natural GnRH through amino acid substitution on different positions. They have greater biological stability and a more increased affinity for the receptors than natural GnRH. GnRH agonists initially increase gonadotropin secretion from pituitary cells, known as the flair-up effect, followed by suppression of pituitary function and gonadotropin secretion due to down-regulation of GnRH receptors. GnRH antagonists bind competitively to the receptors and prevent the endogenous GnRH from exerting its stimulatory effect on the pituitary cells, thus avoiding any flare-up effect. The main purpose of GnRH analogs use in ovarian stimulation is the prevention of untimely LH surges. GnRH agonists can be administrated according to the ultra-short, short and long protocols. The use of GnRH agonists in cycles stimulated for assisted reproductive techniques (ART) is associated with the significant decrease in the cancellation rates, an increase in the number of oocytes and embryos obtained and higher pregnancy rates. Follicle cyst formation is an undesired side effect of agonist administration when long protocol is used. OHSS is the most serious side effect of the ovarian stimulation and its occurence cannot be avoided by GnRH agonist administration. Antagonist protocols have clear advantages, such as a shorter stimulation period, no sexual steroid withdrawal symptoms and significantly lower rate of OHSS. Based on recent results, pregnancy rate after IVF does not depend on the type of applied analogs in ovarian stimulation protocols. Other indications of GnRH analogs in human reproduction are for treatment of endometriosis and uterine fibroids