Gonadotropin-releasing hormone agonist triggering of oocyte maturation in assisted reproductive technology cycles

Abstract

Gonadotropin-releasing hormone agonists (GnRHa) have gained increasing attention in the last decade as an alternative trigger for oocyte maturation inpatients at high risk for ovarian hyperstimulation syndrome (OHSS). They provide a short luteinizing hormone (LH) peak that limits the production ofvascular endothelial growth factor, which is the key mediator leading to increased vascular permeability, the hallmark of OHSS. Initial studies showedsimilar oocyte yield and embryo quality compared with conventional human chorionic gonadotropin (hCG) triggering; however, lower pregnancy rates andhigher miscarriage rates were alarming in GnRHa triggered groups. Therefore, two approaches have been implemented to rescue the luteal phase in freshtransfers. Intensive luteal phase support (iLPS) involves administiration of high doses of progesterone and estrogen and active patient monitoring. iLPS hasbeen shown to provide satisfactory fertilization and clinical pregnancy rates, and to be especially useful in patients with high endogenous LH levels, suchas in polycystic ovary syndrome. The other method for luteal phase rescue is low-dose hCG administiration 35 hours after GnRHa trigger. Likewise, thismethod results in statistically similar ongoing pregnancy rates (although slightly lower than) to those of hCG triggered cycles. GnRHa triggering decreasedOHSS rates dramatically, however, none of the rescue methods prevent OHSS totally. Cases were reported even in patients who underwent cryopreservationand did not receive hCG. GnRH triggering induces a follicle stimulating hormone (FSH) surge, similar to natural cycles. Its possible benefits have beeninvestigated and dual triggering, GnRHa trigger accompanied by a simultaneous low-dose hCG injection, has produced promising results that urgefurther exploration. Last of all, GnRHa triggering is useful in fertility preservation cycles in patients with hormone sensitive tumors. In conclusion, GnRHatriggering accompanied by appropriate luteal phase rescue protocols is a relatively safe option for patients at high risk for OHSS.