**6. Kisspeptin in in vitro fertilization**

Because of its apparent role in reproduction and fertility, there is interest in the use of kisspeptin as a tool to aid in assisted reproductive technology. Exogenous kisspeptin has been used to trigger oocyte maturation in women undergoing in vitro fertilization (IVF) with very low rates of ovarian hyperstimulation syndrome (OHSS) [41, 51]. Oocyte maturation is the process during which an oocyte transitions from metaphase I to metaphase II; at this time, it is capable of becoming fertilized [51]. Jayasena et al. demonstrated that a single kisspeptin bolus was capable of producing an LH surge that induced oocyte maturation in women undergoing IVF [41]. This was an important study, as it was the first to label kisspeptin as an effective maturation trigger. 92% of the study participants who received kisspeptin had at least one embryo available for transfer [41]. A study by Owens et al. then demonstrated that when kisspeptin is administered as an oocyte trigger during IVF cycles, granulosa cell gene expression is altered in such a way that increases FSH and LH receptor expression [52]. This altered gene expression is postulated to augment downstream signaling, resulting in increased sex steroid synthesis [52]. In fact, kisspeptin is currently considered to be the most potent stimulator of GnRH secretion [53, 54].

OHSS is considered a serious adverse event during IVF treatment and is typically related to the use of hCG as a trigger for oocyte maturation. This syndrome is characterized by extreme vascular permeability, which can result in pleural effusions, ascites, renal impairment, and in severe cases, death [51]. This vascular permeability is a downstream effect of hCG-mediated release of vascular endothelial growth factor (VEGF) from the ovary [55]. Kisspeptin has been shown to

directly inhibit ovarian VEGF production, which significantly decreases the risk of OHSS when used as a trigger for ovulation induction [56]. Moreover, kisspeptin acts to release endogenous GnRH, which triggers an LH surge dependent on the individual's own GnRH reserves, and is unlikely to excessively or pathologically stimulate the ovaries [57].
