Developmental Clinical Studies:To determine the effectiveness of kisspeptin to induce oocyte maturation in IVF treatment

In vitro fertilisation (IVF) treatment is widely and successfully used to treat infertility, but can cause the life threatening condition called ovarian hyperstimulation syndrome (OHSS). Mild forms of OHSS occur in approximately 1/3rd of all IVF cycles, whilst moderate or severe OHSS occurs in up to 1/10th of IVF cycles. The cause is the use of a drug in IVF treatment which too powerfully stimulates the release of reproductive hormones. Kisspeptin is a hormone found naturally in men and women and it stimulates reproductive hormone secretion similarly to the stimulation which occurs in women with a normal menstrual cycle. In this study we will find out how effective kisspeptin is in patients requiring IVF treatment. Ultimately the aim of our research will be to determine if the use of kisspeptin in IVF treatment could prevent the potentially life threatening risk of OHSS in women with infertility who are otherwise healthy.

Infertility affects one in six couples in the UK. In vitro fertilisation (IVF) treatment is now widely and successfully used to enable infertile couples to conceive. Approximately 45,000 cycles of IVF are performed in Britain each year. However, IVF treatment can result in the potentially life threatening condition, ovarian hyperstimulation syndrome (OHSS). Mild forms of OHSS occur in approximately 1 in 3 of all IVF cycles, whilst approximately 1 in 10 IVF cycles result in moderate or severe OHSS. The major cause of OHSS is the pharmacological use of human chorionic gonadotrophin (hCG) to stimulate oocyte maturation in current IVF protocols. The development of a more physiological stimulus for oocyte maturation should avoid this dangerous side effect and improve the safety and efficacy of IVF treatment. Kisspeptin is a hormone which stimulates reproductive hormone secretion in animals and is responsible for the endogenous luteinising hormone (LH) surge which results in ovulation. In keeping with this, exogenous administration of kisspeptin has been shown to induce ovulation in rats and sheep. Interestingly in rats primed with gonadotrophins, peripheral administration of kisspeptin promotes ovulation with equal efficacy to that following hCG administration. We have conducted the first studies of kisspeptin administration to humans, demonstrating that acute administration of kisspeptin potently stimulates reproductive hormone secretion in healthy men and women as well as in women with infertility due to hypothalamic amenorrhea. Importantly, we have demonstrated that healthy women with regular menstrual cycles are most sensitive to the effects of kisspeptin immediately prior to ovulation (i.e. in the pre-ovulatory phase). Recent evidence demonstrates that kisspeptin stimulates the release of a limited pool of endogenous gonadotrophin releasing hormone (GnRH) which results in the release of endogenous gonadotrophins. Therefore, the significant advantage of kisspeptin over current treatments is that its effects would depend on the sensitivity of an individual‘s hypothalamic-pituitary gonadal (HPG) axis to stimulation. This would result in a more physiological LH surge and oocyte maturation during IVF treatment, thereby improving safety and efficacy of IVF treatment. The aim of this study is to provide proof of concept that kisspeptin effectively induces oocyte maturation in IVF treatment.