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Title: The use of hormonal strategies to improve the safety of in vitro fertilisation
Author: Clarke, Sophie
ISNI:       0000 0004 9350 4522
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2018
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In vitro fertilisation (IVF) is an increasingly used therapy for patients suffering with infertility. In 2014 67,608 cycles were undertaken in the UK, representing an increase of 4.8% from 2013. However, IVF is not without its complications. Ovarian hyperstimulation syndrome (OHSS) is a serious condition affecting 2-6% of all IVF cycles completed, and is related to the hormonal trigger used to induce oocyte maturation during IVF. Recently kisspeptin, a hypothalamic neuropeptide, has emerged as a potential alternative trigger. However, it has a short half-life, meaning that the duration of its effect on serum luteinising hormone (LH) is less than that observed during the endogenous menstrual cycle. In this thesis, I therefore first explore whether the addition of a second injection of kisspeptin-54 10hrs after the first during IVF treatment results in prolonged LH action in a population of women at high risk of OHSS. I demonstrate that greater numbers of patients achieve a clinically acceptable mature oocyte yield in those receiving two injections of kisspeptin-54 without an increase in rates of OHSS. However, whilst kisspeptin holds therapeutic promise, it has yet to be compared to conventional methods. I undertook a retrospective study comparing rates of OHSS in women at high risk of the condition following different triggers of oocyte maturation. I demonstrate that symptoms, signs and diagnosis of OHSS are greatest following hCG and least following kisspeptin. Finally, having observed that prolongation of LH exposure increases the proportion of women achieving a clinically effective oocyte yield, I investigate the effect of a kisspeptin analogue, kisspeptin-9a, on gonadotrophin secretion in healthy women, demonstrating a unique profile in LH secretion, which requires further studies to identify fully its effects but which may have use during IVF treatment. In summary, this thesis explores the use of kisspeptin during IVF treatment, further demonstrating its promise as a therapeutic trigger, and investigating for the first time the potential of a kisspeptin analogue, kisspeptin-9a.
Supervisor: Dhillo, Waljit ; Owen, Bryn Sponsor: National Institute for Health Research
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral