The use of kisspeptin as a novel physiological oocyte maturation trigger for patients undergoing IVF treatment
File(s)
Author(s)
Christopoulos, Georgios
Type
Thesis
Abstract
Background: Patients with inactivating mutations in kisspeptin signalling are infertile. Kisspeptin-54, the major circulating isoform of kisspeptin in humans, potently stimulates reproductive hormone secretion in humans. Animal studies suggest that kisspeptin is involved in the generation of the luteinising hormone surge, which is required for ovulation. I hypothesised that kisspeptin-54 could be a novel method used to trigger egg maturation in women undergoing in vitro fertilisation therapy.
Methods: This was a proof of concept study. Following superovulation with follicle stimulating hormone, and gonadotrophin releasing hormone antagonist administration to prevent premature ovulation, 53 women were administered a single subcutaneous injection of kisspeptin-54 (1.6nmol/kg, n=2; 3.2nmol/kg, n=3; 6.4nmol/kg, n=24; 12.8nmol/kg, n=24) to induce a luteinising hormone surge and egg maturation. Eggs were retrieved transvaginally 36h after kisspeptin injection, assessed for maturation (primary outcome), and fertilised by intracytoplasmic sperm injection with subsequent transfer of one or two embryos.
Results: Overall, egg maturation was observed in 96% (51/53) of patients. Fertilisation of eggs and transfer of embryos to the uterus occurred in 92% (49/53) of patients. Biochemical and clinical pregnancy rates were 40% (21/53) and 23% (12/53), respectively.
Conclusion: This study demonstrates that a single injection of kisspeptin-54 can induce high rates of egg maturation in women with sub-fertility undergoing in vitro fertilisation therapy. Subsequent fertilisation of eggs matured following kisspeptin-54 administration and transfer of resulting embryos can lead to successful human pregnancy.
Trial registration: ClinicalTrials.gov NCT01667406
Methods: This was a proof of concept study. Following superovulation with follicle stimulating hormone, and gonadotrophin releasing hormone antagonist administration to prevent premature ovulation, 53 women were administered a single subcutaneous injection of kisspeptin-54 (1.6nmol/kg, n=2; 3.2nmol/kg, n=3; 6.4nmol/kg, n=24; 12.8nmol/kg, n=24) to induce a luteinising hormone surge and egg maturation. Eggs were retrieved transvaginally 36h after kisspeptin injection, assessed for maturation (primary outcome), and fertilised by intracytoplasmic sperm injection with subsequent transfer of one or two embryos.
Results: Overall, egg maturation was observed in 96% (51/53) of patients. Fertilisation of eggs and transfer of embryos to the uterus occurred in 92% (49/53) of patients. Biochemical and clinical pregnancy rates were 40% (21/53) and 23% (12/53), respectively.
Conclusion: This study demonstrates that a single injection of kisspeptin-54 can induce high rates of egg maturation in women with sub-fertility undergoing in vitro fertilisation therapy. Subsequent fertilisation of eggs matured following kisspeptin-54 administration and transfer of resulting embryos can lead to successful human pregnancy.
Trial registration: ClinicalTrials.gov NCT01667406
Version
Open Access
Date Issued
2015-02
Date Awarded
2015-07
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Dhillo, Waljit
Publisher Department
Medicine
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)