Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization.


Jayasena, CN; Abbara, A; Comninos, AN; Nijher, GM; Christopoulos, G; Narayanaswamy, S; Izzi-Engbeaya, C; Sridharan, M; Mason, AJ; Warwick, J; Ashby, D; Ghatei, MA; Bloom, SR; Carby, A; Trew, GH; Dhillo, WS; (2014) Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization. The Journal of clinical investigation, 124 (8). pp. 3667-77. ISSN 0021-9738 DOI: 10.1172/JCI75730

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Abstract

BACKGROUND Patients with mutations that inactivate kisspeptin signaling 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 generation of the luteinizing hormone surge, which is required for ovulation; therefore, we hypothesized that kisspeptin-54 could be used to trigger egg maturation in women undergoing in vitro fertilization therapy. METHODS Following superovulation with recombinant follicle-stimulating hormone and administration of gonadotropin-releasing hormone antagonist to prevent premature ovulation, 53 women were administered a single subcutaneous injection of kisspeptin-54 (1.6 nmol/kg, n = 2; 3.2 nmol/kg, n = 3; 6.4 nmol/kg, n = 24; 12.8 nmol/kg, n = 24) to induce a luteinizing hormone surge and egg maturation. Eggs were retrieved transvaginally 36 hours after kisspeptin injection, assessed for maturation (primary outcome), and fertilized by intracytoplasmic sperm injection with subsequent transfer of one or two embryos. RESULTS Egg maturation was observed in response to each tested dose of kisspeptin-54, and the mean number of mature eggs per patient generally increased in a dose-dependent manner. Fertilization of eggs and transfer of embryos to the uterus occurred in 92% (49/53) of kisspeptin-54-treated 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 egg maturation in women with subfertility undergoing in vitro fertilization therapy. Subsequent fertilization of eggs matured following kisspeptin-54 administration and transfer of resulting embryos can lead to successful human pregnancy. TRIAL REGISTRATION ClinicalTrials.gov NCT01667406.

Item Type: Article
Faculty and Department: Faculty of Public Health and Policy > Dept of Health Services Research and Policy
PubMed ID: 25036713
Web of Science ID: 339984000038
URI: http://researchonline.lshtm.ac.uk/id/eprint/2025489

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