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Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization
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Jayasena, Channa N., Abbara, Ali, Comninos, Alexander N., Nijher, Gurjinder M.K., Christopoulos, Georgios, Narayanaswamy, Shakunthala, Izzi-Engbeaya, Chioma, Sridharan, Mathini, Mason, Alexina J., Warwick, Jane, Ashby, Deborah, Ghatei, Mohammad A., Bloom, Stephen R., Carby, Anna, Trew, Geoffrey H. and Dhillo, Waljit S. (2014) Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization. Journal of Clinical Investigation, Volume 124 (Number 8). pp. 3667-3677. doi:10.1172/JCI75730 ISSN 0021-9738.
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Official URL: http://dx.doi.org/10.1172/JCI75730
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.
Item Type: | Journal Article | ||||||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Clinical Trials Unit Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Journal or Publication Title: | Journal of Clinical Investigation | ||||||||||
Publisher: | American Society for Clinical Investigation | ||||||||||
ISSN: | 0021-9738 | ||||||||||
Official Date: | 1 August 2014 | ||||||||||
Dates: |
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Volume: | Volume 124 | ||||||||||
Number: | Number 8 | ||||||||||
Page Range: | pp. 3667-3677 | ||||||||||
DOI: | 10.1172/JCI75730 | ||||||||||
Status: | Peer Reviewed | ||||||||||
Publication Status: | Published | ||||||||||
Access rights to Published version: | Open Access (Creative Commons) |
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