Evaluation of kisspeptin-54 for egg maturation

In virto fertilization (IVF) has helped millions of couples have children. While considered relatively safe, there are risks associated with this procedure. Among the more serious complications is the development of ovarian hyperstimulation syndrome (OHSS), which in extreme cases can be fatal. OHSS results from excessive stimulation of the luteinizing hormone (LH) receptor by human chorionic gonadotropin (hCG), which is commonly used as part of the IVF cycle to promote egg maturation. In this episode, Waljit Dhillo discusses the results from a small clinical trial that evaluated use of the fertility hormone kisspeptin-54 for egg maturation in IVF. Dhillo and colleagues report that kisspeptin-54 treatment resulted in mature eggs that were successfully fertilized and transferred, with pregnancy in 23% of patients.

Published July 18, 2014, by The JCI

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Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization
Channa N. Jayasena, Ali Abbara, Alexander N. Comninos, Gurjinder M.K. Nijher, Georgios Christopoulos, Shakunthala Narayanaswamy, Chioma Izzi-Engbeaya, Mathini Sridharan, Alexina J. Mason, Jane Warwick, Deborah Ashby, Mohammad A. Ghatei, Stephen R. Bloom, Anna Carby, Geoffrey H. Trew, Waljit S. Dhillo
Channa N. Jayasena, Ali Abbara, Alexander N. Comninos, Gurjinder M.K. Nijher, Georgios Christopoulos, Shakunthala Narayanaswamy, Chioma Izzi-Engbeaya, Mathini Sridharan, Alexina J. Mason, Jane Warwick, Deborah Ashby, Mohammad A. Ghatei, Stephen R. Bloom, Anna Carby, Geoffrey H. Trew, Waljit S. Dhillo
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Clinical Research and Public Health

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

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.

FUNDING. Medical Research Council, Wellcome Trust, and National Institute for Health Research.

Authors

Channa N. Jayasena, Ali Abbara, Alexander N. Comninos, Gurjinder M.K. Nijher, Georgios Christopoulos, Shakunthala Narayanaswamy, Chioma Izzi-Engbeaya, Mathini Sridharan, Alexina J. Mason, Jane Warwick, Deborah Ashby, Mohammad A. Ghatei, Stephen R. Bloom, Anna Carby, Geoffrey H. Trew, Waljit S. Dhillo

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