title: 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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01667406.
authors.forename: Channa N
authors.initials: CN
authors.lastname: Jayasena
authors.forename: Ali
authors.initials: A
authors.lastname: Abbara
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Comninos
authors.forename: Gurjinder M K
authors.initials: GM
authors.lastname: Nijher
authors.forename: Georgios
authors.initials: G
authors.lastname: Christopoulos
authors.forename: Shakunthala
authors.initials: S
authors.lastname: Narayanaswamy
authors.forename: Chioma
authors.initials: C
authors.lastname: Izzi-Engbeaya
authors.forename: Mathini
authors.initials: M
authors.lastname: Sridharan
authors.forename: Alexina J
authors.initials: AJ
authors.lastname: Mason
authors.forename: Jane
authors.initials: J
authors.lastname: Warwick
authors.forename: Deborah
authors.initials: D
authors.lastname: Ashby
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Ghatei
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
authors.forename: Anna
authors.initials: A
authors.lastname: Carby
authors.forename: Geoffrey H
authors.initials: GH
authors.lastname: Trew
authors.forename: Waljit S
authors.initials: WS
authors.lastname: Dhillo
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage; D005307:Fertilization in Vitro / Q000009:adverse effects / Q000379:methods*; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007246:Infertility / Q000503:physiopathology / Q000628:therapy; D059648:Kisspeptins / Q000008:administration & dosage* / Q000009:adverse effects / Q000502:physiology; D009865:Oocytes / Q000187:drug effects* / Q000254:growth & development*; D010060:Ovulation / Q000187:drug effects; D011247:Pregnancy; D011271:Pregnancy, Ectopic / Q000209:etiology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D005300:Fertility Agents, Female; C106628:KISS1 protein, human; D059648:Kisspeptins; D011994:Recombinant Proteins; D007987:Gonadotropin-Releasing Hormone; D005640:Follicle Stimulating Hormone; C062876:cetrorelix