title: Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy.
abstract: BACKGROUND
  In vitro fertilization (IVF) treatment is an effective therapy for infertility, but can result in the potentially life-threatening complication, ovarian hyperstimulation syndrome (OHSS).
  
  
  OBJECTIVE
  This study aimed to investigate whether kisspeptin-54 can be used to effectively and safely trigger oocyte maturation in women undergoing IVF treatment at high risk of developing OHSS.
  
  
  METHODS
  This was a phase 2, multi-dose, open-label, randomized clinical trial of 60 women at high risk of developing OHSS carried out during 2013-2014 at Hammersmith Hospital IVF unit, London, United Kingdom.
  
  
  METHODS
  Following a standard recombinant FSH/GnRH antagonist protocol, patients were randomly assigned to receive a single injection of kisspeptin-54 to trigger oocyte maturation using an adaptive design for dose allocation (3.2 nmol/kg, n = 5; 6.4 nmol/kg, n = 20; 9.6 nmol/kg, n = 15; 12.8 nmol/kg, n = 20). Oocytes were retrieved 36 h after kisspeptin-54 administration, assessed for maturation, and fertilized by intracytoplasmic sperm injection with subsequent transfer of one or two embryos. Women were routinely screened for the development of OHSS.
  
  
  METHODS
  Oocyte maturation was measured by oocyte yield (percentage of mature oocytes retrieved from follicles ≥ 14 mm on ultrasound). Secondary outcomes include rates of OHSS and pregnancy.
  
  
  RESULTS
  Oocyte maturation occurred in 95% of women. Highest oocyte yield (121%) was observed following 12.8 nmol/kg kisspeptin-54, which was +69% (confidence interval, -16-153%) greater than following 3.2 nmol/kg. At all doses of kisspeptin-54, biochemical pregnancy, clinical pregnancy, and live birth rates per transfer (n = 51) were 63, 53, and 45%, respectively. Highest pregnancy rates were observed following 9.6 nmol/kg kisspeptin-54 (85, 77, and 62%, respectively). No woman developed moderate, severe, or critical OHSS.
  
  
  CONCLUSIONS
  Kisspeptin-54 is a promising approach to effectively and safely trigger oocyte maturation in women undergoing IVF treatment at high risk of developing OHSS.
authors.affiliation: Department of Investigative Medicine (A.A., C.N.J., S.N., C.I.-E., G.M.K.N., A.N.C., D.P., A.B., R.R., J.K.P., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London, W12 0NN, United Kingdom; IVF Unit (G.C., R.S., S.A.L., G.H.T.), Hammersmith Hospital, London, W12 0HS, United Kingdom; and Imperial Clinical Trials Unit (M.S., D.A.A.), Imperial College London, St Mary's Hospital, Norfolk Pl, London, W2 1PG, United Kingdom.
authors.forename: Ali
authors.initials: A
authors.lastname: Abbara
authors.affiliation: Department of Investigative Medicine (A.A., C.N.J., S.N., C.I.-E., G.M.K.N., A.N.C., D.P., A.B., R.R., J.K.P., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London, W12 0NN, United Kingdom; IVF Unit (G.C., R.S., S.A.L., G.H.T.), Hammersmith Hospital, London, W12 0HS, United Kingdom; and Imperial Clinical Trials Unit (M.S., D.A.A.), Imperial College London, St Mary's Hospital, Norfolk Pl, London, W2 1PG, United Kingdom.
authors.forename: Channa N
authors.initials: CN
authors.lastname: Jayasena
authors.affiliation: Department of Investigative Medicine (A.A., C.N.J., S.N., C.I.-E., G.M.K.N., A.N.C., D.P., A.B., R.R., J.K.P., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London, W12 0NN, United Kingdom; IVF Unit (G.C., R.S., S.A.L., G.H.T.), Hammersmith Hospital, London, W12 0HS, United Kingdom; and Imperial Clinical Trials Unit (M.S., D.A.A.), Imperial College London, St Mary's Hospital, Norfolk Pl, London, W2 1PG, United Kingdom.
authors.forename: Georgios
authors.initials: G
authors.lastname: Christopoulos
authors.affiliation: Department of Investigative Medicine (A.A., C.N.J., S.N., C.I.-E., G.M.K.N., A.N.C., D.P., A.B., R.R., J.K.P., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London, W12 0NN, United Kingdom; IVF Unit (G.C., R.S., S.A.L., G.H.T.), Hammersmith Hospital, London, W12 0HS, United Kingdom; and Imperial Clinical Trials Unit (M.S., D.A.A.), Imperial College London, St Mary's Hospital, Norfolk Pl, London, W2 1PG, United Kingdom.
authors.forename: Shakunthala
authors.initials: S
authors.lastname: Narayanaswamy
authors.affiliation: Department of Investigative Medicine (A.A., C.N.J., S.N., C.I.-E., G.M.K.N., A.N.C., D.P., A.B., R.R., J.K.P., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London, W12 0NN, United Kingdom; IVF Unit (G.C., R.S., S.A.L., G.H.T.), Hammersmith Hospital, London, W12 0HS, United Kingdom; and Imperial Clinical Trials Unit (M.S., D.A.A.), Imperial College London, St Mary's Hospital, Norfolk Pl, London, W2 1PG, United Kingdom.
authors.forename: Chioma
authors.initials: C
authors.lastname: Izzi-Engbeaya
authors.affiliation: Department of Investigative Medicine (A.A., C.N.J., S.N., C.I.-E., G.M.K.N., A.N.C., D.P., A.B., R.R., J.K.P., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London, W12 0NN, United Kingdom; IVF Unit (G.C., R.S., S.A.L., G.H.T.), Hammersmith Hospital, London, W12 0HS, United Kingdom; and Imperial Clinical Trials Unit (M.S., D.A.A.), Imperial College London, St Mary's Hospital, Norfolk Pl, London, W2 1PG, United Kingdom.
authors.forename: Gurjinder M K
authors.initials: GM
authors.lastname: Nijher
authors.affiliation: Department of Investigative Medicine (A.A., C.N.J., S.N., C.I.-E., G.M.K.N., A.N.C., D.P., A.B., R.R., J.K.P., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London, W12 0NN, United Kingdom; IVF Unit (G.C., R.S., S.A.L., G.H.T.), Hammersmith Hospital, London, W12 0HS, United Kingdom; and Imperial Clinical Trials Unit (M.S., D.A.A.), Imperial College London, St Mary's Hospital, Norfolk Pl, London, W2 1PG, United Kingdom.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Comninos
authors.affiliation: Department of Investigative Medicine (A.A., C.N.J., S.N., C.I.-E., G.M.K.N., A.N.C., D.P., A.B., R.R., J.K.P., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London, W12 0NN, United Kingdom; IVF Unit (G.C., R.S., S.A.L., G.H.T.), Hammersmith Hospital, London, W12 0HS, United Kingdom; and Imperial Clinical Trials Unit (M.S., D.A.A.), Imperial College London, St Mary's Hospital, Norfolk Pl, London, W2 1PG, United Kingdom.
authors.forename: Deborah
authors.initials: D
authors.lastname: Peters
authors.affiliation: Department of Investigative Medicine (A.A., C.N.J., S.N., C.I.-E., G.M.K.N., A.N.C., D.P., A.B., R.R., J.K.P., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London, W12 0NN, United Kingdom; IVF Unit (G.C., R.S., S.A.L., G.H.T.), Hammersmith Hospital, London, W12 0HS, United Kingdom; and Imperial Clinical Trials Unit (M.S., D.A.A.), Imperial College London, St Mary's Hospital, Norfolk Pl, London, W2 1PG, United Kingdom.
authors.forename: Adam
authors.initials: A
authors.lastname: Buckley
authors.affiliation: Department of Investigative Medicine (A.A., C.N.J., S.N., C.I.-E., G.M.K.N., A.N.C., D.P., A.B., R.R., J.K.P., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London, W12 0NN, United Kingdom; IVF Unit (G.C., R.S., S.A.L., G.H.T.), Hammersmith Hospital, London, W12 0HS, United Kingdom; and Imperial Clinical Trials Unit (M.S., D.A.A.), Imperial College London, St Mary's Hospital, Norfolk Pl, London, W2 1PG, United Kingdom.
authors.forename: Risheka
authors.initials: R
authors.lastname: Ratnasabapathy
authors.affiliation: Department of Investigative Medicine (A.A., C.N.J., S.N., C.I.-E., G.M.K.N., A.N.C., D.P., A.B., R.R., J.K.P., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London, W12 0NN, United Kingdom; IVF Unit (G.C., R.S., S.A.L., G.H.T.), Hammersmith Hospital, London, W12 0HS, United Kingdom; and Imperial Clinical Trials Unit (M.S., D.A.A.), Imperial College London, St Mary's Hospital, Norfolk Pl, London, W2 1PG, United Kingdom.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Prague
authors.affiliation: Department of Investigative Medicine (A.A., C.N.J., S.N., C.I.-E., G.M.K.N., A.N.C., D.P., A.B., R.R., J.K.P., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London, W12 0NN, United Kingdom; IVF Unit (G.C., R.S., S.A.L., G.H.T.), Hammersmith Hospital, London, W12 0HS, United Kingdom; and Imperial Clinical Trials Unit (M.S., D.A.A.), Imperial College London, St Mary's Hospital, Norfolk Pl, London, W2 1PG, United Kingdom.
authors.forename: Rehan
authors.initials: R
authors.lastname: Salim
authors.affiliation: Department of Investigative Medicine (A.A., C.N.J., S.N., C.I.-E., G.M.K.N., A.N.C., D.P., A.B., R.R., J.K.P., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London, W12 0NN, United Kingdom; IVF Unit (G.C., R.S., S.A.L., G.H.T.), Hammersmith Hospital, London, W12 0HS, United Kingdom; and Imperial Clinical Trials Unit (M.S., D.A.A.), Imperial College London, St Mary's Hospital, Norfolk Pl, London, W2 1PG, United Kingdom.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Lavery
authors.affiliation: Department of Investigative Medicine (A.A., C.N.J., S.N., C.I.-E., G.M.K.N., A.N.C., D.P., A.B., R.R., J.K.P., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London, W12 0NN, United Kingdom; IVF Unit (G.C., R.S., S.A.L., G.H.T.), Hammersmith Hospital, London, W12 0HS, United Kingdom; and Imperial Clinical Trials Unit (M.S., D.A.A.), Imperial College London, St Mary's Hospital, Norfolk Pl, London, W2 1PG, United Kingdom.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
authors.affiliation: Department of Investigative Medicine (A.A., C.N.J., S.N., C.I.-E., G.M.K.N., A.N.C., D.P., A.B., R.R., J.K.P., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London, W12 0NN, United Kingdom; IVF Unit (G.C., R.S., S.A.L., G.H.T.), Hammersmith Hospital, London, W12 0HS, United Kingdom; and Imperial Clinical Trials Unit (M.S., D.A.A.), Imperial College London, St Mary's Hospital, Norfolk Pl, London, W2 1PG, United Kingdom.
authors.forename: Matyas
authors.initials: M
authors.lastname: Szigeti
authors.affiliation: Department of Investigative Medicine (A.A., C.N.J., S.N., C.I.-E., G.M.K.N., A.N.C., D.P., A.B., R.R., J.K.P., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London, W12 0NN, United Kingdom; IVF Unit (G.C., R.S., S.A.L., G.H.T.), Hammersmith Hospital, London, W12 0HS, United Kingdom; and Imperial Clinical Trials Unit (M.S., D.A.A.), Imperial College London, St Mary's Hospital, Norfolk Pl, London, W2 1PG, United Kingdom.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Ashby
authors.affiliation: Department of Investigative Medicine (A.A., C.N.J., S.N., C.I.-E., G.M.K.N., A.N.C., D.P., A.B., R.R., J.K.P., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London, W12 0NN, United Kingdom; IVF Unit (G.C., R.S., S.A.L., G.H.T.), Hammersmith Hospital, London, W12 0HS, United Kingdom; and Imperial Clinical Trials Unit (M.S., D.A.A.), Imperial College London, St Mary's Hospital, Norfolk Pl, London, W2 1PG, United Kingdom.
authors.forename: Geoffrey H
authors.initials: GH
authors.lastname: Trew
authors.affiliation: Department of Investigative Medicine (A.A., C.N.J., S.N., C.I.-E., G.M.K.N., A.N.C., D.P., A.B., R.R., J.K.P., S.R.B., W.S.D.), Imperial College London, Hammersmith Hospital, London, W12 0NN, United Kingdom; IVF Unit (G.C., R.S., S.A.L., G.H.T.), Hammersmith Hospital, London, W12 0HS, United Kingdom; and Imperial Clinical Trials Unit (M.S., D.A.A.), Imperial College London, St Mary's Hospital, Norfolk Pl, London, W2 1PG, United Kingdom.
authors.forename: Waljit S
authors.initials: WS
authors.lastname: Dhillo
mesh_terms: D000328:Adult; D004359:Drug Therapy, Combination; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods; D005640:Follicle Stimulating Hormone / Q000009:adverse effects / Q000627:therapeutic use; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D006727:Hormone Antagonists / Q000627:therapeutic use; D006801:Humans; D007247:Infertility, Female / Q000628:therapy*; D059648:Kisspeptins / Q000627:therapeutic use*; D016471:Ovarian Hyperstimulation Syndrome / Q000139:chemically induced / Q000517:prevention & control*; D010062:Ovulation Induction / Q000379:methods*; D011247:Pregnancy; D012307:Risk Factors
chemical_list: D006727:Hormone Antagonists; C106628:KISS1 protein, human; D059648:Kisspeptins; D007987:Gonadotropin-Releasing Hormone; D005640:Follicle Stimulating Hormone