FP36-3 KISSPEPTIN A NOVEL PHYSIOLOGICAL TRIGGER FOR OOCYTE MATURATION IN IVF TREATMENT

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP36-Ovarian & Uterine Function
Basic/Clinical
Monday, June 17, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 10:55 AM
Room 104 (Moscone Center)

Poster Board MON-572
Ali Abbara*1, Channa Nalin Jayasena1, Gurjinder M Nijher1, Alexander N Comninos1, Georgios Christopoulos2, Deborah Ashby3, Mohammad A Ghatei1, Stephen R Bloom1, Anna Carby4, Geoffray Trew5 and Waljit Singh Dhillo1
1Imperial College London, London, United Kingdom, 2IVF unit Hammersmith Hospital, London, United Kingdom, 3Clinical Trials Unit, Imperial College London, London, United Kingdom, 4IVF unit, Hammersmith Hospital, london, United Kingdom, 5IVF unit, Hammersmith Hospital, London, United Kingdom
In vitro fertilisation (IVF) treatment is an effective treatment for infertility but has potentially life threatening complications such as ovarian hyperstimulation syndrome (OHSS)1. The major cause of OHSS is the pharmacological use of human chorionic gonadotrophin (hCG) to stimulate oocyte maturation during IVF. Developing a more physiological stimulus for oocyte maturation would avoid this dangerous side effect, thereby improving the safety of IVF treatment. Kisspeptin is a recently identified hypothalamic hormone, which acutely and potently increases endogenous LH secretion in a GnRH-dependent manner. We have previously demonstrated that kisspeptin stimulates LH release most potently when administered to healthy women immediately prior to ovulation3. The effects of kisspeptin on oocyte maturation have not been investigated previously.

Aim: to determine if kisspeptin can effectively induce oocyte maturation in women undergoing IVF treatment.

Study design: 10 women underwent a modified FSH/GnRH antagonist IVF protocol using kisspeptin in place of hCG to trigger oocyte maturation. Subcutaneous (sc) daily injections of FSH (Gonal F 150iu) was started from menstrual day 2, and GnRH antagonist (Cetrotide 0.25mg; to inhibit a premature LH surge) was commenced when the lead follicle >14mm, and stopped when 3 ovarian follicles ≥18mm diameter had developed. Kisspeptin-54 (sc bolus 1.6, 3.2, 6.4 or 12.8nmol/kg, n=2-3/dose) was administered 24hrs after the last GnRH antagonist injection. Oocytes were retrieved 36hrs after kisspeptin injection. Following intracytoplasmic sperm injection (ICSI), 1 or 2 embryos were transferred to the uterine cavity. Primary outcome: number of mature oocytes (oocytes in metaphase II; MII).

Results: Kisspeptin resulted in a 7.1±1.9-fold (mean±SEM) increase in LH release 12h following injection. Oocyte maturation was observed at all doses of kisspeptin (9/10 women had oocyte maturation [mean±SEM number of MII oocytes 6.1±1.2]). Embryogenesis occurred in 8/10 women following kisspeptin (mean±SEM 2.8±0.74). Pregnancy data is awaited but to date 1 woman already has a successful ongoing pregnancy and is currently 27 weeks pregnant with a single foetus and no anomalies detected at the 20 week ultrasound scan.

Conclusion:  We show for the first time that kisspeptin can effectively induce oocyte maturation in IVF treatment. Kisspeptin may therefore offer an entirely novel therapeutic option for fertility treatment.

1. Tang T et al. Nat Rev Endocrinol. 2009 5(8):462-5. 2. Golan A et al. Obstet Gynecol Surv. 1989 44(6):430-40. 3. Dhillo WS et al. J Clin Endocrinol Metab. 2007; 92(10):3958-66.

Nothing to Disclose: AA, CNJ, GMN, ANC, GC, DA, MAG, SRB, AC, GT, WSD

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Medical Research Council UKNational Institute for Health Research Wellcome Trust