Kisspeptin – a novel physiological trigger for oocyte maturation in IVF treatment.
Ali Abbara, Channa N. Jayasena, Alexander N. Comninos, Gurjinder M.K. Nijher, Georgios Christopoulos, Shakunthala Narayanaswamy, Chioma Izzi-Engbeaya, Mathini Sridharan, Alexina Mason, Jane Warwick, Deborah Ashby, Mohammad A. Ghatei, Stephen R. Bloom, Anna Carby, Geoffrey Trew & Waljit S. Dhillo.
Abstract: In vitro fertilisation (IVF) treatment is an effective treatment for infertility, but can be associated with the potentially life-threatening complication known as the ovarian hyperstimulation syndrome (OHSS)1,2. The major cause of OHSS is the pharmacological use of human chorionic gonadotrophin (hCG) to initiate oocyte maturation during IVF therapy. Developing a more physiological stimulus for oocyte maturation may avoid this dangerous side effect and thereby improve 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 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: Fifty-three women underwent a modified FSH/GnRH antagonist IVF protocol using kisspeptin in place of hCG to trigger oocyte maturation. Subcutaneous daily injections of FSH (Gonal F 150iu) were started from menstrual day 2, and GnRH antagonist (Cetrotide 0.25mg) was used to prevent a premature LH surge. A subcutaneous bolus of kisspeptin-54 (Dose: 1.6-3.2 (n=5), 6.4 (n=24) or 12.8nmol/kg (n=24) 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: Serum LH was increased 9.0-fold at 12 hours following kisspeptin injection, when compared with serum LH immediately prior to kisspeptin injection. Oocyte maturation (defined as at least one mature oocyte) was observed at all doses of kisspeptin: 96% (51/53) of patients, with a mean of 7.9±3.9 MII oocytes/cycle. Fertilisation occurred in 92% (49/53) of cases, with a mean of 5.6±3.5 zygotes/cycle. Biochemical and clinical pregnancy rates were 40% (21/53) and 23% (12/53), respectively. Ten women have given birth to healthy babies including two sets of twins.
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.
References: 1. Tang T et al. Nat Rev Endocrinol. 2009 5(8):462-5. 2. Golan A et al. bstet Gynecol Surv. 1989 44(6):430-40. 3. Dhillo WS et al. J Clin Endocrinol Metab. 2007; 92(10):3958-66.