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Endocrine Abstracts (2014) 34 OC1.5 | DOI: 10.1530/endoabs.34.OC1.5

1Section of Investigative Medicine, Imperial College London, London, UK; 2Hammersmith IVF Unit, Imperial College NHS Trust, London, UK; 3Clinical Trials Unit, Imperial College London, London, UK.

Background: IVF is an effective treatment for infertility, but can cause the ovarian hyper-stimulation syndrome (OHSS), which is associated with serous effusions, cardiac tamponade, circulatory collapse, and even death. Injection of human chorionic gonadotrophin (hCG) stimulates oocyte maturation during IVF, but is also the major cause of OHSS. The hypothalamic neuropeptide kisspeptin, stimulates endogenous LH secretion in a GnRH-dependent manner. A more physiological stimulus for oocyte maturation may avoid OHSS and thereby improve the safety of IVF treatment.

Aim: To determine if kisspeptin can induce oocyte maturation during IVF treatment.

Methods: Women underwent a modified recombinant FSH/GnRH antagonist IVF protocol, administering kisspeptin instead of hCG to trigger oocyte maturation. Daily recombinant FSH treatment commenced from menstrual day 2. GnRH-antagonist treatment was used to inhibit a premature LH surge. Once three follicles grew to ≥18 mm in diameter, a single s.c. bolus injection of kisspeptin (1.6–3.2 nmol/kg, n=5; 6.4 nmol/kg, n=21; 12.8 nmol/kg, n=21) was administered 24 h after the final GnRH-antagonist injection. Oocytes were retrieved 36 h after kisspeptin injection. Following ICSI, one to two embryos were transferred to the uterine cavity. Primary outcome was the number of mature oocytes (oocytes in metaphase II; MII).

Results: Forty-seven women completed the study. Kisspeptin increased serum LH 9.0±7.5-fold (mean±S.D.) 12 h following injection. Oocyte maturation was observed at all doses of kisspeptin: 96% (45/47) of women had oocyte maturation, with 7.9±4.1 MII oocytes/cycle. Fertilisation occurred in 91% (43/47) cases, with 5.7±3.5 zygotes/cycle. To date, clinical pregnancy has been confirmed on ultrasound at 6 weeks gestation in 10/44 (23%) patients receiving kisspeptin; two of these patients have already given birth to healthy baby boys.

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

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