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Endocrine Abstracts (2014) 35 OC9.4 | DOI: 10.1530/endoabs.35.OC9.4

1Imperial College London, London, UK; 2Hammersmith Hospital IVF unit, London, UK; 3Clinical Trials Unit, Imperial College London, London, UK.


Background: In vitro fertilisation (IVF) is an effective treatment for infertility, but can cause the ovarian hyper-stimulation syndrome (OHSS), which is associated with serous effusions, circulatory collapse, and even death. The use 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: Fifty-three women underwent a modified recombinant FSH/GnRH antagonist IVF protocol, using kisspeptin instead of hCG to trigger oocyte maturation. Daily recombinant FSH treatment was commenced from menstrual day 2. A GnRH-antagonist was used to inhibit a premature LH surge. A single subcutaneous injection of kisspeptin (1.6–3.2 nmol/kg, n=5; 6.4 nmol/kg, n=24; 12.8 nmol/kg, n=24) was administered to induce oocyte maturation. Oocytes were retrieved 36h after kisspeptin injection. Following intracytoplasmic sperm injection (ICSI), 1–2 embryos were transferred to the uterine cavity. Primary outcome was the number of mature oocytes (oocytes in metaphase II; MII).

Results: 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%(51/53), with 7.9±3.9 MII oocytes/cycle. Fertilisation occurred in 92%(49/53) cases, with 5.6±3.5 zygotes/cycle. Clinical pregnancy has been confirmed on ultrasound at 6 week gestation in 12/53(23%) patients receiving kisspeptin and to date 5 patients have already given birth to healthy babies.

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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