Background: In vitro fertilisation is an effective therapy for infertility, but can result in the potentially life-threatening complication, Ovarian Hyper-Stimulation Syndrome (OHSS). We have previously reported that a single injection of kisspeptin results in an LH surge of ~1214 hrs duration, sufficient to safely induce oocyte maturation, but eliminate OHSS. However, the physiological LH surge in a normal menstrual cycle has a plateaux lasting 2428 hrs. Thus, we hypothesised that by administering a second dose of kisspeptin to women with infertility during IVF treatment, the duration of LH-exposure will more closely mimic the physiological LH-surge and hence optimise oocyte yield and pregnancy rates.
Methods: We conducted a phase2 single-blinded randomised placebo-controlled trial of 58 women at high risk of OHSS at Hammersmith IVF unit. Following a standard recombinant FSH/GnRH-antagonist IVF protocol, all patients received a subcutaneous injection of kisspeptin at 9.6 nmol/kg 36 hrs prior to egg retrieval. Patients were then randomised 1:1 to receive either a second dose of kisspeptin 10 hrs later (D; Double), or saline placebo (S; Single). IVF physicians, embryologists and participants were blinded to the randomisation. Retrieved eggs were assessed for maturation, fertilised by ICSI, with subsequent transfer of 12 embryos.
Outcome Measures: 1. Serum LH levels
2. Oocyte Yield (%mature eggs retrieved from follicles ≧14 mm).
3. Implantation rates
4. OHSS occurrence
Results: A double dose of kisspeptin resulted in:
1. Further rise in LH-secretion (mean change in LH at 4 hrs post-second injection (S:−12.1 iU/L, D:+4.0 iU/L; P<0.0001).
2. Optimal oocyte yield (≥60%) in more patients (S:45%, D:72%).
3. Improved implantation rate (S:25%, D:38%).
4. No moderate or severe OHSS.
Conclusion: Two doses of kisspeptin administered to women with infertility during IVF treatment induces a more physiological LH-surge, improves oocyte yield and implantation rates, without OHSS. These findings identify kisspeptin as a safe and highly effective trigger for oocyte maturation in young women suffering with infertility undergoing IVF treatment.
07 Nov 2016 - 09 Nov 2016