Background: Kisspeptin is an endogenous neuropeptide that regulates GnRH release from the hypothalamus. Kisspeptin-54 has been shown to effectively trigger oocyte maturation during in vitro fertilisation (IVF) treatment, but with markedly reduced rates of ovarian hyperstimulation syndrome (OHSS). The kisspeptin receptor agonist, MVT-602, has a longer half-life than native kisspeptin-54 (1.52.2 h vs. 0.5 h) and has potential for development as a novel trigger of oocyte maturation. LH concentrations following kisspeptin-54 are augmented during controlled ovarian stimulation (COS); thus we investigated the LH-profile of MVT-602 in the context of a minimal COS protocol.
Methods: A randomised, double-blind, placebo and active comparator-controlled, phase 2a study was conducted (May-October 2018). Seventy-five healthy women (aged <36 years, BMI 1830 kg/m2) underwent minimal COS (recombinant FSH / GnRH antagonist). Once the dominant follicle reached ≥17 mm, women were randomised to receive a single subcutaneous dose of MVT-602 (0.1, 0.3, 1.0 or 3.0 μg; n=16-17 per group), GnRH agonist triptorelin 0.2 mg (n=5), or placebo (n=5) in a 3:1:1 ratio. Hormone levels were monitored every 24 h for 48 h and then daily for 13 days, or until ovulation was confirmed.
Results: MVT-602 induced an LH surge that peaked at 1624 h to ˜50 IU/l and provided LH-exposure for more than 48 h. Doses of MVT-602 of 0.3 mcg or greater increased LH sooner and with greater consistency. The proportion of women who ovulated within 5 days of trigger administration increased with dose of MVT-602 (Placebo 60%, 0.1 μg 75%, 0.3 μg 82%, 1 μg 88%, 3 μg 100%). LH-rise after GnRH agonist was more pronounced (peak LH >150 IU/l) and occurred sooner (˜4 h) than following MVT-602.
Conclusion: The LH-profile following MVT-602 more closely mirrored that of the natural mid-cycle LH surge providing LH-exposure for >48 h. Thus, MVT-602 could offer an advantageous profile in the triggering of oocyte maturation during IVF treatment.
Trial registration number: 2018-001379-20