Figure 2.

IVF study protocol using kisspeptin-54 to trigger oocyte maturation. The timeline shows the day of menstrual cycle for a typical patient. On day 2 or 3 of the menstrual cycle, daily sc recombinant FSH (Gonal F, 112.5 IU) was commenced. Daily GnRH antagonist injections (cetrotide, 0.25 mg) were commenced after 5 d of recombinant FSH injections. If serum LH was undetectable (< 0.5 IU/L) on day 7 of recombinant FSH injections, the dose of cetrotide was halved to 0.125 mg daily. When at least three ovarian follicles ≥18 mm diameters were visible on ultrasound, a sc bolus injection of kisspeptin-54 (3.2, 6.4, 9.6, or 12.8 nmol/kg) was administered to trigger oocyte maturation (between 2030 and 2300 h). Injections of GnRH antagonist and FSH were stopped 24 and 12 h prior to kisspeptin administration, respectively. Transvaginal ultrasound-directed oocyte retrieval (TVOR) was carried out 36 h following kisspeptin-54 injection, and ICSI was performed using fresh sperm from the male partner. One or two embryos were transferred to the uterine cavity 3–5 d following oocyte retrieval. If pregnancy was confirmed, progesterone and estradiol supplementation were provided for luteal phase support until 12 weeks' gestation. Progesterone 100 mg daily im injections (Gestone, Nordic Pharma) were used from the morning following oocyte retrieval until 6 weeks' gestation, then 400 mg twice daily progesterone suppository/pessary (Cyclogest; Actavis) was continued until 12 weeks' gestation. Estradiol valerate 2 mg orally three times daily (Progynova; Bayer) was commenced from the evening of TVOR until 12 weeks' gestation. All women recruited to the study were regarded as being at high risk of OHSS and were routinely screened for the development of early OHSS (assessed on day of embryo transfer 3–5 d after TVOR) and late OHSS (assessed 11 d after embryo transfer). Biochemical pregnancy (serum βHCG > 10 miU/mL) was assessed 11 d following embryo transfer and clinical pregnancy was assessed by ultrasonography at 6 weeks' gestation.