Induction of Multiple Follicular Development by a Single Dose of Long-Acting Recombinant Follicle-Stimulating Hormone (FSH-CTP, Corifollitropin Alfa) for Controlled Ovarian Stimulation before in Vitro Fertilization

• Published in: The journal of clinical endocrinology and metabolism Vol. 89; no. 5; pp. 2062 - 2070
• Main Authors: Devroey, P., Fauser, B. C., Platteau, P., Beckers, N. G., Dhont, M., Mannaerts, B. M.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01-05-2004; Copyright by The Endocrine Society
• Subjects: Adult; Biological and medical sciences; Drug Administration Schedule; Endocrinopathies; Feeding. Feeding behavior; Female; Fertilization in Vitro; Follicle Stimulating Hormone, Human - administration & dosage; Follicle Stimulating Hormone, Human - adverse effects; Follicle Stimulating Hormone, Human - blood; Follicle Stimulating Hormone, Human - therapeutic use; Follicular Phase - blood; Fundamental and applied biological sciences. Psychology; Hormones - blood; Humans; Luteal Phase - blood; Luteinizing Hormone - blood; Medical sciences; Ovarian Follicle - physiology; Ovulation Induction - methods; Pregnancy; Pregnancy Rate; Recombinant Proteins - administration & dosage; Recombinant Proteins - adverse effects; Recombinant Proteins - blood; Recombinant Proteins - therapeutic use; Treatment Outcome; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Multiple; Nutrition; Induction; Single dose; Corifollitropin alfa; Assisted procreation; Metabolic diseases; Stimulation; Gonadotropin; In vitro fertilization embryo transfer; Ovary; Adenohypophyseal hormone; Female genital system; Recombinant protein; Triggering; Ovarian follicle; Endocrinology; Follicle stimulating hormone
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2003-031766

In a first feasibility study, the efficacy and safety of a single dose of recombinant long-acting FSH (FSH-CTP) were investigated in in vitro fertilization (IVF) patients undergoing controlled ovarian stimulation with a flexible GnRH antagonist protocol. Eligible subjects were randomized to receive a single dose of 120 μg (n = 25), 180 μg (n = 24), or 240 μg (n = 25) corifollitropin alfa (FSH-CTP) or to start daily fixed doses of 150 IU recombinant FSH (rFSH) (n = 24, reference). Subjects who received a single dose of FSH-CTP continued 1 wk after injection (treatment d 8) with fixed daily doses of 150 IU rFSH (Puregon/Follistim) until the day of triggering final oocyte maturation.
The terminal half-life of FSH-CTP was, on average, 65 h and dose independent. Cycle cancellation before human chorionic gonadotropin (hCG) administration occurred in only three subjects treated with FSH-CTP. The median duration of stimulation was 10.0 d in each FSH-CTP group and 9.0 d in the daily rFSH group. The total number of follicles at least 11 mm at stimulation d 8 and at the day of hCG administration tended to increase with dose of FSH-CTP, although a significant dose-response relationship was revealed only for the number of follicles at least 15 mm on the day of hCG (P = 0.03). Serum estradiol levels and inhibin-B levels were not significantly different between the four groups on d 8 and on the day of hCG. In total, 12 subjects (17.6%) in the FSH-CTP groups and two subjects (8.3%) in the rFSH group experienced a premature LH rise (defined as LH ≥ 10 IU/liter) before the start of the GnRH antagonist (P value not significant between groups). This relatively high incidence of women demonstrating an early LH rise in the FSH-CTP groups may be related to the higher initial rises of serum estradiol and the use of a flexible GnRH antagonist protocol. The mean number of oocytes recovered per started cycle was higher in FSH-CTP-treated subjects compared with rFSH-treated subjects (significant at P = 0.03 for the 240-μg FSH-CTP group), but no difference could be noted between the number of good quality embryos (range of means, 3.8–4.8 per attempt), and equal numbers of embryos were available for embryo transfer. In summary, FSH-CTP appeared to be a potent inducer of multiple follicular growth; additional research will be needed to select the optimal FSH-CTP dose and treatment time interval.