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.
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 micro g (n = 25), 180 microg (n = 24), or 240 microg (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 >or= 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- microg 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.
Devroey
P
P
Center for Reproductive Medicine, Dutch-Speaking Brussels Free University, 1090 Brussels, Belgium.
Fauser
B C
BC
Platteau
P
P
Beckers
N G
NG
Dhont
M
M
Mannaerts
B M
BM
D000328:Adult; D004334:Drug Administration Schedule; D005260:Female; D005307:Fertilization in Vitro; D043373:Follicle Stimulating Hormone, Human / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D005498:Follicular Phase / Q000097:blood; D006728:Hormones / Q000097:blood; D006801:Humans; D008183:Luteal Phase / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D006080:Ovarian Follicle / Q000502:physiology*; D010062:Ovulation Induction / Q000379:methods*; D011247:Pregnancy; D018873:Pregnancy Rate; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D016896:Treatment Outcome
D043373:Follicle Stimulating Hormone, Human; D006728:Hormones; D011994:Recombinant Proteins; C437186:follicle stimulating hormone, human, with HCG C-terminal peptide; D007986:Luteinizing Hormone