Human Reproduction, Vol 13, 3023-3031, Copyright © 1998 by Oxford University Press
A multicentre, double-blind, randomized dose-finding study of Org 37462
(ganirelix) was conducted in 333 women undergoing ovarian stimulation with
recombinant follicle stimulating hormone (rFSH; Puregon) to establish the
minimal effective dose preventing premature luteinizing hormone (LH) surges
during ovarian stimulation. For ovarian stimulation, rFSH was given in a
fixed daily dose of 150 IU for 5 days from days 2 to 6 of the menstrual
cycle. From cycle day 7 onward, up to and including the day of human
chorionic gonadotrophin (HCG), Org 37462 (dosages 0.0625, 0.125, 0.25, 0.5,
1.0 and 2.0 mg/0.5 ml) was administered once daily by s.c. injection, and
the rFSH dose was adjusted depending on ovarian response. The lowest
(0.0625 mg) and highest (2.0 mg) dose groups were terminated prematurely on
the advice of an external independent advisory committee. Serum Org 37462
concentrations increased in a linear dose-proportional manner, whereas
serum LH and increases of oestradiol fell with increasing Org 37462 dose.
During Org 37462 treatment, serum LH concentrations > or =10 IU/l were
observed in the lowest dose groups with incidences of 16% (0.0625 mg), 9%
(0.125 mg) and 1.4 % (0.25 mg). On the day of HCG, the number of follicles
> or =11, > or =15 and > or =17 mm were similar in the six dose
groups, whereas serum oestradiol concentrations were highest in the 0.0625
mg group (1475 pg/ml) and lowest in the 2 mg group (430 pg/ml). The median
daily dose of rFSH was between 150 and 183 IU and the overall median
duration of Org 37462 treatment was approximately 5 days in the six
treatment groups. Overall, Org 37462 treatment appeared to be safe and well
tolerated. The mean number of recovered oocytes and good-quality embryos
was similar in all dose groups and ranged from 8.6 to 10.0 and 2.5 to 3.8,
respectively. The mean number of replaced embryos in the different dose
groups ranged from 2.3 to 2.7. The implantation rate was highest in the
0.25 mg group (21.9%) and lowest in the 2 mg group (1.5%). The early
miscarriage rates (first 6 weeks after embryo transfer) were 11.9 and 13%
in the 1 and 2 mg group respectively, whereas in the other dose groups this
incidence was zero (0.0625%) up to a maximum of 3.7% (0.5 mg group). The
vital pregnancy rate (with heart activity) at 5-6 weeks after embryo
transfer was highest in the 0.25 mg group, i.e. 36.8 % per attempt and 40.3
% per transfer, and resulted in an ongoing pregnancy rate 12-16 weeks after
embryo transfer of 33.8% per attempt and 37.1% per transfer. In conclusion,
a daily dose of 0.25 mg Org 37462 prevented LH surges during ovarian
stimulation and resulted in a good clinical outcome.
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A double-blind, randomized, dose-finding study to assess the efficacy of the gonadotrophin-releasing hormone antagonist ganirelix (Org 37462) to prevent premature luteinizing hormone surges in women undergoing ovarian stimulation with recombinant follicle stimulating hormone (Puregon). The ganirelix dose-finding study group
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