Reduction of daily rFSH dose from stimulation day 8 onward in a corifollitropin alfa or rFSH treatment regimen does not compromise clinical outcome.

Introduction: A single dose of corifollitropin alfa given on cycle day 2 to 3 is a
new treatment option for in vitro fertilization (IVF) patients to initiate and sustain
the first 7 days of ovarian stimulation for IVF/intracytoplasmic sperm injection.
Peak follicle-stimulating hormone (FSH) activity is reached within 2 days
after corifollitropin alfa administration and then declines. Daily recombinant
FSH (rFSH) is started on stimulation day 8 to maintain FSH activity above the
threshold needed for multiple follicular development. The daily dose of rFSH to
complete the stimulation ranges between 0 and 200 IU depending on the ovarian
response observed on stimulation day 8. The current analysis investigates
whether, within either the corifollitropin alfa or the daily rFSH treatment regimen,
ongoing pregnancy rates are affected by reducing the daily dose of rFSH
from stimulation day 8 onward to accommodate the patient's follicular response.
Material and Methods: In a large, prospectively randomized double-blind, double-
placebo, multicenter trial (Engage), patients aged 18 to 36 years were treated
with either a single dose of 150 ?g corifollitropin alfa (Elonva, N.V. Organon)
(n = 756) or daily 200 IU rFSH (follitropin beta, Puregon Pen, N.V. Organon)
(n = 750) from day 2 to 3 of menses (stimulation day 1) for the first 7 days, followed
by daily rFSH ? 200 IU from stimulation day 8 onward. A gonadotropinreleasing
hormone antagonist (ganirelix, Orgalutran, N.V. Organon) was administered
from day 5 through to the day of human chorionic gonadotrophin (hCG)
administration; hCG was administered when ? 3 follicles reached ? 17 mm, or
the next day. Depending on the ovarian response on stimulation day 8, investigators
could give patients either a fixed daily dose of 200 IU rFSH or a reduced
dose in an effort to reduce the risk of severe ovarian hyperstimulation syndrome.
This analysis excludes patients who received hCG on or prior to stimulation day
8 and excludes patients who were coasted from stimulation day 8 (i.e. withholding
rFSH dose for one or more days excluding the day of hCG).
Results: In the corifollitropin alfa arm, 74.8% of patients (n = 409), and in the
rFSH arm, 84.5% of patients (n = 430) received daily 200 IU rFSH from stimulation
day 8 onward. In total 25.2% (n = 138) of patients in the corifollitropin
alfa arm and 15.5% (n = 79) in the rFSH arm received a reduced rFSH dose.
Compared with patients who received a fixed 200 IU rFSH dose, patients treated
with corifollitropin alfa and a reduced rFSH dose had higher serum estradiol
levels (7854 vs 4129 pmol/L) and more follicles ? 11 mm on the day of hCG
(20.5 ± 5.3 vs 14.1 ± 6.2) as well as more oocytes (19.3 ± 7.9 vs 12.4 ± 7.4).
These parameters were similarly elevated for patients in the rFSH treatment
arm who received a reduced daily rFSH dose from stimulation day 8 onward
(estradiol levels on the day of hCG, 7212 vs 4239 pmol/L; follicles ? 11 mm on
the day of hCG, 18.0 ± 6.1 vs 12.6 ± 5.3, and oocytes, 16.3 ± 6.2 vs 11.7 ± 6.3).
With rFSH step-down vs fixed rFSH, the numbers of good-quality embryos 3
days after oocyte pickup were 6.5 ± 5.7 vs 4.0 ± 3.8, respectively, in the corifollitropin
alfa arm and 5.5 ± 4.4 vs 4.2 ± 3.7 in the rFSH arm. The ongoing pregnancy
rates were similar in patients who received a reduced rFSH dose and in
those who received a fixed dose of 200 IU rFSH in both the corifollitropin alfa
arm (37.0% vs 40.6%) (P = 0.45) and rFSH arm (31.6% vs 40.7%) (P = 0.13).
Conclusions: Reducing the daily dose of rFSH from stimulation day 8 onward
in a corifollitropin alfa or rFSH treatment regimen offers the flexibility to individualize
care and does not compromise ongoing pregnancy rates.
Support: Financial support for this study was provided by Merck.

Jaar van publicatie:2011

Trefwoorden:corifollitropin alfa