Does treatment flexibility affect clinical outcome of either corifollitropin alfa or daily rFSH regimens?

Introduction: Corifollitropin alfa is a new treatment option for patients undergoing
in vitro fertilization (IVF). A single injection of corifollitropin alfa replaces
daily injections of recombinant follicle-stimulating hormone (rFSH) for the first 7
days of ovarian stimulation. This new treatment regimen has the same flexibility
in terms of the start of stimulation, the daily dose of rFSH from stimulation day 8
onward, and the day of human chorionic gonadotrophin (hCG) administration as
any other ovarian stimulation protocol. This treatment flexibility was allowed during
a large controlled phase 3 trial (Engage) of corifollitropin alfa to facilitate the
logistics of patient treatment and to prevent assessments or oocyte pick-up at the
weekend. Here we evaluate the impact these variables had on clinical outcomes.
Material and Methods: In a large, double-blind, double-dummy, randomized,
multicenter trial, patients 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 or 3 of
menses (stimulation day 1) for the first 7 days, followed by daily rFSH ? 200
IU from stimulation day 8 onward, depending on the follicular response. A gonadotropin-
releasing hormone (GnRH) antagonist (ganirelix, Orgalutran, N.V.
Organon) was administered from stimulation day 5 until ? 3 follicles ? 17 mm
were observed by ultrasound; hCG was either administered the same day or the
next day. Efficacy parameters were analyzed for (1) patients who started stimulation
on cycle day 2 vs on cycle day 3; (2) patients who received rFSH on the
day of hCG vs those who did not; and (3) patients who reached the criteria for
triggering oocyte maturation and received hCG the same day vs the next day.
Results: There were no significant differences in the duration of stimulation,
the ovarian response, the number or quality of embryos or the ongoing pregnancy
rates (PRs) among patients compared in each of the 3 analyses, either in the
corifollitropin alfa arm or in the rFSH treatment arm. (1) Patients who started
treatment on cycle day 2 as compared to cycle day 3 had in the corifollitropin
alfa arm 14.1 ± 8.1 oocytes (n = 350) vs 14.1 ± 7.9 oocytes (n = 376), respectively,
and in the rFSH arm 12.8 ± 6.6 oocytes (n = 360) vs 12.5 ± 6.6 oocytes
(n = 376). Ongoing PRs were respectively 37.3% vs 42.8% in the corifollitropin
alfa arm and 35.0% vs 42.6% in the rFSH arm. (2) Patients who received rFSH
on the day of hCG vs those who did not, had on average 13.6 ± 7.8 oocytes (n = 473) vs 15.1 ± 8.2 oocytes (n = 260) respectively in the corifollitropin alfa
arm and 12.6 ± 6.7 (n = 469) vs 12.8 ± 6.6 (n = 272) in the rFSH arm. Ongoing
PRs were respectively 42.5% vs 35.8% in the corifollitropin alfa arm and
39.9% vs 36.4% in the rFSH arm. (3) The number of oocytes were 14.1 ± 8.2
(n = 503) for patients who received hCG when the criteria were reached vs
14.5 ± 7.1 (n = 211) for patients with 1-day delay of hCG administration in
the corifollitropin alfa arm, and these figures were 12.5 ± 6.7 (n = 524) vs
13.4 ± 6.5 (n = 209) in the rFSH arm. The PRs were respectively 40.0% vs
39.3% in the corifollitropin alfa arm and 37.8% vs 41.6% in the rFSH arm.
Conclusions: Treatment flexibility at the start or completion of ovarian stimulation
does not largely affect clinical outcome either in patients treated with
corifollitropin alfa or with daily rFSH using a GnRH antagonist protocol.
Support: Financial support for this study was provided by Merck.

Publication year:2011

Keywords:corifollitropin alfa, rFSH