Assessment of corifollitropin alfa for assisted reproduction: a review study
4/23/2014 12:40:00 AM
Introduction:
Corifollitropin alfa, a fusion product of recombinant human
follicle-stimulating hormone (rFSH) with a hybrid beta subunit C-terminal
peptide of human chorionic gonadotropin, plays a similar pharmacologic role as
traditional rFSH, but with a longer half life.
Clinical applications of corifollitropin alfa in assisted reproductive realm
have reported that it stimulates multifollicular growth for 7 days with the
same safety and ovarian response as rFSH administration. In 2003, the first
report of live birth using corifollitropin alfa stimulation was released in
Netherland. In 2010, European union approved corifollitropin alfa in its
market, and then Taiwan approved the release of corifollitropin alfa in 2013. To
assess the outcomes of corifollitropin alfa in following embryo development of
IVF program, including fertilization, good embryo formation (culture to the day
3), and blastocyst formation (culture to the day 5), we analyzed the results
generated from the cases stimulating by long-acting rFSH (L-rFSH,
corifollitropin alfa) and by traditional rFSH (T-rFSH) shots in this study.
Materials
and Methods:
Study
Cohort I—General
patients
A total of 252 cycles were recruited since
December, 2012 to September, 2013. There were 91 cycles (average age: 34.9 y/o,
range from 28-42) using L-rFSH stimulation (14 cycles with single shots and 77
cycles with T-rFSH supplements), and 161 cycles (average age: 34.9 y/o, range
from 23-40) using T-rFSH stimulation, which was set as the control cohort (Table 1). The patients with polycystic
ovarian symptoms were excluded from the study cohort. Number of antral
follicles, number of retrieval oocyte, hormone levels after stimulating, number
of mature oocytes(MII) after retrieving and the fertilization rates were
compared between the two groups. Then the good embryo rate (GER) of
day3-culture and the good blastocyst rate (GBR) of day5-culture were determined
from each group.
Table
1
Study
Cohort II—Oocyte Donor
Cohort
A total of 89 oocyte donating cycles were
recruited since December, 2012 to September, 2013. There were 64 cycles using
L-rFSH stimulation, and 25 cycles using T-rFSH stimulation, which was set as the
control cohort. The same parameters associated with embryo yield were also
compared in these two groups.
Treatment
Protocol Design
To assess the more friendly protocol to the
IVF cases, we designed a protocol with fewer injections based on the
traditional rFSH short protocol and the corifollitropin α in GnRH antagonist protocol.
The modified protocols were displayed in
Figure 1.
Figure
1
Statistics
Statistical evaluations were carried out
using nonparametric Student’s t test
with Welch’s corrections. The statistical software, prism (http://www.graphpad.com/scientific-software/prism,
GraphPad) was administrated in the data processing.
Results
Although the number of antral follicles showed
difference between L-rFSH recipients and T-rFSH recipients (10.16±0.44 vs. 8.39±0.31, p<0 .01="" font="" nbsp="">
After oocyte retrieving of L-rFSH recipients and T- rFSH recipients, number of MII oocytes (11.16±0.69 vs. 9.52±0.50, p=0.03), maturation rates (75.8% vs. 78.31%, p=0.16) and fertilization rates (78.72% vs. 77.12%, p=0.26) were no different. In following cultural results of embryos, GER of day3 (61.32% vs. 58.22%, p=0.24) and GBR of day5 (60.39% vs. 57.36%, p=0.21) also performed the similar outcomes from the two groups (Figure 2).
After oocyte retrieving of L-rFSH recipients and T- rFSH recipients, number of MII oocytes (11.16±0.69 vs. 9.52±0.50, p=0.03), maturation rates (75.8% vs. 78.31%, p=0.16) and fertilization rates (78.72% vs. 77.12%, p=0.26) were no different. In following cultural results of embryos, GER of day3 (61.32% vs. 58.22%, p=0.24) and GBR of day5 (60.39% vs. 57.36%, p=0.21) also performed the similar outcomes from the two groups (Figure 2).
Table
2 General IVF case
After oocyte retrieving of L-rFSH
recipients and T- rFSH recipients, number of MII oocytes (11.16±0.69 vs. 9.52±0.50,
p=0.03), maturation rates (75.8% vs. 78.31%, p=0.16) and fertilization rates
(78.72% vs. 77.12%, p=0.26) were no different. In following cultural results of
embryos, GER of day3 (61.32% vs. 58.22%, p=0.24) and GBR of day5 (60.39% vs.
57.36%, p=0.21) also performed the similar outcomes from the two groups (Figure 2).
Figure
2
In the oocyte-donor cohort, the group
stimulated by corifollitropin alfa also displayed similar ovarian responses and
clinical outcomes in the following embryo culture (Table 3, Figure 3).
Table
3 Oocyte
donating cycles
Figure
3
Discussion:
Based on the efficiencies of controlled ovarian stimulation and
embryo culture, no significant differences were observed between the recipients
of L-rFSH and of T-rFSH. Due to the long lasting effect of corifollitropin
alfa, a more patient-friendly option with reduced injective frequencies could
be applied to the overseas cases or cases afraid of injections (Table 4, Table 5).
Table
4 Frequency of Injection
Table
5 Cost List
(The study has been published in 2014 Annual Meeting of Taiwanese Obstetrics and Gynecology Society)
References:
1.
A comparison of long-acting FSH
versus daily FSH did not show evidence of difference in effect on overall live
birth rate or OHSS in 2335 IVF participants (Cochrane Database Syst. Review,
2013)
2.
Long-acting rFSH and
short-acting rFSH treatment protocols provided equal success rates of live
birth and cumulative pregnancy
(Boostanfar et al., Fertil Steril 2012)
3.
Treatment of
poor ovarian responders with corifollitropin α in a GnRH
antagonist protocol results in low pregnancy rates, similarly to
conventional stimulation with a short agonist protocol
4.
(Polyzos et al., Fertil Steril
2013)