GnRH-agonist versus GnRH-antagonists in elective single embryo transfer IVF cycles

Introduction: Controversy still surrounds the issue whether pregnancy rates
after GnRH-antagonists are subtle lower compared to GnRH-agonists in multifollicular
ovarian stimulated cycles for IVF. The aim of this cohort study was to
compare the two protocols in women less than 36 years old undergoing single
embryo transfer (SET) either on day-3 or on day-5 of the embryo culture.
Material and methods: Eligible patients were patients undergoing ovarian
stimulation for elective single embryo transfer, less than 36 years of age and
in their first or second trial. Recruitment of patients occurred on the day of
the embryo transfer. The decision of the day of embryo transfer had been
taken by the treating physician at the outpatient clinic. The GnRH-agonist
long protocol started on day 21 of the preceding cycle with intranasal Buserelin
(600 mg per day). Gonadotrophins (100-300IU) were administered after three
weeks of down-regulation, once hormones were basal. In the GnRH-antagonist
protocol gonadotrophins (100-300IU) were administered from day 2 of the
cycle if the hormonal levels were basal and the antagonist (ganirelix 0.25 mg
daily) was started on day 6 of the stimulation. In both protocols the stimulation
could only initiate if progesterone was lower than 1.5 ng/L and estradiol lower
than 80 ng/ml. Luteal phase was supplemented in all patients with vaginal
administration of 600 mg natural micronised progesterone. Sequential media
were used for embryo culture. Analysis was performed separately according
to the developmental stage of the embryo transferred, as we have shown that
the implantation potential of a single blastocyst is significantly higher than a
single cleavage stage embryo. Clinical pregnancy rate is defined as positive
heart beat at 7 weeks of gestation. Values are expressed as meanþstandard
error of mean (SEM).
Results: 414 cycles were performed with a day-3 embryo transfer, 177 under a
long GnRH-agonist protocol and 237 under a GnRH-antagonist protocol. Age
(30.3þ0.3 vs.30.8þ0.2, p¼0.5); starting gonadotrophins dose (191.1þ5 vs.
187.7þ3); retrieved COCs (10.1þ0.4 vs.10.7þ0.5, p¼0.3); 2PN embryos
(6.0þ 0.5 vs. 5.6þ0.5, p¼0.5); mean embryo quality (1.3þ0.04 vs.1.3þ0.03,
p¼0.8) and the number of embryos cryopreserved (2.9þ0.2 vs. 2.9þ0.2,
p¼0.9) were comparable between the two protocols respectively. However,
with the antagonist the duration of stimulation was significantly shorter (9.9
vs. 12.1 days, p,0.0001) and the total dose of gonadotrophins required was
also significantly lower (1842 vs. 2445 IU, p,0.0001) compared with the long
agonist protocol. The clinical pregnancy rate in the antagonist group was
32.1% compared with 27.7% in the agonist group (OR:1.23; 95%CI:0.80-
1.89). Day-5 embryo transfer was performed in 225 cycles, 105 with GnRHagonist
and 120 with GnRH-antagonist. There was no difference with regards
the age (29.9þ0.3 vs. 30.0þ0.3, p¼0.8); the COCs (11.8þ0.6vs. 11.6þ0.5,
p¼0.9); 2PN embryos (7.6þ0.4 vs. 6.9þ0.3, p¼0.2); mean embryo quality
(1.3þ0.1vs. 1.3þ0.1, p¼0.8) and embryos cryopreserved (2.3þ0.2 vs.
2.2þ0.2, p¼0.8). Nevertheless, with the antagonist the duration of stimulation
was significantly shorter (10.4 vs. 12.1 days, p,0.0001) and the total dose of
gonadotrophins required was significantly lower (1818 vs. 2212 IU,
p,0.0001). Clinical pregnancy rate was similar between antagonist and
agonist (40.0 vs. 36.2%, OR:1.17; 95%CI:0.68-2.01).
Conclusions: The current study is the first comparison attempted between the
two protocols in a SET setting and in blastocyst stage embryo transfers. The
above group of patients represents a well homogenized group with the advantage
of transferring a single embryo eliminating thereby bias introduced by
different number or quality of embryos transferred. The pregnancy outcome
among the two GnRH-analogues is absolutely comparable with the further
advantage of flexibility, shorter stimulation period and reduced use of gonadotrophins
concerning the use of GnRH-antagonist.