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Human Reproduction Vol.19, No.ll pp. 2550-2554, 2004
Advance Access publication August 6, 2004
doi:10.1093/humrep/deh447
Should we advise patients undergoing IVF to start a cycle
leading to a day 3 or a day 5 transfer?
E.M.Kolibianakis¹, K.Zikopoulos, W.Verpoest, M.Camus, H.Joris, A.C.Van Steirteghem
and P.Devroey
Centre for Reproductive Medicine, Dutch-Speaking Brussels Free University Laarbeeklaan 101, 1090 Brussels, Belgium
l
To whom correspondence should be addressed. E-mail: stratis@easynet.be
BACKGROUND: The aim of this study was to compare ongoing pregnancy rates per started cycle between
patients randomized at consultation to have embryo transfer either on day 3 or on day 5 of in-vitro culture.
METHODS: All patients <43 years of age for whom IVF was indicated were allowed to participate in the study
(day 3 group, 234 patients; day 5 group, 226 patients). Ovarian stimulation was performed either using GnRH
antagonists/recombinant FSH (rFSH) (day 3, 70.1% of patients; day 5, 72.6% of patients) or using the long GnRH
agonist protocol/urinary gonadotropins (day 3, 29.9% of patients; day 5 27.4% of patients). RESULTS: The ran-
dom decision to initiate a cycle leading to day 5 as compared with a day 3 transfer was associated with a signifi-
cantly lower chance of embryo cryopreservation (day 3, 61.5%; day 5, 50.4%; P < 0.02). Ongoing pregnancy rate
per started cycle did not differ between the two groups compared [day 3, 32.1%, 95% confidence interval (CI) 26.4-
38.2%; day 5, 33.2%, 95% CI 27.3-39.5%]. CONCLUSIONS: Advising patients at consultation to initiate an IVF
cycle leading to a day 5 as compared with a day 3 transfer does not appear to increase the probability of ongoing
pregnancy, and is associated with a significantly lower probability of obtaining cryopreserved embryos.
Key words: blastocyst transfer/day 3 transfer/GnRH antagonists/ongoing pregnancy rate/recombinant FSH
Introduction
A shift from day 3 to day 5 embryo transfer has occurred in
recent years as several retrospective studies suggested that
replacement of blastocysts enhances the reproductive outcome
of IVF (for review see Kolibianakis and Devroey, 2002).
Randomized controlled trials (RCTs) comparing the two
methods, however, showed that the probability of pregnancy
is not dependent on the type of embryo transferred (Blake
et al, 2004). Moreover, similar implantation rates were
achieved by replacing equal numbers of embryos either on
day 3 or on day 5 of in-vitro culture (Kolibianakis and
Devroey, 2002).
Randomized comparisons between day 3 and day 5 trans-
fer using sequential media have so far been performed
by applying randomization after initiation of stimulation
(Gardner et al, 1998), at oocyte retrieval (Utsunomiya et al,
2002) or at fertilization (Coskun et al, 2000; Karaki et al,
2002; Levron et al, 2002; Rienzi et al, 2002). The patients
included in the above studies satisfied specific criteria regard-
ing the number of follicles present on a certain day of stimu-
lation, the achievement of oocyte retrieval or the presence of
a predefined number of 2PN oocytes. Counseling patients on
the mode of embryo transfer based on the results of these
studies is, of course, conditional. The couple will only know
the type of embryo transfer after a certain stimulation day is
reached, after oocyte retrieval or after insemination of the
oocytes retrieved.
To date, no information about the probability of ongoing
pregnancy in patients randomized to day 3 or day 5 transfer
is available at the moment of consultation, before the out-
come of stimulation or fertilization is known.
The aim of this study was to compare ongoing pregnancy
rates per started cycle between patients randomized, prior to
initiation of stimulation, to have embryo transfer either on
day 3 or on day 5 of in-vitro culture.
Materials and methods
Patient population
Four hundred and sixty patients treated by IVF at the Centre for
Reproductive Medicine of the Dutch-Speaking Brussels Free
University from January 2001 until December 2003 were included
in the study. Patients could enter the study only once. Randomi-
sation was performed by the attending physician according to a
computer-generated list. The sequence of randomization was not
concealed. Inclusion criteria were age <43 years and presence of
indication for IVF. Exclusion criteria were preimplantation genetic
screening (for aneuploidy or for a specific disease) and azoospermia.
The current study was approved by our Institutional Review Board.
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