Introduction
Since the first successful conception via in vitro fertilization (IVF)
40 years ago, advances in protocols have resulted in increasing success
rates. Among them, improvements in culture conditions that allow a
higher number of fertilized oocytes to reach the blastocyst stage and
the development of vitrification techniques with excellent frozen-thawed
blastocyst survival rates with no impact on the implantation potential
are the most important. Nowadays, in the era of personalized medicine,
the practice of fixed protocols is becoming outdated and defining
individualized parameters for each situation is now considered more
appropriate for obtaining higher success rates (i.e., ongoing pregnancy
rates [PRs]) and fewer adverse effects (i.e., multiple pregnancies)
of IVF.
These advances have allowed the evolution of two practices in assisted
reproductive technology (ART): freeze-only strategy and single-embryo
transfer (SET). The freeze-only strategy, in which all available
good-quality embryos are frozen and transfers are delayed for a more
physiologic cycle (natural or hormone replacement cycle), has been
increasingly used. Previous studies have suggested that frozen-thawed
embryo transfers (FETs) in the absence of ovarian stimulation allow
better synchrony between blastocyst and endometrium maturation (1),
which is an essential step in the interaction between an
implantation-competent blastocyst and a receptive endometrium (2, 3).
Hence, transferring embryos in a more physiological uterine environment
could hypothetically improve the overall outcomes (4). The freeze-only
strategy is being used for patients at a risk for ovarian
hyperstimulation syndrome (OHSS) (5) and those undergoing
preimplantation genetic testing for aneuploidy (6). However, there is no
evidence supporting the widespread use of the freeze-only strategy for
all patients undergoing IVF and a number of additional questions need to
be answered (7-9).
The SET is another practice who have been increasing applied after the
improvement in embryo vitrification techniques. SET is the best choice
to reduce multiple pregnancies and the associated risks, as preterm
labour and birth, gestational hypertension, gestational diabetes,
premature birth, premature rupture of membranes, etc (10-12). However,
SET is not always practiced, although there is recommendations for a
reduction in the number of embryos transferred (ET) (13). Double embryo
transfer (DET) is the most common practice worldwide and multiple
pregnancies remain the most important iatrogenic complication of
assisted reproductive technology (ART) (14). Efforts has been towards to
stimulate SET. Studies demonstrate the transfer of two embryos in
sequential SET cycles results in similar cumulative live birth rates
compared to DET, with reduced multiple pregnancy (15, 16). Studies from
our group also confirmed that SET is a valuable practice for good
prognosis patients (17-19), as those younger than 38 years of age, good
ovarian response (at least 4 oocytes collected) and without severe male
factor (20, 21).
Based on the theory that patients at risk of OHSS should undergo
freeze-only approach and at the same time the increased number of
oocytes characterize those patients as good prognosis, which is one of
the indications for SET, we hypothesized that high responder patients
undergoing freeze-only strategy to avoid the OHSS, the use of
consecutive elective single embryo transfers can result in the most
efficient approach in terms of higher pregnancy success rates and less
complications. To answer our question, we assessed retrospectively the
clinical outcomes of IVF cycles of high responder patients who underwent
freeze-only strategy and SET in the last 9 years in our centre. As
control group, we included patients with the same characteristics who
underwent freeze-only strategy and DET.