Implantation
rate is one of the determining factors, if not the
determining factor, in human in vitro fertilization
(IVF). Factors that can affect implantation rate
include oocyte quality (which in turn depends on the
patient's etiology, dietary status, and stimulation
regimen), laboratory conditions, stage of embryonic
development at the time of transfer, embryo transfer
medium, and the embryo transfer procedure itself.
With increasing implantation rates, we have been
able to reduce the number of embryos transferred to
achieve an acceptable pregnancy rate. Implantation
rate is among the most suitable ways to compare
clinics. In other words, implantation rates for
specific groups of patients can be used for
benchmarking the success of IVF. With the move to
low cell-number embryo transfers, the question is
therefore: at what stages of embryo development are
implantation rates highest? This question has been
the subject of recent discussion, and there remains
a lack of consensus.
Not all oocytes or
spermatozoa are destined to give rise to a viable
embryo.
This is due not only to
chromosomal anomalies, but also to cytoplasmic
deficiencies and chromatin damage. Furthermore,
prior to blastocyst formation, one is really
monitoring a cleaving oocyte, as the
maternal-embryonic genome transition is not
complete. Therefore, to assess true embryo viability
(postembryonic genome activation), one must culture
the embryo to the blastocyst stage. This point does
not detract from studies on pronucleate embryo
polarity, as this clearly reflects the inherent
quality of the oocyte, and one cannot make a good
embryo from a poor-quality oocyte. Clearly such data
are useful in indicating which embryos have the
highest potential early on, but implantation rates
greater than 28% have not been reported after the
transfer of pronucleate embryos.
Rather,
the highest rates of implantation in all mammalian
species studied to date have come from the transfer
of embryos to the uterus at the morula and
blastocyst stages. It has been well documented that
nutritional stress, such as that placed on the
embryo when transferred to the wrong part of the
reproductive tract, will cause metabolic
perturbations. Data from animal models have shown
that uterine receptivity is significantly
compromised if the recipient female has undergone
superovulation. It would therefore seem prudent to
minimize the embryo's exposure to such an
environment, and this can be achieved through
blastocyst transfer. Another plausible reason for
the high implantation rates after blastocyst
transfer has been provided by the work of Fanchin et
al, who have shown that uterine contractions are
inversely related to pregnancy rates. It is
therefore probable that by transferring human
embryos at the blastocyst stage, there is
significantly less chance of the embryo being
expelled from the uterus.
To summarize, it is
fortuitous for human medicine that among all the
mammalian species, the human embryo is the only one
that can tolerate the uterus during cleavage-stage
development. However, this does not necessarily make
the transfer of the human embryo to the uterus
previous to compaction an optimized procedure.
Specific criteria to
identify the very best blastocysts to transfer have
been suggested and, if top scores are achieved, are
highly predictive of successful pregnancy. Criteria
as described by Scott et al. defined a “baby-grade
embryo” as having more than 80 intact cells, absence
of cellular granularity, continuous well-defined
outer perimeter of cells with good cell-to-cell
contact, and absence of long thin cells. In a case
series using Scott’s scoring system, a 60% (6/10)
clinical pregnancy rate was achieved when single
embryos were transferred.
