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.
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