What is a Blastocyst?
A blastocyst is an embryo that has developed in culture in the IVF laboratory for at least
five days after egg retrieval and has divided into two different cell types. The surface
cells are called the trophectoderm and will eventually become the placenta, and the
inner cells, called the inner cell mass, will become the fetus. A healthy blastocyst should
hatch from its shell (zona pellucida) by the end of six days or earlier and is then ready to
begin to implant within the lining of the uterus.
Blastocysts have survived an important “survival test.” During the first few days, the
embryo relies on the egg cell (from the mother) for all its growing nutrients. However, in
order to survive past day three or four, the embryo must activate its own genes so that it
can carry on growing and dividing. Unfortunately, not all embryos are able to grow past
this milestone, and in fact, only about one-third of embryos are capable of becoming
blastocysts. If an embryo can propel itself into becoming a blastocyst in vitro, then it
would appear that nature has sent us a message that these embryos are the product of
a “survival of the fittest” test.
There is now abundant evidence that transferring blastocyst embryos into the uterus
five or six days after egg retrieval results in higher implantation rates per embryo
transferred compared to a day three embryo transfer. An embryo reaching the
blastocyst stage has an increased chance of implantation as opposed to a day three
embryo (all things being equal regarding a healthy uterus). It is believed that the
improved implantation rates following a blastocyst transfer is due to selection of the
“best” embryos.
Growing Embryos to Blastocyst Stage
Traditionally, in an IVF cycle, embryos were transferred to the uterus on the second or
third day of development and initial embryonic cell division. BetaPlus Fertility’s
embryology team has moved systematically towards refining the techniques in the
laboratory which now enable many of our patients to avail themselves to transferring
blastocysts as opposed to the older, more traditional methodology of day three
transfers. IVF practitioners were aware that day three embryo transfers were too early
when compared to what happens in naturally conceived pregnancies. In a naturally
conceived pregnancy, the embryo reaches the uterus on day four or five because it
grows and divides in the fallopian tube for several days after fertilization.

Previously, laboratory culture media could only sustain an embryo’s growth for about
three days in vitro. Research throughout the late 1990s identified that as the embryo
develops, its nutritional requirements change due to metabolic factors. This research led
to the development of different laboratory culture media for the embryo’s specific
developmental stages.
BetaPlus Fertility is fortunate to have an embryology team that is highly skilled and a
laboratory that is technologically advanced. It requires much more time and effort to
sustain the dynamic process of embryo development to blastocyst stage. Our
embryologists use specific media to facilitate the embryo’s development to the
blastocyst in vitro during their first three days in culture inside the IVF laboratory.
This newer “sequential media” attempts to reproduce the natural environment of the
maternal reproductive tract. These blastocyst culture conditions do not improve the
health or viability of an individual embryo—sequential media does not transform a poor
embryo into a good embryo, but rather it allows embryos capable of sustained growth to
continue growing in the culture media and reach their maximum inherent capability. The
ability to develop embryos to the blastocyst stage allows our embryology team to have
greater certainty about which embryos are more likely to implant.
Grading Blastocysts
Blastocysts themselves have their own inherent morphology quality standards. BetaPlus
Fertility uses a standard blastocyst scoring system.
This blastocyst grading system assigns three separate quality scores to each blastocyst
embryo:
 Blastocyst development stage – expansion and hatching status
 Inner cell mass (ICM) score, or quality
 Trophectoderm (TE) score, or quality
Expansion grade; blastocyst development and stage status:
 1 Blastocoel cavity less than half the volume of the embryo
 2 Blastocoel cavity more than half the volume of the embryo
 3 Full blastocyst, cavity completely filling the embryo
 4 Expanded blastocyst, cavity larger than the embryo, with thinning of the shell
 5 Hatching out of the shell

 6 Hatched out of the shell
ICM grade; inner cell mass quality:
 A Many cells, tightly packed
 B Several cells, loosely grouped
 C Very few cells
TE grade; trophectoderm quality:
 A Many cells, forming a cohesive layer
 B Few cells, forming a loose epithelium
 C Very few large cells
Is Blastocyst Transfer Right for All Patients?
In general, a blastocyst or embryo transfer procedure is more advantageous for patients
who develop a large number of eggs and embryos. Because only some embryos are
capable of developing into blastocysts, it is possible to have no embryos survive to day
five to transfer. This is especially true if the cycle begins with few eggs and embryos.
The question as to whether the embryos that did not grow into blastocysts could still
have implanted if they were transferred on day three is not able to be definitively
answered at this time. In patients with few embryos on day three or where no embryo
selection is needed, it is still a rational approach to perform a day three transfer (if the
patient wishes to do a transfer on their first fresh cycle) as opposed to trying to grow
these few embryos to blastocysts and then potentially having no embryos to transfer.
At BetaPlus Fertility, however, many of the patients who are regarded as “poor
prognosis” in terms of their ultimate success rate for IVF choose to undergo what we
term “embryo banking” cycles. These patients do several cycles in which we
accumulate embryos for them and when we have gathered about eight or nine embryos,
the patient will have a combination fresh/frozen transfer cycle. The embryos that are
frozen will be thawed and, in combination with the fresh embryos, all the resulting
embryos may undergo PGD (not mandatory) on day three of in vitro culture (see section
on Preimplantation Genetic Diagnosis (PGD) for full explanation).
One of the major limiting factors with doing well with this type of treatment (besides the
normal versus abnormal results of the PGD) is the ability of the IVF laboratory to sustain
the embryos’ growth in the incubators while PGD is being performed and to enable
those embryos that are inherently capable to continue to grow to blastocysts.
Frozen Blastocyst Transfer Cycles

At BetaPlus Fertility, blastocysts have a good survival rate after freezing. The
optimization of a blastocyst cryopreservation program mandates a comprehensive
approach. An appropriate embryo culture system with attention to the protein
supplement and a low oxygen environment has been shown to increase the number of
blastocysts available for cryopreservation and improve the quality of the inner cell mass
and blastocysts post-thaw survival rate.
Blastocyst Embryo Transfer and the Future
Over the past several years, patients at BetaPlus Fertility have completed hundreds of
fresh and frozen blastocyst embryos transfers. The average success rate in patients
under the age of 35 is 46.8 percent. In our egg donation and surrogacy cases, the
ongoing pregnancy rate is over 80 percent per transfer using blastocysts. These results
are being achieved in our program by us routinely transferring a maximum of two
blastocyst embryos. This option has dramatically lowered the risk of patients having to
deal with the stress, adversity, and dilemma of carrying higher order multiples (triplets or
more). Our embryology team is constantly upgrading both laboratory equipment and
their expertise, and we are confident that these advances will ultimately translate into
even higher pregnancy rates for patients.