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 termed the trophectoderm and will eventually become the placenta and 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 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 post 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. The rational behind blastocyst transfer is that an embryo that has failed to reach the blastocyst stage, would be less likely to result in pregnancy as opposed to if it does make it to a blastocyst that embryo has about a 50% chance of implanting (all things being equal regarding a healthy uterus). It is believed that the improved implantation rates following blastocyst transfer are due to selection of the "best" embryos.
Growing embryos to blastocyst stage:
During the past few years La Jolla IVF's embryology team has moved systematically towards refining the techniques in the laboratory that would enable a greater number of patients to avail themselves of transferring blastocysts as opposed to the older more traditional methodology of transferring embryos after three days of in vitro development in the IVF laboratory. Traditionally, in an IVF cycle, embryos have been transferred to the uterus on the second or third day of development and initial embryonic cell division. IVF practitioners were aware that day three embryo transfers were too early when compared to what happens in naturally conceived pregnancies. Physiologically, in the natural conception pregnancies, the embryo reaches the uterus on about day four or five because it grows and divides in the fallopian tube for several days after fertilization.
Until recently, previous laboratory culture media could only sustain an embryo's growth for about three days in vitro. Research throughout the late 90's 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.
La Jolla IVF is fortunate to have an embryology team that is meticulous and technologically advanced. It requires much more time and effort to sustain the dynamic process of embryo development to blastocyst stage. Our embryologist uses specific media to facilitate embryos development in vitro during their first three days in culture inside the IVF laboratory. The media is then changed to a more complex type to enable the embryos to further grow in this new culture for an additional two days. The embryos are therefore exposed from the beginning to specific media designed to meet the nutritional requirements of each stage of the embryos' development.
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, 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. It is important to point out that these blastocysts grading standards are still currently under development. La Jolla IVF's laboratory has reached certain conclusions regarding the degree of predictability when it comes to choosing which blastocyst embryos are destined for live birth success. We have instituted grading scores related to the Inner cell mass and the trophoblast which helps us determine which are the best blastocysts to transfer from amongst those embryos from an individual patient that were actually able to make it to the blastocyst stage. Furthermore, many of our patients are now choosing to perform Preimplantation Genetic Diagnosis (PGD) on their embryos. These embryos have to remain in our incubators and hopefully grow to blastocyst stage while the diagnostic process is being performed on the one cell that was removed from the embryo on day 3. In these instances, not only do we assist the embryos to grow to blastocyst stage but we also obtain additional information which enables us to determine which of these blastocyst stage embryos are designated as being chromosomally normal based on the specific chromosomes that were tested. Therefore, in these cases we are optimizing not only implantation rates but also the prospect that these pregnancies will produce healthy babies.
Blastocyst Transfer for all patients?
There are currently some unresolved issues regarding blastocyst transfer. In general, blastocyst transfers are more advantageous for patients who develop a 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 5 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 3, is not able to be definitively answered at this time. In patients with few embryos on day 3, it is still a rational approach to perform a day 3 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 La Jolla IVF 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 will undergo PGD on day 3 of in vitro culture. One cell is removed from each embryo and is fixated on a slide which is sent for genetic/chromosomal testing. (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:
It appears generally and in particular at La Jolla IVF that blastocysts have a good survival rate after freezing. The optimization of a blastocyst cryopreservation program mandates a comprehensive approach. A sequential 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, improve the quality of the inner cell mass and blastocysts post-thaw survival rate. Critical timing of the cryopreservation of the blastocysts seems essential as the success of frozen blastocysts cycles appears to be dependent on the specific developmental stage of the blastocyst when it is actually frozen. Interestingly, it would seem that as long as quality blastocysts are initially frozen, pregnancy rates do not appear to be affected by the age of the patient.
Blastocyst Embryo Transfer and the Future:
Over the past several years, patients at La Jolla IVF have completed 300 fresh and frozen blastocyst embryos transfers. The average success rate in patients under the age of 38 is 52% per transfer. In our egg donation and /or surrogacy cases, the ongoing pregnancy rate is over 75% per transfer using blastocysts. These results are being achieved in our program by us routinely transferring only 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 with continuing research in the arena of growing blastocysts, we are confident that these advances will ultimately translate into even higher pregnancy rates for patients.
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