Blastocyst (Day 5 or 6) Embryo Transfer
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 cells, termed 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 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. An embryo reaching the blastocyst stage has an increased chance of implantation as opposed to a day 3 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. La Jolla IVF’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 3 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 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. Dr. Barry Behr, our Laboratory Director developed one of the first media to successfully grow embryos to the blastocyst stage.
La Jolla IVF 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 embryos development to the blastocyst in vitro during their first three days in culture inside the IVF laboratory. These blastocyst culture conditions do not improve the health or viability of an individual embryo, i.e. "extended culture" does not transform a poor embryo into a good embryo, it simply provides the embryo with an environment optimal for growth and ability to reach their maximum inherent potential. 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.
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.
Blastocysts themselves have their own inherent morphology quality standards. La Jolla IVF uses a standard blastocyst scoring system.
This blastocyst grading system assigns 3 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|
Blastocyst Transfer 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 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 or where no embryo selection is needed, 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 and all the resulting embryos may undergo PGD (not mandatory) on day 3 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 La Jolla IVF, 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, 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 La Jolla IVF have completed hundreds of fresh and frozen blastocyst embryos transfers. The average success rate in patients under the age of 35 is 46.8%. In our egg donation and surrogacy cases, the ongoing pregnancy rate is over 80% 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.