Blastocyst Stage Embryo Transfer
A recent advance in infertility treatment involves growing human embryos in the laboratory to a later "blastocyst" stage before transferring them into the uterus following in vitro fertilization. This new technique has advantages and disadvantages, however, these cannot be fully evaluated until there is widespread application by many infertility centers to confirm results and analyze risks. We offer blastocyst culture to infertile couples undergoing IVF or ICSI who wish to avail themselves of its potential benefits but who also understand its potential risks.
Fertilization of an egg by a sperm occurs soon after its release from the ovary (ovulation) into the fallopian tube to form a single cell embryo (zygote) containing the genetic material of the sperm and egg. The zygote then divides progressively into a multi-cell embryo. When the embryo contains about 12-16 cells, it is called a "morula". After 5-6 days, the embryo contains many cells and forms a cystic cavity termed the blastocoel within its center. At this stage, the embryo is called a "blastocyst" and has undergone the 1st step in differentiation; it separates into two tissue types, the trophectoderm and the inner cell mass. The trophectoderm is what is destined to become the placenta, while the inner cell mass eventually forms the fetus. In the human, the egg is fertilized in the fallopian tube near the ovary. The developing embryo descends through the tube into the uterine (endometrial) cavity about three to four days after ovulation when it is at the morula stage. The embryo sits in the uterine (endometrial) cavity for about two days during which time it develops into a blastocyst. The blastocyst invades (implantation) the uterine lining about the fifth or sixth day after ovulation so that it can develop a blood supply (placenta) that will allow it to continue to grow into a fetus and then a baby.
Until recently, culture of embryos, in the laboratory, to the blastocyst stage was very difficult because the several culture media that were used to supply nutrients to the embryos were inadequate for extended embryo growth in the laboratory. Therefore, many embryos died before they developed into blastocysts. Improved culture media are now available that sustain embryo growth in the laboratory for several days prior to implantation. Many IVF centers now culture embryos to the later blastocyst stage before transferring them into a woman’s uterus in an attempt to maintain or increase the pregnancy rate. Fewer of the later-stage embryos are transferred to reduce the risk of multiple gestations.
Advantages of blastocyst transfer:
Transfer occurs closer to the natural time that an embryo enters the uterus when the uterine lining may provide a better environment for the embryo.
Allowing embryos to develop in the laboratory for a longer period of time seems to be a better method for selecting the most normal embryos that would be more likely to implant. Theoretically, an embryo that dies in the laboratory before it develops into a blastocyst would also not have continued to develop in the uterus. However, there is no way to know this for sure for any individual embryo.
Because blastocysts are "selected" as the embryos most likely to implant and become pregnancies, fewer embryos need to be transferred to maintain an acceptable pregnancy rate. The pregnancy rate per transfer is higher when blastocyst embryos are transferred on day 5 to 7 than when earlier-stage embryos are transferred on day 2 or 3. However, since not every IVF cycle produces blastocyst stage embryos, the overall pregnancy rate per cycle may not be significantly different.
Because the implantation rate (the number of implantations that occur per embryo) is higher when embryos are allowed to progress to the blastocyst stage, fewer embryos can be transferred while achieving similar or better pregnancy rates for each transfer. This may well be the most important reason to consider blastocyst transfer. This technique significantly reduces the chance of higher order multiple gestations such as triplets.
Blastocysts transfer has risks and disadvantages:
The primary risk of attempting blastocyst transfer is that some embryos will die in the laboratory. Therefore, the total number of embryos available for transfer and freezing will be less. Unfortunately, some couples undergoing IVF will have all their embryos die in the laboratory and will not have any embryos available for transfer. With the increasing experience of the GIVF embryology lab working with blastocyst culture, we can predict with greater accuracy which cycles will be most likely to have successful culture to the blastocyst stage. However, this risk remains.
Blastocyst transfer probably offers more value to couples with a larger number of embryos (at least 8). If the starting number of embryos is low, then the chance of having no embryos for transfer is much higher.
No one knows whether some of the embryos that die in the laboratory would have developed into a normal pregnancy if they had been transferred into the uterus at an earlier stage.
As with transfers done at earlier stages, blastocyst transfer does not guarantee a normal pregnancy. We expect that some pregnancies will miscarry and some babies will develop birth defects similar to that which occurs in couples that are able to achieve pregnancy naturally.
Excess blastocysts may be frozen and some of them will not survive the freeze-thaw process when utilized for a later attempt at achieving pregnancy. This is a similar risk to transferring embryos at earlier stages.
Number of blastocysts to transfer, multiple births, and pregnancy rate
We suggest that no more than two blastocysts be transferred to the uterus at one time because the risk of multiple births would likely be unacceptably high. With time and experience, we may find that only one blastocyst need be transferred in order to achieve an acceptable pregnancy rate with a lower rate of multiple births. As a consequence of a single blastocyst transfer, the overall pregnancy rate may then be no greater than that which we already experience with the transfer of three to four embryos on day two or three after egg retrieval. We also anticipate that individual clinical circumstances may lead us to recommend transfer of more than two blastocysts. Therefore, the final decision regarding the number of embryos transferred will remain a joint decision between the patient and physician on the day of transfer.
Blastocyst culture and embryo transfer is a new, but now fairly routine technology for human assisted reproductive medicine. We anticipate that as we increase our experience with blastocyst transfer that our recommendations for its use may change. Blastocyst transfer may become the routine method of embryo transfer or it may be limited to selected subgroups of patients.
Requirements For Attempting Blastocyst Transfer
The preparations for blastocyst culture are somewhat different for the laboratory and the transfer usually takes place on day 5 rather than day 3, so it is recommended that a discussion take place with your physician prior to your retrieval in order to decide if blastocyst transfer is right for you. In most cases, these decisions can be made based on your age, type of infertility and the expected outcome of your cycle. In an effort to keep scheduling issues as smooth as possible, it is recommended that a decision be made prior to your oocyte retrieval.
These methods have become relatively routine, so it is sometimes possible or even advised by the embryology laboratory to change course during the retrieval cycle itself. If this situation occurs, you will be consulted by your physician during the IVF cycle.
We ask that you please notify the medical staff on or before the day of hCG administration regarding your decision to attempt blastocyst transfer.
Please contact one of the physicians regarding any questions concerning blastocyst culture and transfer.