WHAT IS BLASTOCYST CULTURE?
The word ‘blastocyst’ refers to the stage that the human embryo reaches approximately five to six days after fertilisation. It is the stage of development that the embryo must reach before it can hatch and implant in the lining of the uterus. The blastocyst stage embryo has many cells (typically between 50 and 200) and the cells are organised into two types: the ‘trophectoderm’, whose main role is in implantation; and the ‘inner cell mass’, which will give rise to the foetus itself.
Blastocyst formation as the embryo travels along the female reproductive tract is illustrated in Figure 1.
Until quite recently it was not possible to consistently culture embryos to this stage in the laboratory. However thanks to extensive research, specialised commercial culture media are now available that make ‘in vitro’ blastocyst culture possible.
HOW DOES THIS DIFFER FROM ‘NORMAL’ EMBRYO CULTURE?
Standard practice in IVF involves the replacement of embryos into the uterus after only two or three days, when the embryos are at the cleavage stage of development and composed of between four and eight identical cells.
By culturing the embryos to the blastocyst stage, the in vitro culture period is extended, providing greater opportunity to observe embryo development.
WHY EXTEND THE TIME THAT THE EMBRYOS ARE CULTURED IN THE LABORATORY?
It is known that many embryos, irrespective of their appearance, are destined to arrest at early stages (many will arrest for example between day three and day four). Extending the in vitro culture period beyond those early stages gives the embryologist an opportunity to identify which (if any) of a group of embryos have the best potential for implantation, by identifying those that form a normal blastocyst in culture.
Transfer of embryos at the blastocyst stage may also provide a better coordination between the embryo and the uterus, by putting the embryo back in the right place (the uterus) at the right time (blastocyst stage).
In the female body, the egg is normally fertilised at the top of the fallopian tube and embryo development continues as it moves towards the uterus (see Figure 1). The embryo reaches the uterus after about five days as the embryo is forming a blastocyst. Transferring blastocyst stage embryos in IVF is thought to enhance the chance of pregnancy by more closely mimicking the timing of the ‘normal’ situation than transfer of cleavage stage embryos to the uterus.
SO WHAT ARE THE ADVANTAGES OF BLASTOCYST CULTURE?
- Blastocyst stage embryos are considered to have a higher potential for implantation than earlier embryo stages.
Extended culture provides the embryologist with a better opportunity to separate those embryos that form a blastocyst in vitro and have a good chance of implantation, from those that are destined to arrest at early stages. Blastocysts are therefore considered to be a more ‘select’ group of embryos with a higher chance of pregnancy per embryo.
Perhaps the best way to show this is to give an example:
Consider a couple who have ten eggs retrieved and for whom eight have fertilised the following day. It is impossible to determine at this point which of these eight are most likely to implant and develop into a baby. On day three of development, six of the eight embryos seem to have developed into good quality normal embryos. All six good embryos look like they have the same potential for implantation and it is difficult to select ‘the one’ embryo for transfer.
If the culture period in the laboratory is extended, this allows the natural selection process to continue. By day five, of the six embryos that looked good on day three, only three are still viable and have formed a normal blastocyst. The embryologist therefore has a much better idea as to the best embryos to transfer or cryopreserve compared to day two or day three.
- Blastocyst culture and transfer provides the opportunity to reduce the number of embryos transferred and hence the incidence of multiple births.
As blastocyst culture can help to determine which embryos have the best chance of being able to implant. The number of embryos that we replace into the uterus can be reduced without compromising the chance of pregnancy. This therefore reduces the risk of a multiple pregnancy.
WHAT ARE THE DISADVANTAGES OF BLASTOCYST CULTURE?
- The possibility of no embryos for transfer.
There is always the possibility that extended culture shows that none of a group of embryos are destined to develop to the blastocyst stage. In this case the IVF cycle may end without an embryo transfer at all.
We believe that if blastocyst development does not occur in vitro, it is highly likely that a pregnancy would not have developed if the same embryos had been transferred on day two or day three. Nevertheless, it may be difficult to accept the possibility of going through an IVF treatment cycle and not having the chance of an embryo transfer.
Although seemingly strange, it is in fact possible to view this outcome as an advantage of blastocyst transfer. Although the disappointment of having no embryos for transfer may be great, couples may prefer to know that their embryos are not destined to progress, rather than undergo the stress, time and expense of the two week wait for a negative pregnancy test.
- Reduced number of surplus embryos for cryopreservation.
It is possible to successfully cryopreserve blastocyst stage embryos. However, as extended culture filters out a lot of embryos that are not destined to progress beyond early stages, it is likely that the number of surplus embryos available for freezing will be reduced following extended culture.
IS BLASTOCYST TRANSFER FOR ME?
We are currently recommending blastocyst transfer to most patients who have a reasonable chance of having blastocyst development.
Patients who have had fewer oocytes retrieved, fewer fertilised or fewer dividing embryos by day three in culture may choose to have a cleavage stage embryo. For these patients there may be less to be gained from further embryo ‘selection’.
Blastocyst transfer is also an excellent choice for women who undergo a frozen embryo transfer cycle. The embryologists can thaw most or all of the frozen pronucleate or cleavage stage embryos and see which ones develop to the blastocyst stage.
It is important to consult with your clinician about whether blastocyst culture and transfer is for you.
Figure 1: Blastocyst formation in the female reproductive tract.
The egg is fertilised following ovulation from the ovary and the embryo goes on to divide (cleave) as it travels along the fallopian tube. Blastocyst formation occurs as the embryo reaches the uterus.
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