IVF Process – What is IVF?
IVF stands for “In Vitro Fertilisation” where we take eggs and sperm and put them together outside of the body hoping they will fertilise. The fertilised egg is then termed an embryo.
We grow the embryos in the laboratory and then transfer a single embryo to the woman. Embryos that are not transferred can be frozen (cryopreserved) and used at a later date. Embryos can also be genetically tested before freezing and transferred to the woman once results of the genetic testing are known.
Usually women ovulate one egg each month. We know that the likelihood of an IVF baby increases if we have more eggs for fertilisation. This is why we generally have women undergo Controlled Ovarian Hyperstimulation (COH) before we retrieve the eggs to be used for IVF. There are many different types of stimulation regimes, we determine which is right for you after looking at the results of your investigations, why you need IVF and if you have history with stimulation, what has been the response previously. The aim is to get a good number of quality eggs. The number will be different for women of different ages and different etiologies.
To achieve a number of eggs to continue to grow there is a need for a series of medication that includes injections. The duration on the medication and the type of medication will be determined by what our Fertility Specialist has determined is appropriate for you. We can monitor how the eggs are progressing and approximately how many eggs are present by performing an internal ultrasound of the ovaries. The internal ultrasound shows fluid filled pockets within the ovary and these pockets are called follicles and contain the eggs. The follicles are monitored by internal ultrasound and also by blood tests (which tells us how well the follicles are functioning). When the follicles are of the appropriate size to indicate there are a good number of potentially mature eggs, a final injection is given to mature the eggs. The timing of this injection is really important as this is the last step before the egg retrieval and also determines when your egg retrieval will take place.
Day of egg retrieval is termed day zero. This day is known by lots of names, day of oocyte retrieval, egg pick up (EPU), oocyte pick up (OPU) or egg harvest. The day of EPU is the day you come into theatre and we retrieve the eggs you have been so lovingly nurturing. Our Fertility Specialist together with our embryologist (scientist specialised in IVF) will retrieve all the suitable eggs and keep them in an environment that continues to nurture them. You will notice in theatre the embryologist uses a customised IVF chamber that has the appropriate temperature and pH environment to maintain your eggs.
The same day as the eggs are retrieved is usually when the sperm is prepared. Sperm for the male partner is usually produced on the day and prepared in the laboratory depending on the quality of the sperm. Frozen sperm, either from the partner or from a donor, can be thawed and prepared on the day as well.
If a partner has no sperm in his ejaculate we can extract sperm directly from the testis performing a testicular biopsy. If there is any sperm in the sample we will find it to ensure every patient has the potential of having a baby of their own!
There are generally 2 different types of inseminations that can be used to fertilise the egg. One is “natural” IVF, then other is ICSI.
“Natural” IVF is when we put the egg surrounded with its support cells, together in a dish with thousands of sperm that have been prepared by the laboratory. This means that the sperm have to travel through the support cells, adhere and bind to the shell of the egg called the zona pellucida and then bind and fuse with the membrane of the egg. The sperm then needs to initiate a cascade of reactions for the egg to fertilise. All this means the sperm needs to be mature and have everything it needs to get through all the stages in the fertilisation process, so a form of natural sperm selection occurs with only the fittest sperm able to fertilise the egg.
Intracytoplasmic Sperm Injection (ICSI)
Patients that have not been able to achieve fertilisation with conventional insemination or whose sperm count is extremely low so not appropriate for conventional insemination can have eggs inseminated using ICSI. ICSI involves selecting and immobilising a single sperm and then injecting the sperm directly into the egg.
Only mature eggs can be inseminated. We know the eggs are mature as they have a small cell that sits between the shell, the zona pellucida, and the egg itself, this cell is called the polar body and contains half the genetic material of the egg.
Even though a sperm is deposited directly into the egg this does not mean that fertilisation is guaranteed. ICSI bypasses the physical barriers between the sperm and the egg however we still need the sperm to be able to initiate fertilisation when placed in the egg and we need the egg to be receptive.
Sperm Selection Methods:
HA Sperm Selection: HA Sperm selection with ICSI can be enhanced by using a substance called SpermSlow. SpermSlow is a viscous solution containing hyaluronan (HA) that slows the sperm and the embryologists can select the one that responds to the solution. (Video)
Intracytoplasmic Morphologically Selected Sperm Injection (IMSI) also allows for sperm selection using a magnification of greater than x6000. At this magnification, any sperm head defects, vacuoles or any visible abnormalities can be identified and these sperm will be excluded from use
Polarised Light Egg Visualisation: We can also visualise at the time of ICSI the inside of the egg and the shell of the egg to gain more information about the egg and maybe give insight to its behaviour if poor results have been achieved previously.
Fertilisation Check – On day 1, the day after the egg retrieval, we look at the eggs to see if they have fertilised. We can tell the eggs have fertilised when we see two circles within the eggs called pronuclei. The pronuclei are genetic material complements, one pronucleus comes from the egg and one that comes from the sperm. If there are no pronuclei then the egg has not fertilised and if there are too many then there has been abnormal fertilisation and we cannot culture those eggs further.
In the next few days the embryos undergo a process called cleavage, where they are constantly dividing. On day 5 embryos should be at the blastocyst stage – embryos at this stage usually have over 100 cells, and have two different cell types that can be distinguished. We do know that not all embryos make it to the blastocyst stage and this is because of lots of factors but the main factor seems to be because the embryo does not contain the correct chromosome copy number.
There are three option for viable embryos on day 5
- Transfer: Blastocysts may be transferred into the woman’s uterus under internal ultrasound guidance, in order to ensure the embryo is place in the correct position
- Frozen: Blastocysts may be frozen using a method called vitrification and used at a later date when we can thaw the blastocyst, having synchronised with the woman, and then transfer the thawed blastocyst. Vitrification is ultra rapid freezing which freezes the embryo so fast no ice forms in the embryo which can cause harm.
- PGT: The blastocyst may have a small number of outer cells biopsied and genetically tested either to determine if the blastocyst has the correct choromosome complement or to test for a known genetic disorder. All biopsied embryos are frozen and once the genetic information is know the “normal” embryos are thawed and transferred.