Bath Fertility Centre: Embryos
Embryos
In this section:
Embryo Grading
The ‘quality’ of the embryos can be assessed when the zygote or fertilised egg has divided from a single cell into an embryo containing multiple cells. The process of cell division begins during the afternoon of day 1 as the single cell splits to produce a 2-cell embryo. At the time of the first assessment on day 2 of development we would hope the embryos to have divided into 4-cells, and if cultured until day 3 to have continued to divide to give an 8-cell embryo.
Embryos are graded according to their morphological appearance and are given a score that relates to their development at the time of assessment. This score will to help us select the embryo(s) for replacement which we consider to have the best potential to implant in the uterus and continue development to establish pregnancy. We make our choice based on an assessment of several factors as follows:
- Number of cells
- Regularity of cells
- Degree of fragmentation
- Nuclear content of cells
The assessment is carried out early in the morning to help us select those embryos making fastest progress, which, provided within normal range, is a good indicator of developmental potential. At this time we give each embryo a ‘score’ that is weighted according to the most important aspects of cellular development and based upon the parameters given above. We are then able to select embryos for replacement and set aside any others suitable for freezing.
While we believe that the scores we use give us an indication of potential, they are by no means definitive and are for the present time the best tool we have to help us make our choice. Numerous studies have shown that better score embryos have more chance of implanting. Much research has been done to try to improve our selection methods, but so far there has been no major improvement on currently available grading systems.
Blastocyst Culture
The most frequently asked questions about blastocyst is covered in this section:
- What is Blastocyst?
- Why culture blastocysts?
- Who is suitable for blastocyst culture?
- What are the risks of blastocyst culture?
What is a blastocyst?
A blastocyst is an embryo that has been allowed to develop for 5 days or more after egg collection / insemination. It looks like a hollow sphere and has 2 cell types, the cells around the surface of the sphere (‘trophectoderm’) which form the placenta, and an inner ball of cells, the ‘inner cell mass’ which forms the fetus itself. Until day 5 or 6 of development (days from egg collection) the blastocyst remains within the soft shell-like protective coating, the zona pellucida. Before a blastocyst can implant within the uterus it must hatch out of this coating.
Why culture blastocysts?
There are a number of reasons for suggesting blastocyst culture. Firstly, embryo selection: embryos that have developed as far as the blastocyst stage are fitter and stronger and thus may have more chance of implanting after transfer. Secondly the timing of a blastocyst transfer mimics natural conception as the embryos are replaced at the time they would normally reach the uterus (when they are almost ready to implant), so we know that uterine conditions at this time are ideal for the embryos. For some patients who appear to be at risk of developing OHSS, keeping the embryos growing in the laboratory for longer gives clinic staff extra time to see if OHSS is likely or not. If so, and a patient is not well enough for embryo replacement, we can safely freeze all embryos for use at a future date, or if OHSS symptoms are only mild and we consider it safe to do an embryo transfer we can proceed as originally planned. Finally, for those patients who definitely do not want a multiple pregnancy, we can transfer just one embryo at the blastocyst stage and still have a reasonable chance of pregnancy.
Who is suitable for blastocyst culture?
This technique is suitable only for some patients, as it depends on the number and quality of a couple’s embryos seen in the laboratory each day. Many embryos do not continue developing for five days in the laboratory and our experience has shown that less than half of embryos are capable of development into blastocysts. Very occasionally none reach this stage. Thus in order to progress with blastocyst culture we assess embryos daily to see if there are at least 6 top quality embryos each day, and if not we carry out embryo replacement on day 2 or 3 as usual.
Patients who do not have sufficient embryos for blastocyst culture are not at a disadvantage – the success rate for blastocyst culture and transfer is very similar to standard IVF.
What are the risks of blastocyst culture?
As already mentioned above, there is the possibility that none of the embryos survive to day 5. Unfortunately for a very small number of couples the embryos stop developing after day 3 and treatment stops at this point, without an embryo transfer. To minimise this risk we monitor embryo development daily, and on day 3 we tend to be extra cautious by recalling patients for transfer if we have even the slightest doubt as to the ongoing viability of the embryos. It is thought that as yet unidentified uterine factors can help ‘rescue’ embryos which appear to be slowing in their growth, since some embryos which have seemed to be arrested in development early on have resulted in healthy normal pregnancy after transfer.
Because less than half embryos reach blastocyst stage we tend to freeze fewer blastocysts than embryos at day 2 or 3 of development. However any excess good quality blastocysts remaining after transfer can be frozen, and pregnancy rates for frozen blastocysts are similar to embryos frozen at an earlier stage.
Embryo Transfer
- What happens during my embryo transfer?
- When will my embryos be transferred?
- How many embryos are transferred?
- Single embryo transfer
- If I chose to have a single embryo transferred, can the other embryos be frozen?
What happens during my embryo transfer?
The embryo transfer takes place in the Procedure Room of the clinic; the procedure should be quick and pain-free and only take 5-10 minutes. The embryos are loaded into specially designed transfer catheters and are replaced into the uterus by a member of the nursing team. If more than one embryo is being replaced, they will be transferred together in a tiny droplet of fluid. Once the embryos are inside the uterus they will settle into a niche in the lining where we would hope that they continue their development. Your partner can be with you at the time of the transfer, as with all appointments at the clinic we ask that you refrain from wearing perfume, aftershave and strong smelling cosmetic products.
When will my embryos be transferred?
The exact day of transfer will depend upon the number and the quality of the embryo available for selection. Embryo transfer may take place on day 2, day 3, day 4 or day 5 of development. The final decision about the most appropriate stage for embryo transfer may be made following grading on the morning of the transfer. An element of flexibility when planning transfers will be required as it is the development of the embryos that will dictate the best day for transfer.
How many embryos are transferred?
Patients usually chose to have one or two embryos transferred in a single cycle. Three embryos may be transferred in patients over 40 years of age in exceptional circumstances. The number of embryos recommended for transfer will depend on individual circumstances. Patients’ age, their treatment and obstetric history, and any underlying medical conditions will all be taken into consideration. The quality of the embryos will also guide the embryologists and clinicians when recommending the number of embryos for transfer.
We will ask you to consent to the transfer of embryos and request the number that you would like transferred.
Single embryo transfer
Where the chances of conception are high, the team may suggest that a single embryo be transferred; this will virtually eliminate the risk of a twin pregnancy occurring without substantially decreasing the chances of becoming pregnant. For those patients who chose to have a single embryo transferred the current ongoing pregnancy rate is 39%.
Single embryo transfer should be viewed as a positive step; it would mean that the chances of success are high.
If I chose to have a single embryo transferred, can the other embryos be frozen?
Surplus embryos can be stored for future use if they are deemed to be of good quality. If a single embryo is being recommended for transfer, the overall quality of the cohort of embryos is generally good, therefore opting for a single embryo will not result in the other embryos being ‘wasted’, they will simply be stored for later use. See section on Embryo freezing for further details.
Embryo Freezing
The most frequently asked questions about embryo freezing is covered in this section:
- Why freeze embryos?
- How are embryos frozen?
- Will my embryos be frozen?
- How do I use my frozen embryos?
- How successful is freezing embryos?
- Are there any risks with freezing and thawing embryos?
Why freeze embryos?
If there are embryos of sufficient quality remaining after embryo transfer we will continue to culture them to the blastocyst stage of development prior to freezing. Any blastocysts that have developed can then be frozen or cryopreserved for future use. Using stored embryos for future treatment avoids the need for stimulation, egg collection and fertilisation, and makes maximum use of these very precious resources.
How are embryos frozen?
The cryopreservation process uses a series of specially designed solutions that work to quickly dehydrate and stabilise the embryos before they are plunged directly into liquid nitrogen, this is known as Vitrification. Embryos are stored in small containers that hold a maximum of two embryos. This is followed by storage in large tanks of liquid nitrogen at the extremely cold temperature of minus 196 degrees. All tanks are fitted with alarms which notify us remotely 24 hours a day of any change in temperature which may require our attention.
Before embryos are stored we ask you to make some decisions about the storage – how long you wish to have them stored, what to do with them in the event of divorce, separation, incapacitating illness or death. These are all important decisions for you and your partner to consider, and we will contact you each year that your embryos remain stored to check that your wishes remain the same. If your circumstances have changed or you change your mind, you can contact us at any time to vary the conditions of storage.
Will my embryos be frozen?
Only the best grade embryos have the potential to withstand the freezing process which is somewhat stressful to the cells, and we expect an average 85% of embryos to survive freezing and thawing.
Rather than cryopreserve embryos that may not have the potential to continue their development and therefore result in a pregnancy, we aim to culture all good quality surplus embryos until day 5. At this stage in their development we would expect the embryos to have reached the blastocyst stage. Despite their apparent good quality in earlier stages of development it may be that very few or possibly none of the embryos will reach the blastocyst stage, meaning that the embryos could not be frozen. All suitable blastocysts will be stored for future use.
Embryo freezing should be regarded as a bonus - only about a third of couples will have embryos frozen in any one treatment cycle. There is no charge for the initial freezing of embryos and the first year of storage. Subsequently there is an annual storage fee (currently £175), payable in advance.
How do I use my frozen embryos?
Frozen embryos can be transferred in two types of treatment cycle: if you ovulate reliably embryos can be replaced in your natural cycle, otherwise you will need an ‘artificial’ cycle using drug therapy to prepare the endometrium to receive the embryos. Embryos will be carefully thawed at a time appropriate to their cell number, and the embryo transfer will be scheduled very carefully so that embryo stage and uterine receptivity coincide to ensure the optimum chance of success. The embryo transfer will be performed in the same manner as for your fresh embryos.
How successful is freezing embryos?
Pregnancy rates for frozen embryos transfers are significantly lower than for fresh embryo transfers but depend on the number and quality of embryos frozen. Typically they are between 10-20% per embryo transfer depending on the number, stage and survival of embryos frozen.
Are there any risks with freezing and thawing embryos?
As already mentioned, the greatest risk with freezing and thawing embryos is damage caused by the process itself, despite the care we take to minimise this. Not all embryos are able to withstand the stresses of the necessary dehydration for freezing and rehydration during thawing, hence a reduced survival rate and subsequent failure to resume division and growth for some embryos. This also accounts for the lower pregnancy rate following transfer of frozen-thawed embryos.
In a very few cases no embryos survive, or they may survive but all stop developing early. This means for these patients no embryo transfer takes place.
To date there is no conclusive evidence that freezing and thawing embryos causes long-term damage to them, but as with all assisted conception procedures the technology is relatively new and there have been no really long-term studies carried out. To the best of our current knowledge the techniques employed are safe and not harmful in any way.
Assisted Hatching
The most frequently asked questions about assisted hatching are covered in this section:
- What is assisted hatching and why is it done?
- Who is assisted hatching suitable for?
- Are there any risks in assisted hatching?
What is assisted hatching and why is it done?
In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) rely upon the implantation of one or more embryos transferred to achieve pregnancy. In order for this to happen an embryo needs to hatch out of its surrounding soft shell, the zona pellucida, when it reaches the blastocyst stage at 5-6 days old. There is evidence to suggest that this may be a problem for some patients’ embryos, where a thickened or hardened zona may not allow the hatching process to occur.
Assisted hatching is a laboratory technique where a small hole or slit is made in the shell of an embryo shortly before embryo transfer. When an embryo reaches the blastocyst stage this hole then allows the embryo to emerge (hatch) which may help it implant and establish a pregnancy.
Who is assisted hatching suitable for?
The majority of patients do not require assisted hatching. Studies indicate there may be improved implantation and pregnancy rates for certain groups of patients, including the following:
- Those who have failed to conceive following three or more IVF / ICSI cycles
- If the zona pellucida appears thicker than normal
Assisted hatching is a delicate technique requiring specialist equipment and skill, so there is an additional charge for this procedure. Please see ‘ Costs’ for details.
Are there any risks in assisted hatching?
Because the procedure involves cutting a hole in the zona it is possible that one or more embryos could be damaged during the procedure, although every effort is made to avoid this. The damage rate is less than 1%, and affects one or more cells of an embryo. These embryos can still be transferred if necessary and may retain full potential despite some damage, although we would usually select another suitable embryo to take their place if available.
Since the technique may increase the implantation rate it may also result in more patients having multiple pregnancies. It is also possible that a very small proportion of these multiple pregnancies could involve identical twinning, when a single embryo splits into two through the hole made.