Treatments and investigations

CRYOPRESERVATION (FREEZING) OF EMBRYOS & FROZEN EMBRYO TRANSFER (FET)

When planning your IVF treatment, you may have decided to "bank" embryos which were surplus to your immediate embryo transfer requirements and store them for your future use. This means that from one IVF treatment cycle, you may have several opportunities of becoming pregnant. It also means that you can have children resulting from embryos that arose from the same IVF cycle, but were born several years apart because of the availability of cryopreservation techniques.

There may be other reasons to freeze your embryos:

  • Your IVF treatment may be abandoned after egg retrieval because of concerns that you are at risk of developing severe ovarian hyperstimulation syndrome (OHSS) (see Ovarian Hyperstimulation Syndrome information). In this situation, a fresh embryo transfer will not take place. Embryo transfer will be deferred and all suitable embryos will be frozen.
  • A malignant condition has been diagnosed and treatment for it is likely to affect your future fertility. There is usually time before surgery / radiotherapy / chemotherapy is due to commence, for an immediate IVF treatment cycle to be undertaken with storage of your embryos.
  • Some women will choose to postpone childbirth for a number of reasons and yet be very aware of the problems that may prevent them from becoming pregnant when they are older. They may decide to undergo IVF while still young and have embryos stored until such a time that they are ready to have a child. But there are risks to this approach. IVF itself is not without hazards (see IVF information) and as will be seen below, there is no guarantee of a pregnancy resulting from using frozen embryos.

Consenting to embryo storage

Before embryo storage is undertaken, it is essential that:

  • you are given full information as well as counselling about the implications of consenting to storage;
  • you are given adequate time to consider all aspects of storage;
  • you will have both had HIV and Hepatitis B & C screening as part of your IVF screening procedures;
  • you understand that you may vary or withdraw your consent at any time until the embryo has been transferred to a woman for treatment or used in research, by giving notice to the clinic storing the embryos. This means that if you as one of the gamete providers (the provider of the eggs or the provider of the sperm) withdraw consent to storage for treatment, the clinic cannot transfer those embryos and must take steps to inform the intended recipient of the withdrawal of consent; (from October 2009, the embryos can remain in storage for a further year from the date consent is withdrawn , to allow all interested parties time to give signed consent that the embryos may be destroyed);
  • you further understand that if the embryos were created using donor eggs or donor sperm, that the donors must consent to their use and storage. So in theory the situation could arise where embryos created from your eggs but with donor sperm could not be used for your treatment because the sperm donor has withdrawn his consent;
  • you must specify the length of time of embryo storage, the maximum permitted initial period of storage by law being 10 years). It is important that the clinic is informed if you change your address, as the clinic will need to contact you before the end of a period of storage, to learn if you wish to extend the period of storage, donate the embryos or have the embryos destroyed.

In a sense you a making a will, indicating what you wish should happen to your embryos in storage if you or your partner were to die or become incapacitated and unable to make decisions for yourselves. Your choices are that the embryos should be :

  • allowed to perish;
  • used for treatment by the surviving partner;
  • donated for someone else's treatment;
  • used for research;

You can also specify any other conditions you may have for the use of your embryos.

Cryopreservation

There are essentially two techniques of cryopreservation:

  1. In the standard freezing method, embryos are slowly frozen down to minus 196°C (the temperature of liquid nitrogen) with the risk of damaging ice crystal formation.
  2. A method of embryo storage has been developed called "vitrification". This is a fast freeze process where the embryo undergoes instantaneous "glass-like" solidification without the damaging formation of ice crystals. Vitrification is however, more expensive.

Your embryologist will only carry out cryopreservation for suitable embryos. You must appreciate that approximately 1 in 3 embryos may fail to survive the freezing and subsequent thawing out process when it comes to their future use. Although it would be very disappointing, sometimes none of the embryos survive the freeze/thaw. Very occasionally accidents can happen to embryos in storage. Fracture of a straw containing embryos could mean that those embryos might not be usable or even identifiable. In the event of this very rare occurrence you would be informed of the situation as soon as it was discovered. Theoretically it is possible that a fault could develop with an embryo storage container (dewar) with the loss of all the embryos within it Hopefully this disaster will never occur, but when reliance is put upon any form of technical equipment, there is always the possibility that something could malfunction. The dewars are fitted with auto-dialler alarms so that members of the embryology team are alerted even out of hours should the level of liquid nitrogen drop below a critical point.

FROZEN EMBRYO TRANSFER (FET)

FET treatments can be carried out either during a hormonally supported cycle or in a natural cycle.

Hormonally Supported FET Cycle

This is particularly helpful if your periods are very erratic or infrequent. Your pituitary gland is first "down-regulated" as in IVF (see IVF information) using daily injections or a nasal spray. Once down-regulation has been achieved and ultrasound scanning shows very thin endometrium, the process of building up the endometrium is commenced. To achieve this, you will take oestrogen hormone tablets as well as continuing to self-administer the daily down-regulation treatment, until the endometrial thickness is adequate on scan.

If it is considered that the endometrium is too thin, there is no question of thawing out embryos and wasting them in a cycle where there is no chance of implantation and pregnancy. The embryos will wait in storage until the endometrium is ready. The oestrogen dosage may need to be increased in order to achieve this.

Once the endometrium is satisfactory, the daily down-regulating injections are stopped. While continuing to take the oestrogen tablets, you will now commence using progesterone vaginal pessaries or cream to support the endometrium lining and hopefully encourage implantation.

Embryo thawing is timed so that FET is usually carried out after you have been on the progesterone for three days.

The timing of embryo thawing will depend upon the stage of development reached when cryopreservation was carried out. Embryos that have been frozen shortly after fertilisation at the so-called 2PN stage, are thawed the day before the planned FET, whereas more advanced (cleaved) embryos are thawed out on the day of FET.

The embryos are stored in vials, as single embryos, or in twos. It may happen that all the embryos you have in store will need to be thawed in order to obtain up to two that are suitable for transfer. Sadly, sometimes none of the embryos survive the freezing and thawing out process.

As in normal IVF, the maximum number of embryos that can be transferred is two unless you are over 40 years of age, when in exceptional circumstances three embryos may be transferred. However, transferring three embryos does run the increased risk of a multiple pregnancy.

FET is identical to fresh IVF embryo transfer. During the week after FET you are advised to lead a gentle existence if at all possible.

The oestrogen hormone tablets and progesterone preparation are continued either until a period occurs or until a pregnancy is well established.

Natural Cycle FET

This is a very straightforward process. From the pattern of your previous cycles the centre will know the most likely timing of the LH (luteinising hormone) surge that occurs 24 to 36 hours before spontaneous ovulation. If your periods are moderately irregular, ovulation can usually be made into a predictable event using fertility drugs e.g. clomifene. From about three days before the expected LH surge, you will be have either blood tests or may be asked to use an ovulation predictor kit on a morning urine sample each day.

On the day that blood or urine testing indicates the LH surge, the centre will contact you and arrange to see you in the next 24 to 48 hours to carry out a vaginal scan to determine whether or not the endometrium lining of the uterus has developed adequately. As in hormonally supported FET, the guiding principle is that the embryos will wait in storage until the endometrium is ready. Sometimes it can happen that the endometrium is inadequate in spite of there being an LH surge. In such cases the cycle would be abandoned and a future hormonally supported cycle would be planned.

As in hormonally supported cycles, the timing of embryo thawing will depend upon the stage of development reached when cryopreservation was carried out. 2PN embryos are thawed two days after the LH surge with a view to transfer the following day (LH surge + 3 days). Cleaved embryos are thawed out on the day of embryo transfer.

For sixteen days after FET you will be asked to use the vaginal progesterone preparation.

March 2009