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Frozen Embryo Transfer
A frozen embryo transfer is often abbreviated to FET.

Why are embryos frozen?
When a couple have a treatment cycle of IVF or ICSI the woman’s eggs are developed using injections of follicle stimulating hormone (FSH) and matured using an injection of human chorionic gonadotrophin (hCG). Generally six to ten eggs are ripened within the ovary and removed from the ovary at a procedure called an “egg pick up”. These are fertilised in the laboratory and generally 70% of mature eggs fertilise. 
To minimise the chances of a multiple pregnancy (twin or triplet) occurring, a maximum of two embryos are transferred to the uterus of the female partner. In most instances, a single embryo is transferred.  It is common to have more than one or two embryos by the time of the embryo transfer and so extra embryos can be frozen or stored at very low temperature (called cryopreservation). These frozen embryos can be thawed and transferred to the uterus at a later date.

When are embryos frozen?
Embryos can be stored at any stage from day 1 to day 6. 
If a woman is at risk of the condition called ovarian hyperstimulation embryos are often frozen at day 1, called the pronuclear stage. This is because embryos are most likely to survive the thawing process at this early stage. 
Sometimes embryos are frozen at day 3 and sometimes at day 5 or 6. 
Embryos are rarely frozen on day 4, because of the difficulties interpreting their survival when they are thawed.
Embryos are only frozen, providing a couple have signed a form consenting to the freezing of their embryos. This consent form will also ask the couple to decide on the disposal of any unwanted or unused embryos.

Why are only some embryos frozen?

Not all embryos are suitable for freezing as not all embryos manage to develop sufficiently well in the laboratory. Embryos, which are not well developed at the time of freezing, have little chance of resulting in a pregnancy; and therefore freezing all embryos can give couples false expectations and increased costs. Transfer of embryos that have divided at the appropriate rate and appear to have cells of equal size and shape, with little or no fragmentation have the greatest pregnancy rate. Therefore ACA adopts the policy that embryos that have developed to the 6-cell stage or greater by day 3 of culture can be frozen, providing they have little or no fragmentation. All embryos not suitable for freezing at day 3 will be cultured for a further three days and any good quality blastocysts will be frozen.  Sometimes all embryos are grown to day 5 and frozen at the blastocyst stage. The decision to freeze at different stages will be discussed with you and your partner by your doctor.

How long can a frozen embryo remain in storage?
Frozen embryos can be stored indefinitely. Australian regulatory authorities allow a maximum period of five years for embryo storage. Storage for greater than five years requires that a couple make a written application to prolong the storage for a further period of time.

How can a couple use frozen embryos?
The purpose of freezing embryos is to maximise the chance of achieving an ongoing pregnancy from a single IVF or ICSI cycle. Thawing and transferring a frozen embryo therefore allows a couple to achieve a pregnancy without the medical risks and costs of a fully stimulated IVF or ICSI cycle. 
Before a frozen embryo can be transferred, it is necessary for the lining of the uterus, (called the endometrium), to become thickened and receptive to the implantation of the embryo. Preparation of the endometrium is achieved in a number of ways. There is no research showing that one way is better than another for all women, and therefore the type of preparation will be discussed with you by your doctor. Once the endometrium is prepared the scientists will thaw the embryo or embryos.  Thawing the embryo(s) takes about half an hour and the scientist will look at the embryo under the microscope to determine if it has survived the thawing process.  Some embryos will survive the process fully intact, some will lose one or more cells, and others will fail to survive altogether.  Generally an embryo is thought to have survived the thawing process if half the cells or more remain after the thawing process. If fewer than half the cells have survived the scientist will thaw another embryo, if available. The embryo transfer is performed either a few hours or sometimes a few days after the thawing.

 Thawed Blastocyst

Thawed blastocyst

Reexpanded Blastocyst 2hr later

Re-expanded blastocyst 2 hours later

How is the uterus prepared for the transfer of a frozen embryo?
There are three main ways in which a uterus is prepared for the transfer of a thawed frozen embryo. The best method will be discussed with the couple by the doctor.
1.  Natural menstrual cycle.  If a woman is ovulating regularly the development of the egg within the ovary can be tracked by vaginal ultrasound scanning and blood testing of hormone levels. The thickness of the endometrium is measured at the time of the vaginal ultrasound.  Provided that the egg quality, hormone levels and endometrial thickness are normal the embryo is transferred to the uterus at the correct stage of the development.  Ovulation may occur naturally – following a surge of the hormone LH from the pituitary gland or can be initiated following the injection of a hormone called hCG – human chorionic gonadotrophin, which acts like LH to release the egg. The embryo is then transferred to the uterus an appropriate number of days later e.g. six days later if a blastocyst is transferred or four days later if a day 3 embryo is to be transferred. If a couple have intercourse during the cycle there may be a chance of spontaneous pregnancy in addition to the chance of success from the embryo transfer.
2.  Hormone replacement cycle.  This is often used if a woman is not ovulating regularly, has reduced number or quality of eggs, or has problems with endometrial thickening.  Sometimes a GnRH agonist has to be used to prevent egg development from the ovary interfering with the hormone levels, which affect the endometrium. An oestrogen preparation is given in tablet form to thicken the endometrium. The endometrium thickness is measured by vaginal ultrasound scanning and once it is the appropriate thickness a second hormone, called progesterone is administered vaginally. The embryo is transferred to the uterus at the appropriate time after the progesterone is commenced. Pregnancy testing is performed by blood testing and if the test is positive the hormones must be continued until about eight or nine weeks of pregnancy when the placenta produces enough hormones to keep the pregnancy in place.
3.  FSH ovulation induction.  This is used if a woman is not ovulating regularly but has sufficient eggs in the ovary to ovulate. This requires injections of FSH in lower doses than those used for an IVF or ICSI cycle. If more than two eggs develop in the ovary a couple may be asked to abstain from sexual intercourse because of the risk of a multiple pregnancy. Ovulation may be induced by the injection of hCG.

How successful is a FET?
Providing a frozen embryo has survived thawing fully intact and has demonstrated ongoing development in culture, it has the same chance of resulting in a pregnancy as one of an equivalent grade that has not been cryopreserved
What about couples who have religious or ethical objections to freezing embryos?
Couples who do not wish to freeze embryos, who are planning an IVF or ICSI cycle, need to discuss this with their doctor. In general only one or two embryos will be created from the eggs collected in order to avoid the generation of the extra embryos. This will reduce the overall success rate of an IVF or ICSI cycle.   

Can a couple make more embryos to store?
The recommendations of the NHMRC are that embryos cannot be created whilst a couple has more than l embryo in storage. Therefore a couple can proceed to create more embryos whilst none or only one embryo remains in storage. Should a couple have more than one embryo in storage they must have a FET before more embryos can be created.

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