FROZEN EMBRYO TRANSFER
A cycle of in vitro fertilization (IVF) can be completed using frozen embryos as well as fresh ones. This can be useful in several circumstances. If you have spare embryos after a successful IVF cycle, you can have a frozen embryo transfer (FET) cycle done a couple of years later to avoid having to stimulate your ovaries again. Frozen embryo transfer is also used for women who are using donated embryos.
After a successful IVF cycle, which may have included intracytoplasmic sperm injection (ICSI), one or two of the best embryos or blastocysts that developed are transferred into the uterus. If you have several other high-quality embryos, these are frozen quickly so that they can be stored for use in the future.
Freezing is safe for the embryo. Evidence shows that children born as a result of a frozen embryo transfer are no more likely to have birth defects than children born as a result of IVF with fresh embryos. How are embryos frozen and stored before frozen embryo transfer? Embryos are frozen using a vitrification technique. This involves rapid freezing to prevent any ice crystals forming in the cells of the embryo. The faster the freezing process, the more likely it is that a frozen embryo transfer will result in a successful pregnancy.
Frozen embryos are stored in a special solution in a sterile vial inside a container of liquid nitrogen, which has a temperature of minus 196 degrees Celsius. Labeling is done very carefully and the embryos can only be thawed with the written consent of both parents. Embryos are known to survive for many years once they are frozen, and embryos are currently allowed to be kept for 10 years.
PREPARING THE UTERUS FOR FROZEN EMBRYO TRANSFER
When you have an IVF cycle and use your fresh embryos, the uterus is ready to accept transfer of embryos. If you have a frozen embryo transfer cycle, you may have to have the transfer coordinated with your natural menstrual cycle (if you have one). This can be difficult because it requires constant monitoring to determine when you ovulate so that frozen embryo transfer can be done on the correct day.
Alternatively, your uterus can be prepared using hormone treatments. This involves:
• Suppressing your own natural hormone production using a drug that acts on your pituitary gland. This is usually done for two weeks so that you don’t ovulate unexpectedly before your frozen embryo transfer.
• Having estrogen treatment in the form of tablets, injections, skin patches or vaginal suppositories to mimic a normal menstrual cycle by encouraging the lining of the uterus to thicken. The form of estrogen given usually depends on your infertility clinic; all work equally well.
• Monitoring your uterus using trans-vaginal ultrasound and having regular blood tests to check your blood levels of estrogen.
• Progesterone treatment, which starts once the lining of your uterus, has thickened.
Taking the drug to suppress your pituitary gland usually stops at this point, but you carry on taking estrogen and progesterone together to fully mature the lining. Progesterone can be given in the form of a vaginal gel or suppositories or by injection. Tablets tend not to be used because the progesterone is not absorbed well.
Frozen embryo transfer then takes place a set number of days after progesterone treatment begins. The uterus is only ‘ready’ for a short time, and if this window of opportunity is missed, the treatment cycle needs to start again. Timing varies depending on whether the frozen embryo transfer is being done with 2–3 day embryos or 5–6 day embryos (frozen blastocyst embryo transfer). Blastocysts are usually transferred on day 5 of progesterone treatment.
HOW IS FROZEN EMBRYO TRANSFER ACHIEVED?
A frozen embryo transfer for 2–3 day embryos and blastocysts is done in exactly the same way as a fresh embryo transfer. Only some of the embryos are thawed to start with, a process that takes about an hour. These are checked and if two high-quality embryos are available, these are transferred into your uterus.
If you are using embryos frozen immediately after fertilization, when they are still at the pronuclear stage, the procedure is slightly different. As these embryos are literally only one cell at the point of freezing, there is no way to tell how good quality they are.
They must be thawed and cultured in the laboratory for at least 2–3 days until they reach a stage where they can be assessed and, if necessary, tested. This can make coordinating the process somewhat trickier as it means making sure the embryos and your uterus are ready on the same day.
Reasons for having a frozen embryo transfer
Vitrification of embryos is applied for:
• Storing supernumerary embryos from an IVF cycle
• Patients with a risk of ovarian hyperstimulation syndrome. Transfer will take place in a future non-stimulated cycle with success rate similar to a fresh cycle.
• Poor responder cycles (>39 or POF, ↓AMH). Good quality embryos from several natural or minimal stimulation cycles are vitrified. Normally we will have 1 or 2 good quality embryos maximum collected from each cycle. When enough good quality embryos are collected and vitrified, we will schedule the frozen embryo transfer maximizing the chance of pregnancy for these patients.
Frozen embryo transfer could be done either on cleavage stage embryos (D2 or Day 3) or Day 5 (blastocyst transfer). We perform Laser Assisted Hatching to all of our warmed embryos before transfer free of charge. Statistics show that using vitrified embryos to a subsequent non-stimulated cycle has similar or even better pregnancy rates than a fresh transfer.