Frozen embryo transfer explained
IVF – a (brief) overview
Frozen embryo transfers (FETs) are a common addition to a fresh IVF cycle as they are used when surplus embryos are generated, or when a fresh embryo transfer is not possible. To better understand why FETs are performed, we first need to give a (very) brief overview of the steps of IVF that lead up to embryo transfer:
- Fertility consultation – with specialist staff
- IVF preparation – a number of tests and investigations to develop a personal IVF protocol
- Fertility medication & monitoring – stimulating egg development and tests to monitor progress
- ‘Trigger’ shot & egg retrieval – a carefully timed injection induces ovulation, and your clinician retrieves your eggs
- Fertilisation – your eggs and your partner’s/donor’s sperm are combined in vitro to produce embryos
At this stage one the most significant divergences in the IVF pathway occurs. Some patients may, under the advice of their clinician, undertake additional embryo testing, such as Pre-implantation Testing for Aneuploidies (PGT-A, formerly PGS) or Pre-implantation Testing for Monogenic Diseases (PGT-M, formerly PGD). Additional variations depend on your IVF protocol – particularly whether or not you will be having a ‘fresh’ or ‘frozen’ embryo transfer.
What is an embryo transfer?
After the embryology team have enabled fertilisation of the egg by the sperm, embryo development begins. If your embryos are to be screened, an embryologist will perform an embryo biopsy – carefully removing several cells for subsequent testing at a reproductive genetics laboratory. Once test results are available, a decision is made about which embryos are suitable and the embryo(s) is placed directly into the mother’s uterus (womb)–- this process is known as embryo transfer.
The most important milestones for embryo development at this point in the IVF process are:
- Day 3 – cleavage stage – this is generally the earliest time that an embryo biopsy or embryo transfer will occur
- Day 5/6 – blastocyst stage – two distinct cell types form – an inner cell mass develops, which will subsequently form the embryo and trophectoderm, which will form the placenta.
Research has found little difference between day 3 or 5 embryo transfers1 in terms of success from an entire IVF cycle. In most clinics, however, day 5 is now the most common developmental stage for both biopsy and transfer because this approach can reduce the time to pregnancy.
In addition to testing to ensuring the viability/genetic health of the embryo (PGT-A/M), research has also highlighted the importance of the endometrial factor. The endometrium lines the uterus (womb) and is the tissue into which the embryo is placed during embryo transfer. It is crucial to ensure that the endometrium is both receptive to implantation, and hospitable to further embryo development.
Read more: Endometritis: no symptoms, no problem?
Fresh and frozen transfer – what’s the difference?
The most significant difference between a ‘fresh’ and ‘frozen’ transfer is simple: timing.
In a fresh cycle, after 3, 5 (or 6) days of development, your embryo will be transferred to your uterus to implant in the endometrium.
In contrast, during a so-called ‘freeze-all’ cycle, all of your embryos will be allowed to develop – typically until day 5 – at which point the embryology team will perform a process called vitrification to preserve the embryos. This is an ultra-rapid freezing process that occurs so quickly that dangerous water crystals are not able to form, and the embryo is not damaged. In theory, the embryo can be stored in this state indefinitely and the freezing process does not hinder future embryo development2.
In many cases, your IVF protocol will be a combination of both types – a fresh embryo (or more) may be transferred, whilst your surplus embryos are vitrified for future transfer.
Unlike in a fresh transfer, frozen embryos are not immediately transferred – instead they are stored until you are ready to transfer, at which point they will be thawed. Many patients going through IVF can be put off by the idea of delaying the process, but there are clear advantages, as we will see.
Why perform a frozen embryo transfer?
The advantages of FET are centred around the key difference that we have already mentioned: timing.
In a fresh cycle, your clinical team have only 3-5 days to ensure that everything is perfect in time for embryo transfer – optimisation of the endometrium, embryo, your hormone levels, and many more factors must be assured to maximise your chance of success. In a frozen cycle, this time constraint is removed, and both you and your clinicians have the opportunity to fully prepare.
Here are some specific benefits of the extra time available in an FET:
- Embryo testing – there are significant difficulties in completing embryo testing (PGT-A/M, discussed above) in the short time available in a fresh cycle. An FET makes it much easier to analyse the embryos ready for your transfer.
- Personalised embryo transfer – for around one-third of women3, the ‘theoretical’ optimal time to transfer an embryo is not correct. A frozen transfer allows for specific testing of endometrial receptivity (ERA) to determine your personal window of implantation and give you the best chance of success.
These tests (and, consequently, an FET) are particularly recommended for women over the age of 35, or those who have experienced multiple IVF failures or miscarriage. Over recent years in the UK, there has been a general shift towards FETs as new research has shown the effectiveness of undertaking other investigations that help to maximise the chances of successful implantation and pregnancy. Of course, your specific IVF protocol must be tailored to you as an individual – your doctor should work with you to help you decide what is best for you.
- Coskun, S. et al. “Day 5 versus day 3 embryo transfer: a controlled randomized trial” Human Reproduction vol 15,9 (2000): 1947-1952 doi: https://doi.org/10.1093/humrep/15.9.1947
- Raju, G.A.A.R. et al, “ Neonatal outcome after vitrified day 3 embryo transfers: a preliminary study” Fertility and Sterility vol 92,1 (2009): 143-148 doi: https://doi.org/10.1016/j.fertnstert.2008.05.014