Day 3 or day 5 (blastocyst) embryo transfer – what’s better?

What percentage of 3 day embryos get to the blastocyst stage? Is the embryo transfer day important? What is the difference between a day 3 and a day 5 transfer? Which option should you choose?

If these questions sound familiar, you’re in the right place. Watch the webinar organized by EggDonationFriends and presented by Dr. Carmen Avilés Salas, a gynaecologist at the Reproduction Unit of Clínica Vistahermosa in Spain. Dr. Avilés is a member of the Spanish Society of Gynaecology and Obstetrics (SEGO) and Spanish Fertility Society (SEF). In her presentation, she explains the difference between 3-day and 5-day embryo transfer in minute detail.

Is it better to transfer embryos at the blastocyst stage?

Deciding whether to have a day three or day five embryo transfer is a hotly debated topic. Usually, it’s a decision made by the clinic’s embryologists and other doctors, who advise the patients as to why they believe it’s the best course of action.  But what is it that drives clinics to recommend one over the other, and which questions should clients be asking when faced with this choice?

IVF is used in order to create a viable embryo for transfer under laboratory conditions. Once an egg has undergone fertilisation, either by IVF or ICSI (where one sperm is injected directly into one egg) it is cultivated in an incubator and monitored by the clinic’s embryology team.

In natural conception, a fertilised egg would usually arrive at the uterine cavity at the blastocyst stage, five days after implantation; from there, it would go on to implant resulting in a pregnancy. As IVF aims to simulate this process, why would a three-day transfer even be contemplated, if an embryo wouldn’t naturally arrive in the uterus until day five?

Before starting to look at the arguments surrounding each option, it’s important to note that while a day five transfer may replicate the natural workings of the body more closely, day three transfers can – and do – result in pregnancy.

Not all embryos are created equal; various factors are known to affect their condition. Oocyte quality can be diminished due to reasons such as age or illness, while issues with sperm, such as DNA fragmentation can also affect the resulting embryo’s quality. Each embryo created is unique and will vary in both its development and quality, which is why monitoring embryos is a crucial part of the IVF process.

Clinics use a grading system, rating embryos according to their maximum implantation potential. In order to classify each embryo, labs monitor their development, gathering important information about each set of cells. This information is then used to determine whether transferring at cleavage (day three) or blastocyst (day five) stage is likely to offer the best chance of conception in each situation.

After fertilisation has taken place and the embryo has been created, an embryologist would expect the impregnated oocyte to begin its first cleavage division after approximately 24 hours. The hope then is that these cells continue doubling, reaching four cells after 48 hours, arriving at eight cells on day three. It’s this day three quality of each embryo, Dr. Avilés Salas advises, which is the key determinant for selecting at which stage the transfer should take place.

Alongside cell division, the number of embryos a patient also plays an integral part in the decision-making process. If a patient only has one or two healthy, eight-cell embryos on day three, then a cleavage stage transfer will usually be advised. This would also be the same for patients with lower quality, but viable embryos of perhaps six to seven cells after 72 hours, or embryos with fragmentation issues. It’s currently understood that for these types of embryos survival chances are increased in utero.

Even though a laboratory will replicate the conditions of the uterus as closely as possible, from the temperature to the humidity and oxygen levels, lower grade embryos are less likely to survive until the blastocyst stage in a clinical incubator. Simply put, under these circumstances, transferring an embryo into the uterine cavity on day three allows a greater possibility of pregnancy.

However, if the patient has more than three well-graded, equally divided embryos after 72 hours, then clinics would, most likely, continue cultivating them in an incubator and recommend transferring a blastocyst. A top-grade embryo would typically have the correct number of cells at each stage, and be regular in its appearance and shape; symmetrical, with no fragmentation.

Patients who have repeatedly failed to achieve a pregnancy when using day three embryos could also be offered the option of a blastocyst stage transfer, as would those requiring genetic analysis; Dr Avilés Salas reminds us that embryo biopsies cannot take place before day three.

Day 3 vs. day 5 embryo transfer success rates

When looking at pregnancy rates following three and five-day transfers, data from the Spanish Society of Fertility (SEF) shows that blastocyst (day 5) stage embryos do result in a higher pregnancy rate. Out of 51.2% of cleavage stage transfers, 37.9% ended with a pregnancy. However, out of 11.2% blastocyst transfers, 47.3% were recorded as ending with a positive test result. Both percentages were increased with the use of donor eggs.

While it may appear, that “blast is best”, Dr Avilés Salas advises that it’s important to note the much lower figure (11.2%) of day five transfers, when compared to those taking place on day three (51.2%) as recorded by SEF. She advises that blastocysts aren’t transferred as regularly as cleavage stage embryos, and this is due to the previously discussed reasons; the prevailing wisdom is that with lower quality – or lower amounts of embryos – the chance of pregnancy increases when the embryo is introduced earlier.

It’s a decision which can feel as though it’s out of our control and one which is very clinic led.

It’s important to raise the topic with consultants and embryologists in order to find the right solution for each patient. We should also remember that while we can use research, statistics, and data to aid us in our choices, each situation is different, every embryo is unique, and circumstances are rarely the same for everyone.

Other resources regarding day 3 vs. day 5 embryo transfer:

• Blastocyst culture – day 3 or day 5 embryo transfer?
• What’s recommended – single or multiple embryo transfer?
• Implantation window – its importance, and how to prepare for embryo transfer