Day 5 vs. Day 3 Embryo Transfer – What Are the Pros & Cons?

The Embryo Transfer (ET) is the last step of the In Vitro Fertilization (IVF) process. If the cycle has been a successful one, the patient will get a positive pregnancy test on day 15 post embryo transfer. In other words, she will be able to confirm whether she is pregnant and the treatment has been successful.

Determining the best day for the embryo transfer actually depends on the progression of each patient through the IVF process from the beginning. Keeping this in mind, your IVF coordinator will choose between doing the embryo transfer on day 3 or day 5 of embryo development.

Nowadays, most specialists have a preference for single blastocyst embryo transfers (day 5) in order to prevent multiple pregnancies. The main advantage of blastocyst transfers is that the implantation rates are higher.

Definition of Embryo Transfer

Embryo Transfer (ET) is a fundamental step of IVF procedures whereby the embryo or embryos are placed into the womb of the prospective mother.

In anticipation of the embryo transfer due date, the embryologist has to make two important decisions at the beginning of every transfer cycle:

How many embryos to transfer

Although there is no legal limit as regards the number of embryos to transfer, experts agree that betting on Single Embryo Transfers (SETs) is the best option to prevent multiple births, which increase the number of risks for the woman and the baby.

What's the best day for the transfer

Embryos can be transferred at any stage, that is, from day 1 up until day 6 or 7. However, embryo transfers are typically performed on day 2-3 or day 5-6 because it is at these stages when their quality can be determined with accuracy.

Embryo transfer on day 3 or 5?

Determining the best day for the ET has been a controversial issue for a long time, mainly because there are studies proving that high success rates can be reached on both days.

Day 3 Embryo Transfer

When conception occurs naturally, fertilization takes place in the Fallopian tubes of the woman. After egg fertilization, the embryo begins a journey toward the uterus. That's where embryo implantation occurs.

Embryo implantation in natural pregnancy

But in cases of assisted conception, the embryos are cultured in the laboratory prior to the transfer. Given that the environment surrounding the embryo(s) is obviously different from the conditions of the female reproductive tract, experts need to reduce the number of days during which the embryo is supported in culture media at the laboratory.

So, firstly, we shall explain the main pros and cons of choosing a day 3 embryo transfer:

Pros

The main benefit of day 3 embryo transfers is that there is a larger number of embryos ready to be transferred.

While embryos develop in the culture media, some may cease their development early and become non-viable. This is the reason why some embryologists prefer day 3 transfers, when the embryos have between 6 and 8 cells.

Pros of day 3 embryo transfers

To sum up, we can say that the risk of cancellation on day 3 is lower than if culture is extended to up to day 5-6, Moreover, the number of embryos available for freezing is higher, should you wish to use them in future cycles.

Cons

The different methods used for morphological scoring of pre-implantation embryos are insufficient to select the embryo with the greatest implantation potential.

Even if the embryo with the best apparent quality were selected, there is no definitive proof that embryonic arrest is not going to occur anyway after the embryo transfer. In other words, with day 3 transfers, the risk for the embryo to be a non-viable one is still there.

Embryos that are able to grow from cell stage (day 3) to blastocyst stage (day 5) go through a critical phase that may compromise their viability.

Day 3 embryo transfer disadvantages

Given the high likelihood of early embryonic arrest with SETs, transferring two or even three embryos on day 3 is a common practice. This, at the same time, increases the chances for becoming pregnant with twins or more, with the subsequent risks associated for both the mother-to-be and the babies.

Day 5 Embryo Transfer

Embryo culture using sequential media involves keeping the embryos in the culture media for 5 days. On day 5, the embryos become blastocysts. This complicates things a little bit, as the embryologist will have to pay special attention to the metabolic requirements of the embryos, as they change from day 3 onwards.

As in the case of day 3 embryos, day 5 embryo transfers have a series of advantages and disadvantages that we will explain below:

Pros

In cases where egg fertilization results in multiple embryos, extended embryo culture to day 5 may be a good option. The main advantage is that the embryo with the highest implantation potential is selected "naturally"—most embryos with chromosomal abnormalities are unable to make it to day 5-6.

Advantages of transfer on day 5 of development

Also, the embryo morphology score is more accurate on day 5 than on day 3, as it is more likely to be in line with embryo quality.

Blastocyst embryo transfers can be synchronized with the endometrial lining, which is a major advantage as well, keeping in mind that embryos do not attach to the uterus until day 5 when conception occurs naturally. In other words, the endometrium is more receptive on day 5.

Finally, selecting the embryo with the biggest chance of implanting to the uterus increases the success rates of single embryo transfers, thereby preventing multiple pregnancies.

Cons

In spite of all the advantages, it is still possible for genetically normal embryos are unable to make it to blastocyst stage due to inadequate IVF culture media conditions in the lab.

When pregnancy occurs naturally, the embryo travels through the uterine cavity on day 4 and comes into contact with endometrial cells, which produce molecules that nourish it. For this reason, having the adequate culture media and temperature, humidity, and light conditions can promote embryo development.

Disadvantages of blastocyst transfer

On the other side of the coin, embryo transfer cancellation rates are significantly higher in the day 5-6 group, especially if the number of eggs retrieved is low.

Customized IVF treatment

Irrespective of the opinion of each professional on the best moment for the embryo transfer, embryologists and specialists agree on the need for customizing each treatment cycle.

As a matter of fact, in the words of embryologist Aitziber Domingo, generalizing about the day of the embryo transfer is not possible. She agrees that each patient should be treated individually, evaluating each case on an individual basis.

Aitziber Domingo, BSc, MSc

Determining the embryo transfer due date based on each patient's circumstances is the most recommended option. The following are some of the aspects that determine a day 3 or day 5 embryo transfer:

• Number of embryos obtained
• Embryo quality
• Previous IVF cycle information
• Use of additional techniques: PGD, egg donation, ERA test...
• Conditions of the laboratory

Personalising the timing of embryo transfer

When Preimplantation Genetic Diagnosis (PGD) is required, the embryo is biopsied on day 3 and the results of the genetic screening is typically available within 25-48 hours. So, in these cases, the embryo transfer is done on day 5, which is to say, when the embryos have reached the blastocyst stage.

Extended embryo culture is used in IVF with donor egg cycles as well, given the higher number of good quality embryos available. Success rates of single embryo transfers in donor-egg cycles are amongst the highest.

Finally, when uterine receptivity problems are detected and an ERA test is needed, the embryo transfer will be scheduled for the most appropriate moment of the implantation window, depending on the results of the test.

How to make a decision

Dr. Antonio Forgiarini states that there is actually not an "ideal" day for performing the embryo transfer. It depends basically on endometrial receptivity.

The most important thing to do during the process is to pay attention to the endometrial lining while the embryos are developing, that is to say, that there is synchrony between them. Keeping that in mind, deciding the day of the transfer will depend on many other factors.

Antonio Forgiarini, MD, MSc

In any case, such difficult decision is made by the medical staff but also by the patient or patients. At this point, physician and other staff from the clinic should inform patients about the risks and benefits of each option in order to help them to make a well informed choice.

FAQs from users

What day is best for embryo transfer? the 3rd or 5th day?

Embryonic development in the first few days of the embryo's life is very fast. The embryos that follow a normal development, on the third day of life have about 8 cells and, on the fifth day of life, they are already a structure called a blastocyst, which has more than 200 cells, with an internal cell mass (the part that will form the baby) and a trophectoderm (the part that will form the placenta) already defined.

During this development process, a first selection already occurs in the laboratory itself, since not all embryos reach the blastocyst stage. In fact, some embryos that show good characteristics on day 3 do not reach day 5 (they are blocked or their quality is not good enough).

In this sense, we have more information on embryo quality on the 5th day of development and we can better select which embryos are most likely to give an evolving pregnancy. For this reason, the current trend in most assisted reproduction centres is to transfer on the fifth day of development.

What are the success rates with blastocyst embryo culture?

By blastocyst culture we refer to keeping the embryos in the incubator until day 5-6 of development, that is, until they reach blastocyst stage. By doing this, we perform a much more thorough embryo selection process. The fact they they are capable of making it to blastocyst means that they have a greater implantation potential, as it was able to stay longer in the lab. Pregnancy success rates depend on age, though.

Can the embryo transfer be done on day 3 after PGD?

Today, over 90% of the embryo biopsies that are performed for a PGD procedure are done on day 5, which makes it impossible for embryos to be transferred on day 3. In any case, when the biopsy is carried out on day 3, the result won't be available until day 5, so the embryos will be transferred on day 5 anyway.

I have a history of recurrent miscarriage, when should the embryo transfer be done in my case?

The fact that a woman has had repeated miscarriages in the past has nothing to do with the day of the embryo transfer. In most of the cases, it is associated with the chromosomes of the embryos. Keeping this in mind, ideally the best treatment option in these cases would be IVF with PGD (Preimplantation Genetic Diagnosis). With PGD, we examine 6-8 cells of each embryo. It allows us to find out which embryos are genetically norma and which don't.

What are the advantages of transferring on day 5 compared to day 3?

Existing evidence shows that culturing embryos till stage 5-6 of development, we can increase the pregnancy success rates per fresh and frozen embryo transfer. This is due to the fact that the embryos to transfer or cryopreserve can be selected more properly, since blastocysts have a higher implantation potential. It also improves embryo-endometrial synchrony.

One should keep in mind that about 50 percent of viable embryos will arrest on day 3 of development. In other words, they will not make it to blastocyst stage.

How many embryos should be transferred on day 5?

With day 5 transfers, a major advantage is that we can transfer one embryo without diminishing the success rates, while at the same time the risk for multiple pregnancy is eliminated. The decision depends on the prognosis category for each patient.

How many day 3 embryos make it to blastocyst?

It is estimated that only 20 to 50 percent of day 2-3 embryos are actually able to develop in vitro to day 5, irrespective of the quality of the culture system used. So, one of the main risks of extended culture to day 5 is that there may be a loss of some embryos that would have implanted if they had been transferred earlier.

Is a day 3 or day 5 embryo transfer better?

It depends on each patient. According to the ASRM and SART guidelines, those with a favorable prognosis should opt for 1 embryo transfer, regardless of embryo stage. From ages 38-40, they recommend 2 blastocyst embryo transfers (day 5), and from age 41, 3 blastocysts (day 5) as well.

Can you perform an embryo transfer on day 6?

Yes. Embryo transfers on day 6 are performed when embryo development to blastocyst stage goes slower than usual and it the embryologist determines that doing it on day 6 is the best option.

What percentage of embryos make it to day 5 blastocyst?

It is estimated that only 20-50% of day two embryos can continue developing in vitro to day 5, irrespective of how perfect the in vitro culture system is.

Is day 4 a good day to perform the embryo transfer?

No, this option is not recommended because on day 4 the embryos are at the morula stage. Determining embryo quality at this stage is considerably complicated and, for this reason, it is not possible to determine what's the best moment for the transfer.

Suggested for you

Presently, the selection of the embryos to transfer is done based on their morphology and morphokinetics. To learn more about the criteria followed, visit the following post: Embryo Quality & Grading.

Elective single embryo transfers (eSETs) is becoming an increasingly popular option for patients with mild infertility problems amongst clinics from all around the world. In any case, each patient is different and the transfer cycle should fit her individual needs. Click here to read more: How Many Embryos Should You Transfer for IVF?

The next phase after the ET is the so-called two-week wait or 2WW. Surviving this period is complicated for some women. Want to learn more? Read: Post Embryo Transfer Tips & Precautions – What Should You Expect?