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

Explained by: Carmen Avilés Salas, MD, PhD, UR Vistahermosa
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Day 3 or day 5 (blastocyst) embryo transfer – what’s better?
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The embryo transfer day – day 3 or day 5 (at the blastocyst stage)?

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:

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Questions and Answers from the event

What age of the egg donor would you say is the best to have good quality embryos?

Our donors are between 18 and 25 years old. Sometimes we can have a donor who is 30 years old but this is not usual. We think this is the best age (18-25) because we can have a good number of good quality eggs.

Is 8-cell transfer on day 3 or 5 the optimal cell count? Is 10 or 12 cell count best? (How many cells should an embryo have on day 3?)

If we transfer the embryo on day 3, it has to have 8 cells. If we transfer in the blastocyst stage, the embryo will have more or less 120 cells. We can prepare the transfer on day 3 or on day 5, we can’t perform the transfer on day 4, with about 16 cells – this is not the best option.

We had 9 donor eggs of which 7 fertilised but only 1 made a good blastocyst to embryo transfer day 5. I wonder what would cause only one embryo to progress to day 5 blastocyst. The donor was 21 years old. We were told the one blastocyst was good quality.

We have to take into account the quality, too. Because the egg is the most important cell to form an embryo but if the quality of the sperm is not adequate or we have genetic alteration, then some of the embryos don’t achieve the blastocyst stage. Probably it’s not only the quality of the eggs. We need to know what the quality of the sperm is to see what the problem is.

Is it true that sperm quality mostly affect embryo development from day 3?

It affects the embryo development from day 3, from the beginning and to the end. The sperm quality is very important. The genetic information determines if the embryos can achieve the blastocyst stage and result in pregnancy or not. The egg can solve some of the problems of the sperm, but not all of them. So sperm is important in the whole development of the embryo.

Is there a specific width you prefer for womb/uterine lining for egg transfer?

We perform egg transfer with thin endometrium (6.5 mm), but the best width to perform egg transfer is about 8 mm.

 

What is the main reason for poor fertilization after ICSI embryo transfer?

It’s a good question. The main reason can be the bad quality of the egg, but also the quality of sperm. If we have good quality eggs and good sperm, probably we will have good fertilization. But if one of them is not of good quality or the genetic information is not correct, there will be a low fertilization rate. It depends on the quality of the eggs and sperm.

I realise there must be a lot of different procedures depending on the recipient, but do you recommend egg hatching (assisted hatching)?

Egg hatching is something we can perform but it depends on the part of the embryo that is called pellucidum zone. It depends on the measurements of this part if we perform egg hatching or not. In egg donation, we usually don’t recommend this technique because it doesn’t improve the implantation rate. We recommend hatching when we do frozen embryo transfer or when we do transfer in the ICSI cycle in a woman who is about 40 years old. The quality of embryos is good and they are grade A because they don’t give us a higher success rate.

Would donor embryos be same as frozen blastocyst day 5?

As donor embryos, we can use frozen blastocysts or we can use frozen embryos on day 3. I have mentioned it before the devitrification success rate is 90% so there is no difference between 3 day vs. 5 day embryo transfer in case of devitrified embryos. We usually transfer frozen embryos on day 3 or blastocyst stage because the possibilities are usually higher. But not all the embryos achieve blastocyst stage.

I achieved 18 blastocysts from 3 cycles of my own eggs. Only one was euploid, a perfect grade A and failed to implant when transferred. Both my husband and I are 41 years old. My husband has sperm fragmentation of 15; 9% high fragmentation. Our IVF clinic believes that it is because the age of my eggs that we had 17 aneuploid blastocysts. Yet they say it is unusual that we achieved so many healthy blastocysts. Could my husband’s sperm also be a reason for the aneuploid blastocysts?

Your husband’s sperm can play a part, but the higher probability is that the reason is your eggs. We know that from the age of 35 the genetic material in our eggs is not the best. Probably the main cause of this situation is your eggs.

What do you find is the greatest challenge in your day 3 vs day 5 embryo transfer success rates?

The biggest challenge is the quality of the embryo on day 3 or day 5. If we have grade A embryo, the success rate could be higher than in grade C embryo. It is the same if it’s an embryo on day 3 or day 5. If we compare day 3 or day 5, we will have no chances for blastocysts most times. But the quality of the embryo is the most important thing.

Which protocol would you suggest for egg donation if the sperm morphology is very low? ICSI? IMSI?

We always use ICSI for fertilization in the egg donation program. IMSI doesn’t give us better fertilization rates, because it is something that can help only in very selective cases. When sperm morphology is very low, we will perform MACS that is a technique to improve sperm selection and fertilization with ICSI.

If an egg fails to implant such as in the scenario above (Sheena’s case), is there a procedure that helps embryo to implant?

I think you are asking if egg donation is an option here. Egg donation is an option because probably the eggs are the problem. It could an option to get pregnancy and increase the implantation rate.

OK, thank you for your answer. I just needed to be sure that the problem lies in my eggs before we proceed to donor eggs.

I understand you. There is no way to be sure about that, but the probability that the eggs are the cause is really high, because of your age and statistically, it is like this.

If you are 44, is day 3 or day 5 transfer more successful?

Probably if you are 44, you will have only a few embryos. Probably less than three, with 8 cells on day 3. As I have said before, it depends on the number of embryos on day 3 with 8 cells. If you have more than three, probably embryo on day 5 would be better; if you have less than 3 embryos, probably transfer on day 3 is the best option.

I had one good A grade egg that did not implant. Why?

Because of embryo development. It is important to see the development of the embryo.

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Authors
Carmen Avilés Salas, MD, PhD

Carmen Avilés Salas, MD, PhD

Dr. Carmen Avilés Salas is a specialist in reproductive medicine and genetics with over 15 years of experience graduated from Miguel Hernández University (Alicante, Spain). Currently, from 2018 she’s a Medical Director at PHI. She’s a Member of the SEGO (Spanish Society of Gynaecology and Obstetrics) and SEF (Spanish Fertility Society).
Event Moderator
Dorothy Walas

Dorothy Walas

Dorothy is a Data & Quality Manager at IVF Media Ltd. She has solid background in communication, social media, and content creation. She is always on the lookout for news in the IVF industry and is in touch with IVF organisations, writers, bloggers and clinics. Dorothy believes in transparency of the message sent to patients and easy access to IVF knowledge. She manages the website and social media content to educate patients, spread awareness about egg donation, bust the IVF myths and assist patients in making smart IVF decisions. Dorothy’s personal interests are strongly linked to her work; she is interested in biology, genetics and is an advocate of healthy and active living.

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