Causes & Treatment

IVF Blog – Day 3 or Day 5 Blastocyst Embryos?

Maryam Rahbar | 30 Oct 2019

With IVF there are so many hoops to jump through. Each stage is nerve-wracking and all our emotions are riding on these precious embryos, often described as ‘embabies’. There is much deliberation over whether blastocyst embryos at Day 5 are preferable to Day 3 embryos, so we decided to ask an expert…

Over to Maryam Rahbar…

fertility101.wixsite.com | @fertility101blog

The Topic Up for Debate

Let’s talk about a topic that’s been debated all over the field of fertility: whether embryos should be transferred on Day 5 (as blastocysts) or Day 3 (at the cleavage stage).

I’ll briefly introduce myself. I’m an embryologist, and I’ve been working in this field for about three years, so you could say I’m quite new. I completed my Bachelors in Biology at York University, Toronto. I then studied at the University of Oxford, completing my Masters in embryology. I will be going back to Oxford this year to start my PhD. I grew up admiring the field of embryology and wanting to pursue this career path from an early age, because of my father. He’s the owner of a fertility clinic and an established embryologist worldwide, so I had a great coach. I truly love my job and anything related to reproduction and embryology.

Now, let’s talk about a topic that’s been debated all over the field of fertility: whether embryos should be transferred on Day 5 (as blastocysts) or Day 3 (at the cleavage stage). To this day, there are different opinions about it. Nowadays, most clinics prefer to wait until Day 5 for transfer. There are some advantages and disadvantages to both but in my opinion, the decision should be made taking into account each patient’s history and ongoing cycle. The main reason for the move towards a Day 5 transfer has been the result of us learning more about the potential of the embryo on Day 5. For example, if we have five embryos from ten fertilised eggs that develop to Day 5, we know that these embryos are stronger than the ones that did not develop, and therefore have a higher chance of resulting in a pregnancy.

Day 3 Embryos

Day 3 assessment has less predictive value for the subsequent embryo development. An embryo that looks great on Day 3 will not necessarily develop to blastocyst. With a blastocyst stage transfer the embryos that could potentially maintain their developmental ability in vivo are chosen. We can also grade the embryos at this stage. Whether this is done by the embryologist or with new gadgets such as time-laps or morphologically, the best embryos can be chosen for transfer

PGT

If the patient requires pre-implantation genetic testing, the embryos will have to be cultured until the blastocyst stage for the biopsy. At the blastocyst stage, the cells are easier to differentiate between the trophoblast (which becomes the placenta) and the inner cell mass (which will form the baby). A few cells from the trophoblast can be biopsied and tested. With this technique the inner cell mass can be avoided. There’s new research on less invasive techniques being developed, which would greatly improve PGT-A/M, meaning the embryos have to be frozen, and no fresh transfer will occur. It’s considered an advantage to growing the embryos until blastocyst. That said, PGT-A/M isn’t recommended for all patients, as it’s an invasive technique and new research suggests that it hasn’t had a significant impact for patients who didn’t require it.

Day 5 Embryos

Almost all clinics have moved to Day 5 transfer of embryos. However, research suggests we’ll see a move towards personalised medicine in fertility treatment. Let’s look at an example unrelated to fertility: if there are two patients showing the symptoms of bacterial infection, the same course of treatment may not be suitable for both. I agree that Day 5 transfers are much better for most patients. The main conflict arises when the patient only has one or two embryos. More randomised control trials need to be conducted to identify the best possible time for transfer. However, if there is a patient for example who only produced one egg, which fertilises and grows to Day 3 but doesn’t look that great, I would suggest transferring this Day 3 embryo.

How Many Day 3 Embryos Make it to Blastocyst?

There are many different reactions that take place inside the women’s body that we’re yet to fully discover. An embryo that might not make it to Day 5 in vitro, may develop in vivo – so there’s no reason to take that chance away if we know the embryo has a poor prognosis of making it to blastocyst in vitro. Therefore, for patients who have one embryo and may need a Day 3 transfer, it’s important to have them prepared for a Day 3 transfer, if that’s determined to be the best option. In another case, if a patient has ten eggs collected, with seven fertilised, it doesn’t make sense to transfer on Day 3 because a Day 5 transfer would ensure the transfer of the embryo with the highest potential.

I often get asked about Day 3 to Day 5 embryo survival rates…

Something from my training that comes up again and again is this: “biology is not math”. In biology, even if something theoretically should work, there’s no guarantee that it will. As embryologists, it’s our job to use good judgment to provide the best individualised care for patients.

Everything should be in accordance with the optimal condition and preparedness of the uterus for accepting the embryo. This is usually checked by ultrasound and blood work, to ensure the uterine lining and levels of progesterone are adequate. If the uterus doesn’t seem ready for implantation, it’s best to freeze the embryo and prepare for a frozen embryo transfer cycle – but the difference between fresh and frozen transfer cycles is a hot debate topic itself.

The move towards personalised and individual care is one that will benefit patients greatly – as for whether Day 3 or Day 5 transfer is best, I think the answer isn’t straight-forward, and should be determined on an individualised basis.