Day 3 or Day 5 blastocyst embryos? An embryologist’s 101

There are so many hoops to jump, during IVF. Each stage is nerve-wracking, with myriad emotions riding on these precious embryos. It’s everything.

With every single day in the process representing a whole new milestone, there’s much deliberation over whether blastocyst embryos at Day 5 are preferable to embryos at Day 3. We picked up with expert embryologist and fertility blogger, Maryam Rahbar for her 101 on this all-consuming topic (if you know, you know).

The background

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 to things.

I completed my Bachelors in Biology at York University, Toronto, and then studied at the University of Oxford, completing my Masters in embryology. I’ll be going back to Oxford this year to start my PhD.

Having always admired the field of embryology – and wanting to pursue this career path from an early age – I was pretty set on immersing into this crucial area of reproductive medicine. My father actually owns a fertility clinic and is an established embryologist worldwide, so I had a great coach.

IVF embryo quality, and day 3 vs day 5

Nowadays, most clinics prefer to wait until Day 5 for embryo transfer during IVF.

There are some advantages and disadvantages to both Day 3 and Day 5, 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. Let’s say – and this is a very basic example – 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 are harder to predict

Day 3 assessment has less predictive value for subsequent embryo development. In plain English – it’s harder to predict how a Day 3 embryo will develop.

An embryo that looks great on Day 3 won’t necessarily develop to blastocyst. But with a blastocyst stage transfer, at Day 5, the embryos that could potentially maintain their developmental ability are chosen.

Plus, at the Day 5 stage, we can also grade the embryos. Whether this is done by the embryologist, or with new tech such as time-lapse, we’re more able to choose the best embryos for transfer.

A note on PGT

If the patient requires pre-implantation genetic testing, the embryos will have to be cultured until the blastocyst stage for the biopsy to take place.

At the blastocyst stage, cells are easier to differentiate. We can see more distinction between the trophoblast (which becomes the placenta) and the inner cell mass (which will form the baby). And, a few cells from the trophoblast can be biopsied and tested.

With this technique, we can avoid contact with the inner cell mass, but of course new research on less invasive techniques is constantly in development, which would greatly improve PGT-A/M (testing for aneuploidy and/or monogenetic disease).

So in the context of PGT, it’s considered an advantage to grow the embryos until blastocyst. That said, PGT-A/M isn’t recommended for all patients, as it’s still classed as an invasive technique, with debate ongoing around its impact.

Day 5 embryos

As I’ve covered, almost all clinics have now moved to Day 5 transfer, during IVF. However, we’re increasingly seeing a move towards more personalised medicine, within fertility treatment.

Let’s look at an example unrelated to fertility – if two patients show symptoms of bacterial infection, the same course of treatment may not be suitable for both. The same is starting to carry weight, when planning fertility treatment.

I agree that Day 5 transfers are optimal for most patients. But, the main conflict arises when the patient only has one or two embryos.

We need more randomised control trials in this area, but if a patient has only produced one egg, for example, 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?

So many different processes and reactions take place inside a woman’s body – many of which we’re yet to fully discover.

An embryo that might not make it to Day 5 in vitro (in the lab) may develop in vivo (inside the body) – 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 prepare for this, if it’s looking like 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 help us go for the embryo with the highest potential.

Day 3 vs. day 5 embryo transfer success rates

This is such a common question, and completely natural and expected.

One aspect of my training which comes up again and again is that biology is not maths. 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 done 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 often 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.

In my opinion, the move towards personalised and individual fertility care will benefit patients greatly. And, 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.

Keen for more behind-the-scenes expertise? Catch our day-in-the-life at Ireland’s most popular fertility clinic.