Choosing the best embryo

A day 3 embryo with 8 evenly sized cells, few fragments, graded A.

An expanding blastocyst (stage 4), with a clear clump of fetal cells (top left) (A), and a dense outer layer of placental cells (A), graded 4AA.

A 4AA blastocyst soon after thawing, before transfer. The blastocyst has contracted but will re-expand within a few hours.

EMBRYO selection does not increase the overall chance of a baby from all the embryos available, but it may reduce the time to pregnancy by transferring better embryos first. Day of transfer, embryo grading, timelapse imaging (TiMI) and pre-implantation genetic screening (PGT-A) are all ways of selecting embryos.

Day of transfer

It is only after day 3 that the embryo uses its own genes to drive growth. Only half the embryos picked as the best choice on day 3 turn out to be the best choice on day 5. If you have several fertilised eggs, it makes sense to wait until day 5, when embryos reach the blastocyst stage, to pick the best embryo to transfer. There is no extra cost for blastocyst culture.

What are the benefits of blastocyst culture?

• Blastocyst culture tells you more about the potential of your embryos • It offers better selection than appearance on day 3 • Because of these advantages, we now only freeze embryos which reach the blastocyst stage

What are the risks?

• Though uncommon, it’s possible for good embryos to stop growing in the lab unexpectedly, so there is no embryo to transfer. This is why we transfer embryos on day 2-3 when you have few embryos.

Day 3 grade

A

B

C Typical appearance

7 or 8 cells, even-sized cells, little cellular fragmentation

6 or more than 8 cells, some cells uneven or cellular fragmentation

Fewer than 6, uneven cells, fragmentation

Blastocyst grade Typical appearance

A Many fetal and placental cells

B

C Moderate number of fetal and placental cells

Few fetal or placental cells

Blastocyst stage Typical appearance

1-2 Early blastocyst, with small fluid space

3 The fluid space fills the centre of the blastocyst

4

5-6 The blastocyst has started to expand its diameter

Some or all of the blastocyst has hatched out of its embryo shell

Embryo grading

Embryologists grade embryos according to their appearance and rate of development. Embryos are graded A to C on day 3, where A is the highest grade. For blastocysts, we use stage of development between 1 and 6, plus A-C for the size of the clump of cells that will give rise to the fetus, and A-C for the number of cells that will give rise to the placenta.

When an embryo is frozen, its grade doesn’t change, although a blastocyst often contracts and may take a few hours to return to its original appearance. Generally, higher grade embryos have a higher chance of leading to a baby, but the difference between grades A and B can be quite small. Embryos that take 7 days to develop to a blastocyst or are grade C, have a lower chance of leading to a baby.

Time Lapse Morphometry Imaging (TiMI)

Photographing embryos every 10 minutes captures milestones in an embryo’s development that would otherwise be missed.

What are the benefits?

• Embryos are cultured in an uninterrupted environment and do not need to be taken out of the incubator for inspection • TiMI picks up unusual and detrimental events that would otherwise not be seen.

This identifies 10-15% of embryos with very low potential • Several studies show that using TiMI increases the chance of pregnancy using the first embryo transferred by up to 10%

Who may benefit?

• People who expect to have several good quality embryos • People who have had low quality embryos in previous IVF cycles may learn why their embryo development was poor. Aneuploidy screening (PGT-A)

Many blastocysts have the wrong number of chromosomes, which is called aneuploidy. The proportion of blastocysts with aneuploidy increases from 30% in women younger than 36 to over 80% for women in their early 40’s. Most aneuploid embryos cannot result in a pregnancy, so it makes sense to exclude these embryos. Aneuploidy can also lead to miscarriage or occasionally the birth of an affected child (e.g. Down Syndrome) PGT-A checks the number of chromosomes in each blastocyst by taking a biopsy of 5-6 cells. The blastocysts are frozen for later use, while the biopsied cells are sent to a specialist genetic laboratory for analysis. Blastocysts with a normal number of chromosomes are transferred later in a thaw cycle.

What are the benefits?

• Higher birth rate per embryo transferred • Lower miscarriage rate • Ability to screen embryos for chromosomal abnormalities that could result in having an affected child

Who may benefit?

• Women 38 and older with good ovarian reserve • Women who have had recurrent miscarriage • People not pregnant despite the transfer of several embryos – PGT-A may uncover a higher than expected chromosome abnormality rate • Patients who are willing to go through more than one egg collection cycle to obtain a normal embryo

Useful to know

• PGT-A can be used on embryos that have already been frozen, but some embryos will not survive the extra thawing, biopsy and refreezing • PGT-A does not pick up specific genetic diseases or conditions

What are the complications?

• PGT-A is about 96% accurate – so prenatal testing is still recommended • Some embryos may give complex results because the biopsy contains a mixture of normal and abnormal cells • Sometimes there will not be a result for a technical reason • Some people will not have any blastocysts suitable for biopsy or any normal embryos to transfer.

TiMI

This image shows 16 embryos around the time they divide from 1 cell to 2 cells. The timing of the first few cell divisions is related to the chance of an embryo becoming a blastocyst.

PGT-A

In PGT-A , 5-6 cells are removed using a fine glass needle, shown on the right.

PATHWAY TO A CHILD 73