How embryos develop – from egg retrieval to blastocyst

All the embryos in our lab are grown in time-lapse incubators so we can constantly monitor their development and environment. We do not disturb the incubation of the embryos from the time we inseminate them (via intracytoplasmic sperm injection, known as ICSI) or the time we check for fertilisation (in traditional IVF) until day 3, when we replenish the culture media (the liquid the embryo is bathed in). The embryos are grown in replenished culture media that facilitates embryo development in the second phase of their growth. The media replenishment occurs in bespoke IVF chambers that control the environment and takes place within a few minutes, providing a safe environment for the embryos. Our culture system is highly supportive of embryo development. The embryos are grown up to day 6 after insemination until they reach the blastocyst stage.

Once the eggs have fertilised, we watch them grow and observe their developmental milestones. Some embryos show signs that suggest they may have reduced ability to reach the blastocyst stage. This may be a result of genetic, structural or metabolic issues.

Usually around 30–50% of fertilised eggs become blastocysts. However, this is dependent mainly on maternal age, the reason for infertility and the resulting quality of the embryos. Generally, patients <35 years of age at the time of egg retrieval will have around 50% of the embryos reach the blastocyst stage. Patients 40 years and older will be closer to 30%. Of course, individual results vary greatly.

Egg quality is further influenced by diet and lifestyle factors. By addressing these modifiable factors and prioritising your overall wellbeing, you can boost your chances of conception and a healthy pregnancy.

Find out more: ‘Is there anything I can do to improve my egg quality?’

Many embryos stop growing because they exhibit chromosomal errors (genetic errors) that are ‘lethal’ for the embryo. For a comprehensive discussion, please read ‘Why did my embryos stop growing’.

We expect to see the first embryo division around 24 hours after the egg and the sperm are combined (insemination). Generally, the zygote (fertilised egg) divides from a 1-cell to an even 2-cell stage embryo. However, sometimes the zygote may divide from 1-cell to 3 or 4-cells. This is known as multipolar division and may disrupt normal development. This can happen due to faults in the cell structures involved in cell division, poor energy production, or genetic or structural issues with the egg or sperm.

Embryos with irregular cell division have a lower chance of reaching the blastocyst stage because the DNA may not have divided correctly. These embryos may also have incomplete DNA replication or misalignment (an error in replication), which can result in embryos with missing or extra chromosomes (aneuploidy).

Human embryos are susceptible to fragmentation, which is when little pieces of the cell break off during cell division. A small amount of fragmentation may not affect the ability of the embryo to become a blastocyst. However, when there is considerable fragmentation and it affects several cells, the embryo is less likely to become a blastocyst. When we see large amounts of fragmentation across a set of embryos, we know the number of usable blastocysts may be lower in that cycle.

Scientists are still learning about the causes of fragmentation. There are many suggested reasons why an embryo may fragment, including sperm or egg quality, advanced maternal age, chromosomal abnormalities, adverse culture conditions (their environment), irregularities with the cell cycle, or cells undergoing apoptosis (programmed cell death). We cannot determine the causes of the fragmentation. Some patients may only experience fragmentation in a single cycle, whereas others may experience embryos that continually undergo fragmentation despite interventions.

Sometimes a single cell within the embryo may be excluded, meaning it is separate from the embryo’s main structure. This may be an embryo’s way of removing unwanted cells that are irregular. The exclusion of a cell or a few cells doesn’t affect the developmental potential of the embryo and it can still reach the blastocyst stage.

Both the egg and the sperm can affect embryo development. Although the quality of the egg is critical, sperm do play a significant role in the steps of embryo development. Genetic abnormalities, including abnormal chromosomal structure, increased DNA fragmentation and defective chromatin content, have been associated with poor growth or developmental arrest (where growth stops). Some sperm issues can also be linked to irregular division. Unfortunately, as we can only observe what happens to the embryos and cannot see what is happening internally, we are not able to determine if problems with embryo development are linked specifically to either the sperm or egg, or both. Find out more.

Newlife IVF uses multiple sources of data when selecting which embryos are suitable for transfer to the uterus. These include our internal blastocyst grading system, the appearance and timing of development throughout the 5–6 days while the embryo is grown in the laboratory, together with artificial intelligence (AI). AI in our time-lapse system uses algorithms to score the embryos based on appearance, timing of divisions and other cell cycle events. Like all technology, AI does have its limitations, which is why we use it to support decisions along with our grading system and the embryologist’s regular examinations.

Not all embryos are frozen during IVF. Chosen embryos must meet certain quality standards based on their potential to be viable embryos. Embryologists assess embryos based on:

• Developmental stage: Embryos that reach the blastocyst stage by day 5 or 6 are more likely to implant successfully. Embryos are assessed based on:
  – Expansion: How well the embryo has expanded and formed a fluid-filled cavity (blastocoele)
  – Inner cell mass (ICM): A high-quality ICM is dense with well-organised cells
  – Trophectoderm (TE): The outer layer of cells that will form the placenta. Healthy blastocysts have a clearly visible trophectoderm.
• Viability for freezing and thawing: Only embryos with an appropriate number of healthy ICM and TE cells can survive the freezing and thawing process and will be selected for freezing.

If an embryo does not meet these criteria, it may not be frozen, as it may not be viable for transfer after thawing.