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What is the Morula Stage, and Why is it Important in IVF?

Oct 18, 2024

It’s hard to imagine that cells more petite than a grain of sand could grow to form a beautiful baby, right from their head of hair to their cute tiny toes. In fact, it’s difficult even to consider what a cluster of cells looks like, and your fertility doctor won’t expect you to be handy with a microscope! 

Embryo development comprises small but monumental moments that are just as important to track as your baby’s growth after birth. Understanding the stages of embryo development helps you feel more comfortable and engaged during your IVF journey. Recognizing the differences between each phase—including the crucial morula stage—makes you feel connected to your baby and reassured that the growth milestones are happening as expected. 

Understanding early embryo development

The morula stage fits into the broader process of early post-fertilization embryo development. Before we explore the details of the morula stage, it’s essential for you to be able to visualize the bigger picture. Remember that all this happens before the embryo transfer—so your fertility doctor will monitor the development stages in the lab under a microscope. 

Day 1-2 – Fertilization: The male gamete (sperm) unites with the female gamete (egg). Gamete is just a fancy word for “reproductive cell.” During IVF, the fertilization process occurs in the lab. When the sperm and egg combine, they form a fertilized cell called a zygote. 

Day 3 – Cleavage stage: The zygote (the fertilized egg) divides twice or thrice. Although the zygote is dividing (also referred to as “cleaving”), it doesn’t grow bigger in size or mass yet. 

Day 4 – Morula stage: The cells inside the zygote continue to divide, and the number of cells doubles each time. When this number reaches a cluster of approximately 16, it’s called the morula stage. It’s also around this time that embryologists perform embryo grading (more on this later).

Cells divide to form the Morula

This graphic shows how the cells divide to form the morula. 

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Day 5—Blastocyst stage: The embryo develops a unique cell structure: fetal cells (which form an inner cell mass) and placental cells (also called trophectoderm, or the outer cell mass—kind of like a shell). It also develops a fluid-filled cavity that hatches out of the “shell.”

Day 6-14 – Implantation: After it hatches, the embryo begins to attach to the wall of your uterus (“uterine wall”). It burrows further into the wall and embeds itself. If the implantation is successful, your body will produce the hCG hormone, which signals a developing pregnancy and will trigger a positive pregnancy test.  

Day 14-21—Gastrulation: Until now, the embryo has been a simple ball of cells. At the gastrulation stage, it turns into a complex, multi-layered structure of cells that will eventually develop into organs, tissues, and more. 

Blastula and Gastrula

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What is the morula stage?

The morula stage is a crucial stage of embryo development that usually occurs during day 4 after fertilization (or occasionally on day 5) before the embryo’s blastocoel cavity (the fluid-filled cavity) forms. At this point, the embryo will comprise 16 cells (also called blastomeres) clustered together. Though most industry resources define the number of cells at this stage as 16, different clinics may suggest a different number, ranging from 12 to 32.

These cells are arranged in a tight cluster with a spherical shape and are totipotent (meaning the cells can become any cell type, such as skin or muscle). 

The embryo cells at the beginning of the morula stage are spherical. Throughout the morula stage, the shapes undergo compaction and become polygonal. Embryologists consider a morula fully compacted when most of the embryo has undergone compaction.

If you were to see the morula under a microscope, you’d notice that it resembles the shape of a mulberry. Here’s a fun fact: the word “morula” comes from the Latin word for mulberry, “morus!”

Morula

This graphic shows what the morula looks like. 

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Why is the morula stage critical in IVF?

The morula stage is vital in IVF because it can give embryologists valuable insights into the quality of the embryos. These insights help them choose the healthiest embryos for transfer during embryo grading. 

Embryo grading is monitoring the health of your embryos and, using a grading system, scoring them based on the likelihood that they will result in a successful implantation after the transfer. 

This process happens on day 3 (the cleavage stage) or day 5 (the blastocyst stage), and the morula stage occurs between these two milestones. 

What morula development can tell you

Morula development can be a positive sign of the quality of the blastocyst, as it is the last stage before the blastocyst.

Just as a quick reminder, the morula changes into the blastocyst when:

  • The cells form two main parts: the inner cell mass and the outer “shell.”
  • A fluid cavity begins to form. 

Embryo compaction and morula formation are two significant points of interest for fertility doctors and embryologists. The compaction of the cells/blastomeres (when cells change shape and stick together) can indicate future embryo development success. 

Critically, the embryo should finally start to increase in weight at the morula stage. Remember that the embryo divides during cleavage but doesn’t grow in mass or weight. Typically, embryos that develop two or more days slower than average are considered to have delayed development (although this factor doesn’t automatically disqualify the embryos from being chosen for transfer). 

It’s possible to transfer an embryo at the morula stage, although it’s more common for clinics to transfer embryos at the blastocyst stage.

Morula’s Mulberry Shape

In this picture taken through a microscope, you can see the morula’s mulberry shape.

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Signs of a healthy morula: What does your clinic look for?

During embryo evaluation and embryo grading, the embryologist will analyze various vital factors to determine the health of a morula: 

  • Gap junctions: Gap junctions act like connectors, allowing cells to communicate. Their formation is critical in cell development, allowing tiny molecules to travel between cells. 
  • Degree of compaction:  Compaction is a great sign that the embryo is developing typically—the more compacted the cells are, the higher the quality of the morula.
  • Uniform cell size: The cells should all have a similar shape. 

How new technology influences embryo selection

Traditionally, clinics evaluate embryos using time-lapse imaging (TLI), which takes frequent images of the embryos to monitor their development. But, innovative technology is making waves in the field of embryo scoring. 

Solutions like AIVF use advanced technologies to measure embryos’ shape, size, structure, and growth. AI and computer vision can identify patterns and anomalies in time-lapse embryo images that embryologists could not see, improving reliability, clarity, and standardization during embryo grading. Ultimately, better analysis of embryo imaging leads to informed decision-making about which embryos to transfer, higher success rates, and positive patient outcomes. 

AIVF Dashboard

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Improved success rates for embryo transfer using AI

Understanding each unique stage of your embryo’s development is the secret to staying involved, engaged, and reassured during your IVF journey. Tiny details during embryo development can indicate how the process is going. 

At AIVF, we aim to ensure you feel comfortable and clued up at every stage of your embryo’s growth. One of our solutions, AIVF Day-3 and Day-5, uses advanced technologies to provide accurate and richer insights into your embryos during the early stages. This enables your embryologist to make more informed decisions and avoid human bias or subjectivity. 

All your embryo data stays within our platform, and the entire clinic team can communicate through it. Our integrated messaging dashboard facilitates collaboration and helps clinics make faster decisions. Aside from speeding up your IVF journey, it enables your clinic to provide unique insights and visibility over your embryos’ health.

Because our scoring system is highly detailed, embryologists can confidently select the most viable embryos for transfer, increasing your chances of success. Find an AIVF clinic near you and feel confident that our technology optimizes your chances of a successful pregnancy.