Cleavage vs. Morula vs. Blastocyst: How Embryologists Grade Each IVF Stage
In our last blog, we discussed embryo grading, but did you know there are specific names for later stages of embryo development? This process is a complex and fascinating journey that progresses through several distinct stages: the cleavage stage, morula, and blastocyst. Each phase plays a crucial role in the success of in vitro fertilization (IVF) treatments. This blog aims to elucidate these stages, providing a clear understanding of their characteristics and significance in the IVF process.
Day 1-2: Cleavage Begins
Following fertilization, the zygote undergoes a series of mitotic divisions known as cleavage. During this stage, the embryo divides into smaller cells called blastomeres without an increase in overall size. Healthline explains that by Day 3, a typically developing embryo reaches the 6- to 10-cell stage. Embryos at this point are often referred to as "cleavage-stage" embryos.
Expected development:
Day 1: Still a zygote (single cell)
Day 2: 2-4 cells
Grading factors:
Cell symmetry
Presence of fragments
Evenness of division
Lab significance: Early cleavage patterns can predict blastocyst potential
Day 3: Morula Formation
The morula stage embryo is a solid ball of 12–16 cells formed after several rounds of cleavage divisions, occurring around 3–4 days post-fertilization in humans. Unlike the compaction stage, where cells tightly adhere and flatten to form a cohesive structure, the morula lacks this organized polarization and fluid-filled cavity (blastocoel). Compaction, which precedes morula formation, establishes cell polarity and initiates differentiation, while the morula represents a more advanced but still undifferentiated state before blastocyst formation. The morula stage is a great sign, and a study in Taiwan found that Day 4 morula stage had similar implantation and clinical pregnancy rates as Day 5 blastocyst stage!
Typically 6-8 cells (now called a "cleavage stage embryo")
Key developments:
Embryonic genome activation begins
Cells compact together
Morphological signs of quality:
Even cell sizes
<10% fragmentation
Visible compaction
Day 4: Transition to Blastocyst
As cell division continues, the embryo enters the morula stage, usually occurring on Day 4. The term "morula," derived from the Latin word for mulberry, describes the embryo's appearance as a solid ball of approximately 16 to 32 tightly packed cells. This compact structure is a precursor to the formation of the blastocyst. The morula travels down the fallopian tube toward the uterus, guided by tiny hair-like structures called cilia.
Often called the "morula" stage
Critical changes:
Tight cell compaction
Beginning of cell differentiation
Why this matters: Many embryos arrest at this stage if chromosomal abnormalities exist
Day 5-6: Blastocyst Development
By Day 5 or 6, the embryo develops into a blastocyst, characterized by the formation of a fluid-filled cavity known as the blastocoel. The blastocyst comprises two distinct cell populations: the inner cell mass (ICM), which will develop into the fetus, and the trophectoderm, which will form the placenta. Embryos that reach this stage have a higher potential for implantation.
Fully formed blastocysts show:
Inner cell mass (becomes the baby)
Trophectoderm (becomes placenta)
Fluid-filled blastocoel cavity
Expansion stages:
Early (stage 1-2)
Expanding (stage 3-4)
Hatching/hatched (stage 5-6)
Why Developmental Timing Matters
The Goldilocks Principle
Too fast: May indicate chromosomal issues
Too slow: Higher chance of arrest
Just right: Day 5 blastocysts have the best implantation potential
Arrested Development: Common Stopping Points
Failure to cleave after fertilization (Day 1-2)
Morula arrest (Day 4)
Early blastocyst collapse (Day 5)
Significance in IVF
Caltech does a great job of explaining the timing of embryo development. Check out this study by the famous Caltech developmental biologist Magdalena Zernicka-Goetz!
Understanding these developmental stages is vital in IVF treatments:
Embryo Selection: Embryologists assess embryos at various stages to select those with the highest developmental potential for transfer.
Timing of Transfer: Embryos may be transferred at the cleavage stage (Day 3) or blastocyst stage (Day 5 or 6). Some studies suggest that transferring embryos at the blastocyst stage may lead to higher implantation rates, though the optimal timing can depend on individual circumstances.
Cryopreservation: Embryos can be frozen at different stages, but blastocysts are often preferred for freezing due to their advanced development and higher survival rates upon thawing.
Patient Questions Answered
Q: Why did my embryos stop at Day 3?
A: Most commonly due to chromosomal abnormalities preventing further development.
Q: Is a Day 6 blastocyst worse than Day 5?
A: Slightly lower success rates (about 10% less), but still viable if well-formed.
Q: Can you tell gender at these stages?
A: Not visually - requires genetic testing (PGT-A).
Key Takeaways
✔ Each developmental stage provides crucial information about embryo viability
✔ About 30-50% of fertilized eggs reach blastocyst stage
✔ Day 3 transfers remain common in certain clinical situations
✔ Blastocyst culture allows for better embryo selection
✔ Developmental arrest often indicates chromosomal issues
The progression from cleavage-stage embryos to morulae and then to blastocysts represents critical milestones in early embryonic development. A thorough understanding of these stages enhances the ability to make informed decisions during IVF treatments, ultimately contributing to improved outcomes. Is your clinic educating you on these critical stages?
“The morula stage? It’s like the awkward teenage phase. Still figuring things out, but we can see potential in all that chaos. You got this, little one!”
