Egg Freezing: Mature vs. Immature Eggs

If you're considering egg freezing, or have already frozen your eggs, you may have encountered terms like "mature" and "immature" eggs. Understanding the distinction between these two types of eggs can help you grasp the egg freezing process and its potential outcomes. 

This article will delve into the biological differences between mature and immature eggs, their significance in egg freezing, and what this means for your fertility journey.

The basics of egg development

To comprehend the difference between mature and immature eggs, it's helpful to understand the process of egg development, also known as oogenesis. This process begins before birth and continues throughout a woman's reproductive years.

Primordial follicles: The starting point

At birth, a female's ovaries contain approximately 1-2 million primordial follicles, each housing an immature egg (oocyte). These primordial follicles represent the total pool of potential eggs a woman can produce in her lifetime.

The menstrual cycle and egg maturation

During each menstrual cycle, a subset of these primordial follicles begins to grow and develop. However, typically only one follicle (occasionally more) will fully mature and release an egg during ovulation. The rest of the developing follicles will naturally degenerate.

During egg freezing

The egg freezing process aims to optimize this natural cycle by using medication to produce multiple mature eggs in one cycle, significantly increasing the number of mature eggs available for freezing compared to a natural menstrual cycle.

What are mature eggs?

Mature eggs, also known as secondary oocytes or metaphase II (MII) oocytes, have completed the first meiotic division and are ready for fertilization. 

Mature eggs several distinct features:

• First polar body: The most obvious sign of a mature egg is the presence of the first polar body in the perivitelline space (the area between the egg and its outer shell, called the zona pellucida).
• Size and shape: A mature egg is typically round and of a standard size. However, the study linked above notes that egg size can vary, and this variation doesn't necessarily affect fertilization or embryo quality.
• Cytoplasm: Ideally, a mature egg should have a homogeneous (evenly distributed) cytoplasm. However, slight variations in cytoplasmic appearance are common and may not indicate any problems.
• Zona pellucida (ZP): This is the outer shell of the egg. In a mature egg, it should be clear and of normal thickness.
• Perivitelline space: This is the space between the egg itself and the zona pellucida. In a mature egg, this space should be of normal size, not too large or too small.
• Meiotic spindle: While not visible under regular microscopy, specialized techniques can reveal the presence of a meiotic spindle, which is crucial for proper chromosome alignment.
• Absence of certain features: Mature eggs should not have a visible nucleus (called a germinal vesicle), which is a sign of immaturity.

While these are the ideal characteristics, many eggs retrieved in egg freezing may show one or more variations from these "ideal" criteria. Some variations are considered normal and don't necessarily impact the egg's ability to be fertilized or develop into a healthy embryo. However, certain features, like the presence of smooth endoplasmic reticulum clusters, are considered potentially problematic.

What are immature eggs?

Immature eggs, also called primary oocytes or immature ovum, are eggs that have not completed the process of meiosis, a specialized type of cell division necessary for reproduction. 

During egg freezing, not all eggs will mature, and some will be retrieved that are considered immature. These eggs are generally smaller than mature eggs, and cannot be fertilized by sperm today.

Immature eggs fall into two categories:

1. Germinal vesicle (GV) stage eggs: These are the most immature and are identifiable by the presence of a visible nucleus.
2. Metaphase I (MI) stage eggs: These eggs have begun the maturation process but haven't completed it. They lack both a visible nucleus and a polar body.

While immature eggs are usually not frozen, at Cofertility we try and ask clinics to keep them for our members. It is our hope that in the future, these immature eggs will be able to be reliably matured in the laboratory. 

How many eggs will be mature?

On average, approximately 80% of eggs retrieved during egg freezing are mature, while 20% are immature. 

Several factors can influence the number of mature eggs retrieved:

1. Age: Younger women typically produce a higher percentage of mature eggs. As women age, not only does the total number of eggs decrease, but the proportion of mature eggs may also decline.
2. Ovarian stimulation protocol: The medications and dosages used during the stimulation phase can affect egg maturity. Your fertility doctor will tailor the protocol to optimize the number of mature eggs retrieved.
3. Timing of the trigger shot: The timing of the final maturation trigger is critical. If given too early or too late, it can affect the maturity of the eggs at retrieval.
4. Individual response to stimulation: Every woman's ovaries respond differently to stimulation. Some may produce a higher percentage of mature eggs, while others may have more immature eggs.
5. Underlying fertility conditions: Certain conditions, such as polycystic ovary syndrome (PCOS), can affect egg maturity rates.

During the egg retrieval process, the embryologist will examine each egg under a microscope to determine its maturity. The presence of some immature eggs is normal and expected. In fact, having a mix of mature and immature eggs can be a sign of a healthy response to ovarian stimulation.

While it's natural to focus on the number of mature eggs retrieved, it's important to remember that quality matters as much as quantity. A smaller number of high-quality mature eggs can be more valuable than a larger number of lower-quality eggs.

What’s the difference between immature and mature eggs?

Today, mature eggs are the gold standard. Here's why:

Higher survival rates after thawing

Mature eggs have completed critical developmental stages, making them more resilient to the freezing and thawing process. They're better equipped to withstand the physical stress of vitrification (flash-freezing) and subsequent warming.

Greater potential for fertilization

Once thawed, mature eggs are immediately ready for fertilization. They've already undergone the necessary cellular changes to allow for the entry and processing of sperm DNA.

Improved embryo development

Eggs that were mature at the time of freezing tend to result in higher-quality embryos after fertilization. This can lead to better chances of successful implantation and pregnancy.

What Split Members should know

If you’re part of our Split program, where members freeze their eggs for free when donating half to a family that otherwise can’t conceive, there are a few things you should know:

• You will receive immediate ownership of half of the mature eggs retrieved. If there is an odd number, the intended parent will keep the extra egg.
• You also receive 100% of immature eggs retrieved to the extent clinic policy allows (not all clinics are able to cryopreserve GV eggs).
• We cover ALL egg freezing expenses and 10 years of storage. Of course you can get the eggs sooner if needed.

The reason we give 100% of immature eggs to the Split Member (egg donor) is because, while it’s not possible today, we hope that in the future that embryologists will be able to mature immature eggs in the lab. 

Summing it up

Grasping the difference between mature and immature eggs is helpful to understanding the egg freezing process and setting realistic expectations. While mature eggs are the primary goal of egg freezing, the presence of some immature eggs is normal and doesn't necessarily indicate a problem.

As you consider or proceed with egg freezing, remember that your fertility doctor is your best resource for personalized information. They can provide insights into your individual situation, explain your results, and help you understand what they mean for your fertility preservation goals.

We wish you all the best!