egg quality

If you're participating in Cofertility’s Split Program, where you freeze your eggs for free when donating half to another family that can't otherwise conceive, a necessary step in the process is carrier screening. Carrier screening is a type of genetic test that can tell you whether you carry a gene for certain genetic disorders. This critical step ensures the best possible outcomes for both you and the recipient family.

You may have some questions or find yourself wondering about its necessity, what it involves, and how the results could affect you and the intended parents. This article aims to clarify the process and provide you with essential information to help you feel informed and confident.

By understanding the role of genetic testing, you'll be better equipped to make informed decisions and communicate effectively with healthcare providers, genetic counselors, and anyone else.

Why is genetic testing required for egg donors?

The American Society for Reproductive Medicine (ASRM) has developed guidance for the screening of egg donors that most clinics and egg donation agencies (like ours) follow. This  guidance includes genetic risk assessment, and specifically carrier screening. Why is carrier screening important?

Carrier screening plays an important role in ensuring the health of any potential children resulting from the donation. Many genetic conditions are recessive, meaning a person can carry the gene without showing symptoms. By screening egg donors, we can identify these genetic variants and minimize the risk of passing on inherited disorders.

Importantly, this genetic information is also valuable for you as the donor. It provides insights into your own genetic makeup, which can be beneficial for your future family planning. If you discover you're a carrier for a particular condition, you can make informed decisions about your own reproductive health and discuss potential risks with your healthcare provider.

Additionally, genetic testing helps in the matching process between donors and intended parents. By understanding the genetic profiles of both parties, we can ensure compatibility and reduce the risk of passing on inherited disorders. This contributes to the overall success and safety of the egg donation process.

What is carrier screening?

Carrier screening is a type of DNA test that looks for variants (mutations or DNA changes) in certain genes. These genes are associated with "recessive" conditions, which means a person needs to inherit two copies of the variant gene - one from each parent - to develop the condition.

Understanding autosomal recessive inheritance

We inherit two copies of every gene - one from the egg provider and one from the sperm provider. Autosomal recessive diseases occur when someone has a gene variant in both copies of a certain gene. Individuals who carry only one variant for a recessive disease are called "carriers" and generally don't have any symptoms of the disease.

X-linked inheritance

Some conditions are linked to genes on the X chromosome. Females typically have two X chromosomes, while males have one X and one Y chromosome. For X-linked conditions, males who have a variant are usually affected, while females are typically carriers. This is important in egg donation because a female carrier has a chance of passing the condition to male offspring.

The testing process

Genetic testing for egg donors typically involves the following steps:

1. Sample collection: Either a blood draw, saliva, or cheek swab sample is taken.
2. Laboratory analysis: The sample is sent to a specialized genetics laboratory for analysis.
3. Waiting period: Results usually come back within 2-3 weeks.
4. Result interpretation: A healthcare provider or genetic counselor will interpret the results for you, at no cost to you.

Today’s carrier screening tests often examine more than 100 genes associated with various inherited conditions. This comprehensive approach has replaced older methods that only tested for conditions common in specific ethnic groups.

What can you learn from genetic testing?

Genetic testing, particularly carrier screening, can provide you with a wealth of information about your genetic makeup. Primarily, you'll learn about your carrier status for the genetic conditions included in the panel. Being a carrier means you have one copy of a gene variant associated with a particular condition, but you don't have the condition yourself. This information is helpful for understanding potential reproductive risks, both for your role as an egg donor and for your own future family planning.

In addition to carrier status, genetic testing can sometimes offer insights into your ethnic background. Certain genetic variants are more common in specific populations, which can provide clues about your genetic ancestry. While this isn't the primary purpose of the screening, it can be an interesting secondary finding for some individuals.

Occasionally, carrier screening might reveal unexpected information about your own health. For instance, being a carrier for certain conditions might be associated with an increased risk of developing related health issues. While rare, these findings can be valuable for your long-term health management.

Furthermore, genetic testing results can sometimes shed light on your family health history. You might gain a better understanding of why certain conditions run in your family or discover previously unknown genetic factors that could be relevant to your relatives.

While genetic testing provides valuable information, it doesn't predict everything about your health or your potential offspring. Many factors beyond genetics contribute to overall health and development. Nonetheless, the insights gained from genetic testing can be a powerful tool for making informed decisions about your health and your participation in the egg donation process.

Types of conditions included in carrier screening

Carrier screening generally tests for genes associated with:

• Moderate to severe childhood diseases
• Conditions that lead to a shorter life expectancy
• Disorders causing disability
• Diseases with limited or no treatment options

Some examples of conditions often included in carrier screening are:

• Cystic fibrosis
• Spinal muscular atrophy
• Thalassemia/hemoglobinopathy
• Fragile X syndrome
• Tay-Sachs disease
• Sickle cell anemia

Specific conditions tested can vary depending on the screening panel used.

How genetic test results affect your donor status

In most cases, being a carrier for a genetic condition won't prevent you from being an egg donor. The key is ensuring that your genetic profile doesn't match with any variants carried by the intended parents or sperm provider.

However, there are some rare situations where a positive carrier screen might affect your eligibility, like if you're a carrier for a serious X-linked condition, like Fragile X.

What does a negative carrier screen mean?

A negative or normal screen means that no changes were found in any of the genes on the panel tested by the lab. While this is good news, it's important to remember that no test is perfect. Carrier screening doesn't test for all recessive diseases and can't identify all carriers for the diseases that were tested.

What does a positive carrier screen mean?

A positive carrier screen means that you have been identified as a carrier for one or more genetic conditions tested in the screening. Being a carrier doesn't mean you have the condition yourself. Instead, it means you have one copy of a gene variant associated with a particular condition.

Being a carrier is actually quite common. Most people are carriers for at least one genetic condition, and this usually doesn't affect their health. However, it can have implications for reproductive planning, both for egg donation and your own future family planning.

If you receive a positive result on your carrier screen, there's no need to worry. We cover the cost of talking to a genetic counselor to help you understand what your test results mean. The genetic counselor can explain your results in detail, discuss any potential implications, and answer any questions you may have. This ensures that you have a clear understanding of your genetic status and can make informed decisions moving forward.

Remember, a positive carrier screen doesn't necessarily disqualify you from being an egg donor. The implications depend on the specific condition and the genetic status of the intended parents or sperm provider. The genetic counselor and your Cofertility Member Advocate will guide you through what your results mean for your participation in the egg donation program.

Summing it up

Genetic testing is a required part of the egg donation process. It is a tool to ensure the best possible outcomes for all involved. The information you gain can be valuable not only for your role as an egg donor but also for your own future family planning.

As you go through this process, it's normal to have questions or concerns. Don't hesitate to ask your fertility doctor, genetic counselor, or your Cofertility Member Advocate for clarification or support. They're there to guide you through this important step in your egg donation journey.

Remember, being a carrier for a genetic condition is common and doesn't necessarily impact your overall health or ability to be an egg donor. By participating in genetic testing, you're contributing to informed decision-making and potentially helping create families while gaining valuable insight into your own genetic makeup.

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!