Genetic Carrier Screening and Donor Egg IVF - Everything You Need to Know

Genetic carrier screening is an important part of family building with assisted reproductive technologies (ART), particularly donor egg IVF.  It provides essential information about the genetic makeup of both donors and recipients (the person receiving the eggs), enabling them to make informed decisions about their family-building journey and increasing the chances of a healthy baby. 

Carrier screening helps assess the risk of passing on inherited genetic conditions to future offspring. It empowers intended parents to understand their risks and make proactive choices about their reproductive health. In this article, we’ll dive deeper into what carrier screening is, its significance in donor egg IVF, and the different options available.

What is carrier screening?

Carrier screening is a type of genetic testing that reveals whether an individual "carries" a gene linked to a particular genetic disorder. Being a carrier doesn't mean a person has the disease themselves, but they have the potential to pass the gene to their offspring. This type of screening originally emerged in the 1970s to prevent the transmission of certain diseases, focusing mainly on high-risk ethnic groups with known elevated chances of carrying specific disorders, such as Tay–Sachs disease in the Ashkenazi Jewish populations.¹

Over time, carrier screening has evolved and advanced. In 2010, expanded carrier screening (ECS) emerged as a more affordable and comprehensive option². This allows for testing hundreds of genes, not just the handful targeted in older methods. ECS is offered regardless of a person's ancestry or ethnicity, as it aims to identify carriers for a wider array of genetic conditions. The American College of Medical Genetics and Genomics (ACMG) now recommends a standardized panel for carrier screening, including a list of 113 conditions.³

Most carrier screening today focuses on recessive disorders. These conditions only manifest when a child inherits two copies of a mutated gene, one from each parent. If only one copy is inherited, the person is considered a carrier. Carriers typically don't experience any symptoms of the disorder, or might have very mild ones, and often remain unaware of their carrier status.⁶

ASRM recommendations

The American Society for Reproductive Medicine (ASRM) strongly recommends that all egg donors be screened for cystic fibrosis, spinal muscular atrophy, and conditions like thalassemia and sickle cell disease.⁴ Additionally, screening for fragile X syndrome is recommended for donors with a family history of related disorders, and may be considered for all donors regardless of their history. 

The ASRM also suggests that expanded carrier screening (ECS), which looks at a wider range of genetic conditions, should be considered, ideally using the same panel for both the egg donor and the intended parent.⁴ While this isn't always mandatory, it's the most effective way to assess potential risks to future children. These recommendations are meant to guide decision-making, not create rigid rules. You’ll want to talk to your fertility doctor about tailoring these recommendations to your specific situation.

How is carrier screening done? 

Genetic carrier screening for both egg donors and recipients typically involves a simple blood test or saliva sample. The lab then analyzes the DNA within the sample for specific gene variants or mutations that might increase the risk of certain genetic conditions. The results are usually ready within 3-4 weeks and are discussed with a genetic counselor and/or your fertility doctor.

What does a positive carrier screen mean?

A positive result means that the person tested carries one copy of a gene mutation associated with a specific condition. Research suggests that all individuals carry at least one genetic variant that could lead to a severe recessive childhood disease. Therefore, as expanded carrier screening panels test for a greater number of genes and associated conditions, the likelihood of a positive carrier screen also increases.⁷ 

Remember, being a carrier doesn't mean you have the condition yourself. However, if both you and the donor (or your partner in the case of autologous IVF) are carriers of the same recessive condition, there is a higher risk of your child inheriting the condition.

What does a negative carrier screen mean?

A negative result means that no mutations were detected for the conditions tested. While a negative carrier screening result is reassuring, it's important to understand it doesn't completely eliminate the risk of passing on a genetic condition. Current technology allows us to test for a wide range of known genetic mutations, but it's impossible to screen for every possible one.⁵

Are genetic carrier screens accurate?

While carrier screening is generally reliable, it's important to understand that, like any medical test, there is a small chance of receiving inaccurate results.⁶

• False negative: This occurs when the test indicates a negative result, suggesting the absence of a gene variant, even though the individual is actually a carrier for the condition.
• False positive: This happens when the test indicates a positive result, indicating the presence of a gene variant, even though the individual does not actually carry it.

While false-positive results can lead to anxiety and further testing, false-negative results can be more concerning as they may provide false reassurance about the risk of passing on a genetic condition. That being said, these tests are considered safe and reliable. 

How is carrier screening different from PGS testing?

If you plan to do preimplantation genetic screening (PGS) of embryos, do you also have to do carrier screening? And if you do carrier screening, do you still have to do PGS testing of embryos? It's important to understand that carrier screening and PGS are not the same thing:

• Carrier screening: This tests the egg donor's genes as well as the intended father’s (or sperm donor’s) genes to assess the risk of passing on certain genetic conditions. Your future child could inherit a condition if both parties carry the same recessive gene.
• PGS (also called PGT-A): This tests embryos created during IVF for chromosomal abnormalities. This can help identify embryos with the highest chance of leading to a healthy pregnancy.

While both carrier screening and PGS testing play important roles in IVF, they serve different purposes. Carrier screening identifies potential risks carried in the DNA of the intended mother (or egg donor) and intended father (or sperm donor), while PGS assesses the chromosomal health of embryos after they've been created. 

Most families choose to undergo both carrier screening and PGS. Carrier screening helps you understand if you or the potential donor carry recessive genes, which helps during the donor matching process. Most clinics would not recommend a recipient move forward with a particular donor if both the sperm source and the donor are carriers for the same gene. With Cofertility, we’d offer a free rematch in this scenario. PGS, on the other hand, ensures the embryos being transferred are chromosomally normal, increasing the chances of a successful pregnancy and reducing the risk of miscarriage.

Even if you have a normal carrier screen with no known genetic risks, eggs can still carry an incorrect number of chromosomes, a condition called aneuploidy. Aneuploidy increases with age and affects ~10–25% of eggs in women in their early 30s, and more than 50% of eggs from women over 40. This is why the use of donor eggs is so common for women over 40. 

Ultimately, the decision of whether to pursue either or both types of testing is up to you, best made in consultation with your fertility doctor and a genetic counselor. They can help you weigh the benefits and limitations of each test based on your individual circumstances and family history.

Why is carrier screening important in donor egg IVF?

Carrier screening is important when using donor eggs because it allows both the egg donor and the intended father (or sperm donor) to be tested for the same set of genetic conditions. If both the donor and the intended father (or sperm donor) are carriers for the same condition, the risk of passing that condition to their child increases significantly. By knowing this information beforehand, you and your doctor can make informed decisions about which donor to match with. 

What do different panels mean?

Carrier screening panels can vary in the number and types of conditions they test for. There are smaller panels that focus on common recessive disorders and larger, expanded carrier screening (ECS) panels that look at a broader range of conditions. Many clinics recommend donors complete a panel around 275 genes, but  there isn't one "right" panel for everyone.  Your fertility doctor will be able to help recommend a test that aligns with your individual risk factors and family history.

Do we need to use the same carrier screening test as the donor?

There are several genetic testing companies, including Natera, Fulgent, Myriad, and each has panels of varying sizes. When you’re working with a donor, the testing company doesn’t have to be the same, but you will want to make sure the panel looks at the same set of conditions. This ensures that you are both screened for the same things, allowing for accurate risk assessment. If you’ve already completed testing, you can share the panel you completed ahead of time to ensure that your donor is tested for the same genes.

What's the difference between carrier screening and genetic counseling?

Genetic counseling is a process where a trained healthcare professional, called a genetic counselor, guides individuals or families through complex information about genetic health. They provide support and education about how inherited conditions might affect them or their children, interpret genetic test results, and help them make informed decisions about their healthcare.

Carrier screening is best done in conjunction with genetic counseling. A genetic counselor can help you understand your results, discuss the implications, and navigate any decisions about family planning.

The bottom line

Carrier screening is an important tool in the donor egg IVF journey, offering a window into the genetic health of both donors and recipients. By proactively understanding your genetic risks, you gain the power to make informed decisions about your family-building options. While a positive result may seem daunting, it doesn't automatically rule out certain paths. With guidance from your doctor and a genetic counselor, you can explore various possibilities to ensure the best possible outcome for your future child.

Remember, genetic carrier screening is not about eliminating all risk, as no test is perfect. It's about empowering you with knowledge and enabling you to navigate this process with more confidence. If you're considering egg donation, don't hesitate to talk to your fertility doctor about carrier screening. It's an important step towards building a healthy and happy family.

References

1. Kraft, S.A., Duenas, D., Wilfond, B.S. et al. The evolving landscape of expanded carrier screening: challenges and opportunities. Genet Med 21, 790–797 (2019). https://doi.org/10.1038/s41436-018-0273-4
2. Srinivasan BS, Evans EA, Flannick J, et al. A universal carrier test for the long tail of Mendelian disease. Reprod Biomed Online. 2010;21(4):537-551. doi:10.1016/j.rbmo.2010.05.012
3. Crockin S, Gibbons W. Genetic carrier screening in donors: a challenging frontier. F S Rep. 2023;4(1):20-21. Published 2023 Feb 8. doi:10.1016/j.xfre.2023.02.003
4. ASRM. “Guidance regarding gamete and embryo donation”.  2021. URL.
5. CDC. “Genetic Testing”. 2022. URL. 
6. ACOG. “Carrier Screening”. 2022. URL. 
7. Payne MR, Skytte AB, Harper JC. The use of expanded carrier screening of gamete donors. Hum Reprod. 2021;36(6):1702-1710. doi:10.1093/humrep/deab067