Genetic Carrier Screening in Donor Egg IVF

The Role of Genetic Carrier Screening in Donor Egg IVF

Emily Mounts, MS, CGC By Emily Mounts, MS, CGC December 26, 2022 Intended Parents

As intended parents who are thinking about starting or expanding your family, you may wonder how your own and your egg donor’s genetic health are considered in the donor egg IVF process.

While many factors play into having a healthy baby, genetic carrier screening - DNA testing that looks for variants (mutations, or DNA spelling changes) in certain "recessive" genes - is one of the first tests you may encounter as you begin to search for the right egg donor. Several professional organizations including the American College of Obstetrics and Gynecology recommend that all individuals planning a pregnancy be offered this screening. While genetic testing is always optional, most intended parents are interested in obtaining the valuable information that can be learned from carrier screening.

  1. What is autosomal recessive inheritance?
  2. How is the testing done? What can I expect for the results?
  3. What types of conditions are included in carrier screening? What will I learn?
  4. How do I know if a donor is a good match for me based on carrier screen results?
  5. What if I or my donor have a positive carrier screen?
  6. What are the risks if my donor and I are carriers of the same condition?
  7. What does it mean to have a negative carrier screen?
  8. How does my and my donor’s medical and family history relate to carrier screening?
  9. Will the test tell me anything about my own health?
  10. Can’t preimplantation genetic testing (PGT - embryo biopsy and testing) be used to determine whether my embryos are genetically healthy?
  11. Is there anything else I should know?

1. What is autosomal recessive inheritance?

We each inherit two copies of every gene - one from our egg provider and one from our sperm provider. Autosomal recessive diseases are those that occur when someone has a gene variant in both copies of a certain gene, having inherited one copy from the egg and the other from the sperm. Individuals who carry only one variant for a recessive disease are referred to as "carriers" and generally do not have any symptoms of the disease - or knowledge that they are carriers - since the working copy of the gene is sufficient to keep them healthy.

Being a recessive gene carrier is very common, and most carriers will not have children with the disease that they carry. If you are a carrier, your chance to have a child affected with the recessive condition depends on your donor’s carrier status for that gene, and vice-versa. You are only at high risk to have a child with an autosomal recessive disease if both you and your egg donor are carriers of variants in the same gene: in that case, there is a 25% chance for an affected child. If, however, you and your donor are not found to be carriers of changes in the same gene, most of the time this is a good genetic match as the chance for your child to have a recessive condition associated with the genes tested will be very low.

2. How is the testing done? What can I expect for the results?

Carrier screening can be done on your blood or saliva. The doctor ordering your test will usually have a relationship with a particular genetics laboratory that performs this test. The number of genes that are examined, the technology used, and the cost of the test can differ for each clinic and laboratory. It usually takes about 2-3 weeks from the time the sample is received by the lab for you to receive results.

In the past, decisions about which exact recessive genes a person should be tested for were guided by one’s ethnicity; you only would have been tested for diseases that are most common in your ethnic group. However, the decreasing cost of DNA testing - combined with wider recognition that any of us can carry a variant in any gene, regardless of our ethnicity - has changed this approach. Now it is common for every individual to be tested for a large panel of more than 100 genes using an approach called "expanded" carrier screening.

3. What types of conditions are included in carrier screening? What will I learn?

Carrier screening generally tests for recessive genes that cause moderate or severe childhood diseases, lead to a shorter life expectancy, cause disability, and/or have no treatment options. However, as gene panels increase in size and broader technologies are used, it is common for milder, adult-onset, and treatable conditions to be detected on these panels as well. It is important to understand your and your donor’s specific results in order to decide what to do with the information you learn.

Depending on the number of genes tested and how thorough the technology used by the particular lab is, about 70-80% of healthy people will test positive as a carrier of one or more recessive diseases. It can be surprising to learn that it is actually more common to have a positive ("abnormal") carrier screen than to have a negative ("normal") test result. The vast majority of people who are found to be a carrier of a recessive disease are surprised by this news and have no family history of the condition they carry. Because positive results are so frequent, the need to learn about the combination of your and your prospective egg donor’s results together is a very typical step of the donor egg IVF process and should always be done before the donor’s egg retrieval cycle is started - and ideally, prior to the match being official.

4. How do I know if a donor is a good match for me based on carrier screen results?

In 2-4% of reproductive "matches" (e.g. intended parent and donor), both individuals carry variants in the same gene. Depending on the order in which genetic screening is done by your particular clinic or agency, there are a few scenarios:

You may have your own carrier screening results in hand when selecting your donor, and can actively select a donor who has already tested negative for the condition you are known to carry (or vice-versa - you can usually select a donor who is positive as long as your screen for that gene was negative). In other cases, a donor may only undergo carrier screening after she is selected by you. In this situation, it is important to understand how the match will be handled if you do carry the same gene and what your options will be for choosing a new donor if necessary.

5. What if I or my donor have a positive carrier screen?

Most people (including egg donors) - even those who are very healthy and have a completely healthy family - are found to carry one or more gene variants on carrier screening. In most cases, as long as the intended father has had a normal carrier screen result for any gene the donor is known to be a carrier of, the chance for the child to be affected will be very low. The same is true for the reverse, when the intended father has a positive screen and the donor has a normal result for that gene. Because no test is perfect, however, there is always a small chance for a true carrier to have a falsely "normal" test result. Your physician or genetic counselor can tell you the residual risk - or remaining chance - for a disease to occur in your child if you or your donor is a carrier and the other person is not. Also, because different laboratories test for slightly different sets of genes, if either you or your donor is a carrier it is also important to verify that the other person’s panel indeed included testing for that particular gene.

6. What are the risks if my donor and I are carriers of the same condition?

In this case there is a 25% chance for the pregnancy or child to inherit both recessive variants and be affected with the condition. In most cases, such a match would be discouraged. However, it is important that you understand what is known about the particular variants that were found in each of you, and what the expected disease outcome is if they were to combine in a child. Occasionally, a particular combination of mild gene variants may be expected to result in only very minor symptoms, or not be expected to cause true disease in a child at all. In this scenario, therefore, genetic counseling is a critical step to help you understand the possible outcomes and risks and ultimately determine whether the match is appropriate or not.

7. What does it mean to have a negative carrier screen?

A negative or normal screen is great news (even though, as mentioned earlier, it is less common than having a positive screen!). This means that no changes were found in any of the genes on the panel tested by the lab. It is important to remember that carrier screening does not test for all recessive diseases, and is not able to identify all carriers for the diseases that were tested.

8. How does my and my donor’s medical and family history relate to carrier screening?

While carrier screening is extremely valuable in identifying risks for certain recessive diseases, it plays almost no role in assessing other types of genetic risks, diseases or traits. If you or a close family member have a condition that is possibly genetic (such as cancer, cardiac disease, a birth defect or inherited disorder) you should ask to talk to a genetic counselor to discuss whether you should consider other specialized genetic testing. If you have questions about the information that your potential egg donor reported in her medical or family history, you should also address those concerns with your agency or clinic. Carrier screening is not a substitute for a thorough family history evaluation.

9. Will the test tell me anything about my own health?

As mentioned above, carrier screening is not intended to be an overall genetic health screen. However, in some cases the testing can reveal that someone has an increased risk to develop a health issue. This can occur in two scenarios: (1) when a healthy person is unexpectedly found to have two variants in a specific gene (in which case they may actually have a mild form of that disease), or (2) when someone is found to be a carrier of a recessive disease in which even just carriers have an increased chance to have some symptoms or health issues. For example,

carriers of variants in a few commonly tested recessive genes are known to have an increased chance of getting cancer or Parkinson’s disease. These are rare situations and should they occur, your doctor or genetic counselor may recommend additional medical screening for you.

10. Can’t preimplantation genetic testing (PGT - embryo biopsy and testing) be used to determine whether my embryos are genetically healthy?

The most common type of PGT, PGT-A (for aneuploidy, or an abnormal number of chromosomes) determines how many chromosomes each embryo has. This does not reveal any information about the recessive gene status of the embryos. Specialized PGT testing called PGT-M (for monogenic disease) can look for recessive diseases when there is a known 25% risk to the embryos based on carrier screen results, but of course the need for this is usually avoided by using carrier screening in the donor matching process up front.

11. Is there anything else I should know?

The results of your and your donor’s carrier testing should be saved and shared with the healthcare provider who cares for the pregnancy. While carrier testing is quite accurate overall, it is important to recognize that the size of testing panels can increase over time, and egg donors sometimes undergo another carrier screening test later if they complete a new egg donation cycle for another intended parent. Therefore, it is always possible that you could receive updated information about a donor’s carrier status in the future. You can always check with your clinic or agency to see if there have been any known changes in a donor’s carrier status.

In summary, carrier screening can be a powerful tool in the donor matching process. Your agency, clinic, and/or genetic counselor are all available to help you through this process as you begin the exciting journey of planning your family!

Emily Mounts, MS, CGC
Emily Mounts, MS, CGC

Emily Mounts is board-certified genetic counselor who has worked in reproductive genetics for 25 years. Most recently she directed the fertility genetic testing and counseling program at ORM Fertility in Portland, where she oversaw preimplantation genetic testing, genetic carrier screening, and the gamete donor genetic screening programs for 10 years. She has co-authored multiple publications on fertility genetics and frequently presents at national conferences. She is a former Chair of the American Society for Reproductive Medicine Genetic Counseling Professional Group. Emily completed her Bachelor’s degree at the University of Michigan and her Master’s degree in genetic counseling at the Medical College of Virginia.

Emily currently serves as an independent consultant helping clinics, agencies, labs, and ancillary businesses develop and streamline fertility genetics services, and can be reached through LinkedIn: https://www.linkedin.com/in/emilymounts/ or at emily@focusgeneticconsulting.com.

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