Simplifying genetic carrier screening for gamete donors and recipients

Genetic carrier testing covers different numbers of genes depending on lab and ordering provider. There are differing society guidelines for recommended panel size, and therefore it is difficult to standardize what is being ordered. In the context of gamete donor screening, there are additional challenges of varying standard practice in the field and the fact that donor profiles often need to meet the requirements of an unknown future recipient.  

In this article:

Clinical challenge | Why it matters | Ordering recommendations | Interpreting test results | Next steps | Supporting resources

Clinical challenge: Carrier screening is not always straightforward

One to two percent of biologically unrelated individuals are estimated to be at risk of having a pregnancy with a recessive genetic disorder.¹ Some clinical challenges in identifying those at risk include 

• Choosing the appropriately sized genetic carrier panel for gamete donors  
• Coordinating appropriate carrier screening for recipients  
• Clinical follow-up for findings that could affect the screened individual’s health

Why it matters: The impact on donor selection

Carrier screening can detect when individuals are at risk of having a pregnancy with a serious childhood-onset medical condition. Identifying whether a particular recipient and donor are at risk could greatly influence selection of a donor.

Recommended tests: ASRM, ACOG, and ACMG guidelines

ASRM and ACOG have a relatively small list of conditions that should be tested for, with notes that large panels can be considered.^2,3,4 ACMG 2021 recommendations include the largest panel of genes that should be offered to all individuals, at 113 genes.⁵

Conditions that should be tested for: 

*ACMG recommended using “tier” terminology instead of “expanded” for precision. Tier 3 is conditions with >1/200 carrier frequency. Tier 4 is panels that encompass conditions with a lower carrier frequency than 1/200.

QHerit™ 112 Diseases, Female (meets ACMG Tier 3 recommendations) 

• Test code: 14232
• CPT^® code(s): 81513

QHerit™ 96 Diseases, Male (meets ACMG Tier 3 recommendations) 

• Test code: 14227
• CPT^® code(s): 81443

Interpreting test results: Mapping genetic screening results to next steps

Test results are often lengthy, and having some key points to assess for each test can help providers navigate the report:  

1. Inheritance pattern of the condition identified (ie, autosomal recessive, X linked, etc)  
2. If screened individuals are expected to have symptoms (ie, disease can have an autosomal dominant form, or the patient has 2 variants identified in an autosomal recessive condition) 
3. If recipient test results are available and the donor carries a recessive condition:
   • Was the individual screened for the genes the counterpart was positive for?
   • Do the 2 individuals carry variants (mutations) in the same gene? 
   • If so, are those particular variants expected to cause disease? Some variants are mild or only cause disease in certain combinations

Quest Diagnostics customers can call 866-GENEINFO to reach genetics specialty staff and genetic counselors to help with test interpretation. 

Next steps: Referring patients after carrier screening

Choosing the correct referral group can be unclear; genetic counselors can clarify risks for the next generation. If there are concerns about symptoms in the individual, a medical geneticist or appropriate specialty MD should be contacted. A referral should be considered for the following scenarios: 

• The donor is a carrier of a condition with health implications for themself
• The donor is identified as an affected individual (ie, 2 variants in HFE detected)
• The egg contributor carries an X-linked genetic condition
• The donor and recipient are both carriers of the same autosomal recessive condition

Supporting resources