P-034 Clinical experience with expanded carrier screening results on a sperm donor applicant population
Authors: Isley L , Baldwin K , Park J , Lynch C , Callum P 
Published: June 2023

Abstract

Study question
What is the frequency of clinically significant results from expanded carrier screening (ECS) in a sperm donor applicant population and how should these be managed?

Summary answer
ECS results revealed clinically significant information for approximately 1 in 51 donor applicants, which warrant specific management considerations in the context of third-party reproduction.

What is known already
The American Society of Reproductive Medicine (ASRM) Practice Committee published guidance in January 2021 that outlines the recommended carrier screening approach for gamete donors. However, there is no additional direction related to results management including donor suitability, counseling, and informed consent. Prior studies have illustrated the high frequency of donors who are identified as carriers of one or more recessive disorders on an ECS panel; thus, excluding all prospective gamete donors identified as carriers for recessive conditions is not feasible or appropriate given the availability of reciprocal screening for the reproductive partner.

Study design, size, duration
A retrospective review of donor genetic screening records from July 2017 to December 2021 was performed. Relevant data was extracted and categorized by carrier screening result. Genetic counselors evaluated the health and reproductive risks to the potential donors (PDs) associated with being a carrier of a pathogenic mutation in each gene using published data, reference laboratory interpretations, and the professional health management guidelines.

Participants/materials, setting, methods
ECS was performed on sperm donor applicants as part of the routine donor qualification process. Testing was performed at an outside reference laboratory after participants provided written consent for genetic testing. The genes included on the ECS panel were analyzed using multiple methodologies. Specific methodologies varied based upon laboratory offerings at the time in which the potential donor entered the donor program.

Main results and the role of chance
A total of 966 PDs had ECS during the specified timeframe. Of these applicants, 19 total PDs (1.97%) were identified as having potentially significant health risks based on their ECS results. Of those 19 PDs, eleven were found to be either heterozygous or hemizygous for conditions that may convey significant health risks to carriers. Of these, nine were positive for a variant in a gene typically associated with an AR condition and two carried variants in genes associated with X-linked conditions. Eight additional PDs were found to be either compound heterozygous or homozygous for variants in a gene associated with an autosomal recessive condition.

Limitations, reasons for caution
Donor recruitment was limited to select major metropolitan areas in the U.S.; thus, donor applicants may not represent all ethnic groups or socioeconomic backgrounds. Additionally, this study described results from a single reference laboratory and does not illustrate the variation in ECS panels across genetic testing laboratories.

Wider implications of the findings
While this study examined ECS results in a donor applicant population, findings are also applicable to the general reproductive population and illustrate the necessity of informed consent and post-test counseling. In some cases, ECS may provide insight on potential future health risks and health management opportunities.

Trial registration number
Not applicable