P-569 Reciprocal expanded carrier screening for intended parents and gamete donors: experience of a global surrogacy support network
Authors: Evans D , Johnson-Ellis W , Johnson-ellis M , Bakalova D 
Published: July 2024

Study question

Is expanded carrier screening an effective tool to identify carriers of clinically relevant genes and determine the reproductive risk between a donor and recipient pair?

Summary answer

This study has determined that there is a strong rationale for performing matching according to expanded carrier screening results, especially for gamete donor programs.

What is known already

Carrier screening (CS) identifies carriers of autosomal recessive (AR) and/or X-linked (XL) genetic conditions to establish reproductive risk. If both partners (egg and sperm providers) carry a pathogenic variant in the same gene (co-carriage), there is 25% risk that offspring will be affected. The same risk is present for egg providers who carry an XL disorder. In expanded carrier screening (ECS), many clinically relevant conditions are screened simultaneously using a single-panel approach. The implementation of ECS is becoming commonplace across gamete donor banks. Providing recipients with a matching panel is key in determining reproductive risk and suitable treatment options.

Study design, size, duration

In this retrospective review, data was collected for 104 gamete recipients and 31 gamete donors who underwent ECS between March 2021-January 2024. ECS was provided through a single genetic testing laboratory, using a whole exome sequencing (WES) platform. The panel used for the gamete donors/recipients consisted of approximately 500 AR genes; optional analysis of 66 X-Linked genes was available for biologically female donors/recipients.

Participants/materials, setting, methods

In total, 104 gamete recipients were screened against one or more donor(s) using the same ECS panel. All donors/recipients underwent testing in a clinical setting and received pre/post-test genetic counselling, where required. The testing laboratory provided the referring clinician with the results for each individual. Matching was overseen by My Surrogacy Journey and the relevant donor bank. Donor-recipient match reports were requested from the testing laboratory. Individual and matched reports were used for this review.

Main results and the role of chance

In total, 76.9% (80/104) of gamete recipients presented with a positive result in at least one clinically relevant gene that could have an impact on reproductive planning.

Between the 80 positive gamete recipients, 177 gene variants were carried; variant classification was available for 132 variants (74.6%). The majority of gene variants carried were classified as pathogenic (59.9%), meaning that these variants are associated with causing disease. Most frequently, recipients were carriers of a variant in 1-3 genes (1 gene: 36.3%; 2 genes: 27.5%; 3 genes: 22.5%).

In addition to this, 77.4% (24/31) of gamete donors were identified to carry a variant in at least one clinically relevant gene, which includes one egg donor (3.2%; 1/24) who was a carrier of an XL condition. This meant that despite the lack of co-carriage in the AR gene(s) of interest, the recipient could not proceed with this donor due to the associated risk (25%).

Of the 43 recipients matched with a donor, 9.3% (4/43) showed a high reproductive risk (25%) due to their reciprocal matching results.

This expanded carrier screening strategy demonstrates significant utility in identifying positive carrier status and supporting donor-recipient matching programmes by determining high risk reproductive pairs.

Limitations, reasons for caution

This study was retrospective in nature. The majority of recipients were Caucasian (∼80% of cases). Ethnic groups are not homogenous; there can be significant genetic, cultural, and environmental diversity between/within ethnic groups. Decision outcome data should be collected to improve this work.

Wider implications of the findings

The findings from this analysis suggest that there is a strong rationale for performing donor-recipient matching using an ECS approach. Increasing awareness and accessibility of ECS in this setting should be a global initiative, with the ultimate aim of reducing the burden of genetic disease in donor-conceived offspring.

Trial registration number

N/A