Management considerations for clinically relevant findings on expanded carrier screening in a sperm donor applicant population.

Objective: To describe the clinical experience of managing expanded carrier screening (ECS) results in sperm donor applicants at a sperm bank in the United States, including considerations around suitability determination and appropriate education of prospective donors and recipients. Design: A retrospective review of donor genetic screening records from July 2017 to December 2021. Setting: A U.S.-based sperm bank. Patients: Donor applicants at a sperm bank. Intervention: Not applicable. Main Outcome Measures: To examine the rate of potentially significant health risks on the basis of ECS results to inform donor management and donor/recipient counseling considerations. Results: Nearly 2% of donor applicants were identified as having potentially significant health risks on the basis of their ECS results, and most individuals had no clinical manifestations related to these findings. Conclusion: There are unique challenges related to ECS in third-party reproduction for gamete providers, recipients, and their healthcare providers. A collaborative, multidisciplinary approach is necessary to help mitigate risks to donor offspring and maximize patient experience. Informed consent and access to a trained genetics professional are paramount when facilitating ECS on donor applicants and disseminating results to recipients.

Comparison of methodologies to detect hemoglobinopathy carriers in a multi-ethnic sperm donor population.

An estimated 7% of the world's population are carriers for a hemoglobin disorder. Current guidelines recommend carrier screening by complete blood count, with follow-up hemoglobin electrophoresis or fractionation based on abnormal result or ethnicity. Advances in molecular genetic testing are thought to increase carrier detection. This study compares carrier screening methodologies in a multi-ethnic sperm donor population. A retrospective analysis was conducted using data from a US sperm bank. All men underwent carrier screening for hemoglobin disorders via complete blood count, hemoglobin fractionation, and molecular testing. Results were compared using counts and percentages. McNemar's exact test was used to examine differences in the marginal probabilities of screening methodologies. Of the 438 tested, 25 (5.7%) were identified as carriers of at least one hemoglobin disorder by molecular testing. Seventeen (68%) of those carriers were missed by recommended methods. No identified carriers were detected by recommended methods but missed by molecular testing. The difference between these discordant pairs was significant (p-value < 0.001). The majority (44%) of carriers were mixed ethnicity, followed by 36% White. Results indicate that molecular screening methodologies have a greater ability to detect carriers of hemoglobin disorders compared to currently recommended methods in a multi-ethnic population.

Management of the risks for inherited disease in donor-conceived offspring.

OBJECTIVE: To illustrate the burden of inherited disease on donor-conceived offspring based on mode of inheritance and to provide guidance on methods of risk reduction. DESIGN: An 8.5-year retrospective review of outcome reports and donor management to summarize medical risks to donor-conceived offspring that presented after the sperm donors were qualified for participation in the donor program. SETTING: Not applicable. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Description of our experience with newly identified medical risks in donor-conceived offspring as well as how this information was ascertained and managed. RESULT(S): More than half of the indications to restrict donor specimen distribution were due to multifactorial disorders. Approximately one third of the restrictions involved autosomal recessive disorders. The remainder of the restrictions were due to the other indications, including autosomal dominant disorders. CONCLUSION(S): The risks for multifactorial disorders or undiagnosed autosomal dominant disease cannot be significantly reduced or eliminated with routine donor screening procedures. Ongoing risk assessment is essential to identify new genetic risks for autosomal dominant and multifactorial disorders. These assessments require an investment of resources and genetics professionals in the long-term management of changing health information as well as collaboration among gamete facilities, recipients, donors, and their health care providers.

Genetic evaluation procedures at sperm banks in the United States.

OBJECTIVE: To assess how genetic evaluations of sperm donor applicants are performed in the United States. DESIGN: A questionnaire was designed to assess: 1) the professionals involved in the family history evaluation and genetic screening; 2) the genetic testing, counseling, and informed consent processes; and 3) how the results of genetic evaluations and new risk information is communicated to donors. SETTING: Semen donor facilities. PARTICIPANT(S): Representatives of semen donor facilities. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Descriptive data. RESULT(S): Thirteen responses were received. All of the facilities assessed donors' family histories; eight of the facilities (62%) routinely informed donors about the results of these evaluations. At the majority of facilities (10/13), informed consent for genetic testing is obtained as part of the overall contract to be a sperm donor. Genetic counselors are employed full-time at two facilities and part-time at five others. CONCLUSION(S): There is variability in the education and informed consent processes for semen donor applicants, including variable communication about the limitations of genetic tests and the potential implications for the donors' own children. Further research into the best practices for education and consent for sperm donor applicants may be beneficial to ensure the well-being of the donors and their future offspring.

Outcome and experience of implementing spinal muscular atrophy carrier screening on sperm donors.

Spinal muscular atrophy (SMA) carrier screening was performed on 277 active semen donors and new semen donor applicants; five men tested positive as carriers for SMA. The risk for specific medical problems in donor offspring can be significantly reduced by incorporating new genetic tests, such as spinal muscular atrophy carrier screening, into donor screening practices; however, future efforts should focus on communicating the limitations of genetic screening to donor gamete recipients and on the development of guidelines for implementing new genetic tests on donors.

Genetic testing of sperm donors: survey of current practices.

OBJECTIVE: To determine which genetic tests are being performed on sperm donor applicants in the United States. DESIGN: An electronic survey was distributed to 26 sperm banks to evaluate their genetic testing practices. SETTING: Sperm banks in the United States. PATIENT(S): Not applicable. INTERVENTION(S): None. Survey of current practices. MAIN OUTCOME MEASURE(S): Survey of current practices. RESULT(S): Cystic fibrosis (CF) carrier screening, chromosome analyses, and hemoglobin evaluations are performed on the majority of sperm donor applicants. Tay-Sachs disease carrier screening is performed on most donors with Jewish heritage but there is significant variation in screening for other disorders that occur with increased frequency in this population. Individual sperm banks use different laboratory tests for evaluation of the same conditions, with each test having different carrier detection rates and interpretations. CONCLUSION(S): The genetic testing performed on sperm donors varies significantly at sperm banks across the United States. Therefore, recipients should be clearly informed about the specific evaluations performed on their donor of interest. Thus it is important that sperm banks employ genetic professionals to evaluate the donors' and recipients' medical histories and perform a genetic risk assessment. This will allow clients to make informed decisions about use of semen specimens from an anonymous sperm donor.

Spinal muscular atrophy (SMA) after conception using gametes from anonymous donors: recommendations for the future.

OBJECTIVE: To discuss the diagnosis of spinal muscular atrophy in a child conceived using donor gametes. DESIGN: None. SETTING: None. PATIENT(S): Offspring of gamete donors. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULT(S): A child conceived using gametes from anonymous sperm and ova donors was diagnosed with spinal muscular atrophy type 1. CONCLUSION(S): Gamete donor facilities are not required to perform extensive genetic testing on their donors; however, the well-being of the children conceived through assisted reproductive technologies should be a primary objective of reproductive medicine. The risk for specific medical problems in donor offspring can be significantly reduced by incorporating carrier screening for common, severe disorders such as spinal muscular atrophy into donor screening practices. Future efforts should focus on communicating the limitations of genetic screening to donor gamete recipients and educating them about their reproductive options.