Protocol considerations for multigenerational blinding of preimplantation genetic testing for a monogenic condition for Huntington disease: a case report
Samuel Raine M.D. , Dana R. Siegel M.D. , Liya Rabkina M.S. , Paulina Nassab M.S. , Ana Cervero Ph.D. , Jose Antonio Martinez-Conejero Ph.D. , Hannah Elfman M.S. , Alex J. Polotsky M.D.
{"title":"Protocol considerations for multigenerational blinding of preimplantation genetic testing for a monogenic condition for Huntington disease: a case report","authors":"Samuel Raine M.D. , Dana R. Siegel M.D. , Liya Rabkina M.S. , Paulina Nassab M.S. , Ana Cervero Ph.D. , Jose Antonio Martinez-Conejero Ph.D. , Hannah Elfman M.S. , Alex J. Polotsky M.D.","doi":"10.1016/j.xfre.2025.03.007","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>To report a unique case of preimplantation genetic testing for a monogenic condition (PGT-M) for Huntington disease (HD) using both exclusion-based testing and direct nondisclosure testing across multiple generations and to highlight the strategies used to protect reproductive autonomy and privacy.</div></div><div><h3>Design</h3><div>Case report.</div></div><div><h3>Subjects</h3><div>A reproductive-aged nulliparous couple with the male partner's family history significant for HD who desired to conceive a child with PGT-M to build a family without the risk of HD inheritance while simultaneously maintaining the anonymity of carrier results to the partner and all living family members.</div></div><div><h3>Exposure</h3><div>Two in vitro fertilization (IVF) cycles with exclusion-based PGT-M in the first cycle and direct nondisclosure PGT-M in the second cycle, followed by 2 frozen embryo transfers (FETs).</div></div><div><h3>Main Outcome Measures</h3><div>Number of low-risk euploid blastocysts suitable for embryo transfer.</div></div><div><h3>Results</h3><div>The first IVF cycle using exclusion-based PGT-M resulted in 14 good-quality blastocysts with only 1 blastocyst deemed at low risk of inheriting the at-risk HD haplotype. The first FET was unsuccessful. The male partner’s mother was tested and was found to be an HD carrier. The second IVF cycle used direct nondisclosure PGT-M, which resulted in 12 blastocysts suitable for transfer (both euploid and negative for HD). After the second failed FET, the male partner ultimately decided to undergo genetic testing for HD for himself and was negative for HD mutation. The couple then chose to attempt spontaneous conception and had a live birth of a healthy male infant without complications.</div></div><div><h3>Conclusion</h3><div>Multigenerational blinding of PGT-M for trinucleotide repeat disorders has great utility in preserving patient autonomy while limiting the risk of future progeny inheriting a life-limiting genetic condition. Careful, comprehensive counseling and multilevel strategies should be developed to enact these blinding measures to best serve patients and their families whose genetic information is being used for testing.</div></div>","PeriodicalId":34409,"journal":{"name":"FS Reports","volume":"6 2","pages":"Pages 201-205"},"PeriodicalIF":0.0000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"FS Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S266633412500056X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Objective
To report a unique case of preimplantation genetic testing for a monogenic condition (PGT-M) for Huntington disease (HD) using both exclusion-based testing and direct nondisclosure testing across multiple generations and to highlight the strategies used to protect reproductive autonomy and privacy.
Design
Case report.
Subjects
A reproductive-aged nulliparous couple with the male partner's family history significant for HD who desired to conceive a child with PGT-M to build a family without the risk of HD inheritance while simultaneously maintaining the anonymity of carrier results to the partner and all living family members.
Exposure
Two in vitro fertilization (IVF) cycles with exclusion-based PGT-M in the first cycle and direct nondisclosure PGT-M in the second cycle, followed by 2 frozen embryo transfers (FETs).
Main Outcome Measures
Number of low-risk euploid blastocysts suitable for embryo transfer.
Results
The first IVF cycle using exclusion-based PGT-M resulted in 14 good-quality blastocysts with only 1 blastocyst deemed at low risk of inheriting the at-risk HD haplotype. The first FET was unsuccessful. The male partner’s mother was tested and was found to be an HD carrier. The second IVF cycle used direct nondisclosure PGT-M, which resulted in 12 blastocysts suitable for transfer (both euploid and negative for HD). After the second failed FET, the male partner ultimately decided to undergo genetic testing for HD for himself and was negative for HD mutation. The couple then chose to attempt spontaneous conception and had a live birth of a healthy male infant without complications.
Conclusion
Multigenerational blinding of PGT-M for trinucleotide repeat disorders has great utility in preserving patient autonomy while limiting the risk of future progeny inheriting a life-limiting genetic condition. Careful, comprehensive counseling and multilevel strategies should be developed to enact these blinding measures to best serve patients and their families whose genetic information is being used for testing.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
