Protocol considerations for multigenerational blinding of preimplantation genetic testing for a monogenic condition for Huntington disease: a case report
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 an...
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| Language: | English |
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Elsevier
2025-06-01
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| Series: | F&S Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S266633412500056X |
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| author | 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. |
| author_facet | 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. |
| author_sort | Samuel Raine, M.D. |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-80f8fa7c2da941939c39c0eb6228ee55 |
| institution | OA Journals |
| issn | 2666-3341 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | F&S Reports |
| spelling | doaj-art-80f8fa7c2da941939c39c0eb6228ee552025-08-20T02:36:16ZengElsevierF&S Reports2666-33412025-06-016220120510.1016/j.xfre.2025.03.007Protocol considerations for multigenerational blinding of preimplantation genetic testing for a monogenic condition for Huntington disease: a case reportSamuel Raine, M.D.0Dana R. Siegel, M.D.1Liya Rabkina, M.S.2Paulina Nassab, M.S.3Ana Cervero, Ph.D.4Jose Antonio Martinez-Conejero, Ph.D.5Hannah Elfman, M.S.6Alex J. Polotsky, M.D.7Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Correspondence: Samuel Raine, M.D., Department of Obstetrics and Gynecology; University of Colorado Anschutz Medical Campus, 12631 East 17th Ave, B198-6, Aurora, Colorado 80045.Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Shady Grove Fertility, Greenwood Village, ColoradoUniversity of California San Francisco, Neuro-Memory and Aging Clinic, San Francisco, CaliforniaIgenomix, Miami, FloridaIgenomix, Miami, FloridaIgenomix, Miami, FloridaDepartment of Genetics, Anschutz Medical Campus, University of Colorado, Aurora, ColoradoDepartment of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Shady Grove Fertility, Greenwood Village, ColoradoObjective: 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.http://www.sciencedirect.com/science/article/pii/S266633412500056XNondisclosurePGT-MHuntington's diseaseIVFexclusion-based PGT |
| spellingShingle | 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. Protocol considerations for multigenerational blinding of preimplantation genetic testing for a monogenic condition for Huntington disease: a case report F&S Reports Nondisclosure PGT-M Huntington's disease IVF exclusion-based PGT |
| title | Protocol considerations for multigenerational blinding of preimplantation genetic testing for a monogenic condition for Huntington disease: a case report |
| title_full | Protocol considerations for multigenerational blinding of preimplantation genetic testing for a monogenic condition for Huntington disease: a case report |
| title_fullStr | Protocol considerations for multigenerational blinding of preimplantation genetic testing for a monogenic condition for Huntington disease: a case report |
| title_full_unstemmed | Protocol considerations for multigenerational blinding of preimplantation genetic testing for a monogenic condition for Huntington disease: a case report |
| title_short | Protocol considerations for multigenerational blinding of preimplantation genetic testing for a monogenic condition for Huntington disease: a case report |
| title_sort | protocol considerations for multigenerational blinding of preimplantation genetic testing for a monogenic condition for huntington disease a case report |
| topic | Nondisclosure PGT-M Huntington's disease IVF exclusion-based PGT |
| url | http://www.sciencedirect.com/science/article/pii/S266633412500056X |
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