IVF with PGT for a family with a history of Huntington disease: a successful clinical case

Huntington disease is a late-onset, expansion-based disorder. It has specific considerations for planning and conducting preimplantation genetic testing for monogenic disorders (PGT-M). The disease is a relatively common indication for PGT-M worldwide. Our study describes one of the first successful cases of PGT-M for Huntington disease in Russia, based on published data. IVF with PGT-M followed by PGT-A (preimplantation genetic testing for aneuploidy) was performed for a couple in which the woman had preclinical disease. IVF was performed according to standard protocols. PGT-M was performed using PCR and fragment analysis for six informative STRs selected during the preliminary stage and repeats of the HTT gene. PGT-A was performed using aCGH (array comparative genomic hybridization). A total of seven embryos were tested. The transfer of one embryo, selected based on the results of PGT, resulted in a singleton pregnancy, which resulted in the successful birth of a healthy child. The postnatal diagnosis confirmed the normal status in newborn with regard to Huntington disease.

1. Caron N.S., Wright G.E.B., Hayden M.R. Huntington Disease. 1998 Oct 23 [Updated 2020 Jun 11]. In: Adam M.P., Feldman J., Mirzaa

2. G.M. et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. https://www.ncbi.nlm.nih.gov/books/.

3. Medina A., Mahjoub Y., Shaver L., Pringsheim T. Prevalence and Incidence of Huntington’s Disease: An Updated Systematic Review and Meta-Analysis. Mov Disord. 2022;37(12):2327-2335. doi: 10.1002/mds.29228.

4. Thompson A., Quarrell O., Strong M. Variation in the reported prevalence of Huntington’s disease: a systematic review and guide to interpretation. J Neurol. 2025;272(8):534. doi: 10.1007/s00415-025-13255-1.

5. Seliverstov Yu. A., Dranitsyna M.A., Kravchenko M.A. et al. Epidemiologiya bolezni Gentingtona v Rossiyskoy Federatsii. V kn. Bolezn’ Parkinsona i rasstroystva dvizheniy. Rukovodstvo dlya vrachey. Po materialam IV Natsional’nogo kongressa po bolezni Parkinsona i rasstroystvam dvizheniy [Epidemiology of Huntington’s disease in the Russian Federation. In: Parkinson’s disease and movement disorders. Guide for doctors. Based on materials from the IV National Congress on Parkinson’s disease and movement disorders]. 2017; 244-246. (In Russ.)

6. Deviatkina E.A., Nazarov V.D., Sidorenko D.V. et al. Klinicheskoe znachenie opredeleniya razmerov nukleotidnoj e`kspansii gena HTT u pacientov s bolezn`yu Gentingtona. [Clinical significance of the size of nucleotide expansion of the HTT gene in patients with Huntington’s disease]. Meditsinskaya genetika [Medical Genetics]. 2024;23(4):25-37. (In Russ.) https://doi.org/10.25557/2073-7998.2024.04.25-37

7. Sermon K., Goossens V., Seneca S. et al. Preimplantation diagnosis for Huntington’s disease (HD): clinical application and analysis of the HD expansion in affected embryos. Prenat Diagn. 1998;18(13):1427-1436. doi: 10.1002/(sici)1097-0223(199812)18:13<1427::aid-pd493>3.0.co;2-3.

8. De Rycke M., Berckmoes V. Preimplantation Genetic Testing for Monogenic Disorders. Genes. 2020;11(8);871. https://doi.org/10.3390/genes11080871.

9. ESHRE PGT-M Working Group, Carvalho F., Moutou C., et al. ESHRE PGT Consortium good practice recommendations for the detection of monogenic disorders Human Reproduction Open. 2020:1–18. doi:10.1093/hropen/hoaa018.

10. Ethics Committee of the American Society for Reproductive Medicine. Electronic address: asrm@asrm.org. Use of preimplantation genetic testing for monogenic adult-onset conditions: an Ethics Committee opinion. Fertil Steril. 2024;122(4):607-611. doi: 10.1016/j.fertnstert.2024.05.165.

11. Asscher E., Koops B.J. The right not to know and preimplantation genetic diagnosis for Huntington’s disease. J Med Ethics. 2010;36(1):30-33. doi: 10.1136/jme.2009.031047.

12. Raine S., Siegel D.R., Rabkina L. et al. Protocol considerations for multigenerational blinding of preimplantation genetic testing for a monogenic condition for Huntington disease: a case report. F S Rep. 2025;6(2):201-205. doi: 10.1016/j.xfre.2025.03.007.

13. Van Rij M.C., De Rademaeker M., Moutou C. et al. Preimplantation genetic diagnosis (PGD) for Huntington’s disease: the experience of three European centres. Eur J Hum Genet. 2012;20(4):368-75. doi: 10.1038/ejhg.2011.202.

14. Hornak M., Bezdekova K., Kubicek D. et al. OneGene PGT: comprehensive preimplantation genetic testing method utilizing next-generation sequencing. J Assist Reprod Genet. 2024;41(1):185-192. doi: 10.1007/s10815-023-02998-3.

15. Shi D., Xu J., Niu W. et al. Live births following preimplantation genetic testing for dynamic mutation diseases by karyomapping: a report of three cases. J Assist Reprod Genet. 2020;37(3):539-548. doi: 10.1007/s10815-020-01718-5.

16. Tan V.J., Liang Y., Tan A.S. et al. A Strategy Potentially Suitable for Combined Preimplantation Genetic Testing of Aneuploidy and Monogenic Disease That Permits Direct Detection of Pathogenic Variants Including Repeat Expansions and Gene Deletions. Int. J. Mol. Sci. 2025;26:4532. https://doi.org/10.3390/ijms26104532.

17. Spinella F., Bronet F., Carvalho F. et al. ESHRE PGT Consortium data collection XXI: PGT analyses in 2018. Hum Reprod Open. 2023;19;. doi: 10.1093/hropen/hoad010.

18. Verlinsky Y., Kuliev A. An Atlas of Preimplantation Genetic Diagnosis. 2nd Edition. 2004. Taylor & Francis: 302. https://doi.org/10.1201/b14655.

19. Vspomogatel`ny`e reproduktivny`e texnologii i iskusstvennaya inseminaciya. Klinicheskie rekomendacii (protokol lecheniya). Ministerstvo zdravooxraneniya Rossijskoj Federacii, MZ RF 05 marta 2019 goda № 15-4/i/2-1908. [Assisted reproductive technology and artificial insemination. Clinical guidelines (treatment protocol). Ministry of Health of the Russian Federation, 2019] (In Russ).

20. Gardner D.K., Schoolcraft W.B. In vitro culture of human blastocysts. In: Jansen R., Mortimer D., editors. Toward Reproductive Certainty: Fertility and Genetics Beyond 1999. UK: Parthenon Publishing London; 1999:378-388.

21. Ocenka oocitov i e`mbrionov v laboratorii VRT. Metodicheskie rekomendacii. RARCh [Oocyte and Embryo Evaluation in the ART Laboratory. RAHR (Russian Association of Human Reproduction) Guidelines]. 2021:17. (In Russ.) https://www.rahr.ru/d_pech_mat_metod/MR_evaluation_of_embryos.pdf

22. ESHRE PGT-SR/PGT-A Working Group; Coonen E, Rubio C et al. ESHRE PGT Consortium good practice recommendations for the detection of structural and numerical chromosomal aberrations. Hum Reprod Open. 2020 May 29;2020(3):hoaa017. doi: 10.1093/hropen/hoaa017.

23. Korsak V.S, Smirnova A.A., Shurygina O.V. Registr VRT Obshherossijskoj obshhestvennoj organizacii «Rossijskaya Associaciya Reprodukcii Cheloveka». Otchet za 2022 god. [ART Register of RAHR, 2022]. Problemy` reprodukcii [Russian Journal of Human Reproduction]. 2024;30(6):8-24. (In Russ.) https://doi.org/10.17116/repro2024300618

24. Zhao M., Cheah F.S.H., Tan A.S.C. et al. Robust Preimplantation Genetic Testing of Huntington Disease by Combined Triplet-Primed PCR Analysis of the HTT CAG Repeat and Multi-Microsatellite Haplotyping. Sci Rep. 2019 Nov 11;9(1):16481. doi: 10.1038/s41598-01952769-3.