Mosaicism in preimplantation human embryos

Авторы

  • Алсу Фаритовна Сайфитдинова Российский государственный педагогический университет им. А. И. Герцена; АО «Международный центр репродуктивной медицины» https://orcid.org/0000-0002-1221-479X
  • Олег Сергеевич Глотов СПб ГБУЗ «Городская больница № 40»; Научно-исследовательский институт акушерства, гинекологии и репродуктологии им. Д. О. Отта https://orcid.org/0000-0002-0091-2224
  • Ирина Васильевна Полякова СПб ГБУЗ «Городская больница № 40» https://orcid.org/0000-0002-5738-8443
  • Наталья Константиновна Бичевая АО «Международный центр репродуктивной медицины» https://orcid.org/0000-0001-8866-5821
  • Юлия Артемьевна Логинова DiaCarta, Inc https://orcid.org/0000-0002-1304-5967
  • Рена Алескеровна Кузнецова АО «Международный центр репродуктивной медицины» https://orcid.org/0000-0003-4195-6968
  • Ольга Анатольевна Леонтьева АО «Международный центр репродуктивной медицины» https://orcid.org/0000-0002-3667-0511
  • Елизавета Евгеньевна Невская АО «Международный центр репродуктивной медицины» https://orcid.org/0000-0003-0626-6048
  • Ольга Андреевна Павлова АО «Международный центр репродуктивной медицины»; ООО «Бигль» https://orcid.org/0000-0001-9488-6903
  • Ирина Леонидовна Пуппо Национальный медицинский исследовательский центр им. В. А. Алмазова Минздрава России; АО «Международный центр репродуктивной медицины» https://orcid.org/0000-0001-8538-3845
  • Антон Евгеньевич Шиков СПб ГБУЗ «Городская больница № 40» https://orcid.org/0000-0001-7084-0177
  • Станислав Петрович Уразов СПб ГБУЗ «Городская больница № 40» https://orcid.org/0000-0002-5441-2911
  • Татьяна Владимировна Кузнецова Научно-исследовательский институт акушерства, гинекологии и репродуктологии им. Д. О. Отта https://orcid.org/0000-0003-1738-6782
  • Андрей Михайлович Сарана Санкт-Петербургский государственный университет https://orcid.org/0000-0003-3198-8990
  • Сергей Григорьевич Щербак СПб ГБУЗ «Городская больница № 40» https://orcid.org/0000-0001-5047-2792
  • Владислав Сергеевич Баранов Научно-исследовательский институт акушерства, гинекологии и репродуктологии им. Д. О. Отта https://orcid.org/0000-0002-6518-1207

DOI:

https://doi.org/10.33910/2687-1270-2020-1-3-225-230

Ключевые слова:

mosaicism, human embryos, aneuploidy, preimplantation genetic testing, in vitro fertilization

Аннотация

Since the very first publications on preimplantation genetic testing, researchers have faced a serious problem — a high mosaicism level in the preimplantation human embryos obtained by means of in vitro fertilization cycles. The nature of this mosaicism and its high impact on embryo development draws attention to this issue. In this research we studied the cells from different parts of preimplantation human embryos with mosaicism in the trophectoderm cells detected using Next-generation Sequencing (NGS). Six human blastocysts with mosaicism in their trophectoderm cells were each sectioned in three parts: two containing only trophectoderm cells and one predominantly inner cell mass. These parts were then analyzed individually. Our data indicate that the proportion of aneuploid cells in bioptate taken for preimplantation genetic testing does not necessarily reflect the true chromosomal status of the whole embryo and cannot be extrapolated to that in the embryoblast cells. The results of our study strongly suggest that mosaicism revealed in blastocyst reduces the likelihood of finding the euploid chromosome set in the other parts of the embryo. Karyotypes of cells from different parts of mosaic embryos show low concordance. Chromosomal abnormalities in mosaic embryos are unpredictably diverse, which may lead not only to loss of conception, but also to the development of genetic disease in the offspring. According to our data, the mosaic rate tends to increase in the samples containing trophectoderm adjacent to the embryoblast, which may have physiological significance for the implantation. Comparative studies focused on the concordance of mosaicism level of and the type of chromosomal abnormalities detected in different parts of preimplantation human embryos will improve clinical recommendations regarding the transfer of mosaic embryos.

Библиографические ссылки

Baranov, V. S., Kuznetsova, T. V. (2007) Tsitogenetika embrionalnogo razvitiya cheloveka [Human embryonic development cytogenetics]. Saint Petersburg: N–L Publ., 640 p. (In Russian)

Blaicher, W., Repa, C., Schaller, A. (2000) Acardiac twin pregnancy: Associated with trisomy 2: Case report. Human Reproduction, vol. 15, no. 2, pp. 474–475. PMID: 10655326. DOI: 10.1093/humrep/15.2.474 (In English)

Campbell, S., Mavrides, E., Prefumo, F. et al. (2001) Prenatal diagnosis of mosaic trisomy 8 in a fetus with normal nuchal translucency thickness and reversed end-diastolic ductus venosus flow. Ultrasound in Obstetrics & Gynecology, vol. 17, no. 4, pp. 341–343. PMID: 11339193. DOI: 10.1046/j.1469-0705.2001.00393.x (In English)

Daughtry, B. L., Chavez, S. L. (2016) Chromosomal instability in mammalian pre-implantation embryos: Potential causes, detection methods, and clinical consequences. Cell and Tissue Research, vol. 363, no. 1, pp. 201–225. PMID: 26590822. DOI: 10.1007/s00441-015-2305-6 (In English)

Gardner, D. K., Schoolcraft, W. B. (1999) In vitro culture of human blastocyst. In: R. Jansen, D. Mortimer (eds.). Towards reproductive certainty: Fertility and genetics beyond. New York: The Parthenon Publ., pp. 377–388. (In English)

Gardner, R. J. M., Amor, D. J. (2018) Gardner and Sutherland’s chromosome abnormalities and genetic counseling. 5th ed. New York: Oxford University Press, 784 p. (In English)

Giunta, S., Funabiki, H. (2017) Integrity of the human centromere DNA repeats is protected by CENP-A, CENP-C, and CENP-T. Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 8, pp. 1928–1933. DOI: 10.1073/pnas.1615133114 (In English)

Grati, F. R. (2014) Chromosomal mosaicism in human feto-placental development: Implications for prenatal diagnosis. Journal of Clinical Medicine, vol. 3, no. 3, pp. 809–837. PMID: 26237479. DOI: 10.3390/jcm3030809 (In English)

Greco, E., Minasi, M. G., Fiorentino, F. (2015) Healthy babies after intrauterine transfer of mosaic aneuploid blastocysts. The New England Journal of Medicine, vol. 373, no. 21, pp. 2089–2090. PMID: 26581010. DOI: 10.1056/NEJMc1500421 (In English)

Griffin, D. K. (1996) The incidence, origin, and etiology of aneuploidy. International Review of Cytology, vol. 167, pp. 263–296. PMID: 8768496. DOI: 10.1016/s0074-7696(08)61349-2 (In English)

Korsak, V. S. (ed.) (2019) Rukovodstvo po klinicheskoj ehmbriologii [Clinical embryology guide]. Moscow: SIMK Publ., 224 p. (In Russian)

Kushnir, V. A., Darmon, S. K., Barad, D. H., Gleicher, N. (2018) Degree of mosaicism in trophectoderm does not predict pregnancy potential: A corrected analysis of pregnancy outcomes following transfer of mosaic embryos. Reproductive Biology and Endocrinology, vol. 16, no. 1, article 6. PMID: 29373974. DOI: 10.1186/s12958-018-0322-5 (In English)

Munne, S., Blazek, J., Large, M. et al. (2017) Detailed investigation into the cytogenetic constitution and pregnancy outcome of replacing mosaic blastocysts detected with the use of high-resolution next-generation sequencing. Fertility and Sterility, vol. 108, no. 1, pp. 62–71. PMID: 28579407. DOI: 10.1016/j.fertnstert.2017.05.002 (In English)

PGDIS position statement on the transfer of mosaic embryos in preimplantation ganetic testing for aneuploidy (PGT-A). (2019) PGDIS (Preimplantation Genetics Diagnosis International Society). [Online]. Available from: http://pgdis.org/docs/newsletter_052719.pdf (accessed 12.08.2020). (In English)

Sachdev, N. M., Ribustello, L., Liu, E. et al. (2016) The rate of mosaic embryos from donor egg as detected by next generation sequencing (NGS) varies by IVF laboratory. Fertility and Sterility, vol. 106, no. 3, suppl., e156–e157. DOI: 10.1016/j.fertnstert.2016.07.463 (In English)

Taylor, T. H., Griffin, D. K., Katz, S. L. et al. (2016) Technique to “map” chromosomal mosaicism at the blastocyst stage. Cytogenetic and Genome Research, vol. 149, no. 4, pp. 262–266. DOI: 10.1159/000449051 (In English)

Victor, A. R., Tyndall, J. C., Brake, A. J. et al. (2019) One hundred mosaic embryos transferred prospectively in a single clinic: Exploring when and why they result in healthy pregnancies. Fertility and Sterility, vol. 111, no. 2, pp. 280–293. PMID: 30691630. DOI: 10.1016/j.fertnstert.2018.10.019 (In English)

Weissman, A., Shoham, G., Shoham, Z. et al. (2017) Chromosomal mosaicism detected during preimplantation genetic screening: Results of a worldwide web-based survey. Fertility and Sterility, vol. 107, no. 5, pp. 1092–1097. PMID: 28433368. DOI: 10.1016/j.fertnstert.2017.02.119 (In English)

Wolstenholme, J., Rooney, D. E., Davison, E. V. (1994) Confined placental mosaicism, IUGR, and adverse pregnancy outcome: A controlled retrospective U.K. collaborative survey. Prenatal Diagnosis, vol. 14, no. 5, pp. 345–361. DOI: 10.1002/pd.1970140505 (In English)

Опубликован

2020-09-30

Выпуск

Раздел

Экспериментальные статьи