Aneuploidy and mosaicism: sociomedical significance and improved diagnosis

DOI

https://dx.doi.org/10.18565/aig.2025.27

Baranouskaya A.I., Voronetsky A.N.
Belarusian State Medical University, Minsk, Republic of Belarus

The review contains publications from the PubMed/MEDLINE and eLibrary.ru databases over the past 5 years on the use of preimplantation genetic testing and aneuploidy diagnosis (PGT-A) in the practice of assisted reproductive technologies (ART). PGT-A is used worldwide with a frequency ranging from 2 to 33% depending on national guidelines and patients’ age, however, PGT-A is not used in ART practice in some countries. PGT-A supporters present arguments about the association of aneuploidy with advanced reproductive age, its effect on pregnancy rates and live births. PGT-A opponents raise concerns about the epigenetic effects of mechanical damage to the embryo during biopsy, as well as its prolonged stay in an artificial environment until the blastocyst stage; they also suggest that aneuploidy may be self-corrected during embryo development. The frequency of PGT-A use is directly related to the funding source and the beneficiary. Most researchers find evidence in favor of the rational use of PGT-A. In case of miscarriages, 58% of embryos are aneuploid and embryo selection in the ART protocol reduces the miscarriage rate; in case of ongoing pregnancy, it does not significantly affect the live birth rate. The difficult interpretation of PGT-A results is due to objective reasons. Firstly, the trophectoderm may contain cells with different sets of chromosomes simultaneously; secondly, there is no complete coincidence of the ploidy of the cells of the trophectoderm with the inner cell mass of the blastocyst; thirdly, there is a different degree of mosaicism depending on the proportion of abnormal cells, the type of damaged chromosome, the number of abnormal chromosomes, and the type of chromosomal abnormality. The most commonly used method for performing PGT is next-generation sequencing (NGS). The use of microarrays for the study of single nucleotide polymorphisms (SNP-microarray) is a promising direction in this field.
Conclusion: PGT has strong scientific potential in improving laboratory technologies, development and application of SNP-array, and research into the nature of chromosomal abnormalities. The use of PGT in reproductive medicine remains in demand due to the large proportion of infertile couples of advanced reproductive age, the need for improved outcomes of ART and higher rates of healthy births.

Authors’ contributions: Baranouskaya A.I., Voronetsky A.N. – developing the concept and design of the study, collecting and processing the material, editing the article; Baranouskaya A.I. – writing the text.
Conflicts of interest: Authors declare lack of the possible conflicts of interests.
Funding: The study was carried out without sponsorship.
For citation: Baranouskaya A.I., Voronetsky A.N.
Aneuploidy and mosaicism: sociomedical significance and improved diagnosis.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (6): 37-43 (in Russian)
https://dx.doi.org/10.18565/aig.2025.27

assisted reproductive technology

in vitro fertilization

next-generation sequencing

pre-implantation genetic testing

aneuploidy

mosaicism

implantation

infertility

Full text (in Russian)

Zhang C., Yan L., Qiao J. Effect of advanced parental age on pregnancy outcome and offspring health. J. Assist. Reprod. Genet. 2022; 39(9): 1969-86. https://dx.doi.org/10.1007/s10815-022-02533-w
Vitagliano A., Paffoni A., Viganò P. Does maternal age affect assisted reproduction technology success rates after euploid embryo transfer? A systematic review and meta-analysis. Fertil. Steril. 2023; 120(2): 251-65. https://dx.doi.org/10.1016/j.fertnstert.2023.02.036
Morris G., Mavrelos D., Odia R., Viñals Gonzalez X., Cawood S., Yasmin E. et al. Paternal age over 50 years decreases assisted reproductive technology (ART) success: A single UK center retrospective analysis. Acta Obstet. Gynecol. Scand. 2021; 100(10): 1858-67. https://dx.doi.org/10.1111/aogs.14221
Hanson B.M., Kim J.G., Osman E.K., Tiegs A.W., Lathi R.B., Cheng P.J. et al. Impact of paternal age on embryology and pregnancy outcomes in the setting of a euploid single-embryo transfer with ejaculated sperm: retrospective cohort study. F S Rep. 2020; 1(2): 99-105 https://dx.doi.org/10.1016/j.xfre.2020.06.004
Молчанова А.В., Панкрушина А.Н. Исследование структурных хромосомных перестроек у эмбрионов человека. Вестник Тверского государственного университета. Серия: Биология и экология. 2024; 2(74): 36-46. [Molchanova A.V., Pankrushina A.N. Investigation of structural chromosomal rearrangements in human embryos. Bulletin of Tver State University. Series: Biology and Ecology. 2024; 2(74): 36-46. (in Russian)]. https://dx.doi.org/10.26456/vtbio359
Rana B., Lambrese K., Mendola R., Xu J., Garrisi J., Miller K. et al. Identifying parental and cell-division origins of aneuploidy in the human blastocyst. Am. J. Hum. Genet. 2023; 110(4): 565-74. https://dx.doi.org/10.1016/j.ajhg.2023.03.003
Краснопольская К.В., Самойлова А.А., Исакова К.М., Конькова А.Л., Бочарова Т.В. Характеристика плоидного статуса эмбрионов с различной морфокинетической оценкой по шкале KIDSCORE D5 у женщин оптимального и старшего репродуктивного возраста. Международный научно-исследовательский журнал. 2024; 8(146). [Krasnopolskaya K.V., Samoilova A.A., Isakova K.M., Konkova A.L., Bocharova T.V. Characterization of the ploidic status of embryos with different morphokinetic evaluation according to the KIDSCORE D5 scale in women of optimal and older reproductive age. International Research Journal. 2024; 8(146) (in Russian)]. https://dx.doi.org/10.60797/IRJ.2024.146.12
Arnanz A., Bayram A., Elkhatib I., Abdala A., El-Damen A., Patel R. et al. Antimüllerian hormone (AMH) and age as predictors of preimplantation genetic testing for aneuploidies (PGT-A) cycle outcomes and blastocyst quality on day 5 in women undergoing in vitro fertilization (IVF). J. Assist. Reprod. Genet. 2023; 40(6): 1467-77. https://dx.doi.org/10.1007/s10815-023-02805-z
Pirtea P., Cedars M.I., Devine K., Ata B., Franasiak J., Racowsky C. et al. Recurrent implantation failure: reality or a statistical mirage?: Consensus statement from the July 1, 2022 Lugano Workshop on recurrent implantation failure. Fertil. Steril. 2023; 120(1): 45-59. https://dx.doi.org/10.1016/j.fertnstert.2023.02.014
Society for Assisted Reproductive Technology. Preliminary National Summary Report for 2022. Available at: https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?reportingYear=2022 (accessed October 02, 2024).
Rajendran S., Brendel M., Barnes J., Zhan Q., Malmsten J.E., Zisimopoulos P. et al. Automatic ploidy prediction and quality assessment of human blastocysts using time-lapse imaging. Nat. Commun. 2024; 15(1): 7756. https://dx.doi.org/10.1038/s41467-024-51823-7
Zegers-Hochschild F., Crosby J.A., Musri C., Petermann-Rocha F., Souza M.D.C.B., Martinez A.G. et al.; Latin American Network of Assisted Reproduction. ART in Latin America: the Latin American Registry, 2020. JBRA Assist. Reprod. 2023; 27(3): 514-38. https://dx.doi.org/10.5935/1518-0557.20230025
Smeenk J., Wyns C., De Geyter C., Kupka M., Bergh C., Cuevas Saiz I. et al.; European IVF Monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). ART in Europe, 2019: results generated from European registries by ESHRE. Hum. Reprod. 2023; 38(12): 2321-38. https://dx.doi.org/10.1093/humrep/dead197
Calhaz-Jorge C., Smeenk J., Wyns C., De Neubourg D., Baldani D.P., Bergh C. et al. European IVF-Monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE); Survey on ART and IUI: legislation, regulation, funding, and registries in European countries-an update. Hum. Reprod. 2024; 39(9): 1909-24. https://dx.doi.org/10.1093/humrep/deae163
Cram D.S., Leigh D., Handyside A., Rechitsky L., Xu K., Harton G. et al. PGDIS Position Statement on the Transfer of Mosaic Embryos 2019. Reprod. Biomed. Online. 2019; 39 Suppl. 1: e1-e4. https://dx.doi.org/10.1016/j.rbmo.2019.06.012
Vlajkovic T., Grigore M., van Eekelen R., Puscasiu L. Day 5 versus day 3 embryo biopsy for preimplantation genetic testing for monogenic/single gene defects. Cochrane Database Syst. Rev. 2022; 11(11): CD013233. https://dx.doi.org/10.1002/14651858.CD013233.pub2
Özer L., Aktuna S., Unsal E., Baltaci A., Baltaci V. An incidental detection of a cryptic complex chromosome rearrangement found during NGS based PGT-SR: A case report. J. Reprod. Infertil. 2022; 23(4): 303-9. https://dx.doi.org/10.18502/jri.v23i4.10817
Gleicher N., Albertini D.F., Barad D.H., Homer H., Modi D., Murtinger M. et al.; International Do No Harm Group in IVF (IDNHG-IVF). The 2019 PGDIS position statement on transfer of mosaic embryos within a context of new information on PGT-A. Reprod. Biol. Endocrinol. 2020; 18(1): 57. https://dx.doi.org/10.1186/s12958-020-00616-w
Rhon-Calderon E.A., Hemphill C.N., Vrooman L.A., Rosier C.L., Lan Y., Ord T. et al. Trophectoderm biopsy of blastocysts following IVF and embryo culture increases epigenetic dysregulation in a mouse model. Hum. Reprod. 2024; 39(1): 154-76. https://dx.doi.org/10.1093/humrep/dead238
Alteri A., Cermisoni G.C., Pozzoni M., Gaeta G., Cavoretto P.I., Viganò P. Obstetric, neonatal, and child health outcomes following embryo biopsy for preimplantation genetic testing. Hum. Reprod. Update. 2023; 29(3): 291-306. https://dx.doi.org/10.1093/humupd/dmad001
Cornelisse S., Zagers M., Kostova E., Fleischer K., van Wely M., Mastenbroek S. Preimplantation genetic testing for aneuploidies (abnormal number of chromosomes) in in vitro fertilisation. Cochrane Database Syst. Rev. 2020; 9(9): CD005291. https://dx.doi.org/10.1002/14651858.CD005291.pub3
Yan J., Qin Y., Zhao H., Sun Y., Gong F., Li R. et al. Live birth with or without preimplantation genetic testing for aneuploidy. N. Engl. J. Med. 2021; 385(22): 2047-58. https://dx.doi.org/10.1056/NEJMoa2103613
Olive E., Bull C., Gordon A., Davies-Tuck M., Wang R., Callander E. Economic evaluations of assisted reproductive technologies in high-income countries: a systematic review. Hum. Reprod. 2024; 39(5): 981-91. https://dx.doi.org/10.1093/humrep/deae039
Jin J., Ma J., Wang X., Hong F., Zhang Y., Zhou F. et al. Multi-omics PGT: re-evaluation of euploid blastocysts for implantation potential based on RNA sequencing. Hum. Reprod. 2024; 39(12): 2861-72. https://doi.org/10.1093/humrep/deae237
Kumar A., Im K., Banjevic M., Ng P.C., Tunstall T., Garcia G. et al. Whole-genome risk prediction of common diseases in human preimplantation embryos. Nat. Med. 2022; 28(3): 513-6. https://dx.doi.org/10.1038/s41591-022-01735-0
Kutteh W.H., Papas R.S., Maisenbacher M.K., Dahdouh E.M. Role of genetic analysis of products of conception and PGT in managing early pregnancy loss. Reprod. Biomed. Online. 2024; 49(1): 103738. https://dx.doi.org/10.1016/j.rbmo.2023.103738
Melado L., Lawrenz B., Nogueira D., Raberi A., Patel R., Bayram A. et al. Features of chromosomal abnormalities in relation to consanguinity: analysis of 10,556 blastocysts from IVF/ICSI cycles with PGT-A from consanguineous and non-consanguineous couples. Sci. Rep. 2023; 13(1): 8857. https://dx.doi.org/10.1038/s41598-023-36014-6
Hattori H., Okuyama N., Ashikawa K., Sakuraba Y., Igarashi H., Kyono K. The utility of human two plus one small pronucleated zygotes (2.1PN) based on clinical outcomes and the focused ploidy analysis. J. Assist. Reprod. Genet. 2024; 41(6): 1589-96. https://dx.doi.org/10.1007/s10815-024-03114-9
Савостина Г.В., Перминова С.Г., Тимофеева А.В., Веюкова М.А. Современные методы оценки имплантационного потенциала эмбрионов в программах вспомогательных репродуктивных технологий. Доктор.Ру. 2021; 20(8): 12-8. [Savostina G.V., Perminova S.G., Timofeeva A.V., Veyukova M.A. Modern methods for assessment of the implantation potential of embryos in assisted reproductive programs. Doctor.Ru. 2021; 20(8): 12-8. (in Russian)]. https://dx.doi.org/10.31550/1727-2378-2021-20-8-12-18
Глинкина Ж.И., Сайфитдинова А.Ф., Павлова О.А., Леонтьева О.А., Панина А.Н., Бичевая Н.К., Борозняк И.В. Анализ конкордантности результатов преимплантационного генетического тестирования на анеуплоидии методом Next Generation Sequencing на платформе Illumina в клетках разных областей трофэктодермы. Доктор.Ру. 2022; 21(5): 18-24. [Glinkina Zh.I., Sayfitdinova A.F., Pavlova O.A., Leontyeva O.A., Panina A.N., Bichevaya N.K., Boroznyak I.V. Analysis of concordance of pre-implantation aneuploidy genetic testing results obtained using Next Generation Sequencing on Illumina platform in cells of various parts of trophoblast. Doctor.Ru. 2022; 21(5): 18-24. (in Russian)]. https://dx.doi.org/10.31550/1727-2378-2022-21-5-18-24
Theobald R., SenGupta S., Harper J. The status of preimplantation genetic testing in the UK and USA. Hum. Reprod. 2020; 35(4): 986-98. https://dx.doi.org/10.1093/humrep/deaa034
Sordia-Hernandez L.H., Morales-Martinez F.A., González-Colmenero F.D., Flores- Rodriguez A., Leyva-Camacho P.C., Sordia-Piñeyro M.O. et al. The effects of preimplantation genetic testing for aneuploidy (PGT-A) on patient-important outcomes in embryo transfer cases: a meta-analysis. J. Reprod. Infertil. 2022; 23(4): 231-46. https://dx.doi.org/10.18502/jri.v23i4.10808
Gleicher N., Barad D.H., Patrizio P., Orvieto R. We have reached a dead end for preimplantation genetic testing for aneuploidy. Hum. Reprod. 2022; 37(12): 2730-4. https://dx.doi.org/10.1093/humrep/deac052
Samara N., Peleg S., Frumkin T., Gold V., Amir H., Haikin Herzberger E. et al. New insights regarding origin of monosomy occurrence in early developing embryos as demonstrated in preimplantation genetic testing. Mol. Cytogenet. 2022; 15(1): 11. https://dx.doi.org/10.1186/s13039-022-00582-5
Groff A.F., Resetkova N., DiDomenico F., Sakkas D., Penzias A., Rinn J.L. et al. RNA-seq as a tool for evaluating human embryo competence. Genome Res. 2019; 29(10): 1705-18. https://dx.doi.org/10.1101/gr.252981.119
Riestenberg C.K., Mok T., Ong J.R., Platt L.D., Han C.S., Quinn M.M. Sonographic abnormalities in pregnancies conceived following IVF with and without preimplantation genetic testing for aneuploidy (PGT-A). J. Assist. Reprod. Genet. 2021; 38(4): 865-71. https://dx.doi.org/10.1007/s10815-021-02069-5
Zegers-Hochschild F., Adamson G.D., Dyer S., Racowsky C., de Mouzon J., Sokol R. et al. The International Glossary on Infertility and Fertility Care, 2017. Hum. Reprod. 2017; 32(9): 1786-801. https://dx.doi.org/10.1093/humrep/dex234
De Rycke M, Capalbo A, Coonen E, Coticchio G, Fiorentino F, Goossens V. et al.; ESHRE Working Group on Chromosomal Mosaicism. ESHRE survey results and good practice recommendations on managing chromosomal mosaicism. Hum. Reprod. Open. 2022; 2022(4): hoac044. https://dx.doi.org/10.1093/hropen/hoac044
Viotti M., Victor A.R., Barnes F.L., Zouves C.G., Besser A.G., Grifo J.A. et al. Using outcome data from one thousand mosaic embryo transfers to formulate an embryo ranking system for clinical use. Fertil. Steril. 2021; 115: 1212-24. https://dx.doi.org/10.1016/j.fertnstert.2020.11.041
Practice Committee and Genetic Counseling Professional Group (GCPG) of the American Society for Reproductive Medicine. Electronic address: asrm@asrm.org. Clinical management of mosaic results from preimplantation genetic testing for aneuploidy (PGT-A) of blastocysts: a committee opinion. Fertil. Steril. 2020; 114(2): 246-54. https://dx.doi.org/10.1016/j.fertnstert.2020.05.014
Иванова А.Д., Семёнова М.Л. Хромосомные аберрации в эмбриональном развитии человека как биологическое явление. Acta Naturae (русскоязычная версия). 2023; 15(3): 27-36. [Ivanova A.D., Semjonova M.L. Chromosomal aberrations in human embryonic development as a biological phenomenon. Acta Naturae (Russian version). 2023; 15(3): 27-36. (in Russian)]. https://dx.doi.org/10.32607/actanaturae.25255
Макарова Н.П., Екимов А.Н., Кулакова Е.В., Драпкина Ю.С., Сысоева А.П., Краснова Н.А., Калинина Е.А. Особенности мозаицизма у эмбрионов человека в программах лечения бесплодия методами вспомогательных репродуктивных технологий. Акушерство и гинекология. 2021; 7: 144-51. [Makarova N.P., Ekimov A.N., Kulakova E.V., Drapkina Yu.S., Sysoeva A.P., Krasnova N.A., Kalinina E.A. Characteristics of embryonic mosaicism in infertility treatment with assisted reproductive technologies. Obstetrics and Gynecology. 2021; (7): 144-51. (in Russian)]. https://dx.doi.org/10.18565/aig.2021.7.144-151
Soler N., Bautista-Llàcer R., Escrich L., Oller A., Grau N., Tena R. et al. Rescuing monopronucleated-derived human blastocysts: a model to study chromosomal topography and fingerprinting. Fertil. Steril. 2021; 116(2): 583-96. https://dx.doi.org/10.1016/j.fertnstert.2021.03.038
Chavli E., van den Born M., Eleveld C., Boter M., van Marion R., Hoefsloot L. et al. Chromosomal mosaicism in human blastocysts: a cytogenetic comparison of trophectoderm and inner cell mass after next-generation sequencing. Reprod. Biomed. Online. 2022; 45(5): 867-77. https://dx.doi.org/10.1016/j.rbmo.2022.06.004
Федотова К.В., Панкрушина А.Н. Анализ факторов, влияющих на решение о переносе мозаичных эмбрионов на этапе преимплантационного генетического тестирования. Вестник Тверского государственного университета. Серия: Биология и экология. 2022; 2(66): 39-49. [Fedotova K.V., Pankrushina A.N. Analysis of factors influencing the decision to transfer mosaic embryos at the stage of preimplantation genetic testing. Bulletin of Tver State University. Series: Biology and Ecology. 2022; 2(66): 39-49. (in Russian)]. https://dx.doi.org/10.26456/vtbio251
Bouba I., Hatzi E., Ladias P., Sakaloglou P., Kostoulas C., Georgiou I. Biological and clinical significance of mosaicism in human preimplantation embryos. J. Dev. Biol. 2021; 9(2): 18. https://dx.doi.org/10.3390/jdb9020018
Leigh D., Cram D.S., Rechitsky S., Handyside A., Wells D., Munne S. et al. PGDIS position statement on the transfer of mosaic embryos 2021. Reprod. Biomed. Online. 2022; 45(1): 19-25. https://dx.doi.org/10.1016/j.rbmo.2022.03.013
Janssen A.E.J., Koeck R.M., Essers R., Cao P., van Dijk W., Drüsedau M. et al. Clinical-grade whole genome sequencing-based haplarithmisis enables all forms of preimplantation genetic testing. Nat. Commun. 2024; 15(1): 7164. https://doi.org/10.1038/s41467-024-51508-1
Приказ Министерства здравоохранения Российской Федерации от 31.07.2020 № 803н «О порядке использования вспомогательных репродуктивных технологий, противопоказаниях и ограничениях к их применению». Доступно по: https://publication.pravo.gov.ru/Document/View/0001202010190041?index=1 [Order of the Ministry of Health of the Russian Federation dated July 31, 2020 No. 803n "On the procedure for using assisted reproductive technologies, contraindications and restrictions on their use". Available at: https://publication.pravo.gov.ru/Document/View/0001202010190041?index=1 (in Russian)].
Аншина М.Б., Долгушина Н.В., Колода Ю.А., Корсак В.С., Савина В.М., Смирнова А.А. Терминология ВРТ: Международный глоссарий. Проблемы репродукции. 2019; 25(1): 6-15. [Anshina M.B., Dolgushina N.V., Koloda Iu.A., Korsak V.S., Savina V.M., Smirnova A.A. The International Glossary on Infertility and Fertility Care. Russian Journal of Human Reproduction. 2019; 25(1): 6-15. (in Russian)]. https://doi.org/10.17116/repro2019250116

Received 11.02.2025

Accepted 16.05.2025

Alena I. Baranouskaya, Dr. Med. Sci., Professor, Professor at the Department of Obstetrics and Gynecology with a course for advanced training and retraining, Belarusian State Medical University, 220083, Dzerzhinsky Ave., 83, Minsk, Belarus, elena_baranovska@mail.ru, https://orcid.org/0000-0002-2116-4675
Aliaksandr N. Voronetsky, PhD, Associate Professor at the Department of Pediatric Surgery with a course for advanced training and retraining, Belarusian State Medical University, 220083, Dzerzhinsky Ave., 83, Minsk, Belarus, anvoron@mail.ru, https://orcid.org/0000-0001-7091-376X
Corresponding author: Alena I. Baranouskaya, elena_baranovska@mail.ru

Aneuploidy and mosaicism: sociomedical significance and improved diagnosis

Baranouskaya A.I., Voronetsky A.N.

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