Investigation of human aneuploidy and polyploidy in subcidiary reproductive technology programs

  • Y. V. Gontar LLC «Medical center IGR», Ukraine, 03115, Kiev, Pobedy ave., 121-B; V. N. Karazin Kharkiv National University, Ukraine, 61022, Kharkiv, Svobody sq., 4
  • O. Y. Verlinsky LLC «Medical center IGR», Ukraine, 03115, Kiev, Pobedy ave., 121-B
  • I. E. Ilyin LLC «Medical center IGR», Ukraine, 03115, Kiev, Pobedy ave., 121-B
  • O. M. Fedota V. N. Karazin Kharkiv National University, Ukraine, 61022, Kharkiv, Svobody sq., 4


Aim. To evaluate the frequency of aneuploidy and polyploidy among sperm, preimplantation embryos, the embryos stopped in development, developing fetuses and adults studied in the framework of subsidiary reproductive technologies. Methods. To determine the chromosomes of cells from samples of different biological material cytogenetic and molecular cytogenetic methods were used. Results. The highest frequency of aneuploidy is observed among the preimplantation embryos (69.1 %) and the embryos stopped in development (60.9 %). Aneuploid/euploid chromosome set ratio is similar for both genders in all research objects except embryos stopped in development: for females it was 1:1, for males – 1.8:1. Among the spermatozoa most frequent is aneuploidy along the 18th (27 %) and sex (30.3 %) chromosomes, among preimplantation embryos – along the 13th chromosome (31.1 %), among abortuses along the 18th chromosome (40 6 %), fetuses – along the 21st chromosome (72.2 %). Sex ratio among polyploid preimplantation embryos – 1:1, among the embryos stopped in development – 2.5:1 in favor of males. Conclusions. The high frequency of aneuploidy among the early embryos is a leading cause of implantation failure, spontaneous abortion at different timing or the presence of multiple fetal malformations. Preimplantation genetic screening is essential for reducing the incidence of chromosomal abnormalities and increase in the effectiveness of subsidiary reproductive technologies.

Keywords: chromosomal abnormalities, aneuploidy, polyploidy, karyotype, preimplantation genetic screening.


Geneticheskiy pasport – osnova individualnoy i prediktivnoy meditsiny. Ed. by V. S. Baranov. St.-Petersburg: N-L, 2009. 528 p.

Kurbatova O. L. Etnodemograficheskie protsessy i ekologicheskaia situatsiia v Moskve v svete problemy geneticheskoy bezopasnosti naseleniia. Bezopasnost Rossii: pravovye, sotsialno-ekonomicheskie i nauchno-tekhnicheskie aspekty. Bezopasnost i ustoychivoe razvitie krupnykh gorodov. Moskva: MGF “Znanie”, 1998. P. 311–335.

Pokanievych T. M. Chynnyky ryzyku formuvannia vrodzhenykh vad rozvytku sered novonarodzhenykh (za danymy henetychnoho monitorynhu naselennia Kyivskoi oblasti): dys. kand. med. nauk: 03.00.15. Kyiv, 2003. 148 p.

Neumerzhytska L. V., Baryliak I. R., Shkarupa V. M. Chastota vrodzhenykh vad rozvytku v radioaktyvno zabrudnenykh rehionakh Ukrainy. Fakt. Eksp. Evol. Org. 2007. Vol. 1. P. 486–499.

Djomina E. A., Barilyak I. R. Medical and genetic consequences of radiation catastrophes (Review). Cytology and Genetics. 2010. Vol. 44(3). P. 186-193. doi: 10.3103/S0095452710030102

Pilinskaya M. A., Dybskiy S. S., Dybskaya Ye. B., Pedan L. R. Radiation-induced modification of the chromosome sensitivity of human somatic cells to the testing mutagenic exposure of bleomycin in vitro. Cytology and Genetics. 2010. Vol. 44(2). P. 118–123. doi: 10.3103/S0095452710020088

Chantot-Bastaraud S., Ravel C., Siffori J.P. Underlying karyotype abnormalities in IVF/ICSI patients. Reprod Biomed Online. 2008. Vol.16(4). P. 514–522. doi: 10.1016/S1472-6483(10)60458-0

Machiela M.J., Zhou W., Sampson J.N. et. al. Characterization of large structural genetic mosaicism in human autosomes. Am. Jour. of Hum. Genet. 2015. Vol. 96(3). P. 487–497. doi: 10.1016/j.ajhg.2015.01.011

Radojcic B.A. Chromosome studies in patients with defective reproductive success. Am. J. Reprod. Immunol. 2000. Vol. 44(5). P. 279–283. doi: 10.1111/j.8755-8920.2000.440505.x

Pagter M.S., van Roosmalen M. J., Baas A. F. Chromothripsis in healthy individuals affects multiple protein-coding genes and can result in severe congenital abnormalities in offspring. Am. J. Hum. Genet. 2015. Vol. 96(4). P. 651–656. doi: 10.1016/j.ajhg.2015.02.005

Martin C.L., Ledbetter D.H. Molecular cytogenetic analysis of telomere rearrangements. Curr. Protoc. Hum. Genet. 2015. Vol. 84: 8.11.1–15. doi: 10.1002/0471142905.hg0811s84

Rajcan-Separovic E., Diego-Alvarez D., Robinson W.P. et. al. Identification of copy number variants in miscarriages from couples with idiopathic recurrent pregnancy loss. Hum. Reprod. 2010. Vol. 25(11). P. 2913–2922. doi: 10.1093/humrep/deq202

Reproductive health strategy to accelerate progress towards the attainment of international development goals and targets. Geneva: WHO, 2004. 36 p.

Iuzko A.M., Rudenko N.G. Lechenie besplodiia s ispolzovaniem vspomogatelnykh reproduktivnykh tekhnologiy v Ukraine. Zdorove zhenshchiny. 2014. No 3. P. 153–157.

Carp H., Feldman B., Oelsner G. et. al. Parental karyotype and subsequent live births in recurrent miscarriage. Fertil Steril. 2004. Vol. 81(5). P. 1296–1301. doi: 10.1016/j.fertnstert.2003.09.059

Huang A., Adusumalli J., Patel S., et. al. Prevalence of chromosomal mosaicism in pregnancies from couples with infertility. Fertil Steril. 2009. Vol. 91(6). P. 2355–2360. doi: 10.1016/j.fertnstert.2008.03.044

Grunfeld L., Sandler B., Mukherjee T. et al. Parental karyotype may reveal the source of a pregnancy loss even in the presence of a reportedly euploid fetal karyotype. Fertil Steril. 2011. Vol. 95(3). P. 1120. e9–10. doi: 10.1016/j.fertnstert.2010.10.015

Vorsanova S.G., Iurov Iu.B., Chernyshov V.N. Khromosomnye sindromy i anomalii. Rostov-na Donu, 1999. P. 155–156.

Zerova-Liubimova T.E, Gorovenko N.G. Standarty analiza preparatov khromosom cheloveka (metodicheskie rekomendatsii). Kiev, 2003. P. 10.

Thornhill A.R., deDie-Smulders C.E., Geraedts J.P. et. al. Best practice guidelines for clinical preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS). Human Reproduction. Vol. 20(1). 2005.– P. 35–48. doi: 10.1093/humrep/deh579

Atramentova L. O., Utievs'ka O.M. Statystychni metody v biolohii. Kharkiv, 2007. 288 p.

Orzacka S.H., Stubblefielda J.W., Akmaev V.R. et al. The human sex ratio from conception to birth. Proc. Natl. Acad. Sci. USA 2015. Vol. 112(16). P. E2102–E2111. doi: 10.1073/pnas.1416546112

Rabinowitz M., Ryan A., Gemelos G. Origins and rates of aneuploidy in human blastomeres. Fertil. Steril. 2012. Vol. 97(2). P. 395–401. doi: 10.1016/j.fertnstert.2011.11.034

Bronet F., Nogales M.-C., Martinez E. et al. Is there a relationship between time-lapse parameters and embryo sex? Fertil. Steril. 2015. Vol. 103(2). P. 396–401. doi: 10.1016/j.fertnstert.2014.10.050

Mazur P., Nagornyy V., Mykytenko D. et al. Disproportion of sex ratio within aneuploid embryos after aCGH. Hum. Reprod. 2014. Vol. 29, suppl. 1: Abstr. 30th Annu. Meet. Eur. Soc. Hum. Reprod. Embryol. (Munich, Germany 29 June–2 July, 2014). P. i185 (P. 164).

Mercier S., Morel F., Roux C. et al. Analysis of the sex chromosomal equipment in spermatozoa of a 47,XYY male using two-colour fluorescence in situ hybridization. Mol. Hum. Reprod. 1996. Vol. 2(7). P. 485–488. doi: 10.1093/molehr/2.7.485

MacDonald M., Hassold T., Harvey J. et al. The origin of 47,XXY and 47,XXX aneuploidy: heterogeneous mechanisms and role of aberrant recombination. Hum. Mol. Genet. 1994. Vol. 3(8). P. 1365–1371. doi: 10.1093/hmg/3.8.1365

Ogata T., Matsuo N. Turner syndrome and female sex chromosome aberrations: deduction of the principal factors involved in the development of clinical features. Hum. Genet. 1995. Vol. 95(6). P. 607–629. doi: 10.1007/BF00209476

Sartorelli, E. M., Mazzucatto L. F., de Pina-Neto J. M. Effect of paternal age on human sperm chromosomes. Fertil Steril. 2001. Vol. 76(6). P. 1119–1123. doi: 10.1016/S0015-0282(01)02894-1

Lorda-Sanchez I., Binkert F., Maechleret M. et al. Reduced recombination and paternal age effect in Klinefelter syndrome. Hum. Genet. 1992. Vol. 89(5). P. 524–530. doi: 10.1007/BF00219178

Fogel F.B., Motulski A. Genetika cheloveka. Moskva, 1989. Vol. 1. 312 p.

Wyrobek A. J., Aardema M., Eichenlaub-Ritter U. et al. Mechanisms and targets involved in maternal and paternal age effects on numerical aneuploidy. Environ. Mol. Mutagen. 1996. Vol. 28(3). P. 254–264. doi: 10.1002/(SICI)1098-2280(1996)28:3<254::AID-EM9>3.0.CO;2-D

Eichenlaub-Ritter U. Parental age-related aneuploidy in human germ cells and offspring: a story of past and present. Environ. Mol. Mutagen. 1996. Vol. 28(3). P. 211–236. doi: 10.1002/(SICI)1098-2280(1996)28:3<211::AID-EM6>3.0.CO;2-G

Martin, C. L., Kirkpatrick B. E., Ledbetter D. H. Copy number variants, aneuploidies, and human disease. Clin. Perinatol. 2015. Vol. 42(2). P. 227–242. doi: 10.1016/j.clp.2015.03.001

Biancotti J.-C. Human embryonic stem cells as models for aneuploid chromosomal syndromes. Stem cells. 2010. Vol. 28. P. 1530-1540. doi: 10.1002/stem.483

Kolotiy A.D. Molekuliarno-tsitogeneticheskie issledovaniia mozaichnykh form chislennykh khromosomnykh anomaliy v postnatalnom i embrionalnom razvitii: avtoref. dis. kand. biol.nauk: 03.00.15. Moskva, 2008. 20 p.

Hook E. B., Schreinemachers D.M., Willey A.M. et al. Inherited structural cytogenetic abnormalities detected incidentally in fetuses diagnosed prenatally: frequency, parental-age associations, sex-ratio trends, and comparisons with rates of mutants. Am. J. Hum. Genet. 1984. Vol. 36(2). P. 422–443.

Forrester M. B., Merz R. D. Epidemiology of triploidy in a population-based birth defects registry, Hawaii, 1986–1999. Am. J. Med. Genet. 2003. Vol. 119A(3). P. 319–323. doi: 10.1002/ajmg.a.20152

Wellesley, D., Dolk H., Boyd P.A. et al. Rare chromosome abnormalities, prevalence and prenatal diagnosis rates from population–based congenital anomaly registers in Europe. Eur. J. Hum. Genet. 2012. Vol. 20(5. P. 521–526. doi: 10.1038/ejhg.2011.246