Biopolym. Cell. 2017; 33(6):424-433.
Chromosomal aberrations in spontaneously aborted products of conception from Ukraine
1Tkach I. R., 1Huleyuk N. L., 1, 3Zastavna D. V., 2Weise A., 2Liehr T., 3Ciszkowicz E., 3Tyrka M.
  1. State Institution "Institute of Hereditary Pathology, NAMS of Ukraine"
    31a, M. Lysenko Str., Lviv, Ukraine, 79008
  2. Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics,
    10, Kollegiengasse, Jena, Germany, D-07743
  3. Rzeszow University of Technology,
    6, Al. Powstańców Warszawy, 35-959 Rzeszow, Poland


Aim. To investigate peculiarities of numerical chromosomal imbalances in spontaneous products of conception from Western region of Ukraine. Methods. GTG-banding, interphase mFISH with probe panels for chromosomes 13/21, 14/22, 15, 16, 17, 18, X and Y. Results. Cytogenetic and molecular cytogenetic studies on 419 spontaneously aborted fetuses were performed. An abnor-mal karyotype was detected in 35.80 %. Most often the detected aneuploidies were triploidy (27.3 %), monosomy X (22.7 %), and trisomy 16 (18.7 %), trisomy 21 (6.7 %), trisomy 15 (5.3 %) and trisomy 22 (5.3 %). Conclusion. Detection of chromosomal aneuploidies in samples from products of conception plays a key role to find out the reasons of reproductive failure in hu-mans. Our study showed the effectiveness of combining karyotyping and mFISH with the chosen probe set for increasing the detection rate in spontaneous abortions. Most likely while including cases with normal karyotype acc. to GTG-banding in the mFISH approach it would allow detec-tion of low level mosaics of aneuploidies as well. These studies were conducted for the first time in the western Ukrainian region. The obtained results were compared with the similar results from other countries.
Keywords: spontaneous abortion, G-banding cytogenetic, interphase multicolor fluorescence in situ hybridization (mFISH), chromosome abnormalities


[1] Edmonds DK, Lindsay KS, Miller JF, Williamson E, Wood PJ. Early embryonic mortality in women. Fertil Steril. 1982;38(4):447-53.
[2] Steer C, Campbell S, Davies M, Mason B, Collins W. Spontaneous abortion rates after natural and assisted conception. BMJ. 1989;299(6711):1317-8. PubMed
[3] Zinaman MJ, Clegg ED, Brown CC, O'Connor J, Selevan SG. Estimates of human fertility and pregnancy loss. Fertil Steril. 1996;65(3):503-9.
[4] van den Berg MM, van Maarle MC, van Wely M, Goddijn M. Genetics of early miscarriage. Biochim Biophys Acta. 2012;1822(12):1951-9.
[5] Goddijn M, Leschot NJ. Genetic aspects of miscarriage. Baillieres Best Pract Res Clin Obstet Gynaecol. 2000;14(5):855-65.
[6] Warburton D, Dallaire L, Thangavelu M, Ross L, Levin B, Kline J. Trisomy recurrence: a reconsideration based on North American data. Am J Hum Genet. 2004;75(3):376-85.
[7] Ogasawara M, Aoki K, Okada S, Suzumori K. Embryonic karyotype of abortuses in relation to the number of previous miscarriages. Fertil Steril. 2000;73(2):300-4.
[8] Carp H, Toder V, Aviram A, Daniely M, Mashiach S, Barkai G. Karyotype of the abortus in recurrent miscarriage. Fertil Steril. 2001;75(4):678-82.
[9] Stephenson M, Kutteh W. Evaluation and management of recurrent early pregnancy loss. Clin Obstet Gynecol. 2007;50(1):132-45.
[10] Warburton D, Kline J, Stein Z, Hutzler M, Chin A, Hassold T. Does the karyotype of a spontaneous abortion predict the karyotype of a subsequent abortion? Evidence from 273 women with two karyotyped spontaneous abortions. Am J Hum Genet. 1987;41(3):465-83.
[11] Baranov VS. [A method of shaking-blotting--a simple and reliable means for obtaining direct chromosomal preparations from chorionic biopsies]. Tsitologiia. 1989;31(2):251-3. Russian.
[12] Liehr T, Pellestor F. Molecular cytogenetics: the standard FISH and PRINS procedure In: Ed. Liehr T. Fluorescence In Situ Hybridization (FISH) – Application Guide. Springer, Berlin, Heidelberg. 2009; 23–34.
[13] Diego-Alvarez D, Ramos-Corrales C, Garcia-Hoyos M, Bustamante-Aragones A, Cantalapiedra D, Diaz-Recasens J, Vallespin-Garcia E, Ayuso C, Lorda-Sanchez I. Double trisomy in spontaneous miscarriages: cytogenetic and molecular approach. Hum Reprod. 2006;21(4):958-66.
[14] Diego-Alvarez D, Rodriguez de Alba M, Cardero-Merlo R, Diaz-Recasens J, Ayuso C, Ramos C, Lorda-Sanchez I. MLPA as a screening method of aneuploidy and unbalanced chromosomal rearrangements in spontaneous miscarriages. Prenat Diagn. 2007;27(8):765-71.
[15] Menten B, Swerts K, Delle Chiaie B, Janssens S, Buysse K, Philippé J, Speleman F. Array comparative genomic hybridization and flow cytometry analysis of spontaneous abortions and mors in utero samples. BMC Med Genet. 2009;10:89.
[16] Robberecht C, Schuddinck V, Fryns JP, Vermeesch JR. Diagnosis of miscarriages by molecular karyotyping: benefits and pitfalls. Genet Med. 2009;11(9):646-54.
[17] Zhang YX, Zhang YP, Gu Y, Guan FJ, Li SL, Xie JS, Shen Y, Wu BL, Ju W, Jenkins EC, Brown WT, Zhong N. Genetic analysis of first-trimester miscarriages with a combination of cytogenetic karyotyping, microsatellite genotyping and arrayCGH. Clin Genet. 2009;75(2):133-40. PubMed
[18] Dória S, Carvalho F, Ramalho C, Lima V, Francisco T, Machado AP, Brandão O, Sousa M, Matias A, Barros A. An efficient protocol for the detection of chromosomal abnormalities in spontaneous miscarriages or foetal deaths. Eur J Obstet Gynecol Reprod Biol. 2009;147(2):144-50.
[19] Shearer BM, Thorland EC, Carlson AW, Jalal SM, Ketterling RP. Reflex fluorescent in situ hybridization testing for unsuccessful product of conception cultures: a retrospective analysis of 5555 samples attempted by conventional cytogenetics and fluorescent in situ hybridization. Genet Med. 2011;13(6):545-52.
[20] Sullivan AE, Silver RM, LaCoursiere DY, Porter TF, Branch DW. Recurrent fetal aneuploidy and recurrent miscarriage. Obstet Gynecol. 2004;104(4):784-8.
[21] Halder A, Fauzdar A. Skewed sex ratio and low aneuploidy in recurrent early missed abortion. Indian J Med Res. 2006;124(1):41-50.
[22] Wang BT, Chong TP, Boyar FZ, Kopita KA, Ross LP, El-Naggar MM, Sahoo T, Wang JC, Hemmat M, Haddadin MH, Owen R, Anguiano AL. Abnormalities in spontaneous abortions detected by G-banding and chromosomal microarray analysis (CMA) at a national reference laboratory. Mol Cytogenet. 2014;7:33.
[23] Kooper AJA, Faas BHW, Feenstra I, de Leeuw N and Smeets DFCM. Best diagnostic approach for the genetic evaluation of fetuses after intrauterine death in first, second or third trimester: QF-PCR, karyotyping and/or genome wide SNP array analysis. Mol Cytogen. 2014; 7:6.
[24] Gao J, Liu C, Yao F, Hao N, Zhou J, Zhou Q, Zhang L, Liu X, Bian X, Liu J. Array-based comparative genomic hybridization is more informative than conventional karyotyping and fluorescence in situ hybridization in the analysis of first-trimester spontaneous abortion. Mol Cytogenet. 2012;5(1):33.
[25] Jobanputra V, Sobrino A, Kinney A, Kline J, Warburton D. Multiplex interphase FISH as a screen for common aneuploidies in spontaneous abortions. Hum Reprod. 2002;17(5):1166-70.
[26] Morales C, Sánchez A, Bruguera J, Margarit E, Borrell A, Borobio V, Soler A. Cytogenetic study of spontaneous abortions using semi-direct analysis of chorionic villi samples detects the broadest spectrum of chromosome abnormalities. Am J Med Genet A. 2008;146A(1):66-70.
[27] Eiben B, Bartels I, Bähr-Porsch S, Borgmann S, Gatz G, Gellert G, Goebel R, Hammans W, Hentemann M, Osmers R, et al. Cytogenetic analysis of 750 spontaneous abortions with the direct-preparation method of chorionic villi and its implications for studying genetic causes of pregnancy wastage. Am J Hum Genet. 1990;47(4):656-63.
[28] Jobanputra V, Esteves C, Sobrino A, Brown S, Kline J, Warburton D. Using FISH to increase the yield and accuracy of karyotypes from spontaneous abortion specimens. Prenat Diagn. 2011;31(8):755-9.
[29] Lebedev IN, Ostroverkhova NV, Nikitina TV, Sukhanova NN, Nazarenko SA. Features of chromosomal abnormalities in spontaneous abortion cell culture failures detected by interphase FISH analysis. Eur J Hum Genet. 2004;12(7):513-20.
[30] Vorsanova SG, Kolotii AD, Iourov IY, Monakhov VV, Kirillova EA, Soloviev IV, Yurov YB. Evidence for high frequency of chromosomal mosaicism in spontaneous abortions revealed by interphase FISH analysis. J Histochem Cytochem. 2005;53(3):375-80.
[31] Russo R, Sessa AM, Fumo R, Gaeta S. Chromosomal anomalies in early spontaneous abortions: interphase FISH analysis on 855 FFPE first trimester abortions. Prenat Diagn. 2016;36(2):186-91.