Prevalence and spectrum of chromosome abnormalities among spontaneous and induced early reproductive losses: 2020 miscarriages and 1572 medical abortions
Keywords:early pregnancy losses, spontaneous abortion, medical abortion, anembryony, karyotype, chromosome abnormalities
This article presents the data of a comparative analysis of 9 large studies of non-developing pregnancies (NB) karyotype, published after 2000, as well as results of our own study of NB and medical abortion (MA), performed in the first trimester of pregnancy.
Objective of the study: to assess the prevalence and structure of chromosomal abnormalities (CA) among spontaneous and induced reproductive losses in the first trimester of pregnancy.
Materials and methods. From 1997 to 2019 karyotyping of concept products was carried out for NB (n = 2020) in terms of 5–13 weeks, obtained from women from 7 regions of the South-Eastern and Central regions of Ukraine, and MA (n = 1572) performed in the first trimester of pregnancy.
Results. The efficiency of NB material karyotyping was 94%. Chromosomal pathology (CP) was 56.5% in NB material and 5.4% in MA material; autosomal trisomies – 51% of all CP among NB and 48.2% of all CP among MA; triploidy – 17.8% and 15.3% in the NB and MA groups, respectively; tetraploidy – 8.67% and 12.9%; monosomy X – 12.9% and 10.6%; restructuring – 5.5% and 10.6%; multiple trisomies – 3.2% and 3.5%, that is consistent with the data of other studies.
In this study authors noted a significant predominance of 15, 16, 22 chromosomes trisomy over 13, 18, 21 chromosomes trisomy, as well as a large proportion of diandroid triploidies in comparison with other studies. Differences in the CA structure in anembryonic and NB with an embryo presence were established – multiple predominance of tetraploidies and structural rearrangements in anembryony and 15 chromosome trisomy, as well as X monosomy in an embryo presence. An association of mother's young age with a higher incidence of triploidies among NB was noted.
Conclusions. The absolute majority of CA among NB and MA occurs sporadically, with exception of some structural rearrangements (robertsonian and reciprocal translocations). Our outcome analysis showed that standard karyotyping is still the first-line choice for examining the products of the concept of early pregnancy losses.
“Miscarriage: a new look at an old problem.” Medical Aspects of Women’s Health 2.5 (2007). Available from: [https://mazg. com.ua/en-issue-article-49#Nevynashivanie-beremennosti-novyy-vzglyad-na-staruyu-problemu], last accessed Aug 25, 2020.
Miller, J.F., Williamson, E., Glue, J., et al. “Fetal loss after implantation. A prospective study.” Lancet 2.8194 (1980): 554–6.
Warburton, D., Stein, Z., Kline, J., Susser, M. “Chromosome abnormalities in spontaneous abortion: data from the New York City study.” In: Porter, I.H., Hook, E.B., eds. Human Embryonic and Fetal Death. New York. Academic Press (1980): 261–87.
Santalo, J., Badenas, J., Catala, V., Egozcue, J. “Chromosomes of mouse embryos in vivo and in vitro: effect of manipulation, maternal age and gamete ageing.” Hum Reprod 2 (1987): 717–9.
Boue, J., Boue, A., Lazar, P. “Retrospective and prospective epidemiological studies of 1500 karyotyped spontaneous human abortions.” Teratology 12 (1975): 11–26.
Hassold, T., Chiu, D. “Maternal age-specific rates of numericfl chromosome abnormalities with special reference to trisomy.” Hum Genet 70 (1985): 11–17.
Kline, J., Stein, Z. “Epidemiology of Chromosomal Anomalies in Spontaneous Abortion: Prevalence, Manifestation and Determinants.” In: Bennett, M.J., Edmonds, D.K., eds. Spontaneous and Recurrent Abortion. Chicago. Oxford Blackwell Scientific (1987): 29–50.
Menasha, J., Levy, B., Hirschhorn, K., Kardon, N.B. “Incidence and spectrum of chromosome abnormalities in spontaneous abortions: New insights from a 12-year study.” Genetics in Medicine 7 (2005): 251–63.
Veropotvelyan, M.P., Kodunov, L.O., Veropotvelyan, P.M., et al. “Designated primary population frequency of chromosomal pathology and early embryonic mortality in Ukraine.” Women's Health 9 (2012): 108–14.
van den Berg, M.M., van Maarle, M.C., van Wely, M., Goddijn, M. “Genetics of early miscarriage.” Biochim Biophys Acta 12 (2012): 1951–9.
Jenderny, J. “Chromosome aberrations in a large series of spontaneous miscarriages in the German population and review of the literature.” Mol Cytogenet 7 (2014): 38.
Wu, T., Yin, B., Zhu, Y., et al. “Molecular cytogenetic analysis of early spontaneous abortions conceived from varying assisted reproductive technology procedures.” Mol Cytogenet 9 (2016): 79.
Pylyp, L.Y., Spynenko, L.O., Verhoglyad, N.V. “Chromosomal abnormalities in products of conception of first-trimester miscarriages detected by conventional cytogenetic analysis: a review of 1000 cases.” J Assist Reprod Genet 35.2 (2018): 265–71.
Baranov, V.S., Kuznetsova, T.V. Cytogenetics of human embryonic development. St. Petersburg (2007): 640 p.
Veropotvelyan, M.P. “The cytogenetic monitoring of the population of the city of Krivoy Rog in the first trimester of pregnancy.” In: Materials of the III Congress of medical genetics in Ukraine with an international participation, Oct 2–4, 2002, Lviv.
Nicolini, U., Lalatta, F., Natacci, F., et al. “The introduction of QF-PCR in prenatal diagnosis of fetal aneuploidies: time for reconsideration.” Hum Reprod Update 10.6 (2004): 541–8.
Merel, M.J. “Genetics of early miscarriage.” Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 12 (2012): 1951–9.
Russo, R., Sessa, A.M., Fumo, R. “Chromosomal anomalies in early spontaneous abortions: interphase FISH analysis on 855 FFPE first trimester abortions.” Prenatal Diagnosis 36 (2016): 186–91.
Veropotvelyan, M.P. “Reproductive loss, as a natural good: how to solve chromosomal abnormalities during stagnant activities.” In: Materials of the science-practical school-seminar “Genetic aspects of the impairment of reproductive functional people”. Lviv, July 18–19, 2007.
Veropotvelyan, M.P. Research studies of the role of genetic factors in the etiology and pathogenesis of reproductive disorders at different stages of prenatal development. Thesis abstract for MD degree. Kyiv (2017).
Tkach, I.R. “The contribution of chromosomal abnormalities to the genesis of sporadic and sound early reproductive gates.” Factors of experimental evolution of organisms 21 (2017): 340–4.
Soler, A., Morales, C., Mademont-Soler, I. “Overview of Chromosome Abnormalities in First Trimester Miscarriages: A Series of 1,011 Consecutive Chorionic Villi Sample Karyotypes.” Cytogenet Genome Res 152.2 (2017): 81–9.
Shearer, B., Thorland, E., Carlson, A. “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.” Genetics in Medicine 13 (2011): 545–52.
Wang, B., Chong, T., Boyar, F. “Abnormalities in spontaneous abortions detected by G-banding and chromosomal microarray analysis (CMA) at a national reference laboratory.” Molecular Cytogenetics 7 (2014).
Teles, M., Marques, C. “Frequency of Chromosomal Abnormalities in Products of Conception.” Rev Bras Ginecol Obstet 39.3 (2017).
Subramaniyam, S., Pulijaal, V.R., Mathew, S. “Double and multiple chromosomal aneuploidies in spontaneous abortions: A single institutional experience.” J Hum Reprod Sci 7.4 (2014): 262–8.
Jacobs, P. “The origin of numerical chromosome abnormalities.” Adv Genet 33 (1995): 101–33.
Hassold, T., Chen, N., Funkhouser, J., et al. “A cytogenetic study of 1000 spontaneous abortions.” Ann Hum Genet 44 (1980): 151–78.
Carr, D.H. “Chromosome anomalies as a cause of spontaneous abortion.” Am J Obstet Gynecol 97 (1967): 283–93.
Creasy, M.R., Crolla, J.A., Alberman, E.D. “A cytogenetic study of human spontaneous abortions using banding techniques.” Hum Genet 31 (1967): 177–96.
Lauritsen, J.G. “Aetiology of spontaneous abortion. A cytogenetic and epidemiological study of 288 abortuses and their parents.” Acta Obstet Gynecol Scand Suppl. 52 (1976): 1–29.
Takahara, H., Ohama, K., Fujiwara, A. “Cytogenetic study in early spontaneous abortion.” Hiroshima J Med Sci 26 (1977): 291–6.
Kajii, T., Ferrier, A., Niikawa, N., et al. “Anatomic and chromosomal anomalies in 639 spontaneous abortuses.” Hum Genet 55 (1980): 87–98.
Lin, C.C., De Braekeleer, M., Jamro, H. “Cytogenetic studies in spontaneous abortion: the Calgary experience.” Can J Genet Cytol 27 (1985): 565–70.
Eiben, B., Bartels, I., Bahr-Porsch, S., 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 47 (1990): 656–63.
Zhou, C.R. “Cytogenetic studies of spontaneous abortions in humans.” Chung Hua Fu Chan Ko Tsa Chih 25 (1990): 89–91.
Ohno, M., Maeda, T., Matsunobu, A. “A cytogenetic study of spontaneous abortions with direct analysis of chorionic villi.” Obstet Gynecol 77 (1991): 394–8.
Warburton, D., Byrne, J., Canki, N. “Chromosome anomalies and prenatal development: an atlas.” Oxf Monogr Med Genet 21 (1991): 57–100.
Dejmek, J., Vojtassak, J., Malova, J. “Cytogenetic analysis of 1508 spontaneous abortions originating from south Slovakia.” Eur J Obstet Gynecol Reprod Biol 46 (1992): 129–36.
Gardo, S., Bajnoczky, K. “Cytogenetic analysis of spontaneous abortions with direct analysis of chorionic villi.” Eur J Obstet Gynecol Reprod Biol 47 (1992): 117–120.
Kalousek, D.K., Pantzar, T., Tsai, M., Paradice, B. “Early spontaneous abortion: morphologic and karyotypic findings in 3,912 cases.” Birth Defects Orig Artic Ser 29 (1993): 53–61.
Reddy, K.S. “Double trisomy in spontaneous abortions.” Hum Genet 101 (1997): 339–45.
Sullivan, J., Yusef, R. “Double and triple trisomy in spontaneous abortions: an older maternal age and earlier gestational age than seen in single trisomies.” Genetic in Medicine 2 (2000).
Choi, T.Y., Lee, H.M., Park, W.K. “Spontaneous abortion and recurrent miscarriage: A comparison of cytogenetic diagnosis in 250 cases.” Obstet Gynecol Sci 57.6 (2014): 518–25.
Coelho, F.F., Marques, F.K., Gonçalves, M.S., et al. “Detection of aneuploidies in spontaneous abortions by quantitative fluorescent PCR with short tandem repeat markers: a retrospective study.” Genetics and Molecular Research 15.3 (2015).
Yakut, S., Toru, H.S., Cetin, Z. “Chromosome Abnormalities Identified in 457 Spontaneous Abortions and Their Histopathological Findings.” Turkish Journal of Pathology 2 (2015): 111–8.
Diego-Alvarez, D. “Double trisomy in spontaneous miscarriages: cytogenetic and molecular approach.” Human Reproduction 4 (2006): 958–66.
Mathur, A., Stekol, L., Schatz, D. “The parental origin of the single X chromosome in Turner syndrome: lack of correlation with parental age or clinical phenotype.” Am J Hum Genet 48.4 (1991): 682–6.
Grande, M., Stergiotou, I., Pauta, M. “Parental Origin of the Retained X Chromosome in Monosomy X Miscarriages and Ongoing Pregnancies.“ Fetal Diagn Ther 45.2 (2019): 118–24.
Guillermo, F., Pombar, X.F, Maisenbacher, M. “Monosomy X and Parental Origin of the Retained X Chromosome in Pregnancy Loss.” Obstetrics & Gynecology 133 (2019): 164–5.
Kuliev, A.M. “Lethal factors of human embryogenesis.” In: Lectures on medical genetics. Moscow. Medicine (1974): 160–75.
Fryns, J.P., Hondt, F.D., Goddeeris, P. “Full monosomy 21: a clinically recognizable syndrome.” Hum Genet 37 (1977): 155–9.
Pellissier, M.C., Philip, N., Mattei, M.G., et al. “Monosomy 21: a new case confirmed by in situ hybridization.” Human Genetics 75.1 (1987): 26–9.
Vorsanova, Y.G., Yurov, Y.B., Chernyshov, V.N. Medical cytogenetics (study guide). Moscow, Medpraktika (2006): 300 p.
Fisher, D., Dipietro, A., Murdison, K.A., Lemieux, C.A. “Full monosomy 21: еchocardiographic findings in the third molecularly confirmed case.” Pediatr Cardiol 3 (2013): 733–5.
Schinzel, A. Catalogue of unbalanced chromosome aberration in man. Berlin. Water de Gruyter Inc. (2001): 966 p.
Kudryavtseva, E.V., Kovalev, V.V., Potapov, N.N. “Comparative analysis of cytogenetic research and chromosome microarray analysis of biological material in case of miscarriage.” Project “Clinical and pathogenetic foundations of the formation of "Great obstetric syndromes: forecasting, prevention, tactics"”. Available from: [https://www.researchgate. net/publication/327305954], last accessed Aug 25, 2020.
Yadava, B., Davies, W. “Evidence-based management of recurrent miscarriages.” J Hum Reprod Sci 7.3 (2014): 159–69.
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