Incidence and spectrum of chromosomal abnormalities detected in married couples with early losses of pregnancy

Authors

  • М. П. Веропотвелян Interregional Center of Medical Genetics and Prenatal Diagnostics, Kryvyi Rih, Ukraine https://orcid.org/0000-0003-3962-987X
  • Л. Г. Шаповаленко Multiregional Center of Medical Genetics and Prenatal Diagnosis, Kryvyi Rih, Ukraine
  • О. С. Саваровська Multiregional Center of Medical Genetics and Prenatal Diagnosis, Kryvyi Rih, Ukraine https://orcid.org/0000-0001-9095-3216

DOI:

https://doi.org/10.18370/2309-4117.2017.35.54-60

Keywords:

early pregnancy losses, miscarriage, spontaneous abortions, missed miscarriage, married couples, chromosomal abnormalities

Abstract

The aim of the study was to establish the incidence and spectrum of chromosomal abnormalities (CA) in married couples (MC) with sporadic and habitual early pregnancy losses (EPL) inhabiting south-east and central regions of Ukraine.

Materials and methods: A cytogenetic study of 1869 women, 1788 men, and 1781 married couples (a total of 3657 individuals) with EPL was performed separately.

Results: In 344 cases (9.4%), the patients’ karyotype contained various types of chromosomal rearrangements. Reciprocal translocations were found in 153 cases (48.3% of the total number of CA detected in women and men; in the case of couples with EPL the frequency of translocations was 4.1%), while in women – 84 (44.4% of all CA) cases, in men – 69 (44.5% of all CA), and in married couples – 6 (28.6%).

Robertson’s translocations were found in 13 cases (9 in women and 4 in men), which amounted to 3.8% of all CA; their frequency in couples with EPL was 0.35%.

Pericentric inversions were found in 159 cases (46.2% of the total number of CA), in couples with EPL their frequency made 4.3%, while in women – 82 (43.4% of all CA) cases and in men – 77 (49.7% of all CA).

Pericentric inversion of chromosome 9 was detected in 65 cases, which is 40.89% of the total number of pericentric inversions and 18.89% of the total number of CA. Paracentric inversions in the karyotyped families with EPL are not detected by our study.

Five cases with a mosaic karyotype of 45, Х/46, ХХ (1.5% of all CA), 4 cases with an isochromosome – 45,Х, i(Xq), 2 cases with a mosaic karyotype of polysomy in X (47, XXX / 46, XX), 3 cases of dysomia X – Klinefelter syndrome, 3 deletions of the terminal portion of short arm 46, X, del(X) (p21→pter).

Conclusion: The frequency of CA in women with EPL was 8.5%, in men – 6.4%, and totally in all karyotyped parents – 7.5%, which does not differ from the incidence of CA in couples who have miscarried in other populations.

Author Biographies

М. П. Веропотвелян, Interregional Center of Medical Genetics and Prenatal Diagnostics, Kryvyi Rih

PhD, Chief Physician 

Л. Г. Шаповаленко, Multiregional Center of Medical Genetics and Prenatal Diagnosis, Kryvyi Rih

Head of Cytogenetic laboratory 

О. С. Саваровська, Multiregional Center of Medical Genetics and Prenatal Diagnosis, Kryvyi Rih

Lab assistant at the Laboratory of cytogenetics of the chorion cells and lymphocytes of the Laboratory department of prenatal studies

References

  1. Sidelnikova, V.M., Sukhikh, G.T. Unintention of pregnancy: A guide for practicing doctors. Moscow. Medical Information Agency LLC (2010): 536 p.
  2. Howard, J.A. Carp. Recurrent Pregnancy Loss: Causes, Controversies, and Treatment. 2nd edition. Taylor&Francis Group, LLC (2007).
  3. García-Enguídanos, A., Calle, M.E., Valero, J., et al. “Risk factors in miscarriage: a review.” Eur J Obstet Gynecol Reprod Biol 102.2 (2002):111–9.
  4. Makino, T., et al. “Survey of 1120 Japanese Women With a History of Recurrent Spontaneous Abortions.” Eur J Obstet Gynecol Reprod Biol 44.2 (1992): 123–30.
  5. Radzinsky, V.E., Dimitrovа, V.I., Mayskovа, I.Y. Non-developing pregnancy. Moscow. GEOTAR-Media.
  6. Boue, J., Boue, A., Lazar, P. “Retrospective and prospective epidemiological studies of 1500 karyotyped spontaneous human abortions.” Teratology 12.1 (1975): 11–26.
  7. Kline, J., Stein, Z. Epidemiology of Chromosomal Anomalies in Spontaneous Abortion: Prevalence, Manifestation and Determinants. Spontaneous and Recurrent Abortion. Chicago. Oxford Blackwell Scientific (1987): 29–50.
  8. 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 7.4 (2005): 251–63.
  9. Hassold, T., Chen, N., Funkhouser, J., et. al. “A cytogenetic study of 1000 spontaneous abortions.” Annals of Human Genetics 44.2 (1980): 151–64.
  10. Jacobs, P.A., Hassold, T.J. “The Origin of Numerical Chromosome Abnormalities.” Advances in Genetics (1995): 101–33.
  11. Zimmermann, B., Hill, M., Gemelos, G., et. al. “Noninvasive prenatal aneuploidy testing of chromosomes 13, 18, 21, X, and Y, using targeted sequencing of polymorphic loci.” Prenatal Diagnosis 32.13 (2012): 1233–41.
  12. Veropotvelyan, N.P. “Association of the mother’s age with early reproductive loss of chromosomal etiology.” Woman’s health 2.98 (2015): 44–8.
  13. Veropotvelyan, M.P. “Predictive risk of aneuploidies during future pregnancies, depending on the number of previous reproductive loss and mother’s age.” Woman’s Health 10 (2016): 28–32.
  14. Rubio, C., Simón, C., Vidal, F., et al. “Chromosomal abnormalities and embryo development in recurrent miscarriage couples.” Hum Reprod 18.1 (2003):182–8.
  15. Celep, F., Karagüzel, A., Ozeren, M., Bozkaya, H. “The frequence of chromosomal abnormalities in patients with reproductive failure.” Eur J Obstet Gynecol Reprod Biol 127.1 (2006): 106–9.
  16. Bespalova, O.N. “Genetics of miscarriage.” Journal of Obstetrics and Women’s Diseases LVI (2007): 81–95.
  17. Elghezal, H., Hidar, S., Mougou, S., et al. “Prevalence of chromosomal abnormalities in couples with recurrent miscarriage.” Fertil Steril 88 (2007): 721–3.
  18. Sheth, F.J., Liehr, T., Kumari, P., et al. “Chromosomal abnormalities in couples with repeated fetal loss: An Indian retrospective study.” Indian J Hum Genet 19.4 (2013): 415–22.
  19. Cytogenetic methods of human chromosomes. Guidelines. Kyiv (2003).
  20. Mikelsoor, R., Lissitsina, J. “Cytogenetic analyses of families with fertility problems.” Congress LabMed 1 (2006): 171.
  21. Baranov, V.S., Kuznetsovа, Т.V. Cytogenetics of human embryonic development. St. Petersburg (2007): 640 p.
  22. Guttenbach, M. “Analysis of structural and numerical chromosome abnormalities in sperm of normal men and carriers of constitutional chromosome aberration. A review.” Hum Genet 100.1 (1997): 1–21.
  23. Denisenko, S.V., Dariy, A.S., Kononenko, M.I., Zerova-Lyubimova, T.E. Genetics of reproduction. K.Perz–TA (2008): 652 p.
  24. Vorsanova, S.G., Yurov, Y.B. “Molecular-cytogenetic diagnosis of chromosomal abnormalities in married couples with reproductive disorders.” Reproduction problems 4 (1998): 41–6.
  25. Chromosome abnormalities and genetic counseling. 4th edition. Oxford monographs on medical genetics. Ed. by R.J. McKinlay. Gardner (2011).
  26. Rubio, C., Simon, S., Vidal, F., еt al. “Chromosomal abnormalities and embryo development in recurrent miscarriage couples.” Hum Reprod 18 (2003): 182–8.
  27. Fan, H.T., Zhang, M., Zhan, P., et al. “Structural chromosomal abnormalities in couples in cases of recurrent spontaneous abortions in Jilin Province, China.” Genet Mol Res 22.1 (2016): 15.
  28. Elghezal, H., Hidar, S., Mougou-Zerelli, S., Saad, A. “Prevalence of chromosomal abnormalities in couples with recurrent miscarriage.” Fertility and sterility 88.3 (2007): 721–3.
  29. Simpson, J.L., Meyers, C.M., Martin, A.O., et al. “Translocations are infrequent among couples having repeated spontaneous abortions but no other abnormal pregnancies.” Fertil Steril 51 (1989): 811–4.
  30. De Braekeleer, M., Dao, T.N. “Cytogenetic studies in couples experiencing repeated pregnancy losses.” Human Reprod 5 (1990): 519–28.
  31. Simpson, J.L., Elias, S., Martin, A.O. “Parental chromosomal rearrangements associated with repetitive spontaneous abortions.” Fertil Steril 36 (1981): 584–90.
  32. Jacobs, P.A., Melville, M., Ratcliffe, S.A. “A cytogenetic survey of 11,680 newborn infants.” Ann Hum Genet 37 (1974): 359–76.
  33. Nielsen, J., Sillesen, I. “Incidence of chromosome aberrations among 11,148 newborn children.” Hum Genet 30.1 (1975): 1–12.
  34. Djalali, M., Steinbach, P., Bullerdiek, J., et al. “The significance of pericentric inversions of chromosome 2.” Hum Genet 72.1 (1986): 32–6.
  35. Subrt, I., Kozák, J., Hníková, O. “Microdensitometric identification of the pericentric inversion of chromosome No.2 and of duplication of the short arm of chromosome No.7 in a reexamined case.” Hum Hered 23.4 (1973): 331–7.
  36. Hsu, L.Y.F., Benn, P.A., Tannenbaum, H.L., et al. “Chromosomal polymorphisms of 1, 9, 16, and Y in 4 major ethnic groups: A large prenatal study.” Am J Med Genet 26 (1987): 95–101.
  37. Boué, J., Taillemite, J.L., Hazael-Massieux, P., et al. “Association of pericentric inversion of chromosome and reproductive failure in ten unrelated families.” Humangenetik 30 (1975): 217–24.
  38. Madan, K., Bobrow, M. “Structural variation in chromosome No. 9.” Annals Genet 17 (1974): 81–6.
  39. Metaxotou, C., Kalpini-Mavrou, A., Panagou, M., Tsenghi, C. “Polymorphism of chromosome 9 in 600 Greek subjects.” Am J Hum Genet 30 (1978): 85–9. 623106
  40. Sutherland, G.R., Gardiner, A.J., Carter, R.F. “Familial pericentric inversion of chromosome 19, inv(19) (p13q13) with a note on genetic counseling of pericentric inversion carriers.” Clin Genet 10.1 (1976): 54–9.
  41. Jones, K.W., Corneo, G. “Location of satellite and homogeneous DNA sequences on human chromosomes.” Nat New Biol 233.43 (1971): 268–71.
  42. Bühler, E.M., Tsuchimoto, T., Jurik, L.P., Stalder, G.R. “Satellite DNA III and alkaline Geimsa staining.” Humangenetik 26.4 (1975): 329–33.
  43. Corneo, G., Ginelli, E., Polli, E. “Isolation of the complementary strands of a human satellite DNA.” J Mol Biol 33.1 (1968): 331–5.
  44. Miklos, G.L., John, B. “Heterochromatin and satellite DNA in man: properties and prospects.” Am J Hum Genet 31.3 (1979): 264–80.
  45. Patil, S.R., Lubs, H.A. “A possible association of long Y chromosomes and fetal loss.” Hum Genet 35.2 (1977): 233–5.
  46. Genest, P. “Chromosome variants and abnormalities in 51 married couples with repeated spontaneous abortions.” Clin Genet 16.6 (1979): 387–9.
  47. Nielsen, J. “Large Y chromosome (Yq+) and increased risk of abortion.” Clin Genet 13.5 (1978): 415–6.
  48. Ghosh, P.K., Singh, I.P. “Morphological variability of the human chromosomes in two Indian populations – Rajputs and Punjabis.” Humangenetik 29.1 (1975): 67–78.

Downloads

Published

2017-06-21

How to Cite

Веропотвелян, М. П., Шаповаленко, Л. Г., & Саваровська, О. С. (2017). Incidence and spectrum of chromosomal abnormalities detected in married couples with early losses of pregnancy. REPRODUCTIVE ENDOCRINOLOGY, (35), 54–60. https://doi.org/10.18370/2309-4117.2017.35.54-60

Issue

No. 35 (2017)

Section

Reproductology

License

Copyright (c) 2017 М. П. Веропотвелян, Л. Г. Шаповаленко, О. С. Саваровська

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors who publish with this journal agree to the following terms:

    1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

    1. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.