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The Role of Chromosome Analysis in Patients with Recurrent Pregnancy Loss

Year 2021, Volume: 5 Issue: 1, 8 - 12, 20.04.2021

Burhan Balta Murat Erdoğan Aslıhan Kiraz Zeki Yılmaz

https://doi.org/10.46332/aemj.821259

Abstract

Purpose: Recurrent pregnancy loss (RPL) is called as loss of two or more clinically defined pregnancies. The causes of RPL include chromosomal abnormalities, endocrinological disorders, autoimmune problems, uterine anomalies, and thrombophilic factors. In this study, we aimed to discuss the results of chromosomal analysis of couples who had experienced RPL in central Anatolia and their relationship with RPL.

Materials and Methods: A total of 1420 subjects, 721 females and 699 males with two or more RPL, were included in the study. Chromosome analysis was performed using standard cytogenetic GTG banding technique using peripheral blood lymphocytes. All chromosomes were examined for numerical and structural chromosomal abnormalities.

Results: Normal chromosome formation,46, XX in 698 people and 46, XY in 680 people, was detected in a total of 1378 people (97%). Normal chromosome variant was detected in 15 patients (1%), most commonly 46,XX,9qh+ (0.28%) in 4 patients and 46,XY,9qh+ (0.21%) in 3 patients. In addition, 12 patients had balance reciprocal translocation (0.8%), 6 patients had robertsonian translocation (0.4%), 45,XX,rob (13;14) (q10;q10) in 4 patients, and 45,XY,rob(13;14)(q10;q10) in 2 patients.

Conclusion: In this study, chromosomal translocations were the most important cause of RPL in the chromosomal analysis of the parents (n=18; 1.2%). Approximately 2% of individuals with RPL have numerical and structural chromosomal abnormalities such as reciprocal or robertsonian translocations, inversions, and sex chromosomal abnormalities. In order to have healthy babies,
preimplantation genetic diagnostic tests should be recommended to the patients by obstetricians, medical geneticists and clinical embryologists who are involved in reproductive medicine.

Keywords

chromosome analysis preimplantation genetic testing reciprocal recurrent pregnancy loss translocation

Thanks

We thank all the patients who participated in the study. In addition, we thank laboratory technician Mustafa Kaplan for his contributions to the documentation of patient files.

References

  • 1. Rajcan-Separovic E. Next generation sequencing in recurrent pregnancy loss-approaches and outcomes. Eur J Med Genet. 2019;63(2):103644.
  • 2. Stephenson M, Kutteh W. Evaluation and management of recurrent early pregnancy loss. Clin Obstet Gynecol. 2007;50(1):132-145.
  • 3. Webster A, Schuh M. Mechanisms of Aneuploidy in Human Eggs. Trends Cell Biol. 2017;27(1):55-68.
  • 4. Nybo AA, Wohlfahrt J, Christens P, Olsen J, Melbye M. Is maternal age an independent risk factor for fetal loss? West J Med. 2000;173(5):331.
  • 5. McCallie BR, Parks JC, Trahan GD, et al. Compromised global embryonic transcriptome associated with advanced maternal age. J Assist Reprod Genet. 2019;36(5):915-924.
  • 6. Grande M, Borrell A, Garcia-Posada R, et al. The effect of maternal age on chromosomal anomaly rate and spectrum in recurrent miscarriage. Hum Reprod. 2012;27(10):3109-3117.
  • 7. Wolf GC, Mao J, Izquierdo L, Joffe G. Paternal pericentric inversion of chromosome 4 as a cause of recurrent pregnancy loss. J Med Genet. 1994;31(2):153-155.
  • 8. Goldstein M, Svirsky R, Reches A, Yaron Y. Does the number of previous miscarriages influence the incidence of chromosomal aberrations in spontaneous pregnancy loss? J Matern Fetal Neonatal Med. 2017;30(24):2956-2960.
  • 9. Hassold T, Hall H, Hunt P. The origin of human aneuploidy: where we have been, where we are going. Hum Mol Genet. 2007;16(R2):R203-208.
  • 10. Nicolaidis P, Petersen MB. Origin and mechanisms of non-disjunction in human autosomal trisomies. Hum Reprod. 1998;13(2):313-319.
  • 11. Warburton D. De novo balanced chromosome rearrangements and extra marker chromosomes identified at prenatal diagnosis: clinical significance and distribution of breakpoints. Am J Hum Genet. 1991;49(5):995-1013.
  • 12. Goncalves RO, Santos WV, Sarno M, Cerqueira BA, Goncalves MS, Costa OL. Chromosomal abnormalities in couples with recurrent first trimester abortions. Rev Bras Ginecol Obstet. 2014;36(3):113-117.
  • 13. Cırakoğlu A, Yılmaz Ş, Kuru D, et al. Structural Chromosomal Abnormalities in Couples with Recurrent Pregnancy Loss. Turkiye Klinikleri J Med Sci. 2010;30(4):1185-1188.
  • 14. Tunc E, Tanriverdi N, Demirhan O, Suleymanova D, Cetinel N. Chromosomal analyses of 1510 couples who have experienced recurrent spontaneous abortions. Reprod Biomed Online. 2016;32(4):414-419.
  • 15. Devine DH, Whitman-Elia G, Best RG, Edwards JG. Paternal paracentric inversion of chromosome 2: a possible association with recurrent pregnancy loss and infertility. J Assist Reprod Genet. 2000;17(5):293-296.
  • 16. Nonaka T, Takahashi M, Nonaka C, Enomoto T, Takakuwa K. The analysis of chromosomal abnormalities in patients with recurrent pregnancy loss, focusing on the prognosis of patients with inversion of chromosome (9). Reprod Med Biol. 2019;18(3):296-301.
  • 17. Nielsen J, Friedrich U, Hreidarsson AB. Frequency and genetic effect of 1qh plus. Humangenetik. 1974;21(2):193-196.
  • 18. Gardner RJM, Sutherland GR, Shaffer LG. Chromosome abnormalities and genetic counseling. 4th ed. Oxford; New York: Oxford University Press;2012.
  • 19. Yildirim ME, Karakus S, Kurtulgan HK, Baser B, Sezgin I. The type and prevalence of chromosomal abnormalities in couples with recurrent first trimester abortions: A Turkish retrospective study. J Gynecol Obstet Hum Reprod. 2019;48(7):521-525.
  • 20. Gümüş E. Evaluation of Chromosomal Anomalies and Polymorphisms in Primer Infertility, Azospermia and Habitual Abortion Patient Groups. Van Med J. 2019;26(1):12-17.
  • 21. Bondy CA, Turner Syndrome Study G. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab. 2007;92(1):10-25.
  • 22. Gravholt CH. Epidemiological, endocrine and metabolic features in Turner syndrome. Eur J Endocrinol. 2004;151(6):657-687.
  • 23. Bernard V, Donadille B, Zenaty D, et al. Spontaneous fertility and pregnancy outcomes amongst 480 women with Turner syndrome. Hum Reprod. 2016;31(4):782-788.
  • 24. Russell LM, Strike P, Browne CE, Jacobs PA. X chromosome loss and ageing. Cytogenet Genome Res. 2007;116(3):181-185.
  • 25. Aksglaede L, Juul A. Testicular function and fertility in men with Klinefelter syndrome: a review. Eur J Endocrinol. 2013;168(4):R67-76. 26. Gruchy N, Vialard F, Decamp M, et al. Pregnancy outcomes in 188 French cases of prenatally diagnosed Klinefelter syndrome. Hum Reprod. 2011;26(9):2570-2575.
  • 27. Butler R, Nakhuda G, Guimond C, et al. Analysis of PGT-M and PGT-SR outcomes at a Canadian fertility clinic. Prenat Diagn. 2019;39(10):866-870.

Tekrarlayan Gebelik Kayıplı Hastalarda Kromozom Analizinin Yeri

Year 2021, Volume: 5 Issue: 1, 8 - 12, 20.04.2021

Burhan Balta Murat Erdoğan Aslıhan Kiraz Zeki Yılmaz

https://doi.org/10.46332/aemj.821259

Abstract

Amaç: İki ya da daha fazla klinik olarak tanımlanmış gebeliğin kaybına tekrarlayan gebelik kaybı (TGK) denir. TGK nedenleri arasında kromozom anomalileri; endokrinolojik hastalıklar; otoimmun problemler; uterin anomaliler, trombofilik faktörler yer alır. Biz bu çalışmada orta anadoluda TGK yaşamış çiftlerin kromozom analizi sonuçları ve bunların TGK ile ilişkisini tartışmayı amaçladık.

Araçlar ve Yöntem: İki ve üzerinde düşük yapmış 721 kadın ve 699 eşi erkek toplam 1420 kişi çalışmaya dahil edildi. Kromozom analizi periferal kan lenfositleri kullanılarak standart sitogenetik Giemsa- Tripsin-Giemsa (GTG) bantlama tekniği kullanılarak yapıldı. Hastaların tüm kromozomları sayısal ve yapısal kromozom anomalileri açısından incelendi.

Bulgular: 698 kişide 46,XX, 680 kişide 46,XY olmak üzere toplam 1378 kişide normal kromozom kuruluşu tespit edildi (%97). 15 hastada normal kromozom varyantı tespit edildi (%1). Bunun yanında 12 hastada dengeli resiprokal translokasyon (%0,8), 6 hastada ise robertsoniyan translokasyon tespit edildi(%0,4), 1 hastada 3.kromozomda inversiyon tespit edildi(%0.07). Normal kromozom varyantlarını normal kabul edersek geri kalan değişimlerin hasta popülasyonunda sıklığı yaklaşık %2 ‘dir.


Sonuç: Bizim çalışmamızda TGK’ nın ebeveynlerin kromozom analizinden kaynaklanan en önemli sebebi kromozomal translokasyonlardı 18(%1,2). Bu oran literatürdeki değer çalışmalarla uyumlu idi. En sık tespit edilen translokasyon ise 6 (%0,4) kez saptanan 13 ve 14. Kromozom arasındaki robertsoniyan translokasyon idi. TGK yaşayan bireylerin yaklaşık %2 ‘sinde resiprokal ya da robertsoniyan translokasyonlar, inversiyonlar, cinsiyet kromozom anomalileri gibi sayısal ve yapısal kromozom anomalileri görülmektedir. Bu hastaların sağlıklı bebek sahibi olmaları için preimplantasyon genetik tanı testleri üreme tıbbı ile uğraşan kadın doğum uzmanı, tıbbı genetik uzmanları ve klinik embriyologlar tarafından hastalara önerilmelidir.

Keywords

kromozom analizi preimplantasyon genetik tanı resiprokal tekrarlayan gebelik kaybı translokasyon

References

  • 1. Rajcan-Separovic E. Next generation sequencing in recurrent pregnancy loss-approaches and outcomes. Eur J Med Genet. 2019;63(2):103644.
  • 2. Stephenson M, Kutteh W. Evaluation and management of recurrent early pregnancy loss. Clin Obstet Gynecol. 2007;50(1):132-145.
  • 3. Webster A, Schuh M. Mechanisms of Aneuploidy in Human Eggs. Trends Cell Biol. 2017;27(1):55-68.
  • 4. Nybo AA, Wohlfahrt J, Christens P, Olsen J, Melbye M. Is maternal age an independent risk factor for fetal loss? West J Med. 2000;173(5):331.
  • 5. McCallie BR, Parks JC, Trahan GD, et al. Compromised global embryonic transcriptome associated with advanced maternal age. J Assist Reprod Genet. 2019;36(5):915-924.
  • 6. Grande M, Borrell A, Garcia-Posada R, et al. The effect of maternal age on chromosomal anomaly rate and spectrum in recurrent miscarriage. Hum Reprod. 2012;27(10):3109-3117.
  • 7. Wolf GC, Mao J, Izquierdo L, Joffe G. Paternal pericentric inversion of chromosome 4 as a cause of recurrent pregnancy loss. J Med Genet. 1994;31(2):153-155.
  • 8. Goldstein M, Svirsky R, Reches A, Yaron Y. Does the number of previous miscarriages influence the incidence of chromosomal aberrations in spontaneous pregnancy loss? J Matern Fetal Neonatal Med. 2017;30(24):2956-2960.
  • 9. Hassold T, Hall H, Hunt P. The origin of human aneuploidy: where we have been, where we are going. Hum Mol Genet. 2007;16(R2):R203-208.
  • 10. Nicolaidis P, Petersen MB. Origin and mechanisms of non-disjunction in human autosomal trisomies. Hum Reprod. 1998;13(2):313-319.
  • 11. Warburton D. De novo balanced chromosome rearrangements and extra marker chromosomes identified at prenatal diagnosis: clinical significance and distribution of breakpoints. Am J Hum Genet. 1991;49(5):995-1013.
  • 12. Goncalves RO, Santos WV, Sarno M, Cerqueira BA, Goncalves MS, Costa OL. Chromosomal abnormalities in couples with recurrent first trimester abortions. Rev Bras Ginecol Obstet. 2014;36(3):113-117.
  • 13. Cırakoğlu A, Yılmaz Ş, Kuru D, et al. Structural Chromosomal Abnormalities in Couples with Recurrent Pregnancy Loss. Turkiye Klinikleri J Med Sci. 2010;30(4):1185-1188.
  • 14. Tunc E, Tanriverdi N, Demirhan O, Suleymanova D, Cetinel N. Chromosomal analyses of 1510 couples who have experienced recurrent spontaneous abortions. Reprod Biomed Online. 2016;32(4):414-419.
  • 15. Devine DH, Whitman-Elia G, Best RG, Edwards JG. Paternal paracentric inversion of chromosome 2: a possible association with recurrent pregnancy loss and infertility. J Assist Reprod Genet. 2000;17(5):293-296.
  • 16. Nonaka T, Takahashi M, Nonaka C, Enomoto T, Takakuwa K. The analysis of chromosomal abnormalities in patients with recurrent pregnancy loss, focusing on the prognosis of patients with inversion of chromosome (9). Reprod Med Biol. 2019;18(3):296-301.
  • 17. Nielsen J, Friedrich U, Hreidarsson AB. Frequency and genetic effect of 1qh plus. Humangenetik. 1974;21(2):193-196.
  • 18. Gardner RJM, Sutherland GR, Shaffer LG. Chromosome abnormalities and genetic counseling. 4th ed. Oxford; New York: Oxford University Press;2012.
  • 19. Yildirim ME, Karakus S, Kurtulgan HK, Baser B, Sezgin I. The type and prevalence of chromosomal abnormalities in couples with recurrent first trimester abortions: A Turkish retrospective study. J Gynecol Obstet Hum Reprod. 2019;48(7):521-525.
  • 20. Gümüş E. Evaluation of Chromosomal Anomalies and Polymorphisms in Primer Infertility, Azospermia and Habitual Abortion Patient Groups. Van Med J. 2019;26(1):12-17.
  • 21. Bondy CA, Turner Syndrome Study G. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab. 2007;92(1):10-25.
  • 22. Gravholt CH. Epidemiological, endocrine and metabolic features in Turner syndrome. Eur J Endocrinol. 2004;151(6):657-687.
  • 23. Bernard V, Donadille B, Zenaty D, et al. Spontaneous fertility and pregnancy outcomes amongst 480 women with Turner syndrome. Hum Reprod. 2016;31(4):782-788.
  • 24. Russell LM, Strike P, Browne CE, Jacobs PA. X chromosome loss and ageing. Cytogenet Genome Res. 2007;116(3):181-185.
  • 25. Aksglaede L, Juul A. Testicular function and fertility in men with Klinefelter syndrome: a review. Eur J Endocrinol. 2013;168(4):R67-76. 26. Gruchy N, Vialard F, Decamp M, et al. Pregnancy outcomes in 188 French cases of prenatally diagnosed Klinefelter syndrome. Hum Reprod. 2011;26(9):2570-2575.
  • 27. Butler R, Nakhuda G, Guimond C, et al. Analysis of PGT-M and PGT-SR outcomes at a Canadian fertility clinic. Prenat Diagn. 2019;39(10):866-870.
There are 26 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Original Articles
Authors

Burhan Balta 0000-0003-2672-2493

Murat Erdoğan 0000-0001-8768-4457

Aslıhan Kiraz 0000-0001-7317-2717

Zeki Yılmaz 0000-0002-5985-8066

Publication Date April 20, 2021
Published in Issue Year 2021 Volume: 5 Issue: 1

Cite

APA Balta, B., Erdoğan, M., Kiraz, A., Yılmaz, Z. (2021). The Role of Chromosome Analysis in Patients with Recurrent Pregnancy Loss. Ahi Evran Medical Journal, 5(1), 8-12. https://doi.org/10.46332/aemj.821259
AMA Balta B, Erdoğan M, Kiraz A, Yılmaz Z. The Role of Chromosome Analysis in Patients with Recurrent Pregnancy Loss. Ahi Evran Med J. April 2021;5(1):8-12. doi:10.46332/aemj.821259
Chicago Balta, Burhan, Murat Erdoğan, Aslıhan Kiraz, and Zeki Yılmaz. “The Role of Chromosome Analysis in Patients With Recurrent Pregnancy Loss”. Ahi Evran Medical Journal 5, no. 1 (April 2021): 8-12. https://doi.org/10.46332/aemj.821259.
EndNote Balta B, Erdoğan M, Kiraz A, Yılmaz Z (April 1, 2021) The Role of Chromosome Analysis in Patients with Recurrent Pregnancy Loss. Ahi Evran Medical Journal 5 1 8–12.
IEEE B. Balta, M. Erdoğan, A. Kiraz, and Z. Yılmaz, “The Role of Chromosome Analysis in Patients with Recurrent Pregnancy Loss”, Ahi Evran Med J, vol. 5, no. 1, pp. 8–12, 2021, doi: 10.46332/aemj.821259.
ISNAD Balta, Burhan et al. “The Role of Chromosome Analysis in Patients With Recurrent Pregnancy Loss”. Ahi Evran Medical Journal 5/1 (April 2021), 8-12. https://doi.org/10.46332/aemj.821259.
JAMA Balta B, Erdoğan M, Kiraz A, Yılmaz Z. The Role of Chromosome Analysis in Patients with Recurrent Pregnancy Loss. Ahi Evran Med J. 2021;5:8–12.
MLA Balta, Burhan et al. “The Role of Chromosome Analysis in Patients With Recurrent Pregnancy Loss”. Ahi Evran Medical Journal, vol. 5, no. 1, 2021, pp. 8-12, doi:10.46332/aemj.821259.
Vancouver Balta B, Erdoğan M, Kiraz A, Yılmaz Z. The Role of Chromosome Analysis in Patients with Recurrent Pregnancy Loss. Ahi Evran Med J. 2021;5(1):8-12.
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