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Tekrarlayan Gebelik Kayıpları Nedeniyle Çalışılan 306 Çiftin Kromozom Analizi ve Trombofili Parametrelerinin Değerlendirilmesi: Tek Merkez Deneyimi

Year 2022, Volume: 12 Issue: 2, 280 - 285, 17.05.2022
https://doi.org/10.33631/sabd.1068185

Abstract

Amaç: Bu çalışmanın amacı, hastanemize tekrarlayan gebelik kaybı nedeniyle başvuran çiftlere uygun genetik danışmanlık verebilmek için hem majör kromozom anomalilerinin hem de trombofili parametrelerinin etiyolojideki rolünü araştırmaktır.
Gereç ve Yöntemler: Çalışmamıza tekrarlayan gebelik kaybı nedeniyle Başakşehir Çam ve Sakura Şehir Hastanesi Genetik Hastalıklar Değerlendirme Merkezi'ne başvuran toplam 306 çift dâhil edildi. Tüm hastalarda kromozom analizleri ve 306 bayanda trombofili parametrelerinin analizleri gerçekleştirildi.
Bulgular: Çalışmamızda toplam 306 çiftin 13’ünde (%4,25) polimorfizm dışında kalan kromozomal anomaliler tespit edildi. 4 hastada robertsonian translokasyon, 3 hastada resiprokal traslokasyon, 4 hastada mozaik kromozom kuruluşu, 1 hastada yapısal kromozal dengesizlik (derivatif kromozom) ve 1 hastada sayısal kromozal anomali varlığı tespit edilmiştir. Geriye kalan 293 çiftin kromozom analizi normaldi. Çalışmamızda trombofili parametreleri analiz edilen 306 bayan olgunun yaklaşık %10’unda Faktör V Leiden varyantı saptanırken, Faktör II G20210A varyantı ise yaklaşık %3,5 oranında saptanmıştır. 3 hastada (%1) Faktör V Leiden varyantı homozigot, 27 hastada ise Faktör V Leiden varyantı (%8,8) heterozigot olarak saptanmıştır. 10 hastanın (%3,3) Faktör II G20210A varyantını heterozigot olarak taşıdıkları saptanmıştır. Faktör II G20210A varyantını homozigot olarak taşıtan bir hasta çalışmamızda saptanmamıştır.
Sonuç: Mevcut bilgiler ve geçmişteki literatür çalışmaları eşliğinde tekrarlayan gebelik kaybı nedeniyle değerlendirilen çiftlerde etiyolojiyi aydınlatmak için kromozom analizi ve trombofili parametrelerinin değerlendirilmesini ve bu parametrelerde ilişkili olduğu düşünülen bir neden saptandığında tedavi imkanları bulunduğundan dolayı özellikle yardımcı üreme tekniklerinden önce bu analizlerin yapılmasını önermekteyiz.

References

  • KAYNAKÇA 1) Beksaç S, Demir N, Koç A, Yüksel A. Erken gebelik problemleri ve düşükler. Obstetrik, Maternal - Fetal Tıp ve Perinatoloji, 1. baskı, Medikal & Nobel. 2001;1076–85.
  • 2) American College of Obstetricians and Gynecologists. ACOG practice bulletin. Management of recurrent pregnancy loss. Number 24, February 2001. (Replaces Technical Bulletin Number 212, September 1995). American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 2002;78(2):179-90.
  • 3) Gnoth C, Godehardt E, Frank-Herrmann P, Friol K, Tigges J, Freundl G. Definition and prevalence of subfertility and infertility. Hum Reprod. 2005;20(5):1144-7.
  • 4) Berkay EG, Başaran S. Tekrarlayan Gebelik Kayıplarında Etiyolojinin Açıklanmasına Yönelik Yeni Yaklaşımlar. İst Tıp Fak Derg. 2021.
  • 5) Kolte AM, van Oppenraaji RH, Quenby S, Farquharson RG, Stephenson M, Goddijn ME. Nonvisualized pregnancy loses are prognostically important for unexplained recurrent miscarriage. Human Reproduction.2014; 29:931-7.
  • 6) Goddijn M, Christiensen OB, Elson J. Recurrent Pregnancy Loss, Guideline of European Society of Human Reproduction and Embriology. 2017.
  • 7) Tur-Torres MH, Garrido-Gimenez C, Alijotas-Reig J. Genetics of recurrent miscarriage and fetal loss. Best Pract Res Clin Obstet Gynaecol. 2017; 42:11-25.
  • 8) Jaslow CR, Carney JL, Kutteh WH. Diagnostic factors identified in 1020 women with two versus three or more recurrent pregnancy losses. Fertil Steril. 2010;93(4):1234-43.
  • 9) Metwally M, Ong KJ, Ledger WL, Li TC. Does high body mass index increase the risk of miscarriage after spontaneous and assisted conception? A meta-analysis of the evidence. Fertil Steril. 2008;90(3):714-26. 10) Mehta S, Gupta B editors. Recurrent Pregnancy Loss. Springer Nature Singapore Pte. 2018.
  • 11) Zhang T, Sun Y, Chen Z, Li T. Traditional and molecular chromosomal abnormality analysis of products of conception in spontaneous and recurrent miscarriage. 2018;125(4):414-420.
  • 12) Van den Boogard E, Hermens RG, Verhoeve HR, Kremer JM, van der Veen F, Knegt AC. Selective karyotyping in recurrent miscarriage: are recommended guidelines adopted in daily practice. Hum Reprod. 2011; 26:1965-70.
  • 13) Hellgren M. Hemostasis during pregnancy and puerperium. Haemostasis. 1996;26(4):244-247.
  • 14) Liu X, Chen Y, Ye C, Xing D, Wu R, Li F, Chen L, Wang T. Hereditary thrombophilia and recurrent pregnancy loss: a systematic review and meta-analysis. Hum Reprod. 2021;36(5):1213-1229.
  • 15) Barut MU, Bozkurt M, Kahraman M, Yıldırım E, Imirzalioğlu N, Kubar A, Sak S, Ağaçayak E, Aksu T, Çoksüer H. Thrombophilia and Recurrent Pregnancy Loss: The Enigma Continues. Med Sci Monit. 2018; 24:4288-4294.
  • 16) Hamedi B, Feulefack J, Khan A, Sergi C. Association between factor V Leiden mutation and recurrent pregnancy loss in the middle east countries: a Newcastle-Ottawa meta-analysis. Arch Gynecol Obstet. 2020;302(2):345-354. 17) Karatas A, Eroz R, Albayrak M, Ozlu T, Cakmak B, Keskin F. Evaluation of chromosomal abnormalities and common trombophilic mutations in cases with recurrent miscarriage. Afr Health Sci. 2014;14(1):216-22.
  • 18) Rey E, Kahn SR, David M, et al. Thrombophilic disorders and fetal loss: A meta-analysis. Lancet. 2003; 361:901–8.
  • 19) Perés WS, Aranda F, Udry S, Latino J, de Larrañaga G. Inherited thrombophilia and pregnancy loss. Study of an Argentinian cohort. Med Clin. 2019;152(7):249-254.
  • 20) Eslami MM, Khalili M, Soufizomorrod M, Abroun S, Razi B. Factor V Leiden 1691G>A mutation and the risk of recurrent pregnancy loss (RPL): systematic review and meta-analysis. Thromb J. 2020; 18:11.
  • 21) Ahangari N, Doosti M, Mousavifar N, Attaran M, Shahrokhzadeh S, Memarpour S, Ghayoor Karimiani E. Hereditary thrombophilia genetic variants in recurrent pregnancy loss. Arch Gynecol Obstet. 2019;300(3):777-782. 22) Chen H, Yang X, Lu M. Methylenetetrahydrofolate reductase gene polymorphisms and recurrent pregnancy loss in China: a systematic review and meta-analysis. Arch Gynecol Obstet. 2016;293(2):283-90.
  • 23) Farahmand K, Totonchi M, Hashemi M, Reyhani Sabet F, Kalantari H, Gourabi H, Mohseni Meybodi A. Thrombophilic genes alterations as risk factor for recurrent pregnancy loss. J Matern Fetal Neonatal Med. 2016;29(8):1269-73. 24) Levy B, Wapner R. Prenatal Diagnosis by Chromosomal Microarray Analysis. Fertil Steril. 2018;109(2):201-12.
  • 25) Doğan M, Eroz R, Yüce H, Özdemirli R. Yeni Nesil Dizileme (YND) Hakkında Bilinenler (Literatür Taraması). Duzce Medical Journal, 2017;19(1), 27-30.
  • 26) Damar İH, Eröz R, Kiliçaslan Ö. Frequency of hereditary prothrombotic risk factors in patients with Down Syndrome. Konuralp Medical Journal. 2021;13(1): 89-93.
  • 27) Eroz R, Damar İH, Kılıçaslan O. Thrombosis risk of Alport syndrome patients: evaluation of cardiological, clinical, biochemical, genetic and possible causes of inherited thrombophilia and identification of a novel COL4A3 variant. Blood Coagul Fibrinolysis. 2020;31(4):264-269.
  • 28) Rajcan-Separovic E. Next generation sequencing in recurrent pregnancy loss-approaches and outcomes. Eur J Med Genet. 2020;63(2):103644.
  • 29) Robbins SM, Thimm MA, Valle D, Jelin AC. Genetic diagnosis in first or second trimester pregnancy loss using exome sequencing: a systematic review of human essential genes. J Assist Reprod Genet. 2019;36(8):1539-1548.

Evaluation of Both Chromosome Analysis and Thrombophilia Parameters of 306 Couples Studying for Recurrent Pregnancy Loss: A Single Center Experience

Year 2022, Volume: 12 Issue: 2, 280 - 285, 17.05.2022
https://doi.org/10.33631/sabd.1068185

Abstract

Aim: The aim of this study is to investigate the role of both major chromosomal abnormalities and thrombophilia parameters in the etiology of patients with recurrent pregnancy loss to provide appropriate genetic counseling to couples who applied to our hospital due to recurrent pregnancy loss.
Material and Methods: A total of 306 couples who applied to Başakşehir Çam and Sakura City Hospital Genetic Diseases Diagnosis Center due to recurrent pregnancy loss were included in our study. Chromosome analyzes were performed in all patients and analyzes of thrombophilia parameters were done in 306 women.
Results: In our study, chromosomal anomalies other than polymorphisms were detected in 13 (4.25%) of a total of 306 couples. Robertsonian translocation in 4 patients, reciprocal translocation in 3 patients, mosaic chromosome formation in 4 patients, structural chromosomal imbalance (derivative chromosome) in 1 patient and numerical chromosomal anomaly in 1 patient were detected. Chromosome analysis of the remaining 293 pairs were normal. In our study, Factor V Leiden variant was detected in approximately 10% of 306 female cases whose thrombophilia parameters were analyzed, while Factor II G20210A variant was detected in approximately 3.5%. Factor V Leiden variant was found to be homozygous in 3 patients (1%) and heterozygous for Factor V Leiden variant in 27 (8.8%) patients. It was determined that 10 patients (3.3%) were heterozygous for the Factor II G20210A variant. A patient homozygously carrying the factor II G20210A variant was not found in our study.
Conclusion: In the light of current information and previous literature studies, we recommend that chromosomal analysis and thrombophilia parameters be evaluated in order to clarify the etiology in couples who are evaluated for recurrent pregnancy loss, since there are treatment possibilities when a cause thought to be related to these parameters is detected these analyzes should be performed especially before assisted reproductive techniques,

References

  • KAYNAKÇA 1) Beksaç S, Demir N, Koç A, Yüksel A. Erken gebelik problemleri ve düşükler. Obstetrik, Maternal - Fetal Tıp ve Perinatoloji, 1. baskı, Medikal & Nobel. 2001;1076–85.
  • 2) American College of Obstetricians and Gynecologists. ACOG practice bulletin. Management of recurrent pregnancy loss. Number 24, February 2001. (Replaces Technical Bulletin Number 212, September 1995). American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 2002;78(2):179-90.
  • 3) Gnoth C, Godehardt E, Frank-Herrmann P, Friol K, Tigges J, Freundl G. Definition and prevalence of subfertility and infertility. Hum Reprod. 2005;20(5):1144-7.
  • 4) Berkay EG, Başaran S. Tekrarlayan Gebelik Kayıplarında Etiyolojinin Açıklanmasına Yönelik Yeni Yaklaşımlar. İst Tıp Fak Derg. 2021.
  • 5) Kolte AM, van Oppenraaji RH, Quenby S, Farquharson RG, Stephenson M, Goddijn ME. Nonvisualized pregnancy loses are prognostically important for unexplained recurrent miscarriage. Human Reproduction.2014; 29:931-7.
  • 6) Goddijn M, Christiensen OB, Elson J. Recurrent Pregnancy Loss, Guideline of European Society of Human Reproduction and Embriology. 2017.
  • 7) Tur-Torres MH, Garrido-Gimenez C, Alijotas-Reig J. Genetics of recurrent miscarriage and fetal loss. Best Pract Res Clin Obstet Gynaecol. 2017; 42:11-25.
  • 8) Jaslow CR, Carney JL, Kutteh WH. Diagnostic factors identified in 1020 women with two versus three or more recurrent pregnancy losses. Fertil Steril. 2010;93(4):1234-43.
  • 9) Metwally M, Ong KJ, Ledger WL, Li TC. Does high body mass index increase the risk of miscarriage after spontaneous and assisted conception? A meta-analysis of the evidence. Fertil Steril. 2008;90(3):714-26. 10) Mehta S, Gupta B editors. Recurrent Pregnancy Loss. Springer Nature Singapore Pte. 2018.
  • 11) Zhang T, Sun Y, Chen Z, Li T. Traditional and molecular chromosomal abnormality analysis of products of conception in spontaneous and recurrent miscarriage. 2018;125(4):414-420.
  • 12) Van den Boogard E, Hermens RG, Verhoeve HR, Kremer JM, van der Veen F, Knegt AC. Selective karyotyping in recurrent miscarriage: are recommended guidelines adopted in daily practice. Hum Reprod. 2011; 26:1965-70.
  • 13) Hellgren M. Hemostasis during pregnancy and puerperium. Haemostasis. 1996;26(4):244-247.
  • 14) Liu X, Chen Y, Ye C, Xing D, Wu R, Li F, Chen L, Wang T. Hereditary thrombophilia and recurrent pregnancy loss: a systematic review and meta-analysis. Hum Reprod. 2021;36(5):1213-1229.
  • 15) Barut MU, Bozkurt M, Kahraman M, Yıldırım E, Imirzalioğlu N, Kubar A, Sak S, Ağaçayak E, Aksu T, Çoksüer H. Thrombophilia and Recurrent Pregnancy Loss: The Enigma Continues. Med Sci Monit. 2018; 24:4288-4294.
  • 16) Hamedi B, Feulefack J, Khan A, Sergi C. Association between factor V Leiden mutation and recurrent pregnancy loss in the middle east countries: a Newcastle-Ottawa meta-analysis. Arch Gynecol Obstet. 2020;302(2):345-354. 17) Karatas A, Eroz R, Albayrak M, Ozlu T, Cakmak B, Keskin F. Evaluation of chromosomal abnormalities and common trombophilic mutations in cases with recurrent miscarriage. Afr Health Sci. 2014;14(1):216-22.
  • 18) Rey E, Kahn SR, David M, et al. Thrombophilic disorders and fetal loss: A meta-analysis. Lancet. 2003; 361:901–8.
  • 19) Perés WS, Aranda F, Udry S, Latino J, de Larrañaga G. Inherited thrombophilia and pregnancy loss. Study of an Argentinian cohort. Med Clin. 2019;152(7):249-254.
  • 20) Eslami MM, Khalili M, Soufizomorrod M, Abroun S, Razi B. Factor V Leiden 1691G>A mutation and the risk of recurrent pregnancy loss (RPL): systematic review and meta-analysis. Thromb J. 2020; 18:11.
  • 21) Ahangari N, Doosti M, Mousavifar N, Attaran M, Shahrokhzadeh S, Memarpour S, Ghayoor Karimiani E. Hereditary thrombophilia genetic variants in recurrent pregnancy loss. Arch Gynecol Obstet. 2019;300(3):777-782. 22) Chen H, Yang X, Lu M. Methylenetetrahydrofolate reductase gene polymorphisms and recurrent pregnancy loss in China: a systematic review and meta-analysis. Arch Gynecol Obstet. 2016;293(2):283-90.
  • 23) Farahmand K, Totonchi M, Hashemi M, Reyhani Sabet F, Kalantari H, Gourabi H, Mohseni Meybodi A. Thrombophilic genes alterations as risk factor for recurrent pregnancy loss. J Matern Fetal Neonatal Med. 2016;29(8):1269-73. 24) Levy B, Wapner R. Prenatal Diagnosis by Chromosomal Microarray Analysis. Fertil Steril. 2018;109(2):201-12.
  • 25) Doğan M, Eroz R, Yüce H, Özdemirli R. Yeni Nesil Dizileme (YND) Hakkında Bilinenler (Literatür Taraması). Duzce Medical Journal, 2017;19(1), 27-30.
  • 26) Damar İH, Eröz R, Kiliçaslan Ö. Frequency of hereditary prothrombotic risk factors in patients with Down Syndrome. Konuralp Medical Journal. 2021;13(1): 89-93.
  • 27) Eroz R, Damar İH, Kılıçaslan O. Thrombosis risk of Alport syndrome patients: evaluation of cardiological, clinical, biochemical, genetic and possible causes of inherited thrombophilia and identification of a novel COL4A3 variant. Blood Coagul Fibrinolysis. 2020;31(4):264-269.
  • 28) Rajcan-Separovic E. Next generation sequencing in recurrent pregnancy loss-approaches and outcomes. Eur J Med Genet. 2020;63(2):103644.
  • 29) Robbins SM, Thimm MA, Valle D, Jelin AC. Genetic diagnosis in first or second trimester pregnancy loss using exome sequencing: a systematic review of human essential genes. J Assist Reprod Genet. 2019;36(8):1539-1548.
There are 25 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Research Articles
Authors

Mustafa Doğan 0000-0003-0464-6565

Alper Gezdirici 0000-0002-2432-9279

Cüneyd Yavaş 0000-0002-1597-5922

Recep Eröz 0000-0003-0840-2613

Publication Date May 17, 2022
Submission Date February 4, 2022
Published in Issue Year 2022 Volume: 12 Issue: 2

Cite

Vancouver Doğan M, Gezdirici A, Yavaş C, Eröz R. Tekrarlayan Gebelik Kayıpları Nedeniyle Çalışılan 306 Çiftin Kromozom Analizi ve Trombofili Parametrelerinin Değerlendirilmesi: Tek Merkez Deneyimi. VHS. 2022;12(2):280-5.