TEKRARLAYAN GEBELİK KAYBI OLAN KADINLARDA TROMBOFİLİ İNSİDANSI VE SPEKTRUMU: RETROSPEKTİF BİR ÇALIŞMA

Yıl 2023, Cilt: 4 Sayı: 2, 116 - 120, 28.07.2023

Ayça Kocaağa , Halime Kılıç , Sevgi Güleç

https://doi.org/10.48176/esmj.2023.117

Öz

Amaç: Genellikle 20. gebelik haftasından önce >2 ardışık gebelik kaybı olarak bilinen tekrarlayan gebelik kaybı (RPL), kadınların %3-5'inde görülmektedir. Amaç, RPL'li kadın hastalarda kalıtsal trombofili ile sık görülen varyantların (Metilentetrahidrofolat Redüktaz; MTHFR C677T ve MTHFR A1298C polimorfizmleri; FV Leiden G1691A ve Protrombin G20210A mutasyonu) frekansını değerlendirmektir.
Gereç ve yöntem: Bu retrospektif kohort çalışması 2020 ile 2022 yılları arasındadır. İki veya daha fazla gebelik kaybı olan 380 kadında MTHFR C677T ve MTHFR A1298C polimorfizmleri, FV Leiden G1691A ve Protrombin G20210A mutasyonlarının sıklığını araştırdık.
Bulgular: Hastaların ortalama yaşı 32.6 yıl (dağılım: 18-46) idi. Bu grupta en sık gözlenen varyant, MTHFR677 polimorfizmi için bir heterozigot mutasyonuydu (n=163, %42.8). İkinci en yaygın varyant, %41.1 (n=156) sıklık ile MTHFR A1298C heterozigotluğuydu. En az yaygın varyant ise FII homozigotluğuydu (%0.3). Heterozigot FII ve FV Leiden (G1691A) mutasyonları sırasıyla hastaların %1.8'inde (1/380) ve %8.4'ünde (7/380) bulundu.
Sonuç: Trombofilik varyantların (FV Leiden G1691A ve Prothrombin G20210A) RPL'de önemli bir rolü olduğu görülmektedir. Altta yatan bir trombofili tespiti, RPL'den muzdarip çiftler için erken ve uygun tedaviye başlamak için önemli olabilir.

Anahtar Kelimeler

Factor V Leiden, hereditary thrombophilia, Prothrombin, recurrent pregnancy loss, retrospective study

INCIDENCE AND SPECTRUM OF THROMBOPHILIA IN WOMEN WITH RECURRENT PREGNANCY LOSS: A RETROSPECTIVE STUDY

Öz

Objective: Recurrent pregnancy loss (RPL), which is generally known as >2 consecutive pregnancy losses before 20 weeks' gestation, is seen in between 3-5% of women. The aim is to evaluate the frequency of common variants with hereditary thrombophilia; (Methylenetetrahydrofolate Reductase; MTHFR C677T and MTHFR A1298C polymorphisms; FV Leiden G1691A and Prothrombin G20210A mutation) in female patients with RPL.
Materials and Methods: This retrospective cohort study is between the years 2020 and 2022. We investigated the frequency of the MTHFR C677T and MTHFR A1298C polymorphisms, FV Leiden G1691A and Prothrombin G20210A mutations in 380 females suffering from two or more pregnancy losses.
Results: The mean age of the patients was 32.6 years (range: 18-46). The most frequently observed variant in this group was a heterozygote mutation for the MTHFR677 polymorphism (n=163, 42.8%). The second most common variant was MTHFR A1298C heterozygosity with a frequency of 41.1% (n=156). The least common variant is FII homozygosity (0.3%). Heterozygous of FII and FV Leiden (G1691A) mutations were found in 1.8% (1/380) and 8.4% (7/380) of the patients, respectively.
Conclusion: The thrombophilic variants (FV Leiden G1691A and Prothrombin G20210A) seem to have an important role in RPL. Detection of an underlying thrombophilia may be important to begin early and appropriate treatment for couples suffering from RPL.

Anahtar Kelimeler

Factor V Leiden, hereditary thrombophilia, Prothrombin, recurrent pregnancy loss, retrospective study

Kaynakça

• 1.Abu-Asab NS, Ayesh SK, Ateeq RO, et al. Association of inherited thrombophilia with recurrent pregnancy loss in palestinian women. Obstet Gynecol Int 2011;2011:689684.
• 2.Mehta P, Vishvkarma R, Singh K, et al. MTHFR 1298A>C Substitution is a Strong Candidate for Analysis in Recurrent Pregnancy Loss: Evidence from 14,289 Subjects. Reprod Sci 2022;29:1039-53.
• 3.Alecsandru D, Klimczak AM, Garcia Velasco, JA et al. Immunologic causes and thrombophilia in recurrent pregnancy loss. Fertil Steril 2021;115:561-6.
• 4.Rai R, Regan L. Recurrent miscarriage. Lancet 2006;368:601-11.
• 5.Karatas A, Eroz R, Albayrak M, et al. Evaluation of chromosomal abnormalities and common trombophilic mutations in cases with recurrent miscarriage Afr Health Sci 2014;14:216-22.
• 6.Clifford K, Rai R, Watson H, et al. An informative protocol for the investigation of recurrent miscarriage: preliminary experience of 500 consecutive cases. Hum Reprod 1994;9:1328-32.
• 7.Ahangari N, Doosti M, Mousavifar N, et al. Hereditary thrombophilia genetic variants in recurrent pregnancy loss. Arch Gynecol Obstet 2019;300:777-82.
• 8.Mierla D, Szmal C, Neagos D, et al. Association of Prothrombin (A20210G) and Factor V Leiden (A506G) with Recurrent Pregnancy Loss. Maedica (Bucur) 2012;7:222-6.
• 9.Brenner B, Sarig G, Weiner Z, et al. Thrombophilic polymorphisms are common in women with fetal loss without apparent cause. Thromb Haemost 1999;82:6-9.
• 10.Grandone E, Margaglione M, Colaizzo D, et al. Factor V Leiden is associated with repeated and recurrent unexplained fetal losses. Thromb Haemost 1997;77:822-4.
• 11.Foka ZJ, Lambropoulos AF, Saravelos H, et al. Factor V leiden and prothrombin G20210A mutations, but not methylenetetrahydrofolate reductase C677T, are associated with recurrent miscarriages. Hum Reprod 2000;15:458-62.
• 12.Baré SN, Póka R, Balogh I, et al. Factor V Leiden as a risk factor for miscarriage and reduced fertility. Aust N Z J Obstet Gynaecol 2000;40:186-90.
• 13.López-Jiménez JJ, Porras-Dorantes Á, Juárez-Vázquez CI, et al. Molecular thrombophilic profile in Mexican patients with idiopathic recurrent pregnancy loss. Genet Mol Res 2016;15.
• 14.Bradley LA, Palomaki GE, Bienstock J, et al. Can Factor V Leiden and prothrombin G20210A testing in women with recurrent pregnancy loss result in improved pregnancy outcomes?: Results from a targeted evidence-based review. Genet Med 2012;14:39-50.
• 15.Bauduer F, Lacombe D. Factor V Leiden, prothrombin 20210A, methylenetetrahydrofolate reductase 677T, and population genetics. Mol Genet Metab 2005;86:91-9.
• 16.Liu PF, Ding B, Zhang JY, et al. Association Between MTHFR C677T Polymorphism and Congenital Heart Disease. Int Heart J 2020;61:553-61.
• 17.Ota K, Takahashi T, Han A, et al. Effects of MTHFR C677T polymorphism on vitamin D, homocysteine and natural killer cell cytotoxicity in women with recurrent pregnancy losses. Hum Reprod 2020;35:1276-87.
• 18.Khalife S, Bissar-Tadmouri N. Inherited Thrombophilia in a Lebanese Family of Four Generations: A Case Report of Recurrent Miscarriage. Vasc Health Risk Manag 2020;16:53-6.
• 19.Coulam CB, Jeyendran RS, Fishel LA, et al. Multiple thrombophilic gene mutations are risk factors for implantation failure. Reprod Biomed Online 2006;12:322-7.
• 20.Yadav U, Kumar P, Gupta S, et al. Distribution of MTHFR C677T Gene Polymorphism in Healthy North Indian Population and an Updated Meta-analysis. Indian J Clin Biochem 2017;32:399-410.
• 21.Niktabar SM, Aarafi H, Dastgheib SA, et al. Association of MTHFR 1298A> C Polymorphism with Susceptibility to Non-Syndromic Cleft Lip with or without Palate: A CaseControl Study and Meta-Analysis. Fetal Pediatr Pathol 2021;40:1-17.
• 22.Moll S, Varga EA. Homocysteine and MTHFR Mutations. Circulation 2015;132:e6-9.
• 23.Yang B, Fan S, Zhi X, et al. Geographical and ethnic distribution of MTHFR gene polymorphisms and their associations with diseases among Chinese population. Clin Genet 2017;92:243-58.
• 24.Turgal M, Gumruk F, Karaagaoglu E, et al. Methylenetetrahydrofolate Reductase Polymorphisms and Pregnancy Outcome. Geburtshilfe Frauenheilkd 2018;78:871-8.