Journal of Obstetrics, Gynecology and Cancer Research

Iranian Society of Gynecology Oncology

Current Issue

By Issue

By Author

By Subject

Author Index

Keyword Index

About Journal

Aims and Scope

Editorial Board

Indexing and Abstracting

Related Links

FAQ

Journal Metrics

News

Open access policy

Submission Instruction

call for papers

The Article's Request Form

Publication Ethics

Publishing Charges

Reviewers Section

Duties of Editors

Peer Review Process

The Role of Thrombophilia Factors Polymorphism and Cytogenetic Analysis in Recurrent Pregnancy Loss (RPL) in Northeastern Iran

Document Type : Original Research Article

Authors

1 Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Iranian Blood Transfusion Organization (IBTO), Tehran, Iran

2 Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

3 Department of Hematopathology, Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

4 Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Background & Objective: Recurrent pregnancy loss (RPL) is the occurrence of three or more miscarriages before the 20th week of pregnancy. Thrombophilia factors are one of the common causes of RPL.
Materials & Methods: This retrospective study was performed on women with miscarriages. 620 patients’ documents with pregnancy loss were investigated. Based on the number of pregnancy loss, the women were divided into a control group with less than three miscarriages (212) and RPL group (180). Cytogenetics analysis and thrombophilia factors polymorphism tests were performed for all patients.
Results: In the analysis, none of the studied polymorphisms (MTHFR 677 C⁄T /Factor V Leiden /Prothrombin G20210A/ ACE I/D/ PAI-1) showed a significant relationship between Control and RPL groups (P-value ˃ 0.05). Cytogenetic analysis showed 2 numerical and 9 structural abnormalities among both groups. Statistical analysis indicated a significant association between the number of abortions and age (P value= 0.005, r= 0.139). We even realized that there was a significant relationship between polymorphism number and recurrent number of miscarriages (P value= 0.018, r= 0.6).
Conclusion: We showed that polymorphisms analysis for thrombophilia factors is a more precious test than cytogenetics analysis (study of the banded pattern of chromosomes during metaphase of the cell cycle). We even indicated that no association was found between thrombophilia polymorphisms in the control and RPL groups. This means that screening for Factor V Leiden, prothrombin G20210A, MTHFR C677T, ACE I/D, and PAI-1 and cytogenetic analysis in patients with a history of RPL is not recommended.

Highlights

✅ We showed that polymorphisms analysis for thrombophilia factors is a more precious test than cytogenetics analysis (study of the banded pattern of chromosomes during metaphase of the cell cycle). We even indicated that no association was found between thrombophilia polymorphisms in the control and RPL groups. This means that screening for Factor V Leiden, prothrombin G20210A, MTHFR C677T, ACE I/D, and PAI-1 and cytogenetic analysis in patients with a history of RPL is not recommended.

Keywords

Main Subjects

References
1. Ahangari N, Doosti M, Mousavifar N, Attaran M, Shahrokhzadeh S, Memarpour S, et al. Hereditary thrombophilia genetic variants in recurrent pregnancy loss. Arch Gynecol Obstet. 2019;300(3):777-82. [DOI:10.1007/s00404-019-05224-7] [PMID]
2. Bigdeli R, Younesi MR, Panahnejad E, Asgary V, Heidarzadeh S, Mazaheri H, et al. Association between thrombophilia gene polymorphisms and recurrent pregnancy loss risk in the Iranian population. Syst Biol Reprod Med. 2018;64(4):274-82. [DOI:10.1080/19396368.2018.1456576] [PMID]
3. Gianaroli L, Racowsky C, Geraedts J, Cedars M, Makrigiannakis A, Lobo R. Best practices of ASRM and ESHRE: a journey through reproductive medicine. Hum Reprod. 2012;27(12):3365-79. [DOI:10.1093/humrep/des338] [PMID]
4. Arias-Sosa LA, Acosta ID, Lucena-Quevedo E, Moreno-Ortiz H, Esteban-Pérez C, Forero-Castro M. Genetic and epigenetic variations associated with idiopathic recurrent pregnancy loss. J Assist Reprod Genet. 2018;35(3):355-66. [DOI:10.1007/s10815-017-1108-y] [PMID] [PMCID]
5. Ford HB, Schust DJ. Recurrent pregnancy loss: etiology, diagnosis, and therapy. Rev Obstet Gynecol. 2009;2(2):76-83.
6. Nassour-Mokhtari I, Loukidi B, Moussouni A, Bettioui R, Benhabib R, Merzouk H, et al. Inherited thrombophilia and recurrent pregnancy loss: a single-center case-control study in North-Western Algeria. Egypt J Med Hum Genet. 2020;21(1):1-7. [DOI:10.1186/s43042-020-00077-1]
7. Liu X, Chen Y, Ye C, Xing D, Wu R, Li F, et al. Hereditary thrombophilia and recurrent pregnancy loss: a systematic review and meta-analysis. Hum Reprod. 2021;36(5):1213-29. [DOI:10.1093/humrep/deab010] [PMID]
8. Phillippe HM, Hornsby LB, Treadway S, Armstrong EM, Bellone JM. Inherited Thrombophilia. J Pharm Pract. 2014;27(3):227-33. [DOI:10.1177/0897190014530390] [PMID]
9. Dautaj A, Krasi G, Bushati V, Precone V, Gheza M, Fioretti F, et al. Hereditary thrombophilia. Acta Biomed. 2019;90(10-s):44-6.
10. Hardy ML, Day ML, Morris MB. Redox Regulation and Oxidative Stress in Mammalian Oocytes and Embryos Developed In Vivo and In Vitro. Int J Environ Res Public Health. 2021;18(21):11374. [DOI:10.3390/ijerph182111374] [PMID] [PMCID]
11. Mousavi A, Shooshtari M, Nassiri S, Aipour AA, Akhavan S, Zamani N. Recurrence and Fertility Rate in Females with Borderline Ovarian Tumor. J Obstet Gynecol Cancer Res. 2017;2(4):1-5. [DOI:10.5812/jogcr.62177]
12. Azem F, Many A, Ben Ami I, Yovel I, Amit A, Lessing JB, et al. Increased rates of thrombophilia in women with repeated IVF failures. Hum Reprod. 2004;19(2):368-70. [DOI:10.1093/humrep/deh069] [PMID]
13. Bedaiwy MA, Falcone T, Mohamed MS, Aleem AA, Sharma RK, Worley SE, et al. Differential growth of human embryos in vitro: role of reactive oxygen species. Fertil Steril. 2004;82(3):593-600. [DOI:10.1016/j.fertnstert.2004.02.121] [PMID]
14. Ebisch IM, Thomas CM, Peters WH, Braat DD, Steegers-Theunissen RP. The importance of folate, zinc and antioxidants in the pathogenesis and prevention of subfertility. Hum Reprod Update. 2007;13(2):163-74. [DOI:10.1093/humupd/dml054] [PMID]
15. Su MT, Lin SH, Chen YC, Kuo PL. Genetic association studies of ACE and PAI-1 genes in women with recurrent pregnancy loss: a systematic review and meta-analysis. Thromb Haemost. 2013;109(1):8-15. [DOI:10.1160/TH12-08-0584] [PMID]
16. van Leeuwen M, Vansenne F, Korevaar JC, van der Veen F, Goddijn M, Mol BW. Economic analysis of chromosome testing in couples with recurrent miscarriage to prevent handicapped offspring. Hum Reprod. 2013;28(7):1737-42. [DOI:10.1093/humrep/det067] [PMID]
17. Masihi S, Shirazi E, Moramezi F, Saadati N, Barati M. Comparison of array comparative genomic hybridization and karyotyping in first trimester screening of high-risk pregnancies. J Obstet Gynecol Cancer Res. 2022:17-.
18. Soltani N, Mirzaei F, Ayatollahi H. Cytogenetic Study of Patients with Primary Amenorrhea in the Northeast of Iran. Iran J Pathol. 2021;16(1):57-61. [DOI:10.30699/ijp.2020.115747.2258] [PMID] [PMCID]
19. Shaffer LG, McGowan-Jordan J, Schmid M. ISCN 2013: an international system for human cytogenetic nomenclature: Karger Medical and Scientific Publishers; 2013.
20. Yenicesu GI, Cetin M, Ozdemir O, Cetin A, Ozen F, Yenicesu C, et al. A prospective case-control study analyzes 12 thrombophilic gene mutations in Turkish couples with recurrent pregnancy loss. Am J Reprod Immunol. 2010;63(2):126-36. [DOI:10.1111/j.1600-0897.2009.00770.x] [PMID]
21. Behjati R, Modarressi MH, Jeddi-Tehrani M, Dokoohaki P, Ghasemi J, Zarnani AH, et al. Thrombophilic mutations in Iranian patients with infertility and recurrent spontaneous abortion. Ann Hematol. 2006;85(4):268-71. [DOI:10.1007/s00277-005-0021-0] [PMID]
22. Zetterberg H, Regland B, Palmér M, Ricksten A, Palmqvist L, Rymo L, et al. Increased frequency of combined methylenetetrahydrofolate reductase C677T and A1298C mutated alleles in spontaneously aborted embryos. Eur J Hum Genet. 2002;10(2):113-8. [DOI:10.1038/sj.ejhg.5200767] [PMID]
23. Dissanayake VH, Sirisena ND, Weerasekera LY, Gammulla CG, Seneviratne HR, Jayasekara RW. Candidate gene study of genetic thrombophilic polymorphisms in pre-eclampsia and recurrent pregnancy loss in Sinhalese women. J Obstet Gynaecol Res. 2012;38(9):1168-76. [DOI:10.1111/j.1447-0756.2012.01846.x] [PMID]
24. Udry S, Aranda FM, Latino JO, de Larrañaga GF. Paternal factor V Leiden and recurrent pregnancy loss: a new concept behind fetal genetics? J Thromb Haemost. 2014;12(5):666-9. [DOI:10.1111/jth.12526] [PMID]
25. Mohammad M, Al-Halabi M, Monem F. Prevalence of factor V Leiden mutation and its relation with recurrent spontaneous pregnancy loss in a group of Syrian women. Middle East Fertil Soc J. 2007;12(3):179.
26. Zahed LF, Rayes RF, Mahfouz RA, Taher AT, Maarouf HH, Nassar AH. Prevalence of factor V Leiden, prothrombin and methylene tetrahydrofolate reductase mutations in women with adverse pregnancy outcomes in Lebanon. Am J Obstet Gynecol. 2006;195(4):1114-8. [DOI:10.1016/j.ajog.2006.06.082] [PMID]
27. Alfirevic Z, Mousa HA, Martlew V, Briscoe L, Perez-Casal M, Toh CH. Postnatal screening for thrombophilia in women with severe pregnancy complications. Obstet Gynecol. 2001;97(5 Pt 1):753-9. [DOI:10.1016/S0029-7844(01)01190-5] [PMID]
28. Carp H, Salomon O, Seidman D, Dardik R, Rosenberg N, Inbal A. Prevalence of genetic markers for thrombophilia in recurrent pregnancy loss. Hum Reprod. 2002;17(6):1633-7. [DOI:10.1093/humrep/17.6.1633] [PMID]
29. Pauer HU, Voigt-Tschirschwitz T, Hinney B, Burfeind P, Wolf C, Emons G, et al. Analyzes of three common thrombophilic gene mutations in German women with recurrent abortions. Acta Obstet Gynecol Scand. 2003;82(10):942-7. [DOI:10.1034/j.1600-0412.2003.00293.x] [PMID]
30. Sotiriadis A, Vartholomatos G, Pavlou M, Kolaitis N, Dova L, Stefos T, et al. Combined thrombophilic mutations in women with unexplained recurrent miscarriage. Am J Reprod Immunol. 2007;57(2):133-41. [DOI:10.1111/j.1600-0897.2006.00454.x] [PMID]
31. Parand A, Zolghadri J, Nezam M, Afrasiabi A, Haghpanah S, Karimi M. Inherited thrombophilia and recurrent pregnancy loss. Iran Red Crescent Med J. 2013;15(12):e13708. [DOI:10.5812/ircmj.13708]
32. Buchholz T, Lohse P, Rogenhofer N, Kosian E, Pihusch R, Thaler CJ. Polymorphisms in the ACE and PAI-1 genes are associated with recurrent spontaneous miscarriages. Hum Reprod. 2003;18(11):2473-7. [DOI:10.1093/humrep/deg474] [PMID]
33. Kim JJ, Choi YM, Lee SK, Yang KM, Paik EC, Jeong HJ, et al. The PAI‐1 4G/5G and ACE I/D Polymorphisms and Risk of Recurrent Pregnancy Loss: A Case-Control Study. Am J Reprod Immunol. 2014;72(6):571-6. [DOI:10.1111/aji.12302] [PMID]
34. Kurzawińska G, Barlik M, Drews K, Różycka A, Seremak-Mrozikiewicz A, Ożarowski M, et al. Coexistence of ACE (I/D) and PAI-1 (4G/5G) gene variants in recurrent miscarriage in Polish population. Ginekol Pol. 2016;87(4):271-6. [DOI:10.17772/gp/62203] [PMID]
35. Nikitina TV, Sazhenova EA, Zhigalina DI, Tolmacheva EN, Sukhanova NN, Lebedev IN. Karyotype evaluation of repeated abortions in primary and secondary recurrent pregnancy loss. J Assist Reprod Genet. 2020;37(3):517-25. [DOI:10.1007/s10815-020-01703-y] [PMID] [PMCID]
36. Nybo Andersen AM, Wohlfahrt J, Christens P, Olsen J, Melbye M. Maternal age and fetal loss: population based register linkage study. Bmj. 2000;320(7251):1708-12. [DOI:10.1136/bmj.320.7251.1708] [PMID] [PMCID]
37. Awartani KA, Al Shabibi MS. Description of cytogenetic abnormalities and the pregnancy outcomes of couples with recurrent pregnancy loss in a tertiary-care center in Saudi Arabia. Saudi Med J. 2018;39(3):239-42. [DOI:10.15537/smj.2018.3.21592] [PMID] [PMCID]
38. Alibakhshi R, Nejati P, Hamani S, Mir-Ahadi N, Jalilian N. Cytogenetic Analysis of 570 Couples with Recurrent Pregnancy Loss: Reporting 11 Years of Experience. J Hum Reprod Sci. 2020;13(3):216-20. [DOI:10.4103/jhrs.JHRS_138_19] [PMID] [PMCID]
Journal of Obstetrics, Gynecology and Cancer Research
Volume 8, Issue 4 - Serial Number 33
July and August 2023
Pages 342-349
Files
History
  • Receive Date: 07 July 2022
  • Revise Date: 09 September 2022
  • Accept Date: 21 September 2022
  • Publish Date: 07 July 2023
Share
How to cite
Statistics