Potential role of Factor V Leiden mutation in adverse pregnancy outcomes: An updated systematic review

Authors

  • Nasibeh Roozbeh Mother and Child Welfare Research Center, Hormozgan University of Medical Sciences, BandarAbbas, Iran
  • Farzaneh Banihashemi Mother and Child Welfare Research Center, Hormozgan University of Medical Sciences, BandarAbbas, Iran
  • Mitra Mehraban Fertility and Infertility Research Center, Faculty of Medicine, Hormozgan University of Medical Sciences, BandarAbbas, Iran
  • Fatemeh Abdi Student Research Committee, Nursing and Midwifery Faculty, Shahid Beheshti University of Medical Sciences, Tehran, Iran

DOI:

https://doi.org/10.15419/bmrat.v4i12.389

Keywords:

Factor V Leiden, Mutation, Pregnancy outcomes, Medicine

Abstract

Background: Thrombophilia is an inherited or acquired predisposition for development of thrombosis. One of the common thrombophilia polymorphisms is Factor V Leiden (FVL) mutation, which may contribute to negative pregnancy outcomes. This systematic review study seeks to describe the potential effects of factor V Leiden mutation on adverse pregnancy outcomes.

Methods: Pubmed, Embase, ISI Web of Sciences, Scopus, ScienceDirect, Proquest and Google Scholar, for articles published during 1996-2017. Articles were evaluated by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for standard reporting. As well, the quality of studies was assessed by the Newcastle-Ottawa Scale (NOS).

Results: A total of 14 studies were eligible based on the inclusion criteria. The papers were scored by the STROBE checklist. The range of STROBE score was 15-20. Only 37.5% of the studies confirmed the relationship between fetal loss and FVL. The effect of FVL mutation on spontaneous abortions and In Vitro Fertilization (IVF) failures was demonstrated in all the studies. In the reviewed studies, there was no observed relationship between FVL mutation with intrauterine growth restriction (IUGR), preeclampsia, placental abruption or small for gestational age (SGA).

Conclusion: The reviewed studies showed an unclear association between FVL mutation and stillbirth, IUGR, preeclampsia, or placental abruption. The exact effects of hereditary thrombophilia on pregnancy outcome is also still controversial. However, FVL mutation appeared to have an effect on spontaneous abortions and IVF failures. Therefore, screening patients for thrombophilic polymorphisms might be helpful.

Author Biography

  • Fatemeh Abdi, Student Research Committee, Nursing and Midwifery Faculty, Shahid Beheshti University of Medical Sciences, Tehran, Iran
    abdi@sbmu.ac.ir

References

<ol>
<li class="show">Abdi, F., &amp; Roozbeh, N. (2016). The effects of Humulus Lupulus L.) Hops) on Menopausal Vasomotor Symptoms: A Systematic Review and Meta-analysis. Majallah-i Zanan, Mamai va Nazai-i Iran, 19, 9–17.</li>
<li class="show">Al Husseini, N. F., Rezk, A. Y., Odah, M. M., El Rahman, S. M., &amp; Ali, A. I. (2011). Thrombophilic Genes Mutations in Women with Repeated In-Vitro Fertilization Failure. American Medical Journal, 2(1), 7–12.&nbsp;<a href="https://doi.org/10.3844/amjsp.2011.7.12">https://doi.org/10.3844/amjsp.2011.7.12</a></li>
<li class="show">Ardestani, M. T., Nodushan, H. H., Aflatoonian, A., Ghasemi, N., &amp; Sheikhha, M. H. (2013). Case control study of the factor V Leiden and factor II G20210A mutation frequency in women with recurrent pregnancy loss. Iranian Journal of Reproductive Medicine, 11, 61.</li>
<li class="show">Ayadurai, T., Muniandy, S., &amp; Omar, S. Z. (2009). Thrombophilia investigation in Malaysian women with recurrent pregnancy loss. Journal of Obstetrics and Gynaecology Research, 35(6), 1061–1068.&nbsp;<a href="https://doi.org/10.1111/j.1447-0756.2009.01067.x">https://doi.org/10.1111/j.1447-0756.2009.01067.x</a></li>
<li class="show">Azem, F., Many, A., Yovel, I., Amit, A., Lessing, J. B., &amp; Kupferminc, M. J. (2004). Increased rates of thrombophilia in women with repeated IVF failures. Human Reproduction (Oxford, England), 19(2), 368–370.&nbsp;<a href="https://doi.org/10.1093/humrep/deh069">https://doi.org/10.1093/humrep/deh069</a></li>
<li class="show">Cardona, H., Castañeda, S. A., Cardona Maya, W., Alvarez, L., Gómez, J., Gómez, J., . . . Cadavid, Á. P. (2012). Lack of association between recurrent pregnancy loss and inherited thrombophilia in a group of Colombian patients. Thrombosis, •••, 2012.</li>
<li class="show">Carrington, B., Sacks, G., &amp; Regan, L. (2005). Recurrent miscarriage: Pathophysiology and outcome. Current Opinion in Obstetrics &amp; Gynecology, 17(6), 591–597.&nbsp;<a href="https://doi.org/10.1097/01.gco.0000194112.86051.26">https://doi.org/10.1097/01.gco.0000194112.86051.26</a></li>
<li class="show">Colman, R. W. (2006). Are hemostasis and thrombosis two sides of the same coin? The Journal of Experimental Medicine, 203(3), 493–495.&nbsp;<a href="https://doi.org/10.1084/jem.20060217">https://doi.org/10.1084/jem.20060217</a></li>
<li class="show">Daniela, L., De Lisa, E., Dellepiane, M., Storch, E., Attarian, D., Ferrari, A., . . . Motta, N. (2004). Trombofilia y pérdida recurrente de embarazo. La Revista Medica del Uruguay, 20, 106–113.</li>
<li class="show">De Stefano, V., &amp; Leone, G. (1995). Resistance to activated protein C due to mutated factor V as a novel cause of inherited thrombophilia. Haematologica, 80, 344–356.</li>
<li class="show">Dilley, A., Benito, C., Hooper, W., Austin, H., Miller, C., El-Jamil, M., . . . Patterson-Barnett, A. (2002). Mutations in the factor V, prothrombin and MTHFR genes are not risk factors for recurrent fetal loss. The Journal of Maternal-Fetal &amp; Neonatal Medicine, 11(3), 176–182.&nbsp;<a href="https://doi.org/10.1080/jmf.11.3.176.182">https://doi.org/10.1080/jmf.11.3.176.182</a></li>
<li class="show">Dizon-Townson, D., Miller, C., Sibai, B., Spong, C. Y., Thom, E., Wendel, G., Jr., . . . Moawad, A. (2005). The relationship of the factor V Leiden mutation and pregnancy outcomes for mother and fetus. Obstetrics and Gynecology, 106(3), 517–524.&nbsp;<a href="https://doi.org/10.1097/01.AOG.0000173986.32528.ca">https://doi.org/10.1097/01.AOG.0000173986.32528.ca</a></li>
<li class="show">Doyle, N. M., &amp; Monga, M. (2004). Thromboembolic disease in pregnancy. Obstetrics and Gynecology Clinics of North America, 31(2), 319–344.&nbsp;<a href="https://doi.org/10.1016/j.ogc.2004.03.008">https://doi.org/10.1016/j.ogc.2004.03.008</a></li>
<li class="show">Foka, Z., Lambropoulos, A., Saravelos, H., Karas, G., Karavida, A., Agorastos, T., . . . Kotsis, A. (2000). Factor V Leiden and prothrombin G20210A mutations, but not methylenetetrahydrofolate reductase C677T, are associated with recurrent miscarriages. Human Reproduction (Oxford, England), 15(2), 458–462.&nbsp;<a href="https://doi.org/10.1093/humrep/15.2.458">https://doi.org/10.1093/humrep/15.2.458</a></li>
<li class="show">Gawish, G. E. (2011). Molecular characterization of factor V leiden G1691A and prothrombin G20210A mutations in Saudi newborns with stroke. Biochemical Genetics, 49(9-10), 601–610.&nbsp;<a href="https://doi.org/10.1007/s10528-011-9435-7">https://doi.org/10.1007/s10528-011-9435-7</a></li>
<li class="show">Goodman, C. S., Coulam, C. B., Jeyendran, R. S., Acosta, V. A., &amp; Roussev, R. (2006). Which thrombophilic gene mutations are risk factors for recurrent pregnancy loss? American Journal of Reproductive Immunology, 56(4), 230–236.&nbsp;<a href="https://doi.org/10.1111/j.1600-0897.2006.00419.x">https://doi.org/10.1111/j.1600-0897.2006.00419.x</a></li>
<li class="show">Göpel, W., Ludwig, M., Junge, A. K., Kohlmann, T., Diedrich, K., &amp; Möller, J. (2001). Selection pressure for the factor-V-Leiden mutation and embryo implantation. Lancet, 358(9289), 1238–1239.&nbsp;<a href="https://doi.org/10.1016/S0140-6736(01)06354-1">https://doi.org/10.1016/S0140-6736(01)06354-1</a></li>
<li class="show">Grandone, E., Colaizzo, D., Bue, A. L., Checola, M. G., Cittadini, E., &amp; Margaglione, M. (2001). Inherited thrombophilia and in vitro fertilization implantation failure. Fertility and Sterility, 76(1), 201–202.&nbsp;<a href="https://doi.org/10.1016/S0015-0282(01)01832-5">https://doi.org/10.1016/S0015-0282(01)01832-5</a></li>
<li class="show">Idali, F., Zareii, S., Mohammad‐Zadeh, A., Reihany‐Sabet, F., Akbarzadeh‐Pasha, Z., Khorram‐Khorshid, H. R., . . . Jeddi‐Tehrani, M. (2012). Plasminogen activator inhibitor 1 and methylenetetrahydrofolate reductase gene mutations in Iranian women with polycystic ovary syndrome. American Journal of Reproductive Immunology, 68(5), 400–407.&nbsp;<a href="https://doi.org/10.1111/aji.12002">https://doi.org/10.1111/aji.12002</a></li>
<li class="show">Infante-Rivard, C., Rivard, G.-E., Yotov, W. V., Génin, E., Guiguet, M., Weinberg, C., . . . Feoli-Fonseca, J. C. (2002). Absence of association of thrombophilia polymorphisms with intrauterine growth restriction. The New England Journal of Medicine, 347(1), 19–25.&nbsp;<a href="https://doi.org/10.1056/NEJM200207043470105">https://doi.org/10.1056/NEJM200207043470105</a></li>
<li class="show">Ivanov, P. D., Komsa-Penkova, R. S., Konova, E. I., Kovacheva, K. S., Simeonova, M. N., &amp; Popov, J. D. (2009). Association of inherited thrombophilia with embryonic and postembryonic recurrent pregnancy loss. Blood Coagulation &amp; Fibrinolysis, 20(2), 134–140.&nbsp;<a href="https://doi.org/10.1097/MBC.0b013e32832545f3">https://doi.org/10.1097/MBC.0b013e32832545f3</a></li>
<li class="show">Kazerooni, T., Ghaffarpasand, F., Asadi, N., Dehkhoda, Z., Dehghankhalili, M., &amp; Kazerooni, Y. (2013). Correlation between thrombophilia and recurrent pregnancy loss in patients with polycystic ovary syndrome: A comparative study. Journal of the Chinese Medical Association, 76(5), 282–288. <a href="https://doi.org/10.1016/j.jcma.2013.01.009 ">https://doi.org/10.1016/j.jcma.2013.01.009 </a></li>
<li class="show">Kist, W. J., Janssen, N. G., Kalk, J. J., Hague, W. M., Dekker, G. A., &amp; Vries, J. d. (2008). Thrombophilias and adverse pregnancy outcome—A confounded problem! Thrombosis and Haemostasis, 99, 77.</li>
<li class="show">Kupferminc, M. J., Eldor, A., Steinman, N., Many, A., Bar-Am, A., Jaffa, A., . . . Lessing, J. B. (1999). Increased frequency of genetic thrombophilia in women with complications of pregnancy. The New England Journal of Medicine, 340(1), 9–13.&nbsp;<a href="https://doi.org/10.1056/NEJM199901073400102">https://doi.org/10.1056/NEJM199901073400102</a></li>
<li class="show">Kupferminc, M. J., Rimon, E., Many, A., Sharon, M., Lessing, J. B., &amp; Gamzu, R. (2011). Low molecular weight heparin treatment during subsequent pregnancies of women with inherited thrombophilia and previous severe pregnancy complications. The Journal of Maternal-Fetal &amp; Neonatal Medicine, 24(8), 1042–1045.&nbsp;<a href="https://doi.org/10.3109/14767058.2010.545911">https://doi.org/10.3109/14767058.2010.545911</a></li>
<li class="show">Lissalde‐Lavigne, G., Fabbro‐Peray, P., Cochery‐Nouvellon, E., Mercier, E., Ripart‐Neveu, S., Balducchi, J.-P., . . . Gris, J.-C. (2005). IN FOCUS: Factor V Leiden and prothrombin G20210A polymorphisms as risk factors for miscarriage during a first intended pregnancy: the matched case–control ‘NOHA first’study. Journal of Thrombosis and Haemostasis, 3(10), 2178–2184.&nbsp;<a href="https://doi.org/10.1111/j.1538-7836.2005.01581.x">https://doi.org/10.1111/j.1538-7836.2005.01581.x</a></li>
<li class="show">Mierla, D., Szmal, C., Neagos, D., Cretu, R., Stoian, V., &amp; Jardan, D. (2012). Association of Prothrombin (A20210G) and Factor V Leiden (A506G) with Recurrent Pregnancy Loss. Maedica, 7, 222.</li>
<li class="show">Norrie, G., Farquharson, R. G., &amp; Greaves, M. (2009). Screening and treatment for heritable thrombophilia in pregnancy failure: Inconsistencies among UK early pregnancy units. British Journal of Haematology, 144(2), 241–244.&nbsp;<a href="https://doi.org/10.1111/j.1365-2141.2008.07444.x">https://doi.org/10.1111/j.1365-2141.2008.07444.x</a></li>
<li class="show">Pavlova, E., Chemev, T., Chemev, A., and Karagiozova, Z. (2008). Pregnancy and issues with inherited and acquired thrombophilia. Journal of IMAB-Annula Proceeding, 21-22.<br>Proite, M. M., de Moraes Malinverni, A. C., Oshima, C. T. F., de Souza Ishigai, M. M., Moron, A. F., da Silva, I. D. C. G., &amp; da Silva, F. R. (2016). Mutations in the Gene for Factor V Leiden and G20210A Prothrombin Polymorphism in Women With Recurrent Spontaneous Abortion: A Retrospective Study in a Brazilian Population. Journal of Clinical Gynecology and Obstetrics, 5(3), 85–91.&nbsp;<a href="https://doi.org/10.14740/jcgo412e">https://doi.org/10.14740/jcgo412e</a></li>
<li class="show">Qublan, H. S., Eid, S. S., Ababneh, H. A., Amarin, Z. O., Smadi, A. Z., Al-Khafaji, F. F., &amp; Khader, Y. S. (2006). Acquired and inherited thrombophilia: Implication in recurrent IVF and embryo transfer failure. Human Reproduction (Oxford, England), 21(10), 2694–2698. <a href="https://doi.org/10.1093/humrep/del203 ">https://doi.org/10.1093/humrep/del203 </a></li>
<li class="show">Rai, R., &amp; Regan, L. (2006). Recurrent miscarriage. Lancet, 368(9535), 601–611.&nbsp;<a href="https://doi.org/10.1016/S0140-6736(06)69204-0">https://doi.org/10.1016/S0140-6736(06)69204-0</a></li>
<li class="show">Rey, E., Kahn, S. R., David, M., &amp; Shrier, I. (2003). Thrombophilic disorders and fetal loss: A meta-analysis. Lancet, 361(9361), 901–908.&nbsp;<a href="https://doi.org/10.1016/S0140-6736(03)12771-7">https://doi.org/10.1016/S0140-6736(03)12771-7</a></li>
<li class="show">Ricci, G., Bogatti, P., Fischer-Tamaro, L., Giolo, E., Luppi, S., Montico, M., . . . Morgutti, M. (2011). Factor V Leiden and prothrombin gene G20210A mutation and in vitro fertilization: Prospective cohort study. Human Reproduction (Oxford, England), 26(11), 3068–3077.&nbsp;<a href="https://doi.org/10.1093/humrep/der261">https://doi.org/10.1093/humrep/der261</a></li>
<li class="show">Robertson, L., Wu, O., Langhorne, P., Twaddle, S., Clark, P., Lowe, G., . . . Regan, L. (2006). Thrombophilia in pregnancy: A systematic review. British Journal of Haematology, 132(2), 171–196.&nbsp;<a href="https://doi.org/10.1111/j.1365-2141.2005.05847.x">https://doi.org/10.1111/j.1365-2141.2005.05847.x</a></li>
<li class="show">Rodger, M. A. (2013). An update on thrombophilia and placenta mediated pregnancy complications: What should we tell our patients? Thrombosis Research, 131(Suppl 1), S25–S27.&nbsp;<a href="https://doi.org/10.1016/S0049-3848(13)70015-X">https://doi.org/10.1016/S0049-3848(13)70015-X</a></li>
<li class="show">Roozbeh, N., Azizi, M., &amp; Darvish, L. (2017a). Pregnancy Outcome of Abnormal Nuchal Translucency: A Systematic Review. Journal of Clinical and Diagnostic Research : JCDR, 11, QC12.</li>
<li class="show">Roozbeh, N., Darvish, L., &amp; Abdi, F. (2017b). Hypoglycemic effects of Acacia nilotica in type II diabetes: A research proposal. BMC Research Notes, 10(1), 331.&nbsp;<a href="https://doi.org/10.1186/s13104-017-2646-1">https://doi.org/10.1186/s13104-017-2646-1</a></li>
<li class="show">Roozbeh, N., Nahidi, F., &amp; Hajiyan, S. (2016). Barriers related to prenatal care utilization among women. Saudi Medical Journal, 37(12), 1319–1327.&nbsp;<a href="https://doi.org/10.15537/smj.2016.12.15505">https://doi.org/10.15537/smj.2016.12.15505</a></li>
<li class="show">Safdarian, L., Najmi, Z., Aleyasin, A., Aghahosseini, M., Rashidi, M., &amp; Asadollah, S. (2014). Recurrent IVF failure and hereditary thrombophilia. Iranian Journal of Reproductive Medicine, 12, 467.</li>
<li class="show">Serrano, F., Lima, M. L., Lopes, C., Almeida, J. P., &amp; Branco, J. (2011). Factor V Leiden and prothrombin G20210A in Portuguese women with recurrent miscarriage: Is it worthwhile to investigate? Archives of Gynecology and Obstetrics, 284(5), 1127–1132.&nbsp;<a href="https://doi.org/10.1007/s00404-010-1834-1">https://doi.org/10.1007/s00404-010-1834-1</a></li>
<li class="show">Silver, R. M., Zhao, Y., Spong, C. Y., Sibai, B., Wendel, G., Jr., Wenstrom, K., . . . Miodovnik, M. (2010). Prothrombin gene G20210A mutation and obstetric complications. Obstetrics and Gynecology, 115(1), 14–20.&nbsp;<a href="https://doi.org/10.1097/AOG.0b013e3181c88918">https://doi.org/10.1097/AOG.0b013e3181c88918</a></li>
<li class="show">Simcox, L. E., Ormesher, L., Tower, C., &amp; Greer, I. A. (2015). Thrombophilia and pregnancy complications. International Journal of Molecular Sciences, 16(12), 28418–28428.&nbsp;<a href="https://doi.org/10.3390/ijms161226104">https://doi.org/10.3390/ijms161226104</a></li>
<li class="show">von Kries, R., Junker, R., Oberle, D., Kosch, A., &amp; Nowak-Gottl, U. (2001). Foetal growth restriction in children with prothrombotic risk factors. THROMBOSIS AND HAEMOSTASIS-STUTTGART, 86, 1012–1016.</li>
</ol>

Published

2017-12-18

Issue

Section

Review

How to Cite

Potential role of Factor V Leiden mutation in adverse pregnancy outcomes: An updated systematic review. (2017). Biomedical Research and Therapy, 4(12), 1832-1846. https://doi.org/10.15419/bmrat.v4i12.389

Similar Articles

311-320 of 441

You may also start an advanced similarity search for this article.