Association of inherited thrombophilia with embryonic and postembryonic recurrent pregnancy loss

Ivanov, P; Komsa-Penkova, Regina; Konova, E; Kovacheva, K; Simeonova, M; Popov, Jordan D.

doi:10.1097/mbc.0b013e32832545f3

Cited by 27 publications

(17 citation statements)

References 52 publications

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“…Some authors have suggested that FV Leiden may cause different effects depending on the gestational age and may have a greater impact after 10 weeks [15,16]. Our study lacked the power to come to clear answers here, although we saw a higher prevalence of FV Leiden in losses that occurred after 10 weeks of gestation than in those that occurred earlier.…”

Section: Resultscontrasting

confidence: 54%

Paternal factor V Leiden and recurrent pregnancy loss: a new concept behind fetal genetics?

Aranda

Latino

Larrañaga

2014

Journal of Thrombosis and Haemostasis

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To cite this article: 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: 666-9.Summary. Background: In up to 50% of couples affected by recurrent pregnancy loss, no identifiable cause is established. Fetal and maternal factors may be equally important in the establishment and maintenance of the placental/maternal arteriovenous anastomoses. Therefore, the inheritance of thrombophilia-related genes may be an important factor in the pathophysiology of recurrent pregnancy loss. Most of the research on recurrent pregnancy loss and thrombophilia has focused on maternal factors, but little is known about the paternal contribution. Objectives: On that basis, we studied the association between inherited paternal thrombophilias and recurrent pregnancy loss in a narrowly selective group of 42 Argentine males from couples that presented without any known risk factors for recurrent pregnancy loss. Patients and methods: The genotypic distributions of factor (F) V Leiden and prothrombin G20210A among cases were compared with those from a reference group composed of 200 Argentine men. Results: We found a significant difference in the distribution of FV Leiden between both groups (16.7% vs. 3.0%), but no difference was found in the distribution of prothrombin G20210A (2.4% vs. 2.0%). Those couples with paternal FV Leiden carriage would be six times more likely to experience recurrent pregnancy loss despite no other apparent cause (OR = 6.47; 95% CI, 2.06-20.39). Conclusion: We found evidence of an association between the paternal carriage of FV Leiden and the predisposition to recurrent pregnancy loss, thereby supporting the hypothesis that genetic contributions from both parents are essential factors in the development of this obstetric disorder.

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Section: Resultscontrasting

confidence: 54%

Paternal factor V Leiden and recurrent pregnancy loss: a new concept behind fetal genetics?

Aranda

Latino

Larrañaga

2014

Journal of Thrombosis and Haemostasis

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“…The prothrombin role on implantation was supported by experimental data for reduced infertility due to increased topical concentration of thrombin in both fallopian tubes, although the mechanism of action of locally administrated thrombin is undefined [65]. The possible impact of FII 20210 G>A on the implantation failure is also supported by the found distinct prevalence of FII 20210 G>A and FVL on early pregnancy loss [66]. In recurrent pregnancy loss before 10 week of gestation was established a more pronounced prevalence of 20210 G>A mutation compared with FVL.…”

Section: Fii 20210 G>a: Thrombin Generation Influence On Cytotrophoblsupporting

confidence: 56%

Thrombophilia in Assisted Reproductive Technology — Place and Needs of Thromboprophylaxis

Ivanov¹,

Tomov²,

Tsvyatkovska³

et al. 2013

Pregnancy Thrombophilia - The Unsuspected Risk

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“…Data from the first trimester are particularly problematic, as few studies dif ferentiate between very early anembryonic losses and postem bryonic losses, and this may impact effect size. 72 This and other metaanalyses have been unable to find significant differences in F5 or F2 ORs based on trimester or number of losses. 43,45,46,59 Results from a recent metaanalysis 49 of unselected cohort stud ies reported a lower effect size (F5 OR: 1.52; F2 OR: 1.13) but were generally consistent with our findings (ORs 2.03 and 1.68, respectively) on fetal loss occurrence rates in carrier women.…”

Section: Discussionmentioning

confidence: 99%

“…These data confirmed an effect for both F5 and F2 (P < 0.001). More importantly, there was con cern that the casecontrol data did not provide direct evidence 99 Foka 63 Onderoglu 86 Grandone 66 Brenner 57 Krause 75 Fatini 61 Raziel 91 Agorastos 50 Glueck 64 Sottilotta 97 Hohlagschwandtner 69 Reznikoff-Etievant 92 Souza 98 Ridker 93 Hopmeier 70 Many 78 Murphy 85 Ivanov 72 Sotiriadis 96 Metz 79 Pauer 88 …”

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confidence: 99%

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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

Bradley

Palomaki

Bienstock

et al. 2012

Genetics in Medicine

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Women with recurrent pregnancy loss are offered Factor V Lei den (F5) and/or prothrombin G20210A (F2) testing to identify candidates for anticoagulation to improve outcomes. A systematic literature review was performed to estimate test performance, effect sizes, and treatment effectiveness. Electronic searches were per formed through April 2011, with review of references from includ ed articles. Englishlanguage studies addressed analytic validity, clinical validity, and/or clinical utility and satisfied predefined in clusion criteria. Adequate evidence showed high analytic sensitivity and specificity for F5 and F2 testing. Evidence for clinical validity was adequate. The summary odds ratio for association of recurrent pregnancy loss with F5 in casecontrolled studies was 2.02 (95% confidence interval, 1.60-2.55), with moderate heterogeneity and suggestion of publication bias. Longitudinal studies in women with recurrent pregnancy loss or unselected cohorts showed F5 carriers were more likely to have a subsequent loss than noncarriers (odds ratios: 1.93 and 2.03, respectively). Results for F2 testing were simi lar. For clinical utility, evidence was adequate that anticoagulation treatments were ineffective (except in antiphospholipid antibody syndrome) and had treatmentassociated harms. The certainty of evidence is moderate (high, moderate, and low) that anticoagula tion of women with recurrent pregnancy loss and F5/F2 variants would currently lead to net harms. Pregnancy loss is a common medical problem among repro ductive age women. 1 However, relatively few women having one pregnancy loss experience multiple or "recurrent" preg nancy losses (RPLs). Approximately 5% of such women experi ence a second pregnancy loss and only 1-2% three or more. Genet Med 1Evaluation for RPL often includes ruling out parental chro mosome abnormalities, identifying maternal exposures, and testing for underlying maternal conditions. 1,2 Effective clinical interventions are available for some etiologies, such as correct ing uterine anomalies surgically and treating antiphospholipid syndrome with aspirin and heparin. [3][4][5] The evidence review summarized herein addressed the asso ciation of inherited thrombophilia with RPL, focusing on tests for two genetic variants that are frequently ordered: Factor V Leiden ("F5") and prothrombin G20210A ("F2"). F5 defines a singlenucleotide substitution in the F5 gene (i.e., Factor V Leiden; F5 c.1691G>A; and p.Arg506Gln), 3,6 whereas F2 defines a singlenucleotide substitution in an untranslated region of the F2 gene (i.e., prothrombin G20210A and F2 c.20210G>A). 4,6 Associations between these (and other) heritable thrombo philia variants and serious pregnancy complications (e.g., RPL, fetal growth restriction, placental abruption, and preeclampsia) began to appear in the literature in 1996.6 By 2005, laborato ries were offering clinical testing for F5/F2 as part of "infertil ity" or RPL evaluations. 7 In some states, these tests continue to be available directly to consumers through the intern...

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Association of inherited thrombophilia with embryonic and postembryonic recurrent pregnancy loss

Cited by 27 publications

References 52 publications

Paternal factor V Leiden and recurrent pregnancy loss: a new concept behind fetal genetics?

Paternal factor V Leiden and recurrent pregnancy loss: a new concept behind fetal genetics?

Thrombophilia in Assisted Reproductive Technology — Place and Needs of Thromboprophylaxis

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

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