Thrombophilias and recurrent pregnancy loss: a critical appraisal of the literature

Krabbendam, Ineke; Franx, Arie; Bots, Michiel L.; Fijnheer, Rob; Bruinse, Hein W.

doi:10.1016/j.ejogrb.2004.07.019

Cited by 52 publications

(40 citation statements)

References 107 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The thrombophilic factor V Leiden (FVL) G1691A mutation has been found to be significantly associated with recurrent pregnancy loss (RPL, R3 consecutive pregnancy losses <20 weeks gestation) (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Using meta-analysis, Dudding and Attia (10) reported that FVL was associated with late fetal loss.…”

mentioning

confidence: 97%

“…The relationship between pregnancy loss and thrombophilia is a much-debated topic with well entrenched expert opinion on both sides and many studies reporting significant associations with pregnancy loss (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) and others no associations (13)(14)(15)(16)(17). The thrombophilic factor V Leiden (FVL) G1691A mutation has been found to be significantly associated with recurrent pregnancy loss (RPL, R3 consecutive pregnancy losses <20 weeks gestation) (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Factor V Leiden mutation: a treatable etiology for sporadic and recurrent pregnancy loss

Glueck

Gogenini

Munjal

et al. 2008

Fertility and Sterility

View full text Add to dashboard Cite

mentioning

confidence: 97%

mentioning

confidence: 99%

Factor V Leiden mutation: a treatable etiology for sporadic and recurrent pregnancy loss

Glueck

Gogenini

Munjal

et al. 2008

Fertility and Sterility

View full text Add to dashboard Cite

“…Controlled studies conducted in the European Caucasian women with a history of unexplained RM failed to demonstrate an association between these two polymorphisms and 1st trimester RM [19,39]. The meta-analyses that have adopted this methodology has also revealed a higher ratio of FLV related losses after the 14th week (OR 2.28) compared with 1st trimester RM (OR 1.6-1.91) [20,26,27,40].…”

Section: In a Controlledmentioning

confidence: 99%

Factor V Leiden and prothrombin G20210A in Portuguese women with recurrent miscarriage: is it worthwhile to investigate?

Serrano

Lima

Lopes

et al. 2011

Arch Gynecol Obstet

View full text Add to dashboard Cite

Objective To compare the prevalence of factor V Leiden (FVL) and prothrombin (PT) G20210A mutations in Portuguese women with unexplained recurrent miscarriage (RM) and a control group of parous women. Materials and methods FVL and PT G20210A analysis were carried out in 100 women with three or more consecutive miscarriages and 100 controls with no history of pregnancy losses. Secondary analysis was made regarding gestational age at miscarriage (embryonic and fetal losses). Results Overall, the prevalence of FVL and PT G20210A was similar in women with RM (5 and 3%) compared with controls (5 and 1%) OR 1.36 (CI 95% 0.45-4.08). In RM embryonic subgroup, PT G20210A was observed in 1.3% of women and FVL prevalence (2.6%) was inclusively lesser than that of controls. Both polymorphisms were more prevalent in women with fetal losses than in controls, although statistical significance was not reached due to the small size of the [10 weeks' subgroup. Conclusion These data indicate that neither FVL nor PT G20210A is associated with RM prior to 10 weeks of gestation. Therefore, its screening is not indicated as an initial approach in Portuguese women with embryonic RM and negative personal thromboembolic history.

show abstract

“…Five reviews [38][39][40][41][42] provided historical perspective on F5/ F2 testing and RPL, and seven metaanalyses addressed casecontrol [43][44][45][46][47][48] and cohort 49 studies. No metaanalysis included recent studies, matched our inclusion criteria, and adequately addressed our key questions ( Table 1).…”

Section: Clinical Validitymentioning

confidence: 99%

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

View full text Add to dashboard Cite

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...

show abstract

Thrombophilias and recurrent pregnancy loss: a critical appraisal of the literature

Cited by 52 publications

References 107 publications

Factor V Leiden mutation: a treatable etiology for sporadic and recurrent pregnancy loss

Factor V Leiden mutation: a treatable etiology for sporadic and recurrent pregnancy loss

Factor V Leiden and prothrombin G20210A in Portuguese women with recurrent miscarriage: is it worthwhile to investigate?

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

Contact Info

Product

Resources

About