Increased rates of thrombophilia in women with repeated IVF failures

Azem, Foad; Many, Ariel; Yovel, Israel; Amit, Ami; Lessing, Joseph B.; Kupferminc, Michael J.

doi:10.1093/humrep/deh069

Cited by 174 publications

(134 citation statements)

References 14 publications

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“…On the basis that previous studies have linked pregnancy complications, including miscarriages, with thrombophilias, [32][33][34][35] mainly APS, we examined the number of pregnancies and miscarriages before and after each DVT episode, comparing thrombophilic with non-thrombophilic patients. Before DVTs, female patients in the thrombophilic group had more miscarriages than those in the control group and a greater number of gestational complications, as reported in the literature.…”

Section: Discussionmentioning

confidence: 99%

Long-term clinical and ultrasonographic evaluation of thrombophilic patients with deep venous thrombosis

et al. 2014

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Objective: The purpose of this study was to evaluate the long term clinical and ultrasonographic outcomes of thrombophilic patients with deep venous thrombosis (DVT). Method: Cohort study, retrospective case-control with cross-sectional analysis. Thirty-nine thrombophilic patients and 25 non-thrombophilic patients were assessed 76.3 ± 45.8 months after diagnosis. Demographic and family data were collected, as well as data from clinical and therapeutic progress, and physical and ultrasound examinations of the limbs were performed. Groups were matched for age and gender and the variables studied were compared across groups. Results: Deep venous thrombosis was more frequent in women. The most common thrombophilias were antiphospholipid syndrome and factor V Leiden mutation. There was no difference between groups in terms of the number of pregnancies or miscarriages and the majority of women did not become pregnant after DVT. Non-spontaneous DVT prevailed. Proximal DVT and DVT of the left lower limb were more frequent, and the main risk factor was use of oral contraceptives. All patients were treated with anticoagulation. There was a higher frequency of pulmonary embolism in non-thrombophilic patients. Most patients considered themselves to have a "normal life" after DVT and reported wearing elastic stockings over at least 2 years. Seventy-one percent of patients had CEAP ≥ 3, with no difference between groups. Deep venous reflux was more frequent in thrombophilic patients. Conclusion: There were no significant differences between groups with respect to most of the variables studied, except for a higher frequency of pulmonary embolism in non-thrombophilic patients and greater frequency of deep venous reflux in thrombophilic patients.Keywords: deep vein thrombosis; thrombophilia; postthrombotic syndrome; pulmonary embolism; duplex scan. ResumoObjetivo: A proposta deste estudo foi realizar a avaliação clínica e ultrassonográfica em longo prazo de pacientes com diagnóstico de trombose venosa profunda (TVP), portadores de trombofilia. Método: estudo coorte, caso-controle retrospectivo com análise transversal. Foram estudados 39 pacientes portadores de trombofilia (PT) e 25 pacientes não portadores de trombofilia (PNT), dentro de um intervalo de tempo de 76,3 ± 45,8 meses, após o diagnóstico de TVP. Foram coletados dados demográficos e antecedentes familiares, assim como dados referentes à evolução clínica e terapêutica, tendo sido realizado também exame físico e ultrassonográfico dos membros envolvidos. Os grupos foram pareados quanto à idade e ao sexo, e as variáveis estudadas foram comparadas entre os grupos. Resultados: TVP foi mais frequente em mulheres. As trombofilias mais comumente encontradas foram a síndrome antifosfolípide e a mutação do fator V Leiden. Não houve diferença entre os grupos considerando-se o número de gestações e abortamentos, e a maioria das mulheres não engravidou após o episódio de TVP. A TVP não espontânea prevaleceu. A TVP proximal e em membro inferior esquerdo foi a mais frequente,...

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Section: Discussionmentioning

confidence: 99%

Long-term clinical and ultrasonographic evaluation of thrombophilic patients with deep venous thrombosis

et al. 2014

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“…Current literature has conflicting findings in relation to the role of thrombophilia and its impact on repeat IVF failure. While some studies have suggested that repeat IVF failure may be associated with an increased incidence of thrombophilia [37][38][39][40][41] others have negated such an association [42][43][44]. In a recent systemic review and metaanalysis, pooled data from patients in 8 case control studies showed an overall 3-fold increased risk of ART failure in association with factor V Leiden; while in the 3 cohort studies there was no difference in outcome between those with and those without factor V Leiden mutation [45].…”

Section: Discussionmentioning

confidence: 99%

Reduced protein C Global assay level in infertile women prior to IVF-ET treatment

Younis

Ben‐Ami

Izhaki

et al. 2013

J Assist Reprod Genet

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Purpose In the last few years more robust evidence is emerging to point out at an increased rate of prematurity and low birth weight in singleton pregnancies following ART. Whether this increased rate is related to ART practice or to infertility per se, is still an open question. Our aim in this study was to explore this question by evaluating Protein C (ProC) Global assay in infertile women before ART treatment. Methods A cohort of 95 unselected and consecutive infertile women, eligible for ART, was prospectively recruited for the study. The control group included 77 matched healthy fertile women with a history of spontaneous conceptions. Pro C Global assay was evaluated in both groups. A full thrombophilic work-up was performed in the study group.Results ProC Global assay level was found to be significantly lower in the study as compared to the control group, corresponding to 0.78 ± 0.16 and 0.88 ± 0.16, respectively (P <0.01). As well, abnormal ProC Global assay level of ≤0.8 was significantly higher in the study as compared to control group corresponding to 53 % and 29 %, respectively. ProC Global assay level was significantly lower in women within the study group found to have APCR, factor V Leiden and high factor VIII level, any thrombophilia or combined thrombophilia when compared to women without these thrombophilic risk factors. Conclusions Reduced ProC Global assay level is encountered in infertile women prior to ART treatment. This finding may suggest a unique anticoagulation Protein C pathway in infertile as compared to fertile women. Further studies are encouraged to explore this finding.

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“…Multiple studies support the belief that thrombophilias lead to recurrent implantation failure [4][5][6][7]. Specifically, a small study of patients with at least three failed IVF cycles found that factor V Leiden mutations and prothrombin G20210A mutations were more prevalent in the recurrent implantation failure group versus the fertile control group Clinical Trial Number (ClinicalTrials.gov): NCT01223092…”

Section: Introductionmentioning

confidence: 96%

“…[4]. Another study found the presence of any of the following inherited thrombophilias: prothrombin G20210A, factor V Leiden, methylenetetrahydrofolate reductase (MTHFR), protein S deficiency, protein C deficiency, or antithrombin III deficiency, was more common in recurrent implantation failure patients, especially if they had unexplained infertility, when compared with fertile controls [5]. A similar study testing the same set of inherited thrombophilias showed combinations of two or more of these thrombophilic mutations that were found more often in the recurrent implantation failure group when compared with controls of patients succeeding with their first IVF attempt or fertile patients that achieved pregnancy by natural conception [6].…”

Section: Introductionmentioning

confidence: 99%

Multiple thrombophilic single nucleotide polymorphisms lack a significant effect on outcomes in fresh IVF cycles: an analysis of 1717 patients

Patounakis

Bergh

Forman

et al. 2015

J Assist Reprod Genet

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Purpose The aim of the study is to determine if thrombophilic single nucleotide polymorphisms (SNPs) affect outcomes in fresh in vitro fertilization (IVF) cycles in a large general infertility population. Methods A prospective cohort analysis was performed at a university-affiliated private IVF center of female patients undergoing fresh non-donor IVF cycles. The effect of the following thrombophilic SNPs on IVF outcomes were explored: factor V (Leiden and H1299R), prothrombin (G20210A), factor XIII (V34L), β-fibrinogen (-455G→A), plasminogen activator inhibitor-1 (4G/5G), human platelet antigen-1 (a/b9L33P), and methylenetetrahydrofolate reductase (C677T and A1298C). The main outcome measures included positive pregnancy test, clinical pregnancy, embryo implantation, live birth, and pregnancy loss. Results Patients (1717) were enrolled in the study, and a total of 4169 embryos were transferred. There were no statistically significant differences in positive pregnancy test, clinical pregnancy, embryo implantation, live birth, or pregnancy loss in the analysis of 1717 patients attempting their first cycle of IVF. Receiver operator characteristics and logistic regression analyses showed that outcomes cannot be predicted by the cumulative number of thrombophilic mutations present in the patient. Conclusions Individual and cumulative thrombophilic SNPs do not affect IVF outcomes. Therefore, initial screening for these SNPs is not indicated.

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Increased rates of thrombophilia in women with repeated IVF failures

Abstract: These data suggest that inherited thrombophilia may play a role in the aetiology of repeated IVF failures, particularly in the subgroup with unexplained fertility.

Cited by 174 publications

References 14 publications

Long-term clinical and ultrasonographic evaluation of thrombophilic patients with deep venous thrombosis

Long-term clinical and ultrasonographic evaluation of thrombophilic patients with deep venous thrombosis

Reduced protein C Global assay level in infertile women prior to IVF-ET treatment

Multiple thrombophilic single nucleotide polymorphisms lack a significant effect on outcomes in fresh IVF cycles: an analysis of 1717 patients

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