Risk of thrombophilia in carriers of thrombophilic genetic factors in unsuccessful assisted reproduction

The aim of this study was to evaluate an association of carrier status of common inherited thrombophilic genetic mutations and implantation failure after assisted reproduction (ART): IVF and ICSI. Sixty seven women with failure of embryo implantation and ninety six controls--women without obstetric complication were investigated for carriage of factor V Leiden (FVL), G20210A prothrombin gene mutation, genetic variant C677T in methylentetrahydrofolate reductase gene (MTHFR) and polymorphism A2 in platelet glycoprotein IIb/IIIa (GIPr IIb/IIIa). A significantly higher prevalence of polymorphism A2 in GIPr IIb/IIIa was found in women with implantation failure in ART compared to controls (respectively 26.1% and 12.5%; OR: 2.571, 95% CI: 1.066-6.258, p = 0.033). A higher but not significant prevalence of G20210A prothrombin gene mutation carriage was found inpatients compared to controls (respectively 5.8% and 3.13%, OR: 1.968, 95% CI 0.356-11.539). The carriage of FVL was a little but not significantly higher in controls. The carriage of genetic variant C677T in MTHFR was the same in both groups. These data suggest that polymorphism A2 in GIPr IIb/IIIa and G20210A prothrombin gene mutation could be play a role in the etiology of IVF failures and the carriers of GIPr IIb/IIIa A1/A2 and G20210A prothrombin gene mutation are at higher risk of implantation failure and not successful ART outcome. The carriage of these two genetic defects should be investigated in women undergoing IVF and the antithrombotic or anticoagulant prophylaxis should be indicated for carriers of these two factors.     

Genetic thrombophilias and preeclampsia: a meta-analysis

OBJECTIVE: To assess the relationship between the factor V Leiden (1691 G-A) single nucleotide polymorphism (SNP), the methylene tetrahydrofolate reductase (MTHFR) 677 C-T SNP, and the prothrombin 20210 G-A SNP and the risk of preeclampsia, by conducting a meta-analysis of all case-control studies with data on these polymorphisms and the risk of preeclampsia. DATA SOURCES: MEDLINE (1966 to November 2002), EMBASE (1980 to November 2002). Search terms included "preeclampsia," "thrombophilia," "factor V Leiden," "protein C," "MTHFR," "methylenetetrahydrofolate reductase," "homocysteine," and "prothrombin gene 20210."METHODS OF STUDY SELECTION: Case-control studies of genetic thrombophilias and preeclampsia were included. TABULATION, INTEGRATION, AND RESULTS: We identified 349 titles and reviewed 47 articles for inclusion and exclusion criteria. Thirty-one studies with 7,522 patients were included in the meta-analysis. Data from patients characterized as having severe preeclampsia were extracted and analyzed separately. The pooled odds ratio (OR) for the association of factor V Leiden and all cases of preeclampsia was 1.81 (95% confidence interval [CI] 1.14-2.87) and 2.24 (95% CI 1.28-3.94) for cases of severe preeclampsia. The pooled OR for the MTHFR 677 TT genotype and all preeclampsia was 1.01 (95% CI 0.79-1.29) and 1.38 (95% CI 0.93-2.06) for severe preeclampsia. The OR for the prothrombin 20210 polymorphism and all preeclampsia was 1.37 (95% CI 0.72-2.57) and 1.98 (.94-4.17) for severe preeclampsia. CONCLUSION: This meta-analysis suggests that the factor V Leiden SNP is associated with an increased risk of preeclampsia. Further studies are warranted to determine whether subgroups of high-risk women should be screened for this mutation.     

Evaluation of factor V Leiden, prothrombin and methylenetetrahydrofolate reductase gene mutations in patients with severe pregnancy complications in northern Finland

BACKGROUND: Thrombosis in placenta may lead to severe pregnancy complications. Most important inherited thrombophilias are factor V Leiden mutation, prothrombin mutation, and methylenetetrahydrofolate reductase mutation. The aim of our research was to evaluate the prevalence of inherited thrombophilias in severe pregnancy complications and in normal pregnancies. MATERIAL AND METHODS: The study subjects with severe preeclampsia, intrauterine growth restriction, placental abruption or fetal death were collected during the period 1999-2004 from Oulu University Hospital. We also collected during the same period voluntary parturients with normal pregnancy outcome as the control group. FVL, FII, and MTHFR gene mutations of the patients and controls were analyzed. RESULTS: We found a significant difference in the prevalence of FVL mutation between the groups. There were 9.5% FVL mutations in the study group compared to 1.8% in the control group; the observed difference between prevalences was 7.7% (95% CI 2.0-13.4). No statistical difference was found in the FII or MTHFR mutations between the groups. All FV and FII mutations were heterozygous and all the MTHFR mutations homozygous. CONCLUSION: Women with thrombophilia have a risk for severe pregnancy complications. Randomized controlled trials are needed to assess the influence of low-molecular-weight heparin in pregnant women with thrombophilia.     

Primary habitual abortions are associated with high frequency of factor V Leiden mutation

OBJECTIVE: To analyze the prevalence of the mutation G1691A in factor V gene (Leiden mutation), of mutation C677T in the methylenetetrahydrofolate reductase (MTHFR) gene, and of polymorphism in G20210A in the prothrombin gene in women with recurrent abortions; further, to identify a subgroup at higher risk of being carriers of these mutations. DESIGN: Prospective case control evaluation. SETTING: University clinic. PATIENT(S): Eighty-four women with 3 or more consecutive miscarriages were compared with 69 controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Polymerase chain reactions were performed to identify the mutations G1691A in factor V and C677T in MTHFR genes and the polymorphism G20210A in the prothrombin gene. RESULT(S): In women with primary habitual abortions, 27.8% carried the Leiden mutation. No difference was observed in the prevalence of mutation C677T in the MTHFR gene or in polymorphism G20210A in the prothrombin gene. CONCLUSION(S): The Leiden mutation may play a considerable role for women having primary recurrent abortions.     

Mutations in the factor V,prothrombin and MTHFR genes are not risk factors for recurrent fetal loss

Objective: Recurrent fetal loss, defined as the occurrence of three or more consecutive spontaneous abortions regardless of previous live birth, is a condition that affects about 2% of all reproductive-aged women. The role of gene mutations in recurrent pregnancy loss is not fully understood. The present research examined the relationship between factor V Leiden, factor V HR2, prothrombin G20210A and MTHFR and recurrent fetal loss in a case-control study. Methods: Women aged 22-45 with a history of three or more fetal losses, being seen at a perinatal medicine clinic in New Jersey or Georgia, were eligible as cases. Overall, the study consisted of 60 women with three or more fetal losses and 92 women with at least one successful pregnancy. Results: Factor V HR2 and MTHFR were not related to recurrent fetal loss. The prothrombin G20210A mutation appeared to confer an elevation in risk but the association was based upon small numbers and was not statistically significant (OR 4.8, 95% CI 0.50-47.2). Cases were 90% less likely to have the factor V Leiden mutation than controls (OR 0.10, 95% CI 0.01-0.81). Conclusions: Our study did not demonstrate that women who are carriers of the factor V, prothrombin, or MTHFR mutations are at higher risk of recurrent fetal loss than women without these mutations. In regards to factor V Leiden, the prevalence in our cases (1.7%) was not statistically different from the known population prevalence of 5%. However, the high prevalence in our controls (14%) was unusual. Factor V Leiden may protect against bleeding in early pregnancy.     

Methylenetetrahydrofolate reductase 677 C-->T polymorphism and plasma folate in relation to pre-eclampsia risk among Peruvian women.

OBJECTIVES: Pre-eclampsia is an important cause of maternal and fetal morbidity and mortality worldwide. Hyperhomocyst(e)inemia in pregnancy is associated with an increased risk of pre-eclampsia in most studies. Nutritional and genetic factors regulate homocyst(e)ine levels. A missense mutation 677 C-->T in the gene for methylenetetrahydrofolate reductase (MTHFR) has been associated with an increased pre-eclampsia risk in some, although not most, previously studied populations. METHODS: To further understand the role of this polymorphism in the etiology of pre-eclampsia, we genotyped a total of 125 pre-eclamptics and 179 normotensive pregnant Peruvian women. RESULTS: The wild-type allele frequency among cases and controls was 54% and 58%, respectively. Twenty percent of cases and 17% of controls were homozygous for the 677 C-->T MTHFR genotype (T/T). After adjustment for confounding by covariates including maternal age, nulliparity, pre-pregnancy body mass index and use of prenatal vitamins, women homozygous for the 677 C-->T MTHFR genotype (T/T) experienced a modest, statistically non-significant increased risk of pre-eclampsia (adjusted OR 1.6, 95% CI 0.7, 3.8). Maternal folate deficiency was associated with a statistically non-significant doubling in risk of pre-eclampsia in this population (adjusted OR 2.0, 95% CI 0.9, 4.3). CONCLUSIONS: There was no evidence to suggest that pre-eclampsia risk is positively associated with the T/T genotype overall, or in the context of folate deficiency.     

Thrombophilia and the risk for venous thromboembolism during pregnancy, delivery, and puerperium

The main inherited thrombophilias (antithrombin deficiency, protein C and S deficiency, FVL, the prothrombin gene variant, and MTHFR C677T homozygotes) have a combined prevalence in Western European populations of 15% to 20%. One or more of these inherited thrombophilias is usually found in approximately 50% of women who have a personal history of VTE. Obstetricians must therefore be aware of the interaction between thrombophilias and the procoagulant state of pregnancy and should have an understanding of additional risk factors that may act synergistically with thrombophilias to induce VTE. Such knowledge combined with the appropriate use of thromboprophylaxis and treatment in women who have objectively confirmed VTE continue to improve maternal and perinatal outcomes.     

Frequency of selected thrombophilias in women with placental abruption

OBJECTIVE: There is a growing view that inherited or acquired thrombophilia may predispose a woman towards an adverse pregnancy outcome. The aim of this study was to investigate whether risk factors for placental abruption because of such thrombophilias (such as carriership of factor V Leiden (FVL), prothrombin G20210A gene mutation and homozygous MTHFR C677T) might be used as a predictor for placental abruption. METHODS: A retrospective case-control study conducted at the University Hospital, Palacky University, Olomouc, Czech Republic. One hundred and eighty women with placental abruption out of 20,175 deliveries (0.79%) were compared to 196 unselected gravidae. A detailed medical history was taken with special reference to factors related to hypercoagulation and blood was drawn for polymerase chain reaction analysis. The prevalence of FVL, prothrombin G20210A and MTHFR C677T was related to placental abruption. RESULTS: The heterozygous form of FVL was present in 20of 142 cases (14.1%) in the placental abruption group, compared to ten of 196 (5.1%) in the control group (odds ratio 3.0, 95% confidence interval 1.4-6.7). CONCLUSIONS: We found that factor V Leiden is a significant risk factor for placental abruption.     

Single inherited thrombophilias and adverse pregnancy outcomes

INTRODUCTION: Inherited thrombophilia is believed to be a multiple gene disease with more than one defect. We aimed to determine the association between single thrombophilic patterns and a variety of pregnancy diseases. METHODS: 284 pregnant women were recruited for the present study and were divided in two groups: A group (176 controls) and B group (108 cases). Patients belonging to the B group had one of the following: severe pre-eclampsia, hemolysis, hepatic enzymes increase, hypertension and low platelet count (HELLP) syndrome, gestational hypertension, fetal growth restriction, intrauterine death, abruptio placentae and disseminated intravascular coagulopathy. To detect methylenetetrahydrofolate reductase (MTHFR) A1298C, MTHFR C677T, factor V Leiden, PAI-1, mutant prothrombin G20210A, an inverse hybridization technology was used. Plasma homocysteine, antithrombin (AT) III and protein S were determined. A modified functional activated protein C resistance was detected. RESULTS: MTHFR C677T and hyperhomocysteinemia were more prevalent than other thrombophilias. Deficiency in AT III was significantly linked with pre-eclampsia (relative risk 0.88; 95% CI 0.83-0.94). Activated protein C resistance (APCR) was significantly related to the abruptio placentae (relative risk 0.71; 95% CI 0.61-0.82). COMMENTS: Apart from the linkage between AT III deficiency and the occurrence of pre-eclampsia, and apart from the increased risk of abruptio placentae in pregnant women with altered APCR, we obtained findings in contrast with some of the published literature. In our case series, no association of pre-eclampsia with factor V Leiden or with prothrombin gene mutation was found.     

Inherited thrombophilias are not increased in "idiopathic" small-for-gestational-age pregnancies

OBJECTIVE: The purpose of this study was to determine (1). whether the inherited thrombophilias (the factor V Leiden and prothrombin gene mutations and the methylenetetrahydrofolate reductase [C677T] polymorphism) are increased in women with "idiopathic" (normotensive) small-for-gestational-age pregnancies and/or in their babies and (2). whether fetal carriage of a thrombophilia is associated with abnormal umbilical Doppler studies. STUDY DESIGN: This was a case-controlled study of normotensive women who were delivered of a singleton small-for-gestational-age baby (birth weight, <10th percentile adjusted for sex) with no clinical evidence of chromosomal or congenital abnormality. Control subjects were healthy women who were delivered of appropriate-for-gestational-age babies. RESULTS: One hundred forty-five women with small-for-gestational-age pregnancies and 290 control subjects were recruited. Small-for-gestational-age babies were born at an earlier gestational age (38 +/- 3.0 weeks) and with a lower birth weight (2373 +/- 521 g) than control babies (39.7 +/- 1.3 weeks and 3606 +/- 423 g, P <.01). There were no differences in the rates of factor V Leiden (2.8% vs 3.8%; relative risk, 0.79; 95% CI, 0.34-1.85), prothrombin gene mutation (2.8% vs 3.1%; relative risk, 0.92; 95% CI, 0.40-2.09), and methylenetetrahydrofolate reductase C677T polymorphism (13% vs 9%; relative risk, 1.27; 95% CI, 0.87-1.84) between mothers with small-for-gestational-age babies and control subjects, respectively. Inherited thrombophilias were not increased in small-for-gestational-age babies compared with control babies. Of small-for-gestational-age babies with abnormal umbilical artery Doppler studies (n = 25), 21% had a thrombophilia compared with 11% with normal umbilical artery Doppler studies (n = 68; relative risk, 1.75; 95% CI, 0.81-3.81). CONCLUSION: The rates of these inherited thrombophilias are not increased in normotensive women with small-for-gestational-age pregnancies. Further studies are required to determine whether thrombophilias are increased in small-for-gestational-age babies with abnormal umbilical Doppler study results.     

Preconception counseling for women with thrombophilia

Inherited thrombophilias are a heterogeneous group of coagulation disorders that predispose individuals to thromboembolic events. This group of conditions is the major risk factor for thromboembolism during pregnancy and the puerperium. In addition, thrombophilias have been associated with several adverse obstetric events, including pregnancy loss, preeclampsia, placental abruption, and intrauterine growth restriction. An increased risk for these obstetric complications has prompted many authorities to recommend screening and treating pregnant women for thrombophilias. Optimal obstetric management, however, is controversial as thrombophilias are common and many affected individuals are asymptomatic. Indeed, pregnancy outcome in most women with thrombophilias is normal. The most commonly identified inherited thrombophilias are the factor V Leiden and prothrombin G20210A gene mutations. More rare thrombophilias include protein C and S deficiencies, antithrombin III deficiency. Although relatively common, the association between hyperhomocysteinemia and associated mutations (such as the C677 T methylenetetrahydro-folate reductase) and obstetric complications is controversial.     

Plasminogen activator inhibitor type 1 activity in women with unexplained very early recurrent pregnancy loss

The aim of the study was to assess the independent role of polymorphism 4G/5G (PL 4G/5G)--genotype 4G/4G in plasminogen activator inhibitor type 1 (PAI-1) in the development of very early recurrent pregnancy loss (RPL)--before 10 weeks of gestation of pregnancy. The polymorphism 4G/5G as well as Factor V Leiden (FVL), prothrombin (FII) gene mutation 20210 G > A and polymorphism 677 C > T in methylentetrahydrofolat reductase (MTHFR) gene was investigated in 110 women with recurrent pregnancy loss before 10 weeks of gestation and in 97 healthy women with at least one uncomplicated full-term pregnancy. A significant prevalence of PL 4G/5G in women with RPL was found in comparison to prevalence of the polymorphism in controls (41.8% versus 26.8% respectively in patients and controls, OR: 1.96, 95% CI: 1.05 3.69, p = 0.034). The difference in prevalence of the polymorphism remains still significant after exclusion of patients and control carriers of FVL, FII 202010 G > A and 677 C > T in MTHFR (the prevalence of PL 4G/5G alone was 44.1% and 24% respectively in patients and controls, OR: 2,5, 95% CI: 1,15 5, 45, p = 0.018). The found association of PL 4G/5G in PAI-1 with early recurrent pregnancy loss encourage an extension of the list of inherited thrombophilic factors with this one. This result also could have had an implication for adjustment of further prophylactic low-molecular weight heparin implication in further pregnancy to prevent a poor foetal outcome.     

亚甲基四氢叶酸还原酶、凝血因子V和凝血酶原基因多态性与原因不明复发性早期流产的关系

目的探讨亚甲基四氢叶酸还原酶（MTHFR）基因C677T突变、凝血因子V（FV）基因G1691A突变和凝血酶原（PT）基因G20210A突变与原因不明复发性早期流产（URESA）的关系。方法应用聚合酶链反应．限制性片段长度多态性（PCR-RFLP）技术分析112例URESA患者（病例组）和100例健康妇女（对照组）MTHFR、FV和PT3种基因多态性。结果（1）MTHFR基因的T／T基因型和T等位基因频率,病例组[分别为38．4％（43／112）和59．8％（134／224）]高于对照组[分别为18．0％（18／100）和43．0％（86／200）],两组分别比较,差异均有统计学意义（P＜0．01）。病例组与对照组比较,T／T基因型者发生URESA的相对风险增加（OR=2．8390,95％CI为1．5022～5．3661）。（2）病例组和对照组妇女Fv基因和PT基因均为G／G基因型（即正常带型）。结论MTHFR基因C677T位点多态性与URESA发病密切相关,T／T基因型是其发病的危险因素。FV和PT基因的突变率在中国妇女人群中极低。     

Hypercoagulable state mutation analysis in white patients with early first-trimester recurrent pregnancy loss

Objective: Antiphospholipid antibodies (APA) and other coagulation abnormalities have been associated with an increased risk of venous, arterial, and placental thrombosis and recurrent pregnancy loss (RPL). Factor V Leiden (a point mutation [1691G→A] in the factor V gene), the prothrombin 20210G→A mutation, and homozygosity for a common polymorphism in the methylene tetrahydrofolate reductase (MTHFR) gene (677C→T) have been associated with arterial and venous thrombosis and arterial occlusive disease. We explored an association between these markers of thrombophilic states and RPL.

Design: Prospective case-control evaluation.

Setting: University-associated private practice.

Patient(s): Fifty nonpregnant women with three or more pregnancy losses and 50 healthy, nonpregnant controls.

Intervention(s): None.

Main Outcome Measure(s): Anticardiolipin and antiphosphatidylserine antibodies were detected in serum by ELISA. Polymerase chain reaction was performed to identify the factor V Leiden (1691G→A) mutation, the thermobile MTHFR (677C→T) mutation, and the prothrombin 20210G→A mutation.

Result(s): The following were identified by restriction fragment-linked polymorphism analyses: 1 (2%) factor V Leiden heterozygosity; 1 (2%) prothrombin 20210G→A heterozygosity; and 4 (8%) thermolabile MTHFR homozygosity. None of these mutation frequencies in women with RPL were statistically significantly different from controls.

Conclusion(s): These data suggest that factor V Leiden, thermolabile MTHFR (677C→T), and prothrombin 20210G→A are not found at an increased frequency in women with a history of early RPL.     

Frequency of factor V, prothrombin and methylenetetrahydrofolate reductase gene variants in preeclampsia

BACKGROUND: The association between thrombophilic variants (Leiden mutation of the factor V gene, G20210A mutation of the prothrombin gene and C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene) with preeclampsia was investigated in a north-eastern Italian population. METHODS: Fifty-eight preeclamptic (PE) women and 74 normal pregnancies were evaluated. Genotypes were determined by polymerase chain reaction. RESULTS: The frequency of heterozygous carriers of the factor V Leiden was similar between PE women (5.2%) compared to the control subjects (4.1%; p 0.76). Also the frequencies of G20210A and C677T mutations were similar between PE and control subjects. CONCLUSIONS: In this population, we found no difference in the prevalence of genetic risk factors for thrombosis in women with preeclampsia compared with control subjects.     

Inherited thrombophilia screening in Greek women with recurrent fetal loss

OBJECTIVE: The present study was designed to determine the prevalence of factor V Leiden (FVL), prothrombin gene G20210A (PTG) and methylenetetrahydrofolate reductase (MTHFR C677T) mutations in women from South-Western Greece with recurrent fetal loss (RFL) and negative personal thromboembolic history. MATERIALS AND METHODS: 212 women with RFL and 181 women with at least two pregnancies with normal outcome and no history of pregnancy loss were investigated for the commonest thrombophilic mutations (FVL, PTG, MTHFR C677T). Comparisons between groups were performed by Pearson's chi-square test and odd ratios were calculated. RESULTS: An abnormal genotype was detected in 49 women of the study group (23.1%) and in 41 women of the control group (22.6%). CONCLUSION: Inherited thrombophilia screening is not indicated as an initial approach in Greek women with RFL and negative personal thromboembolic history.     

Screening for pre-eclampsia in a low-risk population at 24 weeks: uterine artery Doppler flow velocimetry and genetic variants of factor V, prothrombin and methylenetetrahydrofolate reductase

AIM: Pre-eclampsia is one of the major causes of maternal and fetal morbidity and mortality. The aim of this study was to evaluate the clinical usefulness of screening of genetic thrombophilic mutations and uterine artery Doppler flow velocimetry at 24 weeks of gestation in the prediction of pre-eclampsia in low risk pregnant women. METHODS: We performed the genetic analysis for Leiden mutation of factor V gene (FV), G20210A mutation of the prothrombin gene (PT) and C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene in 103 women that had already attended routine ultrasonography scanner at 24 weeks at our Department. RESULTS: The frequency of heterozygous carriers of the Leiden FV was 17.4% in women with pre-eclampsia and abnormal artery Doppler flow velocimetry compared with 3.12% in patients with normal pregnancies. This difference was statistically significant (P<0.05). The frequency of mutation G20210A of PT gene was 1.5% vs 4.3% between women with normal pregnancies and with pre-eclampsia. This difference is not statistically significant. The frequency of homozygous patients for the C677T mutation of MTHFR gene among patients with pre-eclampsia was 21.7% and in the control group was 10.3%, but this difference is not statistically significant. No thrombophilic genes variants were found in women with pre-eclampsia and normal uterine artery Doppler flow velocimetry. CONCLUSION: We demonstrated the important association between FV Leiden mutation, abnormal uterine artery Doppler flow velocimetry at 24 weeks and pre-eclampsia in our low-risk population.     

How strong is the association between maternal thrombophilia and adverse pregnancy outcome? A systematic review.

OBJECTIVE: To determine whether inherited and acquired thrombophilias are associated with adverse obstetric complications. STUDY DESIGN: A systematic review; studies where women with adverse obstetric complications were tested for one or more acquired and inherited thrombophilias were included. MAIN OUTCOME MEASURES: Prevalence of thrombophilia in women with severe pre-eclampsia/eclampsia, severe placental abruption, intrauterine growth restriction or unexplained stillbirth. RESULTS: Compared with controls, placental abruption was more often associated with homozygous and heterozygous factor V Leiden mutation, heterozygous G20210A prothrombin gene mutation, homocysteinaemia, activated protein C resistance or anticardiolipin IgG antibodies. Women with pre-eclampsia/eclampsia were more likely to have heterozygous factor V Leiden mutation, heterozygous G20210A prothrombin gene mutation, homozygous MTHFR C677T mutation, protein C deficiency, protein S deficiency or activated protein C resistance compared with controls. Unexplained stillbirth, when compared with controls, was more often associated with heterozygous factor V Leiden mutation, protein S deficiency, activated protein C resistance, anticardiolipin IgG antibodies or lupus anticoagulant. Women with intrauterine growth restriction had a higher prevalence of heterozygous G20210A prothrombin gene mutation, homozygous MTHFR C677T gene mutation, protein S deficiency or anticardiolipin IgG antibodies than controls. There was wide heterogeneity in the prevalence of thrombophilia between the studies. CONCLUSIONS: Women with adverse pregnancy outcome are more likely to have a positive thrombophilia screen but studies published so far are too small to adequately assess the true size of this association. Screening for thrombophilia should not become standard practice until clear evidence emerges that thromboprophylaxis during pregnancy improves perinatal outcome. Further research into the link between the observed association, causality and heterogeneity is required.     

Analyzes of three common thrombophilic gene mutations in German women with recurrent abortions

BACKGROUND: Several etiological factors have been proposed as a cause for recurrent fetal abortions. Changes in blood coagulation during pregnancy may play an important role in the occurrence of recurrent abortions (RA). METHODS: The aim of this study was to investigate the prevalence of factor V Leiden, factor II prothrombin, and methylenetetrahydrofolate reductase (MTHFR) mutations in women with recurrent abortions (> or =2 abortions) in the German population. The mean number of abortions was 3 (range 2-8). RESULTS: Frequencies of the factor V Leiden mutation and the prothrombin G20210A mutation were equally high in the patient group compared with our control group (for factor V Leiden: 11/101 vs. 9/122; p-value: 0.348; for prothrombin G20210A: 2/101 vs. 3/122; p-value: 0.81). Moreover, in both the patient and control groups, 15 of the women were homozygous for the MTHFR C677T allele (15/101 vs. 15/122; p-value: 0.635). The occurrence of FV Leiden, FII and MTHFR mutations was not significantly increased in the patient group compared with our control group. CONCLUSION: The results of the present study reveal no relationship between these common three thrombophilic mutations and recurrent abortions for the German population, and further studies are essentially recommended on whether a thrombophilia evaluation should be performed in patients with recurrent abortions.     

Carriers of thrombophilic factor among women with preeclampsia (preliminary report)

The aim of this study was to determine whether inherited thrombophilia increases the risk of mild preeclampsia. Twenty five women who developed mild preeclampsia and 49 controls--women with previous uneventful pregnancies, were tested for factor V Leiden, C677T gene variant of methylenetetrahydrofolate reductase (MTHFR), polymorphism 4G/5G in plasminogen activator inhibitor 1 (PAI 1), polymorphism A1/A2 in platelet glycoprotein IIb/Illa (GIPrllb/llla A1/A2). The higher but not significant prevalence of C677T gene variant and polymorphism A1/A2 in women with preeclampsia compared with controls was found: 32% and 12.2%, respectively for cases and controls for both factors, with OR: 3.37 (95% CI 0.883-13.2), p > 0.05. The values of OR and RR for these two thrombophilic factors show that platelet integrin polymorphisms (GIPrIIb/llla A1/A2) and C677T gene variant might be have an important role for development of preeclampsia. The carriage of FVL was with a very small prevalence in women with preeclampsia (8%) as compared to controls (6,1%), with OR: 1.333 (CI 95% 0.143-10.864), p > 0.05. The similar results were found for carriage of polymorphism 4G/5G in PAI-1: gene, respectively 24% u 18.4% in women with preeclampsia as compared to controls, OR: 1.404 (95% CI 0.374-5.14), p > 0.05. The results are not significant, because of the small group of selected patients. Larger case-control study should be executed for the evaluation of impact of inherited thrombophilic factors in the development of mild preeclampsia.