The M2 haplotype in the ANXA5 gene is an independent risk factor for idiopathic small-for-gestational age newborns.

Hereditary thrombophilias can impair vascular placental functions and predispose to the birth of small-for-gestational age (SGA) babies. The placental anticoagulant protein annexin A5 (ANXA5) may contribute to this process. A functional haplotype (M2) within the ANXA5 gene is associated with fetal loss and venous thrombosis. This study investigated the prevalence of the M2 haplotype in a group of women with idiopathic SGA newborn babies. Seventy-eight women with at least one previous unexplained SGA birth and 195 controls all from Southern Italy were investigated. Hereditary thrombophilia was found in 13 (16.5%) cases and 21 (11%) controls (P < 0.05.). The M2 haplotype was found in 29% of cases (n = 23) and 15% of controls [n = 30; P = 0.001; OR = 2.3, 95% CI (1.17-4.48)]. Within the case group, 82.5% of the M2 haplotype carriers gave birth to babies with a birthweight below the 3rd percentile [P = 0.01; OR = 2.4, 95% CI (1.26-4.73)]. A logistic regression, corrected for age, parity and gravity showed that the M2 haplotype was independently associated with the delivery of an SGA new born [P = 0.029; OR = 2.6, 95% CI (1.1-6.0)]. In conclusion, the M2 haplotype of the ANXA5 gene confers a risk of delivering SGA babies.

Subclinical atherosclerosis and genetic risk markers in healthy offspring of patients with premature myocardial infarction.

AIM: Healthy young subjects with parental history of premature myocardial infarction (PHPMI) might constitute a privileged population for the study of genetic risk markers (GRM) for atherosclerosis. Aim of this study was to evaluate which, if any, GRM atherosclerosis-associated in previous studies has increased prevalence in a selected population. METHODS: Twenty-four healthy young subjects (12 males and 12 females; mean age 18.0±8.0 years) with PHPMI and 24 age- (±1 year), sex-matched healthy subjects without PHPMI were enrolled in the study. They underwent: 1) fasting measurement of lipid profile, resting blood pressure and body mass index; 2) high resolution B-mode ultrasonographic evaluation of common carotid artery intima-media thickness (IMT); 3) evaluation of Single Nucleotide Polymorphisms (SNPs) for six candidate genes associated with preclinical atherosclerosis. RESULTS: Compared to controls, subjects with PHPMI had increased IMT of common carotid arteries (mean of combined sites: 0.535±0.171 mm versus 0.432± 0.133 mm in controls, P=0.017). Offspring of coronary patients showed an increased prevalence of the unfavourable chemochine (C-X-C motif) ligand 12 (CXCL12) SNP risk genotype (P=0.047). CONCLUSION: In healthy young subjects with PHPMI there is an increased prevalence of the unfavorable CXCL12 SNP risk genotype.

[Anticoagulant prophylaxis in women affected by thrombophilia and previous obstetric complications]. / Profilassi antitrombotica in donne con diagnosi di trombofilia e precedenti complicanze ostetriche.

Pregnancy is a condition of excessive clotting due to a decrease of some coagulation factors and a reduction of anticoagulant proteins, such as protein S. It is known that the causes of congenital or acquired thrombophilia may be associated with an increased risk of venous thromboembolism during pregnancy and/or obstetric complications, such early or late fetal loss, intrauterine fetal deaths, pre-eclampsia, fetal growth restriction. During pregnancy the use of a prophylaxis with antithrombotic drugs is considered at present a promising opportunity to significantly reduce the prevalence of thromboembolic complications, improving maternal and fetal outcomes. This article is a review to most recent evidence of pregnant anticoagulant prophylaxis in women with previous thromboembolic events.

The JAK2 V617F mutation frequently occurs in patients with portal and mesenteric venous thrombosis.

BACKGROUND: Myeloproliferative disorders (MPDs) represent a risk factor for thrombosis in the portal, mesenteric, and hepatic districts. OBJECTIVE: We aimed to assess whether the Janus kinase 2 (JAK2) V617F mutation, an acquired mutation that occurs in MPD patients, is a risk factor for portal and mesenteric venous thrombosis (PMVT) independently of the presence of overt MPDs. PATIENTS AND METHODS: The medical histories of 99 patients presenting with PMVT were obtained. The presence of the JAK2 V617F and VHL 598C > T mutations was determined by polymerase chain reaction followed by restriction enzyme analysis and direct cycle sequence analysis. RESULTS: Over a 10-year period of observation, of the 99 patients presenting with PMVT, the JAK2 V617F mutation was detected in heterozygous state in 17 individuals [17.2%; 95% confidence interval (95% CI) 10.9-25.9]. None of the patients presenting with the JAK2 V617F mutation carried an inherited thrombophilic risk factor. Seven patients with (43.8%; 95% CI 19.8-70.1) and two without (2.4%; 95% CI 0.3-8.4) the JAK2 V617F mutation had a diagnosis of MPD at the occurrence of the venous thrombotic event. After a median follow-up of 41 months (range 3-114 months), three out of the 10 patients carrying the JAK2 V617F mutation were then diagnosed as having idiopathic myelofibrosis (n = 2) or polycythemia vera (n = 1), whereas in seven patients a MPD was not detected. Two of the 83 patients without the JAK2 V617F mutation went on to develop MPDs. CONCLUSIONS: Determination of the JAK2 V617F mutation may contribute to the search for genetic determinants of PMVT and may be useful to recognize patients who should be carefully observed for the subsequent development of overt MPDs.

Low protein Z levels and risk of occurrence of deep vein thrombosis.

BACKGROUND: Protein Z (PZ) serves as a cofactor for activated factor X inhibition by the PZ-dependent protease inhibitor. In vivo and in vitro studies aimed at investigating the role of PZ levels in venous thombosis have produced conflicting results. OBJECTIVES: We investigated whether reduced PZ levels and PZ gene common variants are associated deep vein thrombosis (DVT). PATIENTS AND METHODS: In 197 patients with DVT and in 197 age-matched and sex-matched controls, PZ plasma levels and gene polymorphisms were evaluated by means of an enzyme-linked immunosorbent assay and direct cycle sequence analysis. RESULTS: Similar PZ levels were found in controls (1.44; SD 0.63 microg mL-1) and in patients (1.44; SD 0.96 microg mL-1). The incidence of PZ levels below the 5.0 (0.52 microg mL-1) or the 2.5 percentile of controls (0.47 microg mL-1) was higher in patients (10.2% and 8.7%, respectively) than in controls {4.1% [odds ratio (OR) 2.7, 95% confidence interval (CI) 1.2-7.3], and 2.0% (OR 4.6, 95% CI 1.5-13.9), respectively}. This relationship was independent of the effect of age, sex, and factor V Leiden and FII A(20210) alleles [OR 2.8 (95% CI 1.1-7.3), and OR 4.9 (95% CI 1.4-17.3)]. PZ levels were associated with the intron C G-42A and the intron F G79A polymorphisms in cases (r2=0.129) and in controls (r2=0.140). However, frequencies of the PZ gene polymorphisms were similar in the two groups and were not associated with very low PZ levels. CONCLUSIONS: The present data suggest an association between very low PZ plasma levels and the occurrence of DVT, with PZ gene polymorphisms contributing little to this relationship.

Genetic modulation of oral anticoagulation with warfarin.

Cytochrome P450 CYP2C9 gene variants have been associated with hyperresponsiveness to small doses of warfarin and a higher bleeding complication rate. The aim of this study was to investigate whether CYP2C9 gene variants affect doses of drug prescribed to acquire the target anticoagulation intensity and the occurence of bleeding complications. In a cohort of 180 patients followed up at one specialized clinic from the start of the anticoagulation with warfarin, we have investigated whether CYP2C9 gene variants have affected doses of drug prescribed to acquire the target anticoagulation intensity and the incidence of bleeding complications. The adjusted dose required of warfarin was higher among patients with the CYP2C9*1 haplotype (5.6 mg) than those of patients carrying the CYP2C9*2 (4.7 mg; p = 0.007, Scheffé's test) or the CYP2C9*3 haplotype (4.0 mg; p <0.001, Scheffé's test). The occurrence of bleeding complications was more frequent among patients with the CYP2C9*2 and/or the CYP2C9*3 haplotype than in carriers of the CYP2C9*1 haplotype (OR: 2.57; 95% CI; 1.16-5.73). An interaction between the presence of local bleeding sources and the CYP2C9*2 and/or the CYP2C9*3 haplotype was observed (p <0.001). Patients with both local sites of potential bleeding and CYP2C9*2 and/or the CYP2C9*3 haplotype had the higher estimated risk of bleeding (OR: 12.81; 95% CI: 2.86-57.26). CYP2C9 gene variants modulate the anticoagulant effect of the dose of warfarin prescribed. The incidence of bleeding complications in CYP2C9*2 and CYP2C9*3 carriers was significantly higher than that in noncarriers and interacted with the presence of local bleeding sources.

Fibrinogen plasma levels in an apparently healthy general population--relation to environmental and genetic determinants.

Elevated fibrinogen levels are an independent risk factor for cardiovascular ischemic disease. We investigated the relationship between cardiovascular ischemic risk factors, the fibrinogen Bbeta-chain G/A(-455) polymorphism and plasma fibrinogen levels in 989 apparently healthy subjects. Fibrinogen values were higher in subjects with C reactive protein (C-RP) >0.33 mg/dl, BMI >23.9 kg/m2, total cholesterol >4.84 mmol/l, triglycerides > 1.02 mmol/l, PAI-1 antigen >12.2 ng/ml, carriers of the A allele, first-degree relative history of coronary artery disease, or consuming >10 cigarettes per day (p<0.01). Men and ethanol drinkers showed lower plasma fibrinogen levels (p<0.01). The multivariate analysis confirmed the independent effect of C-RP, age, BMI, total cholesterol, gender, PAI-1, -455 G/A polymorphism, (p<0.05). BMI, total cholesterol, PAI-1, alcohol and smoking habit raised with the increase of age and differed between sexes. The A(-455) allele increasing effect was significant in women, especially in subjects aged <30 years, and in men aged <43 years. These results indicate that environmental factors contributed to a larger extent to fibrinogen variability, whereas the A(-455) allele was associated with a steeper increase in younger age quartiles.

Genetic polymorphism of 5,10-MTHFR reductase gene in offspring of patients with myocardial infarction.

A family history of myocardial infarction is a major determinant of ischemic disease. A C->T677 polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene has been identified as a cause of mild hyperhomocysteinemia, a risk factor for arterial thrombosis. We have investigated the relationship between the MTHFR TT genotype and a family history of myocardial infarction in a cohort of 982 apparently healthy individuals. Subjects whose first-degree relatives suffered from a myocardial infarction, showed raised median age (p <0.001), total cholesterol (p <0.001) and plasma fibrinogen (p = 0.023) and a higher than normal frequency of C-reactive protein levels >0.33 mg/dl (p = 0.012). Moreover, when compared to subjects without such family history, a higher number of homozygotes for the T allele of the MTHFR gene (p = 0.027), and of the 4G allele of the plasminogen activator inhibitor-1 gene (p = 0.002) was found in the subsetting of the offspring of patients with myocardial infarction. In a multiple logistic regression analysis, age (OR 1.02 [95%-CI: 1.00-1.05]), total cholesterol (OR 1.40 [95%-CI: 1.14-1.71]), C-reactive protein levels >0.33 mg/l (OR: 1.87 [95%-CI: 1.10-3.20]), plasminogen activator inhibitor-1 4G/4G (OR: 1.84 [95%-CI: 1.27-2.66]), and MTHFR TT genotype (OR 1.62 [95%-CI: 1.08-2.42]), were all associated with a family history of myocardial infarction. Thus, the MTHFR TT genotype independently accounts for the risk of a family history for myocardial infarction in the present setting.

Factor V Leiden is associated with repeated and recurrent unexplained fetal losses.

Activated protein C resistance (APCR) is responsible for most cases of familial thrombosis. The factor V missense mutation Arg506 > Gln (FV Leiden) has been recognized as the commonest cause of this condition. Recently, it has been suggested that APCR is associated with second trimester fetal loss. We investigated the distribution of FV Leiden in a sample (n = 43) of Caucasian women with a history of two or more unexplained fetal losses. A group (n = 118) of parous women with uneventful pregnancies from the same ethnical background served as control. We found the mutation in 7 cases (16.28%) and 5 controls (4.24%; p = 0.011). A statistically significant difference between women with only early fetal loss vs those with late events (p = 0.04) was observed. Our data demonstrate a strong association between FV Leiden and fetal loss. Furthermore, they indicate that late events are more common in these patients.

Factor V Leiden, C > T MTHFR polymorphism and genetic susceptibility to preeclampsia.

We performed a case-controlled study to investigate whether the FV Leiden mutation and the C > T677 polymorphism of the 5, 10 methylene tetrahydrofolate reductase (MTHFR) are associated with the occurrence of preeclampsia in 96 otherwise healthy preeclamptic women and 129 parous women as controls. FV Leiden carriers were 10 (10.5%) in cases and 3 (2.3%) in controls (OR: 4.9, 95% CI: 1.3-18.3). MTHFR TT homozygotes were 28 (29.8%) in cases and 24 (18.6%) in the control group (OR: 1.8, 95% CI 1.0-3.5). No difference in any of the polymorphisms was found between proteinuric (n = 45) and non-proteinuric (n = 51) patients. Moreover, MTHFR polymorphism does not affect the association between FV Leiden and preeclampsia. In conclusion, FV Leiden mutation and MTHFR TT genotype are associated with the occurrence of preeclampsia, suggesting that, during pregnancy, women carrying these gene variants are prone to develop such a complication.

Coexistence of factor V Leiden and Factor II A20210 mutations and recurrent venous thromboembolism.

Patients carrying the FV Leiden or the FII A20210 mutation have a high risk of venous thromboembolism. Among 542 patients with a documented diagnosis of deep venous thrombosis in one leg consecutively referred for a thrombophilic work-up, we have retrospectively assessed the rate of objectively documented previous recurrence in carriers of both FV Leiden and FII A20210 mutations. Eighty-two patients had experienced 115 episodes of recurrent venous thromboembolism. The rate of recurrent venous thromboembolism was 29.2% among subjects with and 14.5% in those without deficiencies of natural anticoagulant proteins (p = 0.055), and 24.6% among patients with and 14.0% in those without antiphospholipid antibodies (p = 0.036). The frequency of having a recurrent thromboembolism was 16.2%, 20.0%, and 36.4% among carriers of FV Leiden, FII A20210 mutation, or both gene defects, respectively, and 12.8% in subjects carrying neither mutation (p for trend = 0.004). When adjusted for age, sex, and thrombophilic risk factors, the rate was higher among patients with than in those without deficiencies of natural anticoagulant proteins (OR: 3.0; 95% CI: 1.2-7.5), aPL 2.5 (95% CI: 1.3-4.9), or both FV Leiden and FII A20210 gene mutations (OR 4.8; 95% CI: 1.9-12.2). The rate of previous recurrent venous thromboembolism was significantly higher in subjects carrying both FV Leiden and FII 20210 mutations and was comparable to that observed in subjects with deficiencies of natural anticoagulant proteins or antiphospholipid antibodies.

Prothrombotic genetic risk factors and the occurrence of gestational hypertension with or without proteinuria.

Gestational hypertension with or without proteinuria is a multifactorial disease in which the presence of a hypercoagulable state has been suggested. The prothrombin G20210A, the Factor V (FV) Leiden mutations, and the C677T 5-10 methylenetethrahydrofolate reductase (MTHFR) polymorphism were investigated in 140 women with gestational hypertension and in 216 normotensive women from Southern Italy. Nine controls (4.1%) and 16 cases (11.4%; OR: 2.96, 95% CI: 1.27-6.91) carried the prothrombin A20210 allele. FV Leiden mutation was observed in 4 controls (1.8%) and 11 cases (7.9%; OR: 4.53, 95% CI: 1.41-14.53). The TT MTHFR genotype was found in 36 controls (16.6%) and 34 cases (24.4%: OR: 1.61, 95% CI: 0.96-2.74). The impact of potential confounding variables was evaluated using a logistic regression analysis. Nulliparity, Factor V Leiden and prothrombin A20210 carrier status resulted to be independent risk factors of having gestational hypertension with or without proteinuria. Imbalance of haemostasis, through prothrombotic genetic factors, may predispose to the occurrence of gestational hypertension.

ACE gene polymorphism and insulin action in older subjects and healthy centenarians.

OBJECTIVES: To evaluate the possible relationship between angiotensin-converting enzyme (ACE) insertion-deletion (ID) genotype and insulin resistance in a population of healthy older Italian subjects. DESIGN: Prospective recruitment of a convenience sample. PARTICIPANTS: One hundred twenty-five subjects age 62 to 105 in good health and not taking any drug known to interfere with glucose metabolism. RESULTS: In the sample population, the relative frequencies of the ACE genotypes deletion-deletion (DD) (0.424), ID (0.400), and insertion-insertion (II) (0.176) were not significantly different from values predicted by Hardy-Weinberg equilibrium. The genotype distribution was similar in men and women. Subjects carrying the II genotype had a higher FPG (P <.001) and FPI (P <.001) than did subjects with DD or ID genotype. Subjects with II genotype also had a significantly higher HOMA index than did subjects with DD or ID genotype (P for trend <.002). In a multivariate stepwise regression analysis, the ACE ID polymorphism was significantly and independently associated with the HOMA index (P <.001). The same result was confirmed performing multivariate analysis in the younger group and centenarians separately. CONCLUSIONS: In an older population, the presence of II ACE genotype is associated with a high degree of insulin resistance independent of other anthropometric variables known to interfere with insulin action; this association is significant in both the younger subjects and the centenarians.

Impact of childhood cancer on healthy school-age siblings.

One part of a study on the effects of childhood cancer on families focused on the emotional reactions of school-age siblings. The authors identify themes in the siblings' feelings taken from transcripts of interviews with them. Responses were categorized as experience of diagnosis and hospitalization; awareness of prognosis and mortality; need for information; continuing effect of disease or death on the well child; correct understanding of cancer; and hopes and desires for the future. The responses were grouped either in a sibling with a living child category or sibling with a deceased child category. From their analysis, the authors present implications for nurses' interactions with these children: children's need for information; their feelings of being displaced and unimportant; need for encouraging involvement in the life of the ill child. The authors also identify additional questions that could direct future nursing research.

Reduction of mononuclear cytokine production in hemodialysis patients treated with steam-sterilized low-flux polysulphone membranes.

An increased cytokine production, correlated with long term complications of uremic disease, has been described during hemodialysis. To identify possible differences in the cytokine release of differently sterilized membranes, we enrolled six uremic patients on chronic hemodialysis. The patients underwent dialysis with ETO-sterilized low-flux polysulphone membranes (F6, Fresenius AG) for at least three months (A1), they were then switched to steam-sterilized polysulphone membranes (F6-HPS Fresenius AG) and further evaluations after one (B1) and two months (B2) were carried out. A final evaluation (A2) was made one month after switching back to F6 dialyzers. At each time period, samples were drawn to measure IL-1beta released by cultured mononuclear cells (MN). Moreover, dialysate samples were collected to test endotoxin levels. C3a and C5a levels were assessed at 0, 5, 15 and 60 min from starting hemodialysis. Anti-ETO IgE levels were also assayed at A1, B1 and A2. The LAL test revealed a good quality dialysate. The mean pre-dialysis IL-1beta levels were 215 pg/million cells at A1; falling to 49 at B1, and 54 at B2 (p<0.01); there was then a sharp rebound at A2: 284, p<0.01. Post-dialysis levels followed the same pattern. No correlation between the dialysate endotoxin level and cytokine release was found. Complement activation did not change and in all the phases of the study no anti-ETO IgE was detected in any of the subjects. Our data suggest that the steam sterilized polysulphone membrane induces a lower cytokine release than the ETO sterilized membrane, although the mechanism by which it does so remains to be clarified.

Is steam sterilization really making any difference in dialysis-induced cytokine release?

Ethylene oxide (ETO) is presently the most commonly used sterilization method for medical devices. Although alternative sterilization modes such as steam sterilization have been suggested, the effect of steam on dialysis-induced cytokine release is unknown. We enrolled 9 patients on chronic hemodialysis and evaluated at different intervals IL-1beta production while treated with ETO (NC 1785-Bellco) and steam sterilized NC 1785S-Bellco) Synthetically Modified Cellulose (SMC). A basal test during treatment with NC 1785 was performed (A); the same test was set up 4 weeks after treatment with NC 1785S (B) and, lastly, 4 weeks after returning to NC 1785 (C). Peripheral blood mononuclear cells (PBMC) were purified before and after the dialysis session, were isolated on a Ficoll/Hypaque gradient and incubated for 24 h. Spontaneous IL-1beta release was evaluated in the supernatant and in the lysate. In A, IL-1beta levels were (in pg/ml/10(6) cells, in supematant and lysate, respectively): 5.8 +/- 4.8 and 7.6+/-5.2 in pre-HD and 4.68 +/- 3.6 and 9.7 +/- 6.65 in post-HD. These levels showed a clear reduction in B: 2.5 +/- 2.2 and 4.4 +/- 3.1 in pre-HD, and 4.35+/- 6.6 and 7.52 +/- 7.22 in post-HD. In the C test, 4 weeks after the return to the ETO membrane, IL-1beta levels remained unchanged: 2.9 +/- 1.8 and 4.5 +/- 3.1 in pre-HD; and 2.6 +/- 3 and 5.7 +/- 6.6 in post-HD. Statistical analysis showed significant changes in the pre-HD levels both in supematant (p < 0.04) and in lysate (p < 0.04). Steam sterilization of SMC induced a lower spontaneous IL-1beta release, but this effect was not statistically significant due to the large inter-individual variation. Hence, contrary to claims of better biocompatibility, steam sterilization does not result in a reduced production of pro-inflammatory IL-1beta.

[Hypersensitivity to oral anticoagulants: report of a case]. / Ipersensibilità agli anticoagulanti orali: descrizione di un caso.

We report a case regarding a 71 year-old Caucasian man with NYHA functional class III congestive heart failure, who was under warfarin treatment due to left ventricular thrombosis. After a few days, although the drug was not overdosed, the INR increased up to 11.68. Normal values were reestablished only after a 20-day pharmacological wash-out. Surprisingly, no episode of major or minor bleeding occurred. Gene typing of cytochrome P450 CYP2C9, a liver enzyme responsible for warfarin metabolism, showed that the patient was a carrier of both the mutant alleles (CYP2C9*2/*3) of this enzyme. This genetic defect caused a reduced catabolism of S-warfarin and excessive anticoagulation.

Clinical Pregnancies and Live Births in women approaching ART: a follow-up analysis of 157 women after thrombophilia screening.

INTRODUCTION: The role of thrombophilia screening and antithrombotic therapy in unselected women undergone Assisted Reproductive Technologies (ART) is largely unknown. Nonetheless, in many Countries infertile women undergo thrombophilia screening and/or antithrombotic therapy. MATERIALS AND METHODS: We carried out a follow-up study. The original sample (n=1107) consisted of infertile women observed in 13 years. A cohort of 157 women with at least 1 cycle before thrombophilia test and 1 after test was investigated. All underwent thrombophilia screening; an antithrombotic treatment was prescribed in 216 out of 801 cycles. Clinical pregnancy and live birth rates were the main clinical objectives. RESULTS: Overall, 15 (9.6%) women carried thrombophilia. The Cox regression showed that LMWH alone or combined with ASA was significantly associated with the outcome "live birth" "live births" (p: 0.015, HR: 2.8, 95%CI: 1.2-6.6 for combined therapy), independently of the carriership of thrombophilia. Women with a lower number of attempts had a higher likelihood of delivering a live-born child using the combined therapy (p<0.001, HR: 0.7, 95%CI: 0.7-0.8), independently of the presence of thrombophilia. CONCLUSIONS: A potential benefit of LMWH in improving number of live births, independently of the presence of thrombophilia, is suggested. Universal thrombophilia screening before ART is not useful to discriminate women with a worse pregnancy prognosis.

Low-molecular -weight heparin in pregnancies after ART -a retrospective study-.

INTRODUCTION: The utility of an antithrombotic prophylaxis in Assisted Reproductive Technologies (ART) is highly debated. It has been hypothesised that specific effects of heparin on the coagulation system during implantation can improve the number of clinical pregnancies and live births. MATERIALS AND METHODS: We studied a cohort of 327 women undergone at least 1 ART cycle before thrombophilia testing. Overall, a number of 751cycles was analysed. Low-Molecular-Weight Heparin (LMWH) and/or low-dose aspirin (ASA) were prescribed in 132 (17.6%) cycles. Furthermore, all the women underwent thrombophilia screening. RESULTS: The univariate analysis showed that LMWH with/without ASA was significantly associated with both the outcomes clinical pregnancy and live birth, while the use of ASA was not associated with live birth. The logistic regression showed that the use of LMWH was significantly associated with both the outcomes, clinical pregnancy (OR: 6.0, 95%CI: 2.8-15.6) and live birth (OR: 10.7, 95%CI: 3.2-36.1). The type of ART procedure significantly influenced the likelihood of achieving clinical pregnancy. CONCLUSIONS: Present findings suggest that LMWH alone or combined with ASA could have a role in fostering the implantation of embryos and improving the number of live births after ART.