Does aspirin have a role in improving pregnancy outcome for women with the antiphospholipid syndrome? A randomized controlled trial

OBJECTIVE: This pilot investigation was undertaken to assess the efficacy of low-dose aspirin therapy for the treatment of women with antiphospholipid antibodies when recurrent miscarriage is the only sequela. STUDY DESIGN: A double-blind, randomized, placebo-controlled trial was conducted in the setting of the recurrent miscarriage clinic of a tertiary referral obstetric hospital. The participants were 50 women with a history of recurrent miscarriages (>/=3) and antiphospholipid antibodies. Women with systemic lupus erythematosus or a history of thrombosis were excluded. Women were recruited after full investigative screening at the recurrent miscarriage clinic. Women with >/=3 fetal losses and persistently positive results for antiphospholipid antibodies were randomly allocated to receive either aspirin (75 mg daily) or placebo. Investigators, clinicians, and patients were blinded to the treatment. Rates of live births, antenatal complications, and delivery and neonatal outcomes were recorded prospectively. Data were compared by chi(2) analysis with Yates' correction, the Fisher exact test, or the Student t test as appropriate. RESULTS: There were 10 exclusions after random assignment because of inappropriate inclusion. Eighty-five percent of the placebo (17/20) group and 80% of the aspirin-treated group (16/20) were delivered of live infants. This difference was not significant. There were no significant differences in antenatal complications or neonatal morbidity between the groups. CONCLUSIONS: This preliminary study suggests that low-dose aspirin has no additional benefit when added to supportive care for women for whom recurrent early fetal loss is the only sequela of the antiphospholipid syndrome. This live birth rate with supportive care alone exceeds the published live birth rates for women with antiphospholipid antibody-mediated recurrent fetal loss who were treated with heparin or corticosteroids. This trial, like all other trials in this field, is small, but its results bring into question the need for pharmacologic intervention for women with antiphospholipid syndrome for whom recurrent fetal loss is the only sequela. Our results highlight the need for a large randomized controlled trial to identify the optimal treatment for this group of women and justify the inclusion of a placebo arm in any such trial.     

Pregnancy complications in women with recurrent miscarriage associated with antiphospholipid antibodies treated with low dose aspirin and heparin.

OBJECTIVE: To study the obstetric course of women with a history of recurrent miscarriage associated with antiphospholipid antibodies, lupus anticoagulant and anticardiolipin antibodies, treated with low dose aspirin and low dose heparin. DESIGN: Prospective observational study. SETTING: University based tertiary referral clinic. POPULATION: One hundred and fifty pregnant women with a history of recurrent miscarriage associated with persistently positive tests for antiphospholipid antibodies. METHODS: Lupus anticoagulant was detected using the dilute Russell's viper venom time together with a platelet neutralisation procedure. IgG and IgM anticardiolipin antibodies were detected using a standardised enzyme linked immunosorbent assay. An IgG anticardiolipin level > or = 5 per litre units and an IgM anticardiolipin level > or = 3 per litre units was considered positive. Aspirin (75 mg daily) was commenced at the time of a positive pregnancy test and heparin (5000 units subcutaneously 12 hourly, or enoxaparin 20 mg daily) was started when fetal heart activity was demonstrated on ultrasound. Treatment was stopped at the time of miscarriage or at 34 weeks of gestation. RESULTS: One hundred and seven pregnancies (71%) resulted in a live birth. Forty-one pregnancies (27%) miscarried, the majority in the first trimester. One woman had a stillbirth, and one a premature baby who died in the neonatal period. One pregnancy was terminated for a fetal anomaly. Gestational hypertension complicated 17% (18/108) of ongoing pregnancies and antepartum haemorrhage 7% (8/108). Twenty-six babies (24%) were delivered before 37 weeks of gestation. Fifty women (46%) were delivered by caesarean section. The median birthweight of all live born infants was 3069 g (range 531-4300); however 15% (16/108) of the infants were small for gestational age. CONCLUSION: Combination treatment with aspirin and heparin leads to a high live birth rate among women with recurrent miscarriage and antiphospholipid antibodies. However, successful pregnancies are prone to a high risk of complications during all trimesters. Close antenatal surveillance and planned delivery of these pregnancies in a unit with specialist obstetric and neonatal intensive care facilities are indicated.     

Treatment of recurrent miscarriage and antiphospholipid syndrome with low-dose enoxaparin and aspirin

The aim of this retrospective, observational study was to determine the impact of low-dose enoxaparin (20 mg) in conjunction with low-dose aspirin on the pregnancy outcome of women with antiphospholipid syndrome and recurrent miscarriage. The study was conducted in a tertiary referral teaching hospital. A total of 35 women with antiphospholipid syndrome were treated with low-dose enoxaparin and aspirin as soon as pregnancy was confirmed. The outcome of pregnancy was analysed. The miscarriage rate was 7/35 (20%) whereas the live birth rate was 28/35 (80%). In conclusion, low-dose (20 mg) enoxaparin in conjunction with low-dose aspirin treatment produced encouraging results. The findings in this study suggest that there is a case for randomized controlled trials to compare low-dose (20 mg) enoxaparin with higher doses.     

High factor XI, recurrent pregnancy loss, enoxaparin

Of the 149 women with 0 pregnancy losses, 7 (5%) had factor XI level ≥150% versus 5 of 31 (16%) women with recurrent pregnancy loss. Three of the 5 women with high factor XI and recurrent pregnancy loss, with 19 previous pregnancy losses and 0 live births, were given enoxaparin during 5 subsequent pregnancies, and had 6 term live births and 1 miscarriage.     

The role of low molecular weight heparin on recurrent pregnancy loss: A systematic review and meta-analysis

To assess the roles of the low molecular weight heparin (LMWH) on recurrent pregnancy loss (RPL). The relevant studies of all randomized controlled trials (RCTs) were retrieved, and the systematic evaluation was conducted. PubMed, Embase, and Cochrane library databases were searched by using keywords, including low-molecular-weight heparin or LMWH, and recurrent miscarriage or recurrent pregnancy loss in pregnant women from their earliest data to February 2020. Two investigators independently evaluated eligibility. Risk ratios (RRs) and their corresponding 95% confidence interval (CI) were determined. To pool the results, this meta-analysis was performed using random-effect model due to the high heterogeneity among these eight studies. A total of eight RCTs involving 1854 participants were included in the meta-analysis involving 963 patients with RPL who were prescribed LMWH (enoxaparin, tinzaparin, or dalteparin) alone and 891 patients who were treated with no LMWH interventions (placebo, folic acid or non-treatment) were compared. Pooled data from the remaining eight RCTs showed the differences between intervention groups and control groups. Compared with control groups, LMWH had significantly improved live births (RR,1.19; 95%CI, 1.03 to 1.38; P = 0.02), and reduced miscarriage rates (RR, 0.62; 95%CI, 0.43 to 0.91; P = 0.01). The study suggested that LMWH could improve the live births and reduce the miscarriage rates of RPL. Therefore, LMWH might be a good treatment choice for women with unexplained PRL.     

Antiphospholipid syndrome in pregnancy: a randomized,controlled trial of treatment

OBJECTIVE: To compare the efficacy of low-dose aspirin alone versus low-dose aspirin plus low molecular weight heparin in pregnant women with antiphospholipid syndrome and recurrent miscarriage as prophylaxis against pregnancy loss.METHODS: From a regional miscarriage clinic, 119 consecutive women with persistently positive tests for lupus anticoagulant and/or anticardiolipin immunoglobulin G and M antibody were invited to participate in a randomized, controlled trial between 1997 and 2000. After ethical approval and adherence to a written protocol, 12 women were unwilling to participate, five failed exclusion/inclusion criteria, and four were nonpregnant. Laboratory analysis was performed by Sheffield University Coagulation Department, electronically generated randomization by Manchester University Centre for Cancer Epidemiology, and data collection and analysis by a research officer at Leeds University. Viability ultrasound every 2 weeks was provided until 12 weeks' gestation before transfer to the pregnancy support antenatal clinic.RESULTS: Ninety-eight women were randomized before 12 weeks' gestation. Forty-seven received low-dose aspirin 75 mg daily (group A), and 51 received low-dose aspirin plus low molecular weight heparin 5000 U subcutaneously daily (group B) throughout pregnancy. There were 13 pregnancy losses and 34 live births in group A and 11 losses and 40 live births in group B. The live-birth rate was 72% in group A and 78% in group B (odds ratio 1.39, 95% confidence interval 0.55, 3.47). There were no cases of maternal thrombosis in either group.CONCLUSION: A high success rate is achieved when low-dose aspirin is used for antiphospholipid syndrome in pregnancy. The addition of low molecular weight heparin does not significantly improve pregnancy outcome.     

The PROGINS progesterone receptor gene polymorphism and idiopathic recurrent miscarriage.

OBJECTIVE: Progesterone inhibits lymphocyte cytotoxicity, natural killer cell degranulation, and release of proinflammatory cytokines and has been shown to protect against spontaneous miscarriage. We investigated the association between idiopathic recurrent miscarriage (IRM) and the PROGINS 306 base pair insertion polymorphism in intron G of the progesterone receptor gene, which is known to segregate with progesterone-dependent neoplasms. METHODS: In a case-control study we investigated 125 women with a history of three or more consecutive pregnancy losses before 20 weeks' gestation and 79 healthy controls with at least two live births and no history of pregnancy loss. Peripheral venous puncture, DNA extraction, and polymerase chain reaction were used to genotype women for the presence of the PROGINS polymorphism. RESULTS: Allele frequencies among women with IRM and controls were 85.2% and 89.2%, respectively, for allele T1 (wild type) and 14.8% and 10.8%, respectively, for allele T2 (mutant). No association between allele T2 and the occurrence of IRM was found (P =.3; odds ratio [OR] 0.69; confidence interval [CI] 0.34, 1.40). Genotype frequencies were not significantly different between the study group (T1/T1 73.6%, T1/T2 23.2%, T2/T2 3.2%) and the control group (T1/T1 79.7%, T1/T2 19%, T2/T2 1.3%) (P =.4). Between women with primary and secondary IRM, there were no statistically significant differences with respect to allele frequencies (82% versus 87%, P =.4 for allele T1 and 12% versus 13%, P =.6 for allele T2). CONCLUSIONS: We found that the PROGINS polymorphism in the progesterone receptor gene was not associated with IRM in white women.     

Prophylactic and therapeutic enoxaparin during pregnancy: indications, outcomes and monitoring

OBJECTIVES: To evaluate the efficacy and safety of prophylactic and therapeutic enoxaparin in pregnancy. STUDY DESIGN: Three-year prospective audit. SETTING: Tertiary level obstetric hospital. POPULATION: Fifty-two women who received subcutaneous enoxaparin, either a prophylactic dose (40 mg daily) in 26 pregnancies or therapeutic dose (1 mg/kg twice daily) in 32 pregnancies. MATERIALS AND METHODS: Pregnant women treated with enoxaparin were prospectively entered into a register. Data were retrieved by case note review. MAIN OUTCOME MEASURES: Pregnancy outcomes, treatment complications and anti-Xa levels. RESULTS: In the prophylactic group there were no fetal losses, thromboembolic events or complications related to enoxaparin. In the therapeutic group there were four first trimester miscarriages, a termination and 27 live births. Therapeutic enoxaparin prevented further thromboembolism without complications. One woman was treated with intermediate dose enoxaparin when she presented at 5 weeks' gestation on warfarin and 7 weeks after a venous thromboembolism. She developed a recurrent pulmonary embolus 3 weeks later and was subsequently treated with therapeutic enoxaparin. In the therapeutic group the enoxaparin dose/kg correlated poorly with anti-Xa levels, and dose adjustments were made. Therapeutic mean (SD) trough and peak anti-Xa levels were 0.33 U/mL (0.14) and 0.86 U/mL (0.24) in the first trimester and 0.48 U/mL (0.19) and 0.84 U/mL (0.23) in the third trimester. CONCLUSIONS: In the present series, prophylactic and therapeutic enoxaparin treatment during pregnancy was effective and safe. Studies are required to determine the optimal duration of treatment with therapeutic enoxaparin following venous thromboembolism in pregnancy and the clinical relevance of anti-Xa monitoring.     

Anticoagulant therapy and pregnancy

Low dose aspirin therapy is one of the anticoagulant treatments used during pregnancy. Anticoagulant agents may be useful for several disorders, such as recurrent miscarriage, pre-eclampsia, fetal growth restriction and infertility. However, it is unclear whether anticoagulant therapy can increase the live birth rate in all of these cases. Recent data suggest that a low-dose aspirin and heparin combination therapy is effective in the prevention of recurrent pregnancy loss in women with antiphospholipid syndrome. Thrombogenic diseases, for example, protein C deficiency, protein S deficiency, factor XII deficiency and hyperhomocysteinemia, may cause pregnancy loss. The etiology of recurrent miscarriage is often unclear and may be multifactorial, with much controversy regarding diagnosis and treatment. Although 70% of recurrent pregnancy losses are unexplained, anticoagulant therapy is effective in maintaining pregnancy without antiphospholipid antibody syndrome. We conclude that a low-dose aspirin and heparin combination therapy can be useful for unexplained cases of recurrent pregnancy loss without antiphospholipid antibody syndrome. (Reprod Med Biol 2008; 7 : 1–10)     

Enoxaparin treatment in women with mechanical heart valves during pregnancy

OBJECTIVE: This prospective audit reports pregnancy outcomes, anticoagulation complications, and anti-Xa levels in women with mechanical heart valves who were treated with therapeutic enoxaparin plus aspirin during pregnancy. STUDY DESIGN: Between 1997 and 1999, 11 women with mechanical heart valves were treated with enoxaparin, 1 mg/kg twice daily, and aspirin, 100 to 150 mg daily during 14 pregnancies. Predose and 4-hour postdose anti-Xa levels were monitored monthly. RESULTS: There were 9 live births, 3 miscarriages, and 2 terminations. In 48 months of enoxaparin treatment, one woman who had a documented valve thrombosis when she presented at 8 weeks' gestation also had a valve thrombosis at 20 weeks' gestation. There were no enoxaparin-related hemorrhagic complications. Mean (SD) anti-Xa levels were 0.46 (0.12) U/mL predose and 0.89 (0.22) U/mL 4 hours postdose. CONCLUSION: Successful pregnancy outcome may be achieved with therapeutic subcutaneous enoxaparin, but its efficacy at preventing valve thrombosis remains uncertain. Further data are required before use of enoxaparin during pregnancy in women with mechanical heart valves can be recommended.     

Antiphospohlipid syndrome in obstetrics

Antiphospholipid syndrome is characterised by a variety of clinical and immunological manifestations. The clinical hallmarks of this syndrome are thrombosis and poor obstetric outcomes, including miscarriages, fetal loss and severe pre-eclampsia. The main antiphospholipid antibodies include lupus anticoagulant, anticardiolipin and anti-β2-glycoprotein I. The combination of aspirin and heparin is considered the standard of care for women with antiphospholipid syndrome and embryo-fetal losses; however, aspirin in monotherapy may have a place in women with recurrent early miscarriage. A good benefit-risk ratio of low-molecular-weight heparin in pregnancy thrombosis treatment has been reported. Warfarin must be avoided if possible throughout the first trimester of pregnancy. Adequate pregnancy management of women with antiphospholipid syndrome should include co-ordinated medical-obstetrical care, a close follow-up protocol and a good neonatal unit. Close blood pressure control and early detection of proteinuria, together with Doppler studies of the utero-placental circulation should be included in the management protocol.     

Use of intravenous immunoglobulin for treatment of recurrent miscarriage: a systematic review

BACKGROUND: Intravenous immunoglobulin (IVIG) is a fractionated blood product whose off-label use for treating a variety of conditions, including spontaneous recurrent miscarriage, has continued to grow in recent years. Its high costs and short supply necessitate improved guidance on its appropriate applications. OBJECTIVE: We conducted a systematic review of randomised controlled trials evaluating IVIG for treatment of spontaneous recurrent miscarriage. SEARCH STRATEGY: A systematic search strategy was applied to Medline (1966 to June 2005) and the Cochrane Register of Controlled Trials (June 2005). SELECTION CRITERIA: We included all randomised controlled trials comparing all dosages of IVIG to placebo or an active control. DATA COLLECTION AND ANALYSIS: Two investigators independently extracted data using a standardised data collection form. Measures of effect were derived for each trial independently, and studies were pooled based on clinical and methodologic appropriateness. MAIN RESULTS: We identified eight trials involving 442 women that evaluated IVIG therapy used to treat recurrent miscarriage. Overall, IVIG did not significantly increase the odds ratio (OR) of live birth when compared with placebo for treatment of recurrent miscarriage (OR 1.28, 95% CI 0.78-2.10). There was, however, a significant increase in live births following IVIG use in women with secondary recurrent miscarriage (OR 2.71, 95% CI 1.09-6.73), while those with primary miscarriage did not experience the same benefit (OR 0.66, 95% CI 0.35-1.26). AUTHOR'S CONCLUSIONS: IVIG increased the rates of live birth in secondary recurrent miscarriage, but there was insufficient evidence for its use in primary recurrent miscarriage.     

Plasmapheresis and pregnancy outcome in patients with antiphospholipid syndrome.

OBJECTIVE: To assess plasmapheresis with low dose prednisone on obstetric and neonatal outcomes among unsuccessfully treated pregnant women with documented antiphospholipid syndrome (APS). METHODS: Eighteen pregnant women received prednisone (10 mg/day) and plasmapheresis at 7.08+/-0.6 weeks of gestation, for 3 sessions per week, until lupus anticoagulant activity suppressed and IgG anticardiolipin lowered. Serial pulsatility indexes (PI) of umbilical and uterine arteries were performed. RESULTS: The live birth rate was 100%; mild pre-eclampsia 5.5%; preterm deliveries 22.22%; intrauterine growth restriction 11.11%; thrombocytopenia 5.5%; oligohydramnios and fetal distress 16.6%. There were no perinatal deaths, thrombotic events or lupus flare. Uterine artery PI was reduced and umbilical artery PI was >95th percentile. CONCLUSION: Plasmapheresis and low dose prednisone were associated with a low rate of obstetric and neonatal complications. Plasmapheresis may be used to treat pregnant women with documented APS when first lines (aspirin and/or heparin) fail to prevent pregnancy loss.     

A polymorphism of the interleukin-1beta gene and idiopathic recurrent miscarriage

OBJECTIVE: Proinflammatory cytokines have been described to be involved in the pathogenesis of idiopathic recurrent miscarriage (IRM). We investigated the association between IRM and a polymorphism in exon 5 of the interleukin-1beta gene (IL1B) and interleukin-1beta (IL-1beta) serum levels. DESIGN: Case control study. SETTING: Academic research institution. SUBJECTS: One hundred thirty-one women with a history of three or more consecutive pregnancy losses before 20 weeks' gestation and 68 healthy controls with at least two live births and no history of pregnancy loss. INTERVENTIONS: Peripheral venous puncture. MAIN OUTCOME MEASURES: An IL1B exon 5 (position +3953) gene polymorphism was analyzed by PCR amplification followed by restriction fragment length polymorphism analysis. IL-1beta serum levels were analyzed by a commercially available ELISA. RESULTS: Allele frequencies in women with IRM and controls were 77.9% and 80.8%, respectively, for the E1 allele (wild type), and 22.1% and 19.2%, respectively, for the E2 allele (mutant). No association between the E2 allele and the occurrence of IRM was found (P=.57, odds ratio =.83). Genotype frequencies and IL-1beta serum levels were not significantly different between the study group and the control group. CONCLUSIONS: This is the first report on an IL1B polymorphism in IRM. Although known to alter IL-1beta expression, the investigated IL1B polymorphism is not associated with IRM and increased serum levels in a large Caucasian population.     

Recurrent miscarriage associated with antiphospholipid antibodies: prophylactic treatment with low-dose aspirin and fish oil derivates

PROBLEM: The aim of this study was to evaluate the effects of two different prophylactic protocols, low-dose aspirin and fish oil derivates, in the treatment of patients with recurrent pregnancy loss associated with antiphospholipid antibodies (APA) syndrome. METHODS: A prospective study included 30 patients who were alternately assigned to treatment. Each patient had had at least two consecutive spontaneous abortions, positive antiphospholipid antibodies on two occasions, and a complete evaluation. RESULTS: Among patients treated with low-dose aspirin, 12 out of the 15 (80%) pregnancies ended in live births. In the fish oil derivate group 11 out of the 15 (73.3%) ended in live births (p > 0.05). There were no significant differences between the low-dose aspirin and the fish oil derivates groups with respect to gestational age at delivery (39.9 +/- 0.4 vs 39 +/- 1.5 weeks), fetal birth weight (3290 +/- 200g vs 3560 +/- 100 g), number of cesarean sections (25% vs 18%), or complications. CONCLUSION: There were no significant differences in terms of pregnancy outcome between women with recurrent pregnancy loss associated with APA syndrome treated with low-dose aspirin or fish oil derivates.     

Angiopoietin-2 polymorphism in women with idiopathic recurrent miscarriage

OBJECTIVE: To investigate the relationship between idiopathic recurrent miscarriage and a polymorphism of the gene encoding for angiopoietin-2 (ANGPT2), an autochthonous modulator of angiogenesis during pregnancy. DESIGN: Prospective case control study. SETTING: Academic research institution. PATIENT(S): One hundred thirty-one women with a history of three or more consecutive pregnancy losses before 20 weeks' gestation, and 125 healthy, postmenopausal controls with at least two live births and no history of pregnancy loss. INTERVENTION(S): Peripheral venous puncture. MAIN OUTCOME MEASURE(S): Polymerase chain reaction and restriction fragment length polymorphism analysis were performed to identify the different ANGPT2 alleles. RESULT(S): No association between mutant (mt) allele and the occurrence of idiopathic recurrent miscarriage was found. Between women with primary and secondary idiopathic recurrent miscarriage, no statistically significant differences with respect to allele frequencies were observed. CONCLUSION(S): This is the first report on the ANGPT2 gene polymorphism in women with idiopathic recurrent miscarriage, demonstrating that the investigated polymorphism is not associated with idiopathic recurrent miscarriage in a white population.     

Hereditary thrombophilias are not associated with a decreased live birth rate in women with recurrent miscarriage

OBJECTIVE: To assesses the live birth rate without treatment in women with hereditary thrombophilia who have recurrent miscarriage and women without thrombophilia who have recurrent miscarriage. DESIGN: Prospective observational study. SETTING: Tertiary referral unit in university hospital. PATIENT(S): One hundred twenty women with thrombophilia and 65 women without thrombophilia. MAIN OUTCOME MEASURE(S): Number of live births or repeated miscarriages. RESULTS: Of the 185 patients, 44 with thrombophilia and 26 without thrombophilia have conceived. Nineteen of the 44 pregnancies (43.2%) in thrombophilia patients have terminated in live births, compared with 8 of 26 pregnancies (30.8%) in patients without thrombophilia. This difference is not statistically significant. CONCLUSIONS: Hereditary thrombophilia did not seem to affect the live birth rate in women with recurrent miscarriage.     

Management of essential thrombocythaemia during pregnancy

Essential thrombocythaemia is a rare myeloproliferative disorder that often presents with haemorrhagic or thrombotic complications. It may be detected incidentally in an asymptomatic younger adult and there are only a few case reports of essential thrombocythaemia in pregnant women. The risks posed by essential thrombocythaemia during pregnancy and its optimal management are uncertain. To determine if there is increased incidence of obstetric complications seen in women who have essential thrombocythaemia, we collected a large case series from a number of tertiary obstetric units in Australia and New Zealand. There were 30 pregnancies in 12 women who had essential thrombocythaemia. There were 17 live births (57%), 7 stillbirths (23%), 5 miscarriages (17%) and 1 ectopic (3%). Five pregnancies were complicated by placental abruption. When the outcomes of those women who received treatment with aspirin or interferon were compared to those that did not receive any treatment, there was a trend towards a higher livebirth rate (79% v. 38%, p = 0.06). Seven women were treated with aspirin and 5 had successful outcomes with no fetal complications. Four women were treated with alpha-interferon which reduced their platelet counts and all had successful outcomes with no fetal complication. These findings suggest that there is a high incidence of miscarriage, stillbirth and abruption in women with essential thrombocythaemia. Their pregnancies should be carefully monitored. Treatment with low dose aspirin and/or the use of alpha-interferon may be associated with an improved pregnancy outcome.     

Combined thrombophilic polymorphisms in women with idiopathic recurrent miscarriage

OBJECTIVE: To identify associations or interrelations between carriage of the methylenetetrahydrofolate reductase (MTHFR) C677T, the MTHFR A1298C, the factor V Leiden G1691A, the factor II prothrombin G20210A, the human platelet antigen (HPA) 1 C12548T, and the apolipoprotein (APO) B R3500Q polymorphisms and idiopathic recurrent miscarriage (IRM). DESIGN: Prospective case control study. SETTING: Academic research institution. PATIENT(S): One hundred forty-five women with a history of three or more consecutive pregnancy losses before 20 weeks gestation and 101 healthy postmenopausal women with at least two live births and no history of pregnancy loss. INTERVENTION(S): Peripheral venous punctures. MAIN OUTCOME MEASURE(S): Multiplex polymerase chain reaction was performed to identify the different alleles of six candidate genetic risk factors for IRM (MTHFR C677T, MTHFR A1298C, factor V Leiden G1691A, factor II prothrombin G20210A, HPA 1 C12548T, and the APO B R3500Q). RESULT(S): Allele and genotype frequencies of all polymorphisms were not significantly different between the study and the control groups. Also, no significant associations occurred between combinations of polymorphisms and the occurrence of IRM. CONCLUSION(S): Our data fall short of showing any significant association between single polymorphisms of the MTHFR, the Factor V Leiden, the Factor II Prothrombin, the HPA 1 and APO B genes or combinations of these polymorphisms and the occurrence of IRM.     

Effects of enoxaparin on late pregnancy complications and neonatal outcome in women with recurrent pregnancy loss and thrombophilia: results from the Live-Enox study

Women with thrombophilia and a history of recurrent pregnancy loss have poor pregnancy outcomes. Prophylaxis with enoxaparin 40 mg/day or 80 mg/day resulted in favorable gestational and neonatal outcomes.