A prospective, controlled multicenter study on the obstetric risks of pregnant women with antiphospholipid antibodies.

OBJECTIVES: A prospective, controlled multicenter study was performed to estimate the obstetric risks of antiphospholipid antibodies (the lupus anticoagulant and anticardiolipin antibodies). In addition, the risks of prior thrombosis, obstetric history, systemic lupus erythematosus, and high-dose prednisone treatment were evaluated. STUDY DESIGN: After screening for antiphospholipid antibodies in patients with lupus erythematosus or women with prior fetal loss(es), 59 subsequent pregnancies with and 54 without these antibodies were followed. RESULTS: The presence of the lupus anticoagulant and a history of at least three spontaneous abortions could predict fetal loss (p = 0.032 and 0.001, respectively). In live born infants, a low birth weight could be predicted by the presence of anticardiolipin antibodies (p = 0.034), prior intrauterine fetal death (p = 0.025), and treatment with high-dose prednisone (p = 0.002). No relationships were seen between antiphospholipid antibodies and small-for-gestational-age newborns and pregnancy-induced hypertension or preeclampsia. The disappearance of antiphospholipid antibodies during pregnancy was not correlated with live birth. CONCLUSION: It is concluded that the presence of antiphospholipid antibodies is a risk factor for adverse pregnancy outcome.     

Treatment outcome in women suffering from recurrent miscarriages and antiphospholipid syndrome

OBJECTIVE: To evaluate the outcomes of treatment in patients suffering from recurrent spontaneous abortion and antiphospholipid syndrome. MATERIALS AND METHODS: 148 observed women suffering from recurrent abortion with presence of lupus anticoagulant antibodies (LA) and/or high moderate concentration of anticardiolipin antibodies (ACA) have been divided randomly into followed three treated groups: I--56 patients treated by low-dose of acetylsalicylic acid (LDA, 75 mg daily); II--39 patients treated by low molecular weight heparin (applied in dose of 20 g daily); III--53 patients treated by LDA and low molecular weight heparin simultaneously. RESULTS: It has been affirmed that coincidental application of low-dose of acetylsalicylic acid and low molecular weight heparin statistically more often increase the percentage of successful pregnancy in comparison with application of low molecular weight heparin or acetylsalicylic acid alone. In the group where only low-dose of acetylsalicylic acid was applied the success of pregnancy equaled 89.3%, in the group where only low molecular weight heparin was applied the successful pregnancy equaled 81.1% and in the group with acetylsalicylic acid and low molecular weight heparin being applied together the successful pregnancy equaled 92.5%. In has simultaneously been affirmed that the percentage of pregnancy loss is statistically higher in the women suffering from isolated occurrence of lupus anticoagulant antibodies (21.2%) in comparison with the women suffering from occurrence of anticardiolipin antibodies (6.7%) and anticardiolipin antibodies with lupus anticoagulant antibodies simultaneously. CONCLUSION: 1. Simultaneous application of low-doses of acetylsalicylic acid and low molecular weight heparin seems to be the best solution in patients suffering from recurrent spontaneous abortion and antiphospholipid syndrome. 2. The occurrence of anticardiolipin antibodies in the serum of blood in patients suffering from antiphospholipid syndrome is a better foretelling factor for the future pregnancy outcome than the occurrence of lupus anticoagulant antibodies.     

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.     

Clearance of antiphospholipid antibodies in pregnancies treated with heparin

OBJECTIVE: To describe the natural history of serum antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies) in pregnant women treated with heparin, and to identify a possible association between changes in antibody status and outcomes of subsequent pregnancies. METHODS: Thirty-six women with antiphospholipid antibodies who had three or more repeated miscarriages were enrolled. Intravenous heparin was used for each of the first pregnancies after referral. Changes in antibody status were investigated with relation to outcomes of the index and subsequent pregnancies. RESULTS: Eighteen of 23 pregnancies in 36 antibody-positive women treated with heparin resulted in term or preterm deliveries with live-born infants, and five ended in abortions. Antibodies cleared in ten of 12 term pregnancies, in five of six preterm pregnancies, and in one of five abortions. There was a statistically significant difference between the term pregnancy and abortion groups (P <.05). Eleven second and third pregnancies in nine women in whom antibodies cleared resulted in term or preterm deliveries of live-born infants, without heparin therapy. The second and third pregnancies in one woman whose antibodies persisted ended in miscarriages despite repeated heparin administration. CONCLUSION: Antiphospholipid antibodies cleared spontaneously in some pregnant women treated with heparin. Subsequent pregnancies among women in whom antibodies cleared were managed successfully without medication, whereas pregnancies in women with persistent antibodies required treatment.     

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.     

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)     

Obstetric performance in patients with the lupus anticoagulant and/or anticardiolipin antibodies.

Antiphospholipid antibodies, notably the lupus anticoagulant and anticardiolipin antibodies, are associated with recurrent fetal wastage, pregnancy complications, and thromboses. Aggressive medical treatment using aspirin and steroids has been recommended. Fifty-one patients with antiphospholipid antibodies, only four with underlying connective tissue disorders, were followed through 53 pregnancies. Aggressive therapy was used in 33 pregnancies, 90.9% of which resulted in successful obstetric outcomes, a highly statistically significant difference compared with previous pregnancies in the same patients. Most pregnancies among nine patients receiving single-agent therapy (aspirin or steroids alone) and eight patients not treated also had successful outcomes. A 48.6% complication rate was found in association with therapy, particularly gestational diabetes mellitus. There was no statistical correlation between dose or duration of therapy and development of treatment-related complications. Although a subgroup of patients with antiphospholipid antibodies will benefit from aggressive therapy, the high complication rate warrants close observation.     

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.     

Antiphospholipid antibodies and the investigation of recurrent miscarriage

Recurrent miscarriage (three or more consecutive miscarriages) affects 1% of the female population and this causes severe psychological morbidity in both the sufferer and their partner. For many years the aetiology of recurrent miscarriage in the majority of cases has remained unclear. Treatment regiments to improve pregnancy outcome were based on poorly-designed studies, often without control cohorts, which have subsequently been shown to be of no proven benefit. Over the past 15 years accumulating evidence has implicated the presence of antiphospholipid antibodies (APAbs) in the aetiology of recurrent miscarriage. APAbs can be found in 15% of the recurrent miscarriage population, and are associated with first and second-trimester miscarriages as well as other obstetric complications. Aspirin and subcutaneous heparin administration are of clinically-proven benefit in lowering the miscarriage rate in women with this condition. Maternal side effects of aspirin and heparin are rare but include thrombocytopenia and osteoporosis. No direct teratogenic effects of aspirin and heparin have been demonstrated but pregnancies complicated by APAbs need to be monitored closely for evidence of pre-eclampsia and intrauterine growth restriction.     

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.     

Immunoglobulin A anti-beta2-glycoprotein antibodies in women who experience unexplained recurrent spontaneous abortion and unexplained fetal death

OBJECTIVE: Studies in rheumatologic populations suggest that immunoglobulin A antiphospholipid antibodies are strongly associated with the clinical manifestations of antiphospholipid syndrome. However, the association between immunoglobulin A antiphospholipid antibodies and pregnancy loss is uncertain. We determined whether immunoglobulin A antiphospholipid antibodies, specifically anti-beta(2)-glycoprotein I and anticardiolipin, are associated with the obstetric features of antiphospholipid syndrome. STUDY DESIGN: Sera from 4 groups of women were studied: (1) 133 women who experienced unexplained recurrent spontaneous abortion, (2) 48 women who experienced unexplained fetal death, (3) 145 healthy fertile control subjects, and (4) 67 women with well-characterized antiphospholipid syndrome. Serum immunoglobulin A, immunoglobulin G, and immunoglobulin M anti-beta(2)-glycoprotein I and anticardiolipin antibodies were determined by enzyme-linked immunoassay. RESULTS: Groups of women who experienced unexplained recurrent spontaneous abortion and unexplained fetal death had a higher proportion of women who had positive test results for immunoglobulin A anti-beta(2)-glycoprotein I antibodies than fertile control subjects (P < .01, chi-square test); these subjects also had higher levels of autoantibody (P = .001, Kruskal-Wallis). Women who experienced recurrent spontaneous abortion had a higher proportion of women with positive test results for immunoglobulin A anticardiolipin antibodies compared to fertile control subjects (P < .05, chi-square test); this group also had higher levels of autoantibody (P = .0065, Kruskal-Wallis test). Linear regression analysis showed significant correlation between anti-beta(2)-glycoprotein I immunoglobulin A and anti-beta(2)-glycoprotein I immunoglobulin G (R = .609; P =.0001) and less correlation between anticardiolipin immunoglobulin A and anticardiolipin immunoglobulin G (R = .093; P = .065). CONCLUSION: Immunoglobulin A anti-beta(2)-glycoprotein I antibodies are more common in women who experience unexplained recurrent spontaneous abortion and unexplained fetal death whose initial test results are negative for lupus anticoagulant and immunoglobulin G anticardiolipin antibodies compared to fertile control subjects. Therefore, these antibodies may identify additional women with clinical features of antiphospholipid syndrome who are not identified through traditional testing. It is unclear whether these antibodies are directly pathogenic, a result of the pregnancy losses, or markers for an underlying, yet uncharacterized autoimmune disorder.     

Acquired thrombophilias and pregnancy

Acquired thrombophilias are hypercoagulable states secondary to various aetiologies. In particular, during pregnancy the risks are exaggerated due to the underlying physiological changes. The commonest cause of acquired thrombophilia in pregnancy is antiphospholipid syndrome. Antiphospholipid syndrome (APS) is a complex multisystem disorder that has been associated with varied medical and obstetric complications. The pathogenesis of APS has been further elucidated in recent studies. The two most clinically significant antiphospholipid antibodies that are associated with recurrent pregnancy loss and thromboembolism are anticardiolipin antibodies (aCL) and lupus anticoagulant (LA). The laboratory diagnosis is based on the presence of moderate to high positive aCL and/or LA antibodies. It is crucial that APS is not inappropriately diagnosed as this has implications for counselling and management with thromboprophylaxis during pregnancy. Over the last decade there have been significant changes in the laboratory and clinical criteria for the diagnosis of APS. National and international collaborations have made efforts to standardize the laboratory methods. There have been very few randomized placebo-controlled trials of drug therapy and so not all drug treatment strategies have a strong evidence base. With current management strategies, using low-molecular-weight heparin and aspirin, a greater than 70% live birth rate may be achieved in affected pregnancies. A multidisciplinary approach in the management of these women is vital.     

Preliminary results of the heparin treatment in anticardiolipin and antihistone antibodies seropositive pregnant women

The presence of elevated titres of anticardiolipin antibodies (ACA) and antihistone antibodies (AHA) in the blood serum is considered as one of serious reasons of repeated pregnancy losses. According to some reports, heparin significantly improves live birth rates in these cases. The aim of the work is an evaluation of the results of the heparin therapy in pregnant women with elevated titres of ACA and/or AHA in blood and bad obstetric anamnesis, or after sterility treatment. Our material consisted of three groups: the first one was composed of 25 ACA- and/or AHA-seropositive pregnant women 30.0 +/- 4.1 years old with 1-5 early miscarriages in past, the second one of six seropositive patients 31.3 +/- 2.8 years old, actually pregnant after the treatment of unexplained sterility (two of them after assisted reproduction) and, finally, in the third group were placed five pregnant ACA- and AHA-seronegative pregnant women 30.8 +/- 2.2 years old with 2-4 abortions of unexplained etiology in past. The ACA IgA, IgM and IgG and AHA IgG levels in blood sera were determined by ELISA. As a positive titre ACA in the class IgA was considered > 7 APL/ml, in the class IgM > 4 MPL/ml, IgG > 7 GPL/ml and in case of AHA IgG > 25 GPL/ml. The patients were treated by heparin 7500-30,000 units daily during all the pregnancy under the control of kaolin-kephalin time. In the first group, where 53 pregnancies from 56 were miscarried (94.6%), after the heparin therapy in 10 women 9 pregnancies of 11 (81.8%) were terminated by live birth (p < 0.001). One of the patients died three days after cesarean section because of myocardial infarction, probably due to sudden stopping of heparin. In the second group three women after heparin treatment delivered live babies, but three untreated aborted. In the last group only two women treated by heparin delivered live babies and three, despite treatment, miscarried. It should be concluded, that heparin therapy in ACA- and/or AHA-positive pregnant women might be a recommended therapeutic method. In cases of antiphospholipid syndrome a special precaution should be undertaken, when stopping the heparin. It seems, that double assay of ACA and AHA in patients with conception troubles might be usefull.     

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.     

Prospective study of anticardiolipin antibodies in immunized and untreated women with recurrent spontaneous abortions.

OBJECTIVE: To investigate whether active leukocyte immunization increases levels of anticardiolipin antibodies in women with recurrent spontaneous abortions. To assess the impact of anticardiolipin antibodies on pregnancy outcome in these women. DESIGN: Patients who had received various treatments in an ongoing randomized trial were studied prospectively. SETTING: A department of clinical immunology investigating women with recurrent spontaneous abortions from all over Denmark. PATIENTS: Eighty-nine patients with unexplained recurrent spontaneous abortions whose pregnancies had been completed during the course of the trial. INTERVENTIONS: After randomization, 44 patients were actively immunized with husband's or third party leukocytes, and 27 patients received placebo. Eighteen patients received anticoagulation therapy in pregnancy. MAIN OUTCOME MEASURES: Changes in levels of immunoglobulin (Ig)M class and IgG class anticardiolipin antibodies after active immunization. Frequency of new miscarriages in patients who were positive or negative for anticardiolipin antibodies. RESULTS: Neither IgM nor IgG anticardiolipin antibodies changed significantly after active immunization (P greater than 0.2). The interim results of the immunization trial showed a success rate of 68% in the treated group versus 56% in the placebo group (not significantly different). Relative risk of miscarriage in anticardiolipin antibody-positive patients compared with anticardiolipin antibody-negative patients was 1.3 (95% confidence interval 0.7 to 2.2; P = 0.4) in the combined study groups. CONCLUSIONS: Patients eligible for active immunization did not exhibit significant changes in anticardiolipin antibody levels subsequent to the treatment. The treatment did not seem to provide any overall benefit with respect to pregnancy outcome. Prospectively, the risk of miscarriage in patients positive for anticardiolipin antibodies was not significantly increased.     

Antiphosphatidyl serine antibodies are more common in normotensive women with small for gestational age pregnancies

BACKGROUND: Small for gestational age (SGA) babies are more common in women with antiphospholipid antibodies but data are limited about the prevalence of antiphospholipid antibodies in women who have delivered SGA babies. AIM: To determine whether elevated levels of anticardiolipin, antiphosphatidyl serine and/or antibeta2 glycoprotein I antibodies are more common in normotensive women who delivered SGA babies compared with women who delivered appropriate for gestational age babies. METHODS: Case-control study. Cases were normotensive women who delivered an SGA baby (birthweight <10th%) without chromosomal or congenital abnormality. Controls were healthy women who delivered a baby at term with birthweight >10th percentage. RESULTS: A total of 137 women with SGA pregnancies and 290 controls had antiphospholipid antibodies measured. The prevalence of anticardiolipin and antibeta2 glycoprotein I antibodies did not differ between SGA cases and controls. Antiphosphatidyl serine IgG antibodies were more common in women with SGA pregnancies than controls seven (5%) versus five (1.7%), relative risk (RR) 1.84 (1.12-3.03). There was no difference in the prevalence of 'any antiphospholipid antibodies' between SGA 10 (7.2%) and controls 16 (5.6%). There was a trend to more abnormal umbilical Doppler studies in SGA pregnancies with positive antiphospholipid antibodies three (50%) versus 19 (24%), RR 2.9 (0.62-13). CONCLUSIONS: Antiphospholipid antibodies were uncommon in this cohort of SGA pregnancies. Further studies are needed in SGA pregnancies with abnormal umbilical Doppler studies to determine if screening for antiphospholipid antibodies is worthwhile in this severe subgroup.     

Antiphospholipid Antibodies in Pregnancy

We assessed the relationship between antiphospholipid antibodies and recurrent miscarriage, fetal deaths, and the pregnancy complications--placental abruption, fetal growth retardation and preeclampsia. The subjects were 81 women with a history of 3 or more miscarriages, 62 with a history of fetal death in the index pregnancy, 105 with a poor obstetric history or pregnancy complications and 13 with systemic lupus erythematosus. Antiphospholipid antibodies were found in 41% of women with a history of recurrent miscarriages, 29% with a history of recent intermediate fetal death or stillbirth, 19% with a poor obstetric history and 69% with systemic lupus erythematosus. There is a high incidence of antiphospholipid antibodies in complicated pregnancies. Patients presenting with the above pregnancy disorders should be tested for antiphospholipid antibodies because of the risk conferred on a fetus by their presence and to expand the treatment options.     

High serum luteinizing hormone and testosterone concentrations do not predict pregnancy outcome in women with recurrent miscarriage

OBJECTIVE: To investigate the relationship between Day 8 serum luteinizing hormone (LH) and testosterone (T) concentrations, and body mass index (BMI) with pregnancy outcome in women with recurrent miscarriage. DESIGN: Prospective observational study. SETTING: National recurrent miscarriage clinic. PATIENT(S): Three hundred forty-four women (median age 32 years; range 18-44) with a history of recurrent first trimester miscarriage (median 4; 3-14; <12 weeks gestation) who conceived spontaneously and who received no pharmacological treatment during pregnancy were studied. All women were antiphospholipid antibody negative and had a normal peripheral karyotype as did their partners. INTERVENTION(S): Outcome of untreated pregnancies. MAIN OUTCOME MEASURE(S): Day 8 serum LH and T concentrations and BMI were correlated with pregnancy outcome. RESULT(S): One hundred and ninety-two (55.8%) women had a live birth and 152 (44.2%) women miscarried. Polycystic ovarian morphology was diagnosed in 174 women (50.6%). There was no significant relationship between follicular phase LH concentrations and pregnancy outcome. Pregnancy outcome was similar in women with normal and high serum T concentrations. BMI value was not significantly different between women who had a live birth and those who miscarried. CONCLUSION(S): The analysis of this large cohort of women with recurrent miscarriage demonstrates that prepregnancy Day 8 serum LH and T concentrations, and BMI do not have a statistically significant relationship with pregnancy outcome.     

The prevalence and biologic significance of lupus anticoagulant and anticardiolipin antibodies in a general obstetric population

Circulating antibodies to negatively-charged phospholipids have been implicated in the genesis of adverse pregnancy outcomes. However, it has yet to be established that these antibodies are causative or that they are invariably associated with untoward perinatal outcomes. To address this issue, the prevalence of lupus anticoagulant and anticardiolipin antibodies was recorded in a low-risk obstetric population, and the outcome of untreated pregnancies were evaluated. Two of 737 patients (0.27%) had lupus anticoagulant documented by a prolonged activated partial thromboplastin time that did not correct this mixing studies. In comparison, greatly elevated concentrations of immunoglobulin M-anticardiolipin antibodies or immunoglobulin G-anticardiolipin antibodies were identified in 16/737 (2.2%) patients by means of an enzyme-linked immunosorbent assay. Spontaneous abortions occurred in both lupus anticoagulant-positive patients, suggesting that the activated partial thromboplastin time used was a relatively insensitive but specific marker for antiphospholipid antibody-associated adverse pregnancy outcomes. In contrast, although 12 of 16 anticardiolipin antibodies-positive pregnancies were complicated by perinatal loss, preterm delivery, or fetal growth retardation, four patients had uncomplicated pregnancies. Moreover, the distribution of anticardiolipin antibodies concentrations in these four patients was not clustered among the lowest anticardiolipin antibodies values, and anticardiolipin antibodies concentrations correlated weakly with adverse outcomes. These findings suggest that antiphospholipid antibodies are related to adverse pregnancy outcomes in a complex fashion and that therapy is not always required for acceptable outcomes in patients without other risk factors.     

Antiphospholipid syndrome and recurrent miscarriages

Sixty percent of recurrent spontaneous abortions are unexplained. Antiphospholipid syndrome is a multisystem disease with the predominant features of venous and arterial thrombosis, recurrent pregnancy loss, foetal death and the presence of antiphospholipid antibodies. Many epidemiological studies focus on antiphospholipid autoantibodies syndrome (APS) as a cause of recurrent spontaneous abortion (RSA). It is found that 7-25% of RSA would have APS as the main risk factor. 'Association not being synonymous with cause', the proportion of abortions due to the APS is difficult to estimate for several reasons: definition of recurrent abortion is variable, the assays for antiphospholipid antibodies are not well standardised, inclusion of patients in the study group according to the antibodies titre is author dependent. Recent studies suggest association of antiphospholipid antibodies syndrome not only with recurrent abortions but also with infertility. New mechanisms are described by which antiphospholipid antibodies could cause placental thrombosis and infarction, acting directly on the surface anticoagulant expressed on trophoblastic cells. Only lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) assays are sufficiently standardised to be usable in routine. Testing for other antiphospholipid antibodies (aPLs) should remain investigational. Several treatments have been proposed: low doses of aspirin, low or immunosuppressive doses of corticosteroids, and preventive or effective dose of heparin, intravenous immunoglobulin.