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 miscamage 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 2 5 per litre units and an IgM anticardiolipin level 2 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 miscamage or at 34 weeks of gestation.Results One hundred and seven pregnancies (7 1 %) 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 whq died in the neonatal period. One pregnancy was terminated for a fetal anomaly. Gestational hypertension complicated 17% (1 8/108) 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 5314300); however 15% (16/108) of the infants were small for gestational age. ConclusionCombination treatment with aspirin and heparin leads to a high live birth rate among women with recurrent miscamage 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.

The purpose of this study was to determine the prevalence of thyroid antibodies in women with recurrent miscarriage and to observe whether their presence was predictive of future pregnancy outcome. A total of 870 consecutive, non-pregnant women with a history of three or more pregnancy losses and normal parental karyotypes were investigated for the presence of thyroglobulin antibodies (TgAb) and for thyroid microsomal antibodies (TmAb). Thyroid antibodies were found in 162 (19%) women. TgAb only were found in eight women (5%); TmAb only in 98 (60%) and both TgAb and TmAb were found in 56 (35%). Thirteen women had a history of thyroid disease and a further 15 women were found to have abnormal thyroid function. All 28 were excluded from the pregnancy outcome study. Among the remaining 134 thyroid antibody positive women, 36 women were not tested and normal thyroid stimulating hormone results were obtained for 98. In the group proven euthyroid, 14 of 24 untreated pregnancies resulted in live births (58%). Among the 710 thyroid antibody negative women, 47 of 81 untreated pregnancies resulted in live births (58%). The future risk of pregnancy loss in women with unexplained recurrent miscarriage is not affected by their thyroid antibody status.

Recurrent miscarriage and later pregnancy complications are in some cases associated with placental thrombosis and infarction. The aim of this study was to assess the value of low dose aspirin (75 mg daily) in improving the subsequent livebirth rate amongst women with either unexplained recurrent early miscarriage (<13 weeks gestation; n = 805) or unexplained late pregnancy loss (n = 250). Amongst women with recurrent early miscarriages, there was no significant difference in the livebirth rate between those who took aspirin (251/367; 68.4%) compared with those who did not take aspirin [278/438; 63.5%; odds ratio (OR) 1.24; 95% confidence interval (CI) 0.93-1.67]. This relationship was independent of the number of previous early miscarriages. In contrast, women with a previous late miscarriage who took aspirin had a significantly higher livebirth rate (122/189; 64.6%) compared with those who did not take aspirin (30/61; 49.2%: OR 1.88; 95% CI 1.04-3.37). The empirical use of low dose aspirin amongst women with unexplained recurrent early miscarriage is not justified. We are currently investigating the role of incremental doses of aspirin in the treatment of women both with early miscarriages associated with thrombophilic abnormalities and in those with late pregnancy losses.

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Summary.We have investigated the potency of the C677T mutation in the methylene tetrahydrofolate reductase (MTHFR) gene as a genetic risk factor in women with a history of early (р12 weeks gestation) and/or late (>12 weeks gestation) recurrent miscarriage (three or more consecutive pregnancy losses). Fifty-seven of the total 173 (32·9%) patients were heterozygous for the MTHFR mutation, 14/173 (8·1%) were homozygous (allele frequency 0·25). The prevalence of the MTHFR mutation in these women did not differ significantly from that in the control group of parous women with uneventful pregnancies, where 30/67 (44·8%) were heterozygous and 6/67 (9·0%) homozygous for the mutation (allele frequency 0·31; odds ratio for homozygous T/T 0·90, 95% CI 0·30-2·4). There was no association between the trimester of pregnancy loss and MTHFR genotype. We conclude that the C677T MTHFR mutation is not a risk predictor in women with a history of early or late recurrent miscarriage.