Recurrent miscarriage

Recurrent miscarriage is the spontaneous loss of three or more consecutive pregnancies with the same biological father in the first trimester; it affects 1% to 2% of women, in half of whom there is no identifiable cause. Overall, 75% of affected women will have a successful subsequent pregnancy, but this rate falls for older mothers and with increasing number of miscarriages. Recurrent miscarriage causes considerable distress and psychological morbidity. Antiphospholipid syndrome, with anticardiolipin or lupus anticoagulant antibodies, is present in 15% of women with recurrent first- and second-trimester miscarriage. We examined evidence from RCTs and systematic reviews of RCTs in women with three or more unexplained recurrent miscarriages. For many of the interventions, we found few high-quality studies available. There is a need for further high-quality RCTs in this field to inform clinical practice. We don't know whether lifestyle adaptation (to stop smoking, reduce alcohol consumption, and lose weight) or low-dose aspirin increase the likelihood of a successful pregnancy in women with unexplained recurrent miscarriage. We found no RCTs on the effects of lifestyle interventions. We only found one small RCT (54 women) with low-dose aspirin that met our inclusion criteria. Hence, it was difficult to draw any robust conclusions. We found one further larger RCT (364 women) on low-dose aspirin (in women with two or more recurrent miscarriages), which was outside our inclusion criteria for this BMJ Clinical Evidence overview. We don't know whether progesterone supplementation or corticosteroids reduce miscarriage rates compared with placebo in women with unexplained recurrent miscarriage. The evidence on progesterone was difficult to interpret because of methodological weaknesses in the trials, such as quasi-randomisation, and because many of the trials were old. However, further RCTs are currently under way, which may clarify the position. We found one small pilot RCT on corticosteroids in a sub-group of women with unexplained recurrent miscarriage who had high levels of uterine natural killer (uNK) cells on screening. However, we found no RCTs in the general population of women with unexplained recurrent miscarriage. Intravenous immunoglobulin treatment does not seem likely to improve live birth rates compared with placebo in women with unexplained recurrent miscarriage, and it may be associated with adverse effects.