Unexplained recurrent miscarriage: how can we explain it?

Unexplained recurrent miscarriage (RM) can be a challenging and frustrating condition for both patients and clinicians. For the former, there is no diagnosis available for consolation, while for the latter there is little evidence-based treatment to offer. However, the majority of these patients have an excellent prognosis without the need for any treatment. Epidemiological associations suggest that the reason for this is that the majority of women with unexplained RM are in fact healthy individuals, with no underlying pathology, who have suffered three miscarriages purely by chance. Nevertheless, a certain proportion of women with unexplained RM will continue to miscarry, and preliminary studies suggest the presence of pathology in some women of this group. As a result, two types of unexplained RM can be described: Type I unexplained RM, which occurs by chance in women who have no underlying pathology and has a good prognosis; and Type II unexplained RM, which occurs due to an underlying pathology that is currently not yet identified by routine clinical investigations and has a poorer prognosis. Distinguishing between Types I and II unexplained RM can be achieved by considering several factors: the age of the woman, the definition used for RM (i.e. whether biochemical pregnancy losses are considered as miscarriages), the number of previous miscarriages suffered and the karyotype of the products of conception, where available. A better understanding of the two types of unexplained RM could lead to more targeted referrals, investigations and treatments, which would improve cost-effectiveness and overall clinical care.