Recurrent spontaneous miscarriage is still a challenging diagnostic and therapeutic quagmire

Recurrent spontaneous miscarriage (RSM), affecting 1-2% of women of reproductive age seeking pregnancy, has been a clinical quagmire and a formidable challenge for the treating physician. There are many areas of controversy in the definition, aetiology, investigations and treatment of RSM. This review will address the many factors involved in the aetiology of RSM which is multifactorial in many patients, with antiphospholipid syndrome (APS) being the most recognized aetiological factor. There is no identifiable cause in about 40-60% of these patients, in which case the condition is classified as idiopathic or unexplained RSM. The RSM investigations are extensive and should be undertaken in dedicated, specialized, well-equipped clinics/centres where services are provided by trained specialists. The challenges faced by the treating physician are even more overwhelming regarding the decision of what should be the most appropriate therapy offered to patients with RSM. Our review will cover the diverse modalities of therapy available including the role of preimplantation genetic testing using recent microarray technology, such as single nucleotide polymorphism and comparative genomic hybridization, as well as preimplantation genetic diagnosis; the greatest emphasis will be on the treatment of APS, and there will be important comments on the management of patients presenting with idiopathic RSM. The controversial areas of the role of natural killer cells in RSM, the varied modalities in the management of idiopathic RSM and the need for better-planned studies will be covered as well.