Reviews in Gynaecological Practice 3 (2003) 46–50 Review Recurrent miscarriage: an overview Feroza Dawood 1 , Siobhan Quenby * , Roy Farquharson 2 University Department of Obstetrics and Gynaecology, Liverpool Women’s Hospital, Crown Street, Liverpool L8 7SS, UK Received 20 January 2003; accepted 4 February 2003 Abstract Recurrent miscarriage (RM) is a clinical condition of heterogeneous aetiology. Classification of recurrent pregnancy loss is a crucial tool in the investigation and exploration of pathophysiological mechanisms. Some of the previous causes of RM, such as polycystic ovaries, and endocrinopathies are now viewed with scepticism, paving the way for a modern, refined and evidence-based approach. While the antiphospholipid syndrome continues to be a prominent feature in RM, the traditional thrombotic pathogenetic mechanism has been extrapolated, encompassing the direct effect of anticardiolipin antibodies on trophoblast invasion. Furthermore, the emergence of other thrombophilias, have gained more consideration as aetiological factors. At the molecular and biological phases, more light has been shed on immunological influences and the role of a hostile endometrium. The fate of normal and abnormal embryos has challenged traditional concepts of RM, giving birth to the paradigm of nature’s quality control. © 2003 Elsevier Science B.V. All rights reserved. Keywords: Embryonic losses; Fetal losses; Decidual immunology; Antiphospholipid syndrome; Thrombophilia 1. Introduction Recurrent miscarriage (RM), defined as three consecutive pregnancy losses less than 24 weeks of gestation, is a con- dition that affects 1% of fertile couples. Despite burgeoning areas of research in this perplexing field, in approximately 50% of cases the clinical situation remains inexplicable. This review emphasises recent trends and theories in this challenging area. 1.1. Pregnancy loss classification As our knowledge of the intricacies of early pregnancy development expands, it is becoming more apparent that dif- ferent pathologies occur at different stages of pregnancy. By adopting a pregnancy loss classification, one can approach diagnosis and appropriate treatment with a greater degree of finesse. A suggestion of pregnancy loss classification is set out below Table 1. * Corresponding author. Tel.: +44-151-702-4332; fax: +44-151-702-4024. E-mail addresses: Feroza.Dawood@lwh-tr.nwest.nhs.uk (F. Dawood), squenby@liv.ac.uk (S. Quenby), roy.farquharson@lwh-tr.nwest.nhs.uk (R. Farquharson). 1 Tel.: +44-151-702-4345; fax: +44-151-702-4024. 2 Tel.:+44-151-702-4001; fax: +44-151-702-4137. 2. Embryonic losses 2.1. Karyotype abnormalities The majority of miscarriages occur in the embryonic pe- riod. One of the most remarkable and as yet unexplained as- pects of embryonic losses, is the fact that the majority (90%) of karyotypically abnormal pregnancies miscarry in the first trimester and the majority (93%) of karyotypically normal pregnancies continue [1]. This has led to the innovative ap- proach of viewing miscarriage as a natural process of quality control and RM as failure of this quality control. In support hereof, when pre-implantation genetic diagnosis (PGD) was used to investigate women with RM, it was discovered that they produce more aneuploid embryos than normal women [2]. When PGD is used to discard karyotypically abnormal embryos (known as aneuploidy screening), the miscarriage rate after IVF decreases [3]. Culture and karyotyping of miscarried pregnancies from women suffering RM has detected a 29–57% abnormality rate [4,5]. However, these figures may underestimate the ac- tual incidence of chromosomal anomalies, as conventional cytogenetic analysis of miscarried tissue depends on cultur- ing and karyotyping, a technique limited by external con- tamination, culture failure and selective growth of maternal cells. Analysis of spontaneous miscarriages by the technique 1471-7697/03/$ – see front matter © 2003 Elsevier Science B.V. All rights reserved. doi:10.1016/S1471-7697(03)00004-2