Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Recent thoughts on management and prevention of recurrent early pregnancy loss Ai-Wei Tang a and Siobhan Quenby b Introduction The term recurrent pregnancy loss (RPL) is used in about 1% of fertile women trying to conceive, when miscarriage occurs consecutively in three or more pregnancies [1]. It is classified as recurrent ‘early’ pregnancy loss when this occurs before 12 weeks gestation [2]. Evaluation is com- monly started after the third pregnancy loss but, depend- ing on the discretion of the physician and presence of other factors such as maternal age, can start after two pregnancy losses as the prevalence and frequency of causes found are similar in both groups [3]. The hetero- geneity of the condition and the existence of conflicting evidence in the treatment of underlying associated aetiol- ogies contribute to the challenge in the management of RPL. Furthermore, despite a wide range of investi- gations, no apparent cause is found in more than 50% of cases of RPL [4]. Although most women in this group are eager to try any form of treatment, the beneficial effects of most of these empirical treatments are yet to be proven, and thus they should not be routinely recommended. Thus, RPL is a stressful condition for both patients and clinicians alike. Recognized aetiological associations of early RPL include parental and foetal chromosomal abnormalities [5,6], structural uterine abnormalities [7], antiphospholi- pid syndrome (APS) [8], some thrombophilia [9], auto- immune disease and endocrinological disorders such as polycystic ovarian syndrome (PCOS) and untreated dia- betes [10]. There are few observational studies that give prognostic implications for positive tests for conditions associated with RPL. There are even fewer high-quality, large-scale randomized controlled trials (RCTs) showing a School of Reproductive and Developmental Medicine, University of Liverpool, Liverpool and b Clinical Sciences Research Institute, University of Warwick, Coventry, UK Correspondence to Ai-Wei Tang, MBChB, MRCOG, School of Reproductive and Developmental Medicine, 1st Floor, Liverpool Women’s Hospital, Crown Street, Liverpool L8 7SS, UK E-mail: atang@liv.ac.uk Current Opinion in Obstetrics and Gynecology 2010, 22:446–451 Purpose of review To provide an overview of the latest views and evidence available to clinicians managing couples with recurrent early pregnancy loss (RPL). Recent findings RPL is a heterogeneous condition associated with many pathologies, none of which is found in more than 50% of couples after routine investigations. The recommended treatment of low-dose aspirin and heparin in women with antiphospholipid syndrome has a weak evidence base. Recent randomized controlled trials (RCTs) of low-dose aspirin and heparin have failed to find an improvement in live birth rates, even in the presence of thrombophilia. Although parental karyotypic abnormalities are associated with RPL, conservative management of such couples may be optimal. Observational studies of hysteroscopic metroplasty have promising results, but evidence from RCTs is awaited. Progestogen therapy may improve pregnancy outcomes, but further RCTs are needed. Immunological factors are thought to be important in idiopathic RPL. Research is focused on natural killer cells and cytokines in influencing implantation as potential therapeutic treatments. Currently, RCTs have not substantiated a benefit for immunotherapy. Summary Management of RPL remains challenging, with many controversial issues regarding the underlying pathophysiology. Improvements in live birth rates in subsequent pregnancies have not been found in RCTs of treatment for most of the associated conditions. All women can be offered supportive care in subsequent pregnancies. Empirical treatment is widely used in idiopathic RPL. A better option may be to encourage women to participate in high-quality and methodologically sound studies to guide optimal management. Keywords live birth rates, management, pregnancy outcome, recurrent pregnancy loss Curr Opin Obstet Gynecol 22:446–451 ß 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins 1040-872X 1040-872X ß 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI:10.1097/GCO.0b013e32833e124e