Journal of Clinical and Diagnostic Research, 2018, Oct, Vol-12(10):QE01-QE05 1 1 DOI: 10.7860/JCDR/2018/36703.12078 Review Article Obstetrics and Gynaecology Section An Update on Recurrent Early Pregnancy Loss: Causes, Controversies and Cure INTRODUCTION Pregnancy is a remarkable phenomenon, however 15-25% of pregnancies end up in sporadic abortions. Less than 5% and 1% of women experience two and three consecutive pregnancy losses respectively [1]. The American Society of Reproductive Medicine defines RPL as a distinct disorder characterised by two or more documented clinical pregnancy losses excluding biochemical losses (not necessarily consecutive) [2]. European Society for Human Reproduction and Embryology [3] refers it as two or more pregnancy losses and the Royal College of Obstetricians and Gynaecologists [4], refer it as three consecutive pregnancy losses, including non-visualised ones. The expected probability of having three consecutive spontaneous abortions is about 0.3-0.4% however, the epidemiological studies have shown higher incidence [5]. The prevalence of RPL differs among international societies, as definition varies, affecting 2-5% of couples [6]. Miscarriage or spontaneous abortion is a loss of a clinical pregnancy before 20 completed weeks or the loss of an embryo/foetus of <400 gm [7]. European Society of Human Reprodction and Embryology (ESHRE) mentions it as pregnancy loss before 24 weeks or before the age of viability, which is different in different countries [8]. Primary RPL indicates two or more pregnancy losses in a woman who has not had a pregnancy beyond the age of viability; secondary RPL means multiple pregnancy losses in a women, who has a pregnancy beyond the age of viability and tertiary RPL indicates many pregnancy losses before and after the normal pregnancies [9]. The definition, investigations, and management of RPL are one of the most debated topics. This study was aimed to provide an overview of aetiologies, work-up, and an evidence-based approach to manage RPL. AETIOLOGIES AND EVALUATION FOR RPL 1. Cytogenetic Abnormalities Up to 60% of sporadic early miscarriages are attributed to chromosomal abnormalities (aneuploidies) [10]. Genetic abnormalities leading to pregnancy loss include chromosomal aberrations (numerical and structural), and gene mutations. Amongst them, the most common parental abnormality is balanced translocations, found in 3-5% of cases of RPL, compared to 0.7% in the general population [11]. Up to 60% are seen as reciprocal translocation, affecting non-homologous chromosomes and rest are Robertsonian translocations, involving acrocentric chromosomes. Paracentric and pericentric inversions are less commonly observed [11]. Other karyotypic abnormalities are ring chromosomes, deletions and duplications and mosaicism. 2. Structural Uterine Defects Uterine anomalies are found in 19% of women with RPL [12] and are acquired or congenital. Congenital Uterine Anomalies (CUA) are found in 8.4-12.6% of women with RPL compared to 1-1.5% in general population [13]. The septate uterus is the most common CUA associated with spontaneous miscarriages [14]. Other anomalies like unicornuate, bicornuate and uterine didelphys are associated with late pregnancy losses and preterm birth [14]. Acquired uterine anomalies are leiomyoma, polyp and intrauterine synechiae (adhesions), clinical significance for RPL association is unclear [15]. Intrauterine synechiae occurs when the endometrial basal layer has been destroyed frequently following curettage, other causes are uterine surgery or infection, or a complicated birth [16]. Submucosal myomas and polyps are found in 4.5% of women and 2-3% of women with RPL respectively [13]. Cervical incompetence usually causes second trimester losses, and it can be acquired following surgical trauma or is associated with CUA [13]. 3. Immunological Abnormality Because a foetus is genetically not identical to the only mother, an immunological modification is necessary to prevent immune rejection. Multiple immunogenic causes have been proposed. The autoimmune condition of importance for RPL is Antiphospholipid Syndrome (APS), which is an acquired thrombophilia. It accounts KRUPA SHAH 1 , PARVATI BHAT 2 , RAJESHWARI BHAT 3 , RUBY SULTANA 4 Keywords: Antiphospholipid antibodies, Cytogenetic abnormalities, Immunology, Recurrent miscarriage, Uterine anomalies ABSTRACT Recurrent Pregnancy Loss (RPL) is an important reproductive issue, affecting 1-5% of couples. It is characterised by repeated miscarriage, impairing the ability to have a live birth. The proven causes are diverse, such as cytogenetic abnormality, uterine anomalies, antiphospholipid antibody, metabolic and endocrine abnormalities, and about 50% cases of RPL remain still unexplained. To facilitate the diagnosis, different screening tests have been recommended, such as antiphospholipid antibody tests, thyroid stimulating hormone, glucose tolerance test, chromosomal assessment, ultrasound testing etc. RPL is associated with psychological trauma and financial burden. An evidence-based treatment is available for the majority of causes and it is seen that most of the women eventually become pregnant with an appropriate treatment plan, regardless of the cause. It has also been shown that patients presenting no abnormality on various tests may achieve a good rate of live births without special treatment. This study also includes certain controversial aetiologies and unconventional tests. This review touches on the management of various abnormalities in brief. Recurrent pregnancy loss has a significant negative life impact due to its repetitive nature; however, emotional care along with appropriate management improves chances of future pregnancy.