Genetic factors influencing recurrent pregnancy loss: lessons learnt from recent studies

Abstract

Recurrent spontaneous abortions, also known as recurrent miscarriages (RMs), of unknown etiology provide a fundamental basis to understand the processes of embryogenesis and implantation. It is a distressing condition for the couple as well as the treating clinician. RM presents a varied etiology with a different combination of factors playing a role in its manifestation. Despite recent advances in the investigation and management of RM, a relatively large proportion of the cases remain idiopathic. An abortion is any loss before 20 gestational weeks [1]. RM is defined as the loss of two or more consecutive pregnancies spontaneously before the 24th week of gestation [2]. The modern definition, however, is the spontaneous loss of two or more consecutive pregnancies before 20 weeks of gestation [3,4]. A large number of pathological factors have been attributed to the etiology of RM, including chromosomal abnormalities, anatomic defects, immunological factors, endocrine disturbances and thrombophilia, to name a few. This has inevitably led to an understanding of the molecular genetic basis of these etiological factors, primarily with regard to the immunological and thrombophilic factors. Consequently, there has been a constant rise in the number of genetic association studies in different populations, including those from India. However, a definite conclusion on the molecular genetic etiology of RM is still lacking. In this article, we present a comprehensive review of such molecular genetic association studies based on the underlying genetic factors of three major etiologic categories in RM: immunological factors, thrombophilic factors and endocrine factors. Etiology of RM Genetic disordersChromosomal abnormalities occur in 50% of all conception products from first-trimester miscarriages, 5% of late pregnancy miscarriages and 0.5% of live births. These chromosomal anomalies could be due to aneuploidy (monosomy, trisomy and polyploidy) or structural abnormalities, such as translocations and inversions. Approximately 3% of cytogenetically abnormal conceptions are due to structural rearrangements [5]. Anatomical disordersAnatomical investigations are normally performed by hysterosalpingography, hysteroscopy or ultrasound scans. However, hysteroscopy and advanced imaging techniques (3D ultrasonography and MRI) and laparoscopy (if necessary) Recurrent miscarriage (RM) is the loss of three or more consecutive pregnancies before the 24th week of gestation. RM occurs chiefly owing to either a problem with the pregnancy or the environment where it implants and further development occurs. A large number of pathological factors have been attributed to the etiology of RM. A number of genetic association studies in different populations, including that of India, have been conducted, yet with no definite conclusions. This review analyzes various genetic association studies that have been conducted based on the underlying immunological, thrombophilic and endocrine factors in RM, and outlines the salient features of the findings an...