Recurrent Spontaneous Abortion: An Overview of Genetic Backgrounds and Impact of Male Factors: A Review

Genetic factors in the form of maternal or fetal single gene disorders, chromosomal abnormalities, inherited thrombophilia and other genes involved are the main causes of recurrent abortion (RA). The risk of miscarriage is highest among couples where the woman is >35 years of age and the man >40 years of age. In about 50–70% of miscarriage, a chromosome abnormality is identified in the products of conception, this chromosomal abnormality derived from one parent or the recurrence of a numerical abnormality. In about 3-5% of couples with two or three spontaneous pregnancy losses, a balanced chromosome rearrangement was found in one member of the couple. Also man’s factors have an important role in RA since the man gamete contributes one-half of the genomic content to the embryo. Moreover the paternally expressed genes may have an impact on implantation, placental proliferation, and placenta quality. So any situation which leads damage of sperms DNA (e.g. varicocele) will be associated with a reduction in some fertility indices. Address for correspondence: Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. P.O. Box 80205, Jeddah 21589, Saudi Arabia Phone: 026401000 ext. 20187 Mobile: 00966531021514, 00201006531378 E-mail: [email protected] INTRODUCTION Spontaneous abortion is defined as the spontaneous loss of pregnancy before 24 weeks of gestation, and sometimes it is considered before 20 weeks due to advances in neonatal care(Speroff and Fritz 2005; Jauniaux et al. 2006; Branch et al. 2010). Recurrent abortion is referred to the miscarriage of two or more consecutive pregnancies in the first or early second trimester of gestation (Carp et al. 2002). Among all factors the only undisputed causes of recurrent pregnancy loss are genetic factors, anatomic or immunologic, even after a comprehensive evaluation recurrent pregnancy loss remains unexplained in well more than half of affected couples (Branch et al. 2010). GENETIC FACTORS OF RA Single Gene Disorders Certain genetic mutations thought to be involved with implantation may predispose a patient to infertility or even miscarriage (Harper 2010). An example of a single gene disorder associated with recurrent pregnancy loss of maternal origin is myotonic dystrophy. The cause of the abortion is unknown, but it may be related to abnormal gene interactions combined with disordered uterine function (Harper 2010). So diagnosis of myotonic dystrophy should be considered for a woman with recurrent miscarriage who has a family history of myotonia, and progressive muscle weakness especially in the setting of early onset cataracts (Gupta and Kabra 2011). Other maternal diseases associated with increased fetal wastage includes connective tissue disorders (for example, Marfan and EhlersDanlos syndromes) (Bick 2003; Yudaeva 2009), and hematologic abnormalities like sickle cell anemia due to increased risk of placental vessels microinfarcts (Hsu et al. 2007). Fetal causes of RA include autosomal dominant lethal skeletal dysplasias (for example, thanatophoric dysplasia and type II osteogenesis imperfecta) (Senat et al. 2007), autosomal recessive disorders (for example, Alpha thalassemia major) (Chui and Waye 1998), and X-linked disorders that are lethal in males may cause recurrent pregnancy loss (Allison and Schust 2009). So when loss of multiple male fetuses is noted in the family prdigree, lethal X-linked dominant disorders should be considered (for example, incontinentia pigmenti) (Gupta and Kabra 2011). Inherited Thrombophilias Inherited predisposition to thrombophilia is one of the main causes of RPL( recurrent preg© Kamla-Raj 2013 Int J Hum Genet, 13(2): 79-83 (2013)