Role of Genetic Factors in Recurrent Pregnancy Loss

Genetic Factors Responsible for Recurrent Pregnancy Loss

Chromosomal abnormalities of the embryo account for at least 50% of first-trimester sporadic Miscarriages and 30% to 60% of further miscarriages in couples with recurrent miscarriage. More recently, analysis of miscarriage tissue by comparative genomic hybridization (a technique that detects chromosomal abnormalities without the need for culture) showed that conventional cytogenetic analysis underestimates the incidence of chromosomal anomalies and that the contribution of chromosomal abnormalities to first-trimester miscarriage is nearly 70%.


Parental Chromosomal Rearrangement (Translocation)

In approximately 3% to 5% of couples with recurrent miscarriage, one partner carries a balanced structural chromosomal abnormality. Women are more likely than men to carry most types of chromosomal rearrangements.The most common types of parental chromosomal abnormalities are balanced translocations. Although carriers of a balanced translocation are usually phenotypically normal, their pregnancies are at increased risk for miscarriage and may result in a live birth of a child with multiple congenital malformations or mental handicaps because of an unbalanced chromosomal arrangement. The risk of miscarriage is affected by the size and genetic content of the rearranged chromosomal segments.A less common chromosomal abnormality that may cause recurrent miscarriage is a chromosome inversion. This has been reported in 0.2% of couples with recurrent miscarriage.

Embryonic Aneuploidy and Polyploidy (Abnormal numbers of chromosomes)

Aneuploidy is caused by nondisjunction during meiosis that leads to the production of an extra chromosome (trisomy) or the deletion of a chromosome (monosomy). Triploidy occurs when there is a complete set of extra chromosomes. This usually arises from fertilization of the oocyte by two spermatozoa or from failure of one of the maturation divisions of either the oocyte or the spermatozoon. Tetraploidy (four times the haploid number) is usually caused by failure to complete the first zygotic division. In couples with recurrent miscarriage, conventional cytogenetic analysis reports the incidence of trisomy, polyploidy, and monosomy X in miscarriage tissue as 30%, 9%, and 4%, respectively. Most trisomies are the result of meiotic error as a result of advanced maternal age; however, gonadal mosaicism and sperm aneuploidies also increase the risk of trisomic conceptions. The risk of sex chromosome monosomy and polyploidy conceptions do not increase with maternal age.

Molecular Mechanisms - The latest thoughts:

Recent advances in molecular genetic technology highlighted the importance of certain mechanisms,such as single-gene mutations and skewed X chromosome inactivation,in the etiology of pregnancy loss.