What Are the Genetic Causes of Recurrent Pregnancies?

What Are the Genetic Causes of Recurrent Pregnancies?

Recurrent pregnancy loss is defined as 2 or more clinically proven embryonic and/or fetal losses before the 20th week of pregnancy. 3-5% of couples experience recurrent pregnancy loss and in more than 50% of these, the cause cannot be clarified.

Causes of Recurrent Pregnancy Loss

  • Genetics
  • Anatomical (Structural anomalies of the reproductive system)
  • Endocrine (Diabetes, Thyroid hormone disorders, etc.)
  • Antiphospholipid antibody syndrome
  • Immunological causes
  • Infections
  • Environmental factors: obesity, smoking and alcohol use
  • Unknown

Genetic Causes of Recurrent Pregnancy Loss

Genetic causes constitute an important part of recurrent pregnancy losses. It is thought that an important part of pregnancy loss of unknown cause, some anatomical problems in the mother and hormonal disorders are due to genetic causes. Genetic loss can be caused by parents or fetal causes.

Genetic Causes of the Fetus/ Embryo

  • Chromosomal diseases
  • Fetal aneuploidy (Down syndrome, Turner syndrome
  • Copy number changes (microdeletion or microduplications)
  • Single gene or multiple gene mutations (errors)
  • Epigenetic changes

The frequencies and specific types of chromosomal anomalies are associated with gestational week and maternal age. Numerical chromosomal abnormalities (aneuploidies) are the most common cause of miscarriage, especially in the first trimester (first 12 weeks). Most aneuploidies are caused by random errors in germ cell development. Usually, the parental chromosome analysis is normal and it is not expected to repeat in the next pregnancy. Among the genetic causes of recurrent pregnancy loss due to the fetus, there are copy number changes, single gene mutations and other genetic causes (epigenetics) apart from chromosomal anomalies.

Parental Genetic Causes

  • Presence of a structural chromosomal disorder or numerical mosaic chromosomal disorder in one or both of the couples
  • Carrier of a single or multiple gene mutation in one or both of the couples
  • Mutation in the genes that predispose to clotting in the mother

Genetic Tests

Couples with a history of recurrent pregnancy loss must be evaluated by a medical geneticist. Information such as the number and week of pregnancy loss in these couples, the presence of structural anomalies accompanying the fetus (such as cystic hygroma, cleft palate) are very valuable in the planning of genetic tests.

  • Chromosome analysis (from parents, abortion material)
  • aCGH (Microarray, microarray) analysis from low material
  • Disease-specific gene sequence analysis
  • Whole exome analysis (WES)
  • Optical mapping

The Importance of Genetics in Diagnosis and Treatment

  • Determining the cause of recurrent pregnancy loss reduces the anxiety in couples and directs them to the next stage.
  • Couples with chromosomal disorders or mutant (mistaken) gene carriers are offered the option of in vitro fertilization.
  • It ensures that people with a similar family history or who are likely to experience similar problems are identified and accurate pregnancy planning is made.