Pregnancy losses (miscarriages) usually happen as a result of factors in the foetus or in the mother. However, in 50% of cases, the pregnancy losses that happen during the first trimester of pregnancy are caused by chromosomal abnormalities in the embryo and the number of cases are higher number in women of an advanced age. Abnormalities can be numerical and/or structural. Numerical abnormalities (the most common type of abnormality) occur in embryos that have one or several chromosomes too many (trisomy/polysomy) or too few (monosomy). Structural abnormalities (less common), on the other hand, involve duplicates or a total absence of certain chromosomal regions, or an exchange of genetic material between two chromosomes (translocation), or a chromosomal region that has been reversed inside the chromosome itself (inversion).
What genetics techniques are used to detect chromosomal abnormalities in pregnancy losses?
Once the tissue from the pregnancy loss has been retrieved, the techniques that are most commonly used for detecting chromosomal abnormalities include FISH (fluorescent in situ hybridisation) and the karyotype technique. The FISH method can analyse if there are abnormalities in any of the chromosomes within a 24-hour period. The chromosomes that are analysed most frequently are chromosomes 21, 13, 18 (causes of Down’s, Patau and Edwards syndromes, respectively), the sex chromosomes (X and Y) and chromosomes 16 and 22 (common in pregnancy losses). A karyotype, however, allows us to see all the chromosomes and to compare numerical or structural abnormalities in any of the 46 chromosomes in each of the foetus’ cells. However, its disadvantage is that cells need to be cultivated and this usually takes around 15 days. Furthermore, there is the chance of cell growth not occurring or there being some contamination from the mother.
Nowadays, we have access to techniques that provide more conclusive results in comparison with conventional karyotypes. For example, array CGH which can detect smaller abnormalities. However, the disadvantages of this technique include the fact that it is expensive and that it does not detect balanced chromosomal abnormalities (translocations or inversions) nor cases of polysomy.
When should a pregnancy loss be analysed?
Analyses can be performed when a women has a pregnancy loss that has an unknown cause and particularly when couples have recurrent spontaneous pregnancy losses.
What is the clinical purpose of a genetic analysis following a pregnancy loss?
Analyses of this kind allow couples to understand if genetics is the cause of the pregnancy losses and, as such, minimise the risks in any future pregnancies. Furthermore, couples who are scheduled to have assisted reproduction treatment can use this information to obtain appropriate genetics guidance for that treatment and achieve the successful pregnancy they want. With this in mind, genetics techniques currently include tests such as comprehensive chromosome screening (a-CGH/NGS) which make it possible to transfer chromosomally normal embryos.