Approximately 50 % of miscarriages occur due to chromosomal defects.
Chromosomally healthy individuals have 46 chromosomes — 22 pairs of autosomes and 1 pair of sex chromosomes (XX =female; XV =male). This chromosomal make-up results from meiotic divisions in both the sperm and egg, such that under normal circumstances, the egg and sperm, each containing 23 chromosomes (haploid), and will unite to form a single organism, with 46 chromosomes (diploid). Therefore, any errors in cell division, so called non-disjunction errors, can result in an egg with for example 24 chromosomes, rather than 23. Therefore, when a sperm enters, the 23 chromosomes contained therein, result in a new organism, which now contains 47 chromosomes, rather than 46. This embryo will be far less likely to come to term and the result will be a miscarriage, on the basis of a chromosomal abnormality.
Recurrent Miscarriage is also known as RPL,
recurrent pregnancy loss.
There are NUMEROUS different chromosomal abnormalities and to cover all of them is beyond the scope of this piece. Suffice it to say, however, chromosomal abnormalities are a frequent cause of miscarriage.
There are several different ways to approach the chromosomal causes of recurrent miscarriages.
The first is to take a family history to determine if there are any family members who may have a chromosomal abnormality, such as Down’s syndrome (trisomy 21), or Turner’s syndrome (45 XO). If it is determined that there is a strong family history of chromosomal problems, the services of a trained genetic counselor should be used, to develop a family tree to identify these problems with greater clarity and therefore, help to counsel the patients.
A Karyotype is frequently ordered in the work-up of patients with RPL.
A karyotype is a blood test on both the female and male partners. This will provide information on their genetic make-up. A normal make has a 46XY chromosomal pattern and the female has a 46 XX pattern. Any deviation from this, represents an abnormality and a possible explanation for the miscarriages. The problem with Karyotype analyses, is that the test is rather expensive, is low yield (not very likely to show problems) and will miss so-called point mutations (small genetic defects within the structure of the chromosome, which may be incompatible with life). However, it remains an important screening test that should be undertaken relatively early in the work-up.
The Karyotype may identify translocation disorders (where a piece of one chromosome is not located at the site it is supposed to be), or inversion problems (a segment of the chromosome is turned upside down). When this occurs, the person may be completely normal because there is balance and the abnormality is balanced by another chromosome, thereby cancelling the defect. However, when passed on to the offspring, imbalance occurs and this will inevitably result in a miscarriage.
This diagnosis is important because using IVF with PGD (pre-implantation genetic diagnosis), the defect can be diagnosed and only those embryos that are normal will be replaced. Another reason to perform a karyotype analysis in the context of RPL, relates to male patients with severe oligospermia (very low sperm count). Not infrequently, these patients may be found to have a Y chromosome microdeletion defects. Depending on what the defect is determined to be, it may be necessary to use donor sperm. The key issue is that even if it is not possible to correct the problem, helping the couple to understand their situation, can go a long way to helping them through this most difficult time in their lives.