Chromosomal Testing of Products of Conception

Approximately 15% of pregnancies end in a spontaneous abortion. In addition, once a woman has suffered one, the possibility of suffering a second is higher. Therefore, if this case would to occur, we could be dealing with a case of recurrent or repeated miscarriage (up to 1% of couples suffer this). Specialists indicate that it would be necessary to begin a study from the fourth spontaneous abortion, even though, depending on the age of the couple, it is possible to begin from the third one.

The cause of repetitive spontaneous abortions can be various; however, in many cases it is difficult to associate a specific pathological condition as the true cause of the embryo loss. Among the most probable causes, we can find factors that can cause thrombophilia or uterine pathologies, but also other nutritional or environmental factors. The age of the mother is also decisive, as well as the presence of genetic alterations which can be inherited or produced de novo during the development of the embryo.

Among the studies to be carried out on couples that suffer repetitive spontaneous abortions, it can be extremely useful to carry out a karyotype on both members of the couple, and even on the rest of the aborted remains. The presence of any type of chromosomal alternation will be studied (the most frequent are reciprocal balanced translocations), and if the patient is asymptomatic, when producing gametes it could be possible that these are genetically altered. The combination of the gametes with the partner’s will generate an embryo that will most likely have chromosomopathy and, with that (in the majority of cases) pregnancy loss.

Another alternative would be to carry out a technique called FISH. With this technique it is possible to analyse whether the chromosomes have an adequate amount or, on the contrary, if they show any loss of gain with regard to the genetic material, by means of specific probes that specifically hybrid in the chromosomes of the patient.

However, both techniques have some disadvantages. A traditional karyotyping implies carrying out a cell culture, which should grow over a few days until an adequate amount of cells allow us to analyse the minimum number of metaphase stages. In addition, this technique has been used for more than 50 years with practically any variation, which means that its production is highly traditional giving it a highly subjective feature. In the FISH technique, however, we will analyse only some of the fragments in some chromosomes. There is a limit of probes that can be used and, in order to completely analyse the whole karyotype, we must combine these probes making this process greatly laborious.

In practice, a traditional karyotyping assay is usually prepared, and only if an alternation is found, will the FISH assay be planned. If, on the other hand, a FISH assay is directly carried out, it usually concentrates on the chromosomes that are easily altered, such as 13, 18, 21, X and Y. Finally, we should stress that in both cases, the results can be extremely variable depending on the area in which the patient lives and of the person who carries out the analysis.

At Bioarray, we have a new technique available to analyse the aborted remains. The array for detecting chromosomal anomalies in spontaneous abortions has been specifically designed to identify chromosomal alternations that are found in the remains, so that the presence of alternations can be detected, both in the parents as well as the embryo. Our array is based on carrying out a molecular karyotyping which is able to multiply by 10 the resolution of the traditional karyotyping, eliminating any chance of subjective interference and avoiding the need to carry out cell cultures (also reducing the time to provide the result).

Uses:

• Repetitive spontaneous abortions of an unknown cause.
• Genetic diagnosis of the aborted remains. Detection of aneuploidies.
• Genetic counselling for couples who suffer from miscarriages.
• Therapeutic decision.

Advantages:

• Very little material is needed.
• A much higher resolution is obtained with regard to conventional karyotyping.
• A cell culture is not necessary.
• Quicker diagnosis. The couple can take the necessary measures, resuming their attempt to become pregnant in the lowest time possible.
• We eliminate any alteration in the result due to subjective causes.

Bibiography

• Perrin, A. et al. Fertil Steril. 2010; 93: 2075.e3-6
• Rajcan-Separovic, E. et al. Mol Hum Reprod. 2010; 16: 125-34
• Dória, S. et al. Eur J Obstet Gynecol Reprod Biol. 2009;147:144-50.

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