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Infertility & Recurrent Miscarriages
Experiencing Recurrent Miscarriages? It Might Be Genetic.
According to the American Society of Reproductive Medicine(ASRM), recurrent miscarriage refers to when successive pregnancies fail during weeks 12 to 20 (the second trimester). Recurrent miscarriages can have a variety of causes. These include the maternal age (at higher risk if above 35), environment (smoking and alcohol consumption), endocrine problems, blood clotting or immunological factors, such as a damaged immune system.

As stated by Family Health Service of the Department of Health, recurrent miscarriages affect about 1 in 100 women in Hong Kong; but not many consider the cause to be genetic or seek a recurrent miscarriage test. If none of the environmental factors seem to be the cause of the recurrent miscarriages, it might be time for you and your partner to consider a genetic test.
The Chromosomal Effect
Outside of lifestyle factors, chromosomal defects are the major cause of recurrent miscarriages. Testing for the genetic and chromosomal factors can help eliminate any other causes as reasons for recurrent miscarriages. There are two types of chromosomal abnormalities: aberrations in chromosome numbers and defects in chromosome structure (translocations, inversions, deletions or duplications).

Carriers of balanced chromosome rearrangements are being easily overlooked since  the symptoms of reproductive problems may not be present in any other facet of life, considering individuals can be completely healthy outside of reproductive issues. Rearranged chromosomes will have difficulty pairing up for division during meiosis, leading to gain or loss of chromosome material (Fig. 1). These imbalances are usually lethal for embryonic development, resulting in recurrent miscarriage. Sometimes, the pregnancy continues to term, producing an infant with a combination of physical problems, health problems or learning difficulties.
Carrier with normal chromosome
Carrier with balanced chromosome rearrangement
Gametes
(Sex Cells)
Possible
Results
Fertilixation
Duplication
-Deletion
Duplication
-Deletion
Translocation
Carrier
Normal
Fig 1. If one of the parent is the carrier of balanced chromosome rearrangement, the genetic defect maybe exemplified in 50% of the offspring.
Testing for Chromosomal Imbalances
To understand if the cause of the recurrent miscarriages is genetic, both parent’s will have their chromosomes mapped in a process known as karyotyping. This will determine if there are any abnormalities within the chromosomes that could be the cause of contributing to the recurrent miscarriages.

Our Hong Kong facility is capable of performing multiple genetic tests for at-risk couples or couples who are experiencing recurrent miscarriages. The test includes 2 parts:
(i)
Karyotyping: the gold standard method for detecting chromosomal disorders. Cytogenetics can detect numerical abnormalities and all structural abnormalities of size larger than 15Mb (Fig. 2a & 2b).
(ii)
Array-based Comparative Genomic Hybridization(aCGH): covers small-sized structural abnormalities, could serve the purpose of detecting copy number variants (CNVs) such as deletions and insertions with a 10-fold increased resolution compared with karyotyping (Fig. 3).
By combining the Karyotyping test and the microarray analysis, we can achieve a complete genetic map that will determine comprehensively if there is a chromosomal factor involved in the recurrent miscarriages.
Figure 2a. Metaphase Chromosome Spread
Figure 2a. Metaphase Chromosome Spread
Figure 2b. Metaphase Karyotype by Cytogenetics Analysis
Figure 2b. Metaphase Karyotype by Cytogenetics Analysis
Figure 3. A small deletion of 4 Mb detected on Chromosome 2 using array CGH.
Figure 3. A small deletion of 4 Mb detected on Chromosome 2 using array CGH.