Balkan Journal of Medical Genetics

CHROMOSOMAL ABNORMALITIES IN EARLY PREGNANCY LOSSES: A STUDY OF 900 SAMPLES
Bozhinovski Gj, Terzikj M, Kubelka-Sabit K, Jasar Dz, Lazarevski S, Livrinova V, Plaseska-Karanfilska D
*Corresponding Author: * Corresponding Author: Professor, Dijana Plaseska-Karanfilska,MD, PhD, Research Centre for Genetic Engineering and Biotechnology “Georgi D. Efremov”, Macedonian Academy of Science and Arts, Skopje, North Macedonia, mail: dijana@manu.edu.mk
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DISCUSSION

Foetal chromosomal abnormalities have been recog- nized as a major cause of EPLs [4]. Several methods have been used for the detection of chromosomal abnormalities with different detection rates [17-21]. Using a combina- tion of QF-PCR and MLPA analyses, the chromosomal abnormality rate in our study was 56.25%, which agrees with the majority of previously published data. Chromo- somal trisomies were the most frequent abnormalities (66.20%), followed by triploidy (15.28%) and monosomies (10.88%). Multiple chromosomal aneuploidies and partial chromosomal abnormalities were also identified. Thus, our approach could detect most of the chromosomal abnormalities known to cause EPLs. In comparison to the conventional cytogenetic meth- ods, our approach does not require viable tissue material, lowering the rate of unsuccessful analyses and has a po- tential to detect maternal cell contamination. Indeed, in our study 14.67% of the POC samples showed maternal contamination and were excluded from further analysis. Furthermore, the use of QF-PCR enables not only detec- tion of maternal cell contamination, but also detection of foetal triploidy, which could not be possible by using only MLPA analysis. Although QF-PCR/MLPA approach could not accurately detect other polyploidies, such as tetraploidy, these abnormalities rarely occur and represent only less than 3% of all chromosomal abnormalities in EPLs [19]. Some disadvantages of the QF-PCR and MLPA methods used in present study include the inability to detect balanced structural chromosomal rearrangements, as well as interstitial deletions and duplications, ring chromosomes, and inversions. Some of these variations could be detected with other molecular approaches such as aCGH and NGS-based methodologies, but because of their higher price, they are not widely used in the investigation of EPLs samples [5, 6]. In our study, a significantly higher frequency of chro- mosomally abnormal POCs was observed in the group of women ≥36 years (71.37%) compared to the groups <30 (43.4%; OR=3.25; p<0.0001) and 31-35 years (53.9%; OR=1.52, p=0.018). Thus, our study confirms previous observations of increased EPL aneuploidy rate in women with advanced age [13, 22]. Extensive research has been performed with the aim to explain the reason behind the increased rate of aneuploidy with advanced maternal age. Some of the leading causes identified include recombina- tion failure, cohesion and spindle deregulation, abnor- malities in post-translational modification of histones and tubulin, and mitochondrial dysfunction [23, 24]. The high trisomy rate in our study (66%), with tri- somy 16 being the most frequent, followed by trisomies 22, 21, 13 and 15 is in accordance with the data from previous published studies [21, 25-27]. The trisomy rate increased with maternal age, being the highest (79.68%) in women >36 years of age and lowest in women <30 years (48.70%). On the other hand, our study showed higher rates of monosomies and triploidy in younger women, which has been also shown by other authors [26, 28]. The distribution of individual trisomies differed among the three age groups. The frequency of trisomy 16 (calculated on all studied samples) was similar in the three groups, while trisomies 22, 21, 15 as well as other rare trisomies showed the highest frequencies in the group >36 years (Table 5). Many previous studies have also shown that trisomies 21 and 22 are more common in women with advanced age and have shown that they occur mostly because of maternal non-disjunction in meiosis I. Both chromosomes 21 and 22 are acrocentric and, on average, each is held by a single chiasma, which can be commonly lost during meiosis [29]. Thus, our study confirms the find- ings that trisomies 22, 21 and 15 occur due to age-related factors, but also imply that other, non-age-related factors might be involved in the occurrence of trisomy 16. Our results favour the findings of lower chromosomal aneuploidy rate in recurrent compared to the sporadic EPLs [7], however with a similar distribution of the chromosomal abnormalities and trisomies 16 and 22 being the most com- mon in both groups [30]. The differences observed among the women with different ethnic origins as well as those with and without live births could be related to the maternal age. Although, we have observed some differences in the chromosomal aneuploidy rates among women with differ- ent ABO blood groups and RhD status (with higher rates in groups A and AB, as well as in RhD positive women) further larger studies are required to confirm our findings. Our results show that triploidy and monosomies oc- cur more frequently in POCs eliminated in gw 9-11, while trisomies are more common in gw 6-8 POCs, findings observed also by other studies [31]. Thus, our study sug- gests that chromosomal trisomies have a more negative effect on POCs, causing earlier elimination during the pregnancy in contrast to the triploidies and monosomies. We have observed a slight predominance of chromo- somally abnormal POC in females than in males (58.86% vs. 53.56%), although without statistical significance. The female predominance was also observed by other authors indicating relative weakness in female embryo formation and development, supported by an animal model where, male embryos development was favoured in comparison to female development [32, 33].

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