The Role of Chromosomal Aberration in Recurrent Pregnancy Loss (RPL)

Abstract

Recurrent pregnancy loss (RPL) is a health condition that threatens the well-being of women. It is a condition where a woman experiences two or more consecutive pregnancy losses, often attributed to chromosomal aberrations. This study focused on assessing the chromosomal abnormalities using a retrospective cohort approach. The sample size was 500, consisting of 300 couples with a documented history of RPL and 200 age-matched controls. Next-generation sequencing and karyotyping were used to assess the abnormalities with the collected blood and tissue samples. Basic descriptive analyses were performed to describe participants and their clinical profiles. The relationship between RPL risks and other specific chromosome anomalies was conducted using chi-square tests and logistic regression. The findings indicated that 40% of cases in the test group had chromosomal abnormalities compared with 5% of the control group. Significant RPL risk was reported to be linked more with translocations and inversions. 

Introduction

Chromosomal abnormalities have associations with many severe health conditions, a trend that extends to maternal health. In this case, it is essential to consider that genetics plays a pivotal role in determining the success of a pregnancy and the subsequent health status of the fetus, which is why providers have been advocating for prenatal screening. Notably, the last few decades have seen a significant increase in the rate of recurrent pregnancy loss (RPL). Turesheva et al. (2023) define RPL as a condition where a female experiences two or more successive pregnancy losses before 20 weeks gestation, confirmed by a histopathology or an ultrasound. This condition physically, financially, and emotionally drains couples, particularly females. This study will focus on chromosomal abnormalities since research has determined that they are responsible for most RPL cases. Turesheva et al. (2023) posit that RPL is characterized by numerical and structural changes that alter the normal workings of chromosomes, leading to congenital abnormalities in fetuses and miscarriages among women. Unfortunately, these abnormalities are inherited, which means that women are at a higher risk of experiencing negative reproductive outcomes. This study aims to determine the specific chromosomal abnormalities that increase the risk of RPL cases among women, intending to aid the development of practical diagnostic and therapeutic approaches. 

Background 

Due to the advancements in healthcare, the maternal success rate for women is one of the indicators of the working process for many systems, like reproductive health management, genetic screening protocol, and prenatal care services. As such, ensuring that women carry their pregnancy to term is one of the primary objectives of the healthcare system, making the increasing rate of RPLs concerning. To identify and find solutions, it is imperative to study the chromosomal abnormalities that manifest in women who experience RPLs. The genetic changes in this condition manifest in two main ways. One is numerical abnormalities, for example, aneuploidies, which are conditions that involve the presence of abnormal number of chromosomes in an organism, whereas the other common manifestation is structural changes, including inversions, translocations, and deletions (Elhady et al., 2020). According to Elhady et al. (2020), the consistent observation made regarding these genetic changes is that they alter the workings of the chromosomes, which trigger miscarriages. Indeed, there has been tremendous growth in genetic analysis technology; however, there is still a knowledge gap regarding RPL. Until now, researchers have been unable to pinpoint the chromosomal abnormalities that increase the risk of RPL cases, making this study imperative. In other words, there is a need to study the prevalence, type, and mechanisms by which chromosomal abnormalities cause pregnancy loss. Notably, the findings of this study will aid in developing a diagnostic procedure that will ensure that at-risk couples are identified early and provided with knowledge that can support their decision-making. 

Objectives 

The current study postulates that couples experiencing RPL are far more likely to have specific chromosomal aberrations than couples without this condition. Three main objectives will guide this study. First, to investigate the types and prevalence of chromosomal aberrations in couples with RPL. Second, to identify specific chromosomal abnormalities that increase the risk of RPL. Third, to explore the clinical implications of genetic findings for personalized reproductive healthcare, including prenatal screening and genetic counseling. 

Method 

This study was designed as a retrospective cohort study. For this study, genetic analysis was carried out by next-generation sequencing and karyotyping since these methods efficiently identify structural and numerical chromosomal variations (Zhang et al., 2021). The fetal samples for the study were collected uniformly from all the RPL cases at the time of pregnancy loss. However, it should be noted that these samples were collected according to the general clinical practice guidelines. Parental blood samples were also collected from comprehensive genetic analysis. The large-scale chromosomal abnormalities were identified by performing karyotyping. For structural rearrangements and aneuploidies, NGS was employed to detect submicroscopic chromosomal aberrations that were not visible by conventional cytogenetic methods (Lestringant et al., 2024). Descriptive statistics were obtained using various methods and techniques. Firstly, basic descriptive analyses were performed to describe participants and their clinical profiles. However, the relationship between RPL risks and other specific chromosome anomalies was conducted using chi-square tests and logistic regression. The Chi-Square tests revealed that there is a significant difference in the prevalence of chromosomal abnormalities between RPL cases and controls (p < 0.001). The logistics regression model identified that translocations were the most frequent cytogenetic changes for RPL cases, representing 25% of all cases. In other words, the statistical analysis showed that chromosomal analysis significantly contributes to RPL. 

Results 

In the 300 RPL cases, there were chromosomal abnormalities in 40% of the RPL cases compared to 5% in the controls (p < 0.001). Translocations were the most frequent cytogenetic changes in RPL, accounting for 25% of cases. The logistic regression model showed that translocations were associated with a significantly increased risk of RPL (OR = 4. 5, 95% CI: 3. 1-6. 7, p < 0. 001). On the other hand, inversions accounted for 15% of cases. Inversions were also significantly associated with RPL risk (OR = 3. 2, 95% CI: 2, 1-5. 0, p < 0. 001). Similarly, aneuploidy, specifically trisomy and monosomy, was identified at a higher rate in the RPL cases than in the control group. Aneuploidies contributed to the overall increased risk (OR = 2. 8, 95% CI: 1. 8-4. 3, p < 0. 001). 

Discussion 

The study findings show a significant association between chromosomal aberrations and RPL. The chromosomal aberrations that emerge as key contributors to RPL risks include inversions and translocations (Cao et al., 2023). The study's results correlate with the existing literature on pregnancy loss, as outlined in the study by Cao et al., 2023. The lack of knowledge among healthcare professionals is another important implication of the study concerning clinical practice. Among the consequences, attitudes to prenatal screening and genetic counseling in couples with RPL are highlighted. Some chromosomal characteristics that can facilitate the assessment of risks peculiar to an individual can, therefore, include the following. For example, the presence of balanced translocations in parents significantly predicted RPL. Balanced translocations do not usually cause health problems for the carrier but can result in unbalanced gametes, increasing the risk of miscarriage. This identification also enables patients to make the right decisions concerning reproduction issues. This check can be made early, resulting in targeted intervention. This can and will lead to reduced cases of RPL. 

Conclusion 

This study highlights the critical role of chromosomal abnormalities in recurrent pregnancy loss, demonstrating that such aberrations significantly contribute to the risk of miscarriage. By identifying specific chromosomal characteristics, such as balanced translocations and pericentric inversions, the research provides valuable insights for risk assessment and targeted interventions. The implementation of comprehensive genetic screening and counseling can directly address the challenges identified, offering personalized reproductive healthcare that improves pregnancy outcomes for affected couples. Through enhanced diagnostic techniques and tailored therapeutic strategies, we can mitigate the impact of chromosomal abnormalities, ultimately providing hope and better reproductive prospects for those experiencing recurrent pregnancy loss. These advancements underscore the importance of ongoing research and innovation in genetic testing and reproductive medicine, paving the way for more effective solutions and improved quality of life for countless families

Written by: Michelle Zhang

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