Genetic findings in miscarriages and their relation to the number of previous miscarriages

Hafezi, N; Amrani, M.; Schweiger, Susann; Dewenter, Malin; Thomas, Padmaja B.; Lieb, Christoph; Hasenburg, Annette; Skala, Christine

doi:10.1007/s00404-020-05859-x

Cited by 13 publications

(12 citation statements)

References 35 publications

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“…Advanced maternal age is related to an increased incidence of meiotic errors due to the extended period of oocyte meiotic arrest before ovulation [ 28 , 29 ]. The risk of cytogenetic errors was reported to be significantly higher in women over 40 years old [ 30 , 31 ]. There seems to be conflicting data on the frequency of chromosome abnormalities in sporadic miscarriages, as opposed to recurrent pregnancy loss (RPL), with some reports claiming that such abnormalities occur less often in RPL, and others reporting no correlation [ 32 , 33 , 34 , 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

Cytogenetic Analysis of Sporadic First-Trimester Miscarriage Specimens Using Karyotyping and QF-PCR: A Retrospective Romanian Cohort Study

Popescu-Hobeanu

Riza

Streaţă

et al. 2022

Genes

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It is well known that first-trimester miscarriages are associated with chromosome abnormalities, with numerical chromosome abnormalities being the ones most commonly detected. Conventional karyotyping is still considered the gold standard in the analysis of products of conception, despite the extended use of molecular genetic techniques. However, conventional karyotyping is a laborious and time-consuming method, with a limited resolution of 5–10 Mb and hampered by maternal cell contamination and culture failure. The aim of our study was to assess the type and frequency of chromosomal abnormalities detected by conventional karyotyping in specimens of sporadic first-trimester miscarriages in a Romanian cohort, using QF-PCR to exclude maternal cell contamination. Long-term cultures were established and standard protocols were applied for cell harvesting, slide preparation, and GTG banding. All samples with 46,XX karyotype were tested for maternal cell contamination by QF-PCR, comparing multiple microsatellite markers in maternal blood with cell culture and tissue samples. Out of the initial 311 specimens collected from patients with sporadic first-trimester miscarriages, a total of 230 samples were successfully analyzed after the exclusion of 81 specimens based on unsuitable sampling, culture failure, or QF-PCR-proven maternal cell contamination. Chromosome abnormalities were detected in 135 cases (58.7%), with the most common type being single autosomal trisomy (71/135—52.6%), followed by monosomy (monosomy X being the only one detected, 24/135—17.8%), and polyploidy (23/135—17.0%). The subgroup analysis based on maternal age showed a statistically significant higher rate of single trisomy for women aged 35 years or older (40.3%) compared to the young maternal age group (26.1%) (p = 0.029). In conclusion, the combination of conventional karyotyping and QF-PCR can lead to an increased chromosome abnormality detection rate in first-trimester miscarriages. Our study provides reliable information for the genetic counseling of patients with first-trimester miscarriages, and further large-scale studies using different genetic techniques are required.

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Section: Introductionmentioning

confidence: 99%

Cytogenetic Analysis of Sporadic First-Trimester Miscarriage Specimens Using Karyotyping and QF-PCR: A Retrospective Romanian Cohort Study

Popescu-Hobeanu

Riza

Streaţă

et al. 2022

Genes

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“…Advanced maternal age (≥ 35 ) is a well-known independent factor associated with the frequencies of cytogenetic abnormalities in early miscarriages [1,12,14]. In this study, the frequencies of abnormal karyotype in women aged up to 30 years, between 30 and 34 years, as well as between 35 and 39 were comparable, while the frequency was signi cantly higher in women ≥ 40 years old.…”

Section: Discussionmentioning

confidence: 51%

Comprehensive analysis of early pregnancy loss based on cytogenetic findings from a tertiary referral center

Xie

et al. 2021

Preprint

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Background Pregnancy loss is one of the most common complications during pregnancy. Clinical consultation and comprehensive understanding of the etiology are critical for reducing anxiety, distress, and depression. This study aimed to perform a comprehensive analysis for products of conception (POC) in miscarriage based on genetic etiology and clinical information. Methods Retrospective observation was performed on cytogenetic findings of 1252 POC form spontaneous pregnancy loss over an 11-year period. The frequencies and profiles of chromosomal abnormalities were discussed according to the classification of women with different maternal age, previous miscarriage history, normal live birth history, and different mode of conception. Results A total of 667 (53.2%) chromosomal abnormalities were observed, including 597 (47.7%) cases of numerical abnormalities, 33 (2.6%) cases of unbalanced structural abnormalities, 32 (2.6%) cases of mosaicism, and 5 (0.4%) cases of balanced rearrangement. In group of women above 40 years of age, the detection rates of chromosomal abnormalities and viable autosomal trisomy were significantly higher than those in groups of ≤ 29, 30 ~ 34, 35 ~ 39 years of age (p < 0.05). The detection rate of abnormal karyotype in women with normal live birth history was 61.1%, significantly higher than 52.5% in women without normal live birth history (p < 0.05). There was no significant difference among women without, with 1–2, and ≥ 3 previous miscarriages in the rate of abnormal karyotype (p > 0.05), and viable autosomal trisomy was less common in women with ≥ 3 previous miscarriages. The frequency of chromosomal abnormalities was 49.0% and 41.0% in women with assisted conception and natural conception (p > 0.05), respectively, and monosomy X was more frequently detected in women with natural conception. Conclusion The frequencies and profiles of chromosomal abnormalities in early miscarriages are strongly associated with clinical information including the maternal age, previous miscarriage, live birth history, and mode of conception. Even in women with a first miscarriage, or with a history of normal live births, chromosomal analysis of POC should be recommended for etiological assessment.

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“…The most frequent cause of miscarriage is chromosomal abnormality. Almost 50 years of cytogenetic studies of spontaneous abortions have demonstrated abnormality rates of around 50–60% [ 10 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. Trisomies are the most frequently detected anomalies (58–61%), followed by monosomy X (8–13%), polyploidies (2–13%), and structural anomalies (7–9%) [ 11 , 12 , 41 ].…”

Section: Genetic Causes Of Miscarriagementioning

confidence: 99%

“…Aneuploidy, the presence of an abnormal number of chromosomes, is thought to be a major cause of human first-trimester pregnancy loss [ 11 , 13 , 14 , 44 , 45 , 46 , 48 , 173 , 174 ]. Aneuploidy rates are remarkably high in early human embryos, with more than 50% of IVF embryos diagnosed as aneuploid, including those from young, fertile couples [ 175 , 176 , 177 ].…”

Section: Stem Cell-based Studies Of Chromosomal Aneuploidy and Mosaic...mentioning

confidence: 99%

Stem Cell-Based Trophoblast Models to Unravel the Genetic Causes of Human Miscarriages

Nikitina

Lebedev

2022

Cells

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Miscarriage affects approximately 15% of clinically recognized pregnancies, and 1–3% of couples experience pregnancy loss recurrently. Approximately 50–60% of miscarriages result from chromosomal abnormalities, whereas up to 60% of euploid recurrent abortions harbor variants in candidate genes. The growing number of detected genetic variants requires an investigation into their role in adverse pregnancy outcomes. Since placental defects are the main cause of first-trimester miscarriages, the purpose of this review is to provide a survey of state-of-the-art human in vitro trophoblast models that can be used for the functional assessment of specific abnormalities/variants implicated in pregnancy loss. Since 2018, when primary human trophoblast stem cells were first derived, there has been rapid growth in models of trophoblast lineage. It has been found that a proper balance between self-renewal and differentiation in trophoblast progenitors is crucial for the maintenance of pregnancy. Different responses to aneuploidy have been shown in human embryonic and extra-embryonic lineages. Stem cell-based models provide a powerful tool to explore the effect of a specific aneuploidy/variant on the fetus through placental development, which is important, from a clinical point of view, for deciding on the suitability of embryos for transfer after preimplantation genetic testing for aneuploidy.

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Genetic findings in miscarriages and their relation to the number of previous miscarriages

Cited by 13 publications

References 35 publications

Cytogenetic Analysis of Sporadic First-Trimester Miscarriage Specimens Using Karyotyping and QF-PCR: A Retrospective Romanian Cohort Study

Cytogenetic Analysis of Sporadic First-Trimester Miscarriage Specimens Using Karyotyping and QF-PCR: A Retrospective Romanian Cohort Study

Comprehensive analysis of early pregnancy loss based on cytogenetic findings from a tertiary referral center

Stem Cell-Based Trophoblast Models to Unravel the Genetic Causes of Human Miscarriages

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