Chromosomal copy number analysis of products of conception by conventional karyotyping and next‐generation sequencing

Tamura, Yuki; Santo, Mitsuo; Araki, Yasuhisa; Matsubayashi, Hidehiko; Takaya, Y.; Kitaya, Kotaro; Doshida, Masakazu; Yamaguchi, Kensei; Mizuta, Shimpei; Takahashi, Chie; Kim, Namhyo; Okuno, Koichiro; Takeuchi, Takumi; Ishikawa, Tomomoto

doi:10.1002/rmb2.12351

Cited by 15 publications

(15 citation statements)

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“…Autosomal trisomies composed a significantly large proportion. In line with previous reports [ 1 , 4 , 13 , 14 ], chromosomes 1 and 19 were rarely involved in trisomies, which may indicate that, chromosome 1 and 19 require more precise dosage for early embryonic development. Apart from numerical anomalies, structural abnormalities accounted for approximately 3.0% of the total abnormalities.…”

Section: Discussionsupporting

confidence: 91%

“…Advanced maternal age ( ≥ 35 ) is a well-known independent factor associated with the frequencies of cytogenetic abnormalities in early miscarriages [ 1 , 13 , 16 ]. In this study, the frequencies of abnormal karyotype in women aged up to 30 years, 30–34 years, as well as 35–39 years similar, but all of them were significantly lower than that in women ≥ 40 years old.…”

Section: Discussionmentioning

confidence: 99%

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

Xie

et al. 2021

Mol Cytogenet

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Background Pregnancy loss is one of the most common complications during pregnancy. Clinical consultation based on etiology analysis are critical for reducing anxiety and distress. This study aimed to perform a comprehensive analysis for products of conception (POC) in miscarriage based on genetic etiology and clinical information. Methods A retrospective study was conducted according to cytogenetic findings of 1252 POC from spontaneous pregnancy loss over 11 years. The frequencies and profiles of chromosomal abnormalities were discussed according to the classification of women with different maternal ages, previous miscarriage history, normal live birth history, and different modes of conception. Results A total of 667 (53.2%) chromosomal abnormalities were observed, including 592 (47.3%) cases of numerical abnormalities, 38 (3.0%) cases of structural abnormalities, and 37 (3.0%) cases of mosaic aberrations. In women above 40 years of age, the rates of chromosomal abnormalities and viable autosomal trisomy were significantly higher than those in women with ≤ 29, 30–34, and 35–39 years of age (p < 0.05). The frequency 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 differences among women without, with 1–2, and ≥ 3 previous miscarriages regarding the rate of abnormal karyotype (p > 0.05); viable autosomal trisomy was less common in women with ≥ 3 previous miscarriages than women with < 3 miscarriages. The frequency of chromosomal abnormalities was 49.0% and 55.0% in women with assisted conception and natural conception (p > 0.05), respectively; monosomy X was more frequently detected in women with natural conception than assisted conception. Conclusion The frequencies and profiles of chromosomal abnormalities in early miscarriages are strongly associated with clinical information including maternal age, previous miscarriage, live birth history, and mode of conception. Cytogenetic analysis of POC should be recommended to women with a first miscarriage and women with normal live birth history.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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

Xie

et al. 2021

Mol Cytogenet

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show abstract

“…Autosomal trisomies were highly prevalent, with trisomy 16 being the most frequent nding. Chromosome 1 and 19 were rarely involved, in line with previous reports [1,12,13]. The phenomenon could be explained by the mechanism of gamete meiosis, but the exact mechanism is still unclear.…”

Section: Discussionsupporting

confidence: 86%

“…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: 52%

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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“… 6 , 7 , 8 Recently, SNP microarray, next‐generation sequencing (NGS), quantitative fluorescence PCR (QF‐PCR), and multiplex ligation‐dependent probe amplification (MLPA), none of which require cell culture, have been reported as alternative approaches to the cytogenomic analysis of a POC. 9 , 10 , 11 , 12 , 13 , 34 …”

Section: Introductionmentioning

confidence: 99%

Usefulness of combined NGS and QF‐PCR analysis for product of conception karyotyping

Kato

Miyai

Suzuki³

et al. 2022

Reprod Medicine & Biology

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Purpose Since chromosomal abnormalities can be detected in more than half of miscarriages, cytogenetic testing of the product of conception (POC) can provide important information when preparing for a subsequent pregnancy. Conventional karyotyping is the common diagnostic method for a POC but can be problematic due to the need for cell culture. Methods We here conducted shallow whole‐genome sequencing (sWGS) using next‐generation sequencing (NGS) for alternative POC cytogenomic analysis. Since female euploidy samples can include 69,XXX triploidy, additional QF‐PCR was performed in these cases. Results We here analyzed POC samples from miscarriages in 300 assisted reproductive technology (ART) pregnancies and detected chromosomal abnormalities in 201 instances (67.0%). Autosomal aneuploidy (151 cases, 50.3%) was the most frequent abnormality, consistent with prior conventional karyotyping data. Mosaic aneuploidy was detected in seven cases (2.0%). Notably, the frequency of triploidy was 2.3%, 10‐fold lower than the reported frequency in non‐ART pregnancies. Structural rearrangements were identified in nine samples (3%), but there was no case of segmental mosaicism. Conclusions These data suggest that NGS‐based sWGS, with the aid of QF‐PCR, is a viable alternative karyotyping procedure that does not require cell culture. This method could also assist with genetic counseling for couples who undergoes embryo selection based on PGT‐A data.

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Chromosomal copy number analysis of products of conception by conventional karyotyping and next‐generation sequencing

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 15 publications

References 14 publications

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

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

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

Usefulness of combined NGS and QF‐PCR analysis for product of conception karyotyping

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