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      Effect of assisted reproductive technology on the molecular karyotype of missed abortion tissues

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          Abstract

          Missed abortion is one of the common complications of assisted reproductive technology (ART). Genetic abnormality is the most important factor. However, the effect of ART on the molecular karyotype of products of conception (POC) remains unknown. We explored the effect of ART on the molecular karyotype of POC in miscarriage. POC were obtained from women undergoing ART. Single nucleotide polymorphism (SNP) microarray was used to analyze the molecular karyotype. A total of 1493 POC were collected for SNP array analysis. The total rate of karyotypic abnormalities was 63.1% (943/1493). The proportion of karyotypic abnormalities was 70.4% (193/416) in >35-year-old group, which was significantly higher than that (60.6%) (343/566) in <30-year-old group and that (60%) (307/511) in the 30–35-year-old group. In natural conception (NC) group, the proportion of karyotypic abnormalities was 64.6% (201/311), whereas in ART group it was 62.7% (742/1182) and, there was no significant difference. The ratio between male and female fetuses was 1:1.13 (698/795). The rate of karyotypic abnormalities in male was 62.9% (439/698) and that in female was 63.4% (504/795), and these values did not differ significantly ( P=0.84). Molecular karyotypic abnormality is the most important reason in miscarriage, and female age is a significant factor influencing the karyotypic abnormalities. Comparison with NC, ART, and gender of aborted embryos may not increase the rate of molecular karyotypic abnormality in miscarriage.

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          Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies.

          Chromosomal microarray (CMA) is increasingly utilized for genetic testing of individuals with unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), or multiple congenital anomalies (MCA). Performing CMA and G-banded karyotyping on every patient substantially increases the total cost of genetic testing. The International Standard Cytogenomic Array (ISCA) Consortium held two international workshops and conducted a literature review of 33 studies, including 21,698 patients tested by CMA. We provide an evidence-based summary of clinical cytogenetic testing comparing CMA to G-banded karyotyping with respect to technical advantages and limitations, diagnostic yield for various types of chromosomal aberrations, and issues that affect test interpretation. CMA offers a much higher diagnostic yield (15%-20%) for genetic testing of individuals with unexplained DD/ID, ASD, or MCA than a G-banded karyotype ( approximately 3%, excluding Down syndrome and other recognizable chromosomal syndromes), primarily because of its higher sensitivity for submicroscopic deletions and duplications. Truly balanced rearrangements and low-level mosaicism are generally not detectable by arrays, but these are relatively infrequent causes of abnormal phenotypes in this population (<1%). Available evidence strongly supports the use of CMA in place of G-banded karyotyping as the first-tier cytogenetic diagnostic test for patients with DD/ID, ASD, or MCA. G-banded karyotype analysis should be reserved for patients with obvious chromosomal syndromes (e.g., Down syndrome), a family history of chromosomal rearrangement, or a history of multiple miscarriages. Copyright (c) 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
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            Maternal age and fetal loss: population based register linkage study.

            To estimate the association between maternal age and fetal death (spontaneous abortion, ectopic pregnancy, stillbirth), taking into account a woman's reproductive history. Prospective register linkage study. All women with a reproductive outcome (live birth, stillbirth, spontaneous abortion leading to admission to hospital, induced abortion, ectopic pregnancy, or hydatidiform mole) in Denmark from 1978 to 1992; a total of 634 272 women and 1 221 546 pregnancy outcomes. Age related risk of fetal loss, ectopic pregnancy, and stillbirth, and age related risk of spontaneous abortion stratified according to parity and previous spontaneous abortions. Overall, 13.5% of the pregnancies intended to be carried to term ended with fetal loss. At age 42 years, more than half of such pregnancies resulted in fetal loss. The risk of a spontaneous abortion was 8.9% in women aged 20-24 years and 74.7% in those aged 45 years or more. High maternal age was a significant risk factor for spontaneous abortion irrespective of the number of previous miscarriages, parity, or calendar period. The risk of an ectopic pregnancy and stillbirth also increased with increasing maternal age. Fetal loss is high in women in their late 30s or older, irrespective of reproductive history. This should be taken into consideration in pregnancy planning and counselling.
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              Maternal age and fetal loss: population based register linkage study

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                Author and article information

                Journal
                Biosci Rep
                Biosci. Rep
                ppbioscirep
                BSR
                Bioscience Reports
                Portland Press Ltd.
                0144-8463
                1573-4935
                23 August 2018
                31 October 2018
                15 October 2018
                : 38
                : 5
                Affiliations
                Reproductive Medical Center, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
                Author notes
                Correspondence: Yingpu Sun ( syp2008@ 123456vip.sina.com )
                Article
                10.1042/BSR20180605
                6435534
                30139813
                © 2018 The Author(s).

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

                Page count
                Pages: 8
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                Research Article
                29

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