Association between fetal chromosomal abnormalities and the frequency of spontaneous abortions

Fetal chromosomal abnormalities are a common cause of spontaneous abortion. The present study investigated the association between fetal chromosomal abnormalities and the frequency of spontaneous abortions to enable clinicians to provide more informed genetic counseling. A total of 182 patients with a history of spontaneous abortions were recruited from July 2015 to August 2017. G-banding cytogenetic analysis and novel high-throughput ligation-dependent probe amplification (HLPA) techniques were performed on conception in all 182 patients to detect chromosomal abnormalities. Low-coverage whole-genome sequencing (WGS) was performed in 74 patients to detect copy number variations (CNVs). There were no significant differences in the incidence of karyotype abnormalities between patients with sporadic miscarriages (48.0%; SM group) and patients suffering recurrent spontaneous abortions (44.8%; RSA group). The maternal age was markedly higher in patients with 3 miscarriages. WGS indicated that the incidence of pathogenic CNVs in the RSA group was higher than that in the SM group, but the difference was not significant. In conclusion, a high incidence of karyotype abnormalities and pathogenic CNVs was observed in patients with spontaneous abortion. However, no association between fetal chromosomal abnormalities and the number of spontaneous abortions was observed. HLPA assays may be used as an alternative method for fetal karyotype analysis and determination of CNVs in patients with SM and RSA.

[1]  Y Wang,et al.  Clinical application of SNP array analysis in first‐trimester pregnancy loss: a prospective study , 2017, Clinical genetics.

[2]  Asan,et al.  Clinical application of whole‐genome low‐coverage next‐generation sequencing to detect and characterize balanced chromosomal translocations , 2017, Clinical genetics.

[3]  M. Laan,et al.  Copy number variation profile in the placental and parental genomes of recurrent pregnancy loss families , 2017, Scientific Reports.

[4]  Jianxia Fan,et al.  A copy number variation genotyping method for aneuploidy detection in spontaneous abortion specimens , 2017, Prenatal diagnosis.

[5]  Y. Yaron,et al.  Does the number of previous miscarriages influence the incidence of chromosomal aberrations in spontaneous pregnancy loss? , 2017, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[6]  Mudan Lu,et al.  Novel rapid molecular diagnosis of fetal chromosomal abnormalities associated with recurrent pregnancy loss , 2016, Acta obstetricia et gynecologica Scandinavica.

[7]  G. Sukhikh,et al.  Comparison of the results of preimplantation genetic screening obtained by a-CGH and NGS methods from the same embryos , 2016, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[8]  E. Sazhenova,et al.  Comparative Cytogenetic Analysis of Spontaneous Abortions in Recurrent and Sporadic Pregnancy Losses , 2016, Biomedicine Hub.

[9]  D. Massalska,et al.  First‐trimester spontaneous pregnancy loss – molecular analysis using multiplex ligation‐dependent probe amplification , 2016, Clinical genetics.

[10]  Jun Zhang,et al.  Low-pass whole-genome sequencing in clinical cytogenetics: a validated approach , 2016, Genetics in Medicine.

[11]  D. Cram,et al.  Traditional karyotyping vs copy number variation sequencing for detection of chromosomal abnormalities associated with spontaneous miscarriage , 2015, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[12]  Jinhua Xu,et al.  Genomic variations of the mevalonate pathway in porokeratosis , 2015, eLife.

[13]  M. Laan,et al.  Extensive load of somatic CNVs in the human placenta , 2015, Scientific Reports.

[14]  A. Brusco,et al.  Large cryptic genomic rearrangements with apparently normal karyotypes detected by array-CGH , 2014, Molecular Cytogenetics.

[15]  H. Moon,et al.  Spontaneous abortion and recurrent miscarriage: A comparison of cytogenetic diagnosis in 250 cases , 2014, Obstetrics & gynecology science.

[16]  M. Rabinowitz,et al.  Genomic Imbalance in Products of Conception: Single-Nucleotide Polymorphism Chromosomal Microarray Analysis , 2014, Obstetrics and gynecology.

[17]  M. Botcherby,et al.  Diagnostic utility of novel combined arrays for genome-wide simultaneous detection of aneuploidy and uniparental isodisomy in losses of pregnancy , 2014, Molecular Cytogenetics.

[18]  Jia-Chi Wang,et al.  Abnormalities in spontaneous abortions detected by G-banding and chromosomal microarray analysis (CMA) at a national reference laboratory , 2014, Molecular Cytogenetics.

[19]  A. Tchirkov,et al.  Prevalence of aneuploidies in products of spontaneous abortion: interest of FISH and MLPA. , 2014, Morphologie : bulletin de l'Association des anatomistes.

[20]  M. Kilby,et al.  Additional information from chromosomal microarray analysis (CMA) over conventional karyotyping when diagnosing chromosomal abnormalities in miscarriage: a systematic review and meta‐analysis , 2014, BJOG : an international journal of obstetrics and gynaecology.

[21]  O. Christiansen,et al.  New insights into mechanisms behind miscarriage , 2013, BMC Medicine.

[22]  D. Ledbetter,et al.  Chromosomal microarray versus karyotyping for prenatal diagnosis. , 2012, The New England journal of medicine.

[23]  J. Balasch,et al.  The effect of maternal age on chromosomal anomaly rate and spectrum in recurrent miscarriage. , 2012, Human reproduction.

[24]  V. Peinado,et al.  Chromosomal abnormalities in embryos from couples with a previous aneuploid miscarriage. , 2012, Fertility and sterility.

[25]  M. Laan,et al.  Genetics of Recurrent Miscarriage: Challenges, Current Knowledge, Future Directions , 2012, Front. Gene..

[26]  R. Silver,et al.  Clinical practice. Recurrent miscarriage. , 2010, The New England journal of medicine.

[27]  Laura K Conlin,et al.  Mechanisms of mosaicism, chimerism and uniparental disomy identified by single nucleotide polymorphism array analysis. , 2010, Human molecular genetics.

[28]  D. Oepkes,et al.  Comparison of Multiplex Ligation-Dependent Probe Amplification and Karyotyping in Prenatal Diagnosis , 2010, Obstetrics and gynecology.

[29]  L. Westphal,et al.  Etiology of recurrent pregnancy loss in women over the age of 35 years. , 2007, Fertility and sterility.

[30]  Yuzhu Peng,et al.  A novel competitive fluorescent multiplex STR polymorphism assay for rapid, reliable and single‐tube screening of 22q11.2 copy‐number aberrations , 2009, Electrophoresis.

[31]  J. Schouten,et al.  High‐throughput analysis of chromosome abnormality in spontaneous miscarriage using an MLPA subtelomere assay with an ancillary FISH test for polyploidy , 2006, American journal of medical genetics. Part A.

[32]  J. P. Meza-Espinoza,et al.  Use of the International System for Human Cytogenetic Nomenclature (ISCN). , 2006, Blood.

[33]  M. Qumsiyeh,et al.  Array comparative genomic hybridization profiling of first‐trimester spontaneous abortions that fail to grow in vitro , 2005, Prenatal diagnosis.

[34]  Fred Kavalier,et al.  Investigation of recurrent miscarriages , 2005, BMJ : British Medical Journal.

[35]  T. Porter,et al.  Recurrent Fetal Aneuploidy and Recurrent Miscarriage , 2004, Obstetrics and gynecology.

[36]  Tatsuo Yamamoto,et al.  Chromosome abnormalities identified in 347 spontaneous abortions collected in Japan , 2004, The journal of obstetrics and gynaecology research.

[37]  C. Rubio,et al.  Chromosomal abnormalities and embryo development in recurrent miscarriage couples. , 2003, Human reproduction.

[38]  M. Ogasawara,et al.  Embryonic karyotype of abortuses in relation to the number of previous miscarriages. , 2000, Fertility and sterility.

[39]  J. Stern,et al.  Frequency of abnormal karyotypes among abortuses from women with and without a history of recurrent spontaneous abortion. , 1996, Fertility and sterility.