Human Reproduction Archives
Human Reproduction Archives
SYSTEMATIC REVIEW Reproductive Health

Copy number variations as a risk factor for couples with idiopathic recurrent miscarriage: A systematic review

Sheila Janaina Sestari, Bruno Faulin Gamba, Francis Patrício França Ferreira, Roberta Machado de Oliveira Frota Curado, Eduardo Camelo de Castro, Nádia Aparecida Bérgamo, Lucilene Arilho Ribeiro-Bicudo

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Objective: It is well established that inherited chromosomal alterations such as copy number variations (CNVs) are associated to miscarriage. However, most studies focus on evaluating CNVs only in products of conception. The aim of this systematic review was to highlight the importance of investigating CNVs in couples with a history of recurrent miscarriage as well as their role in pregnancy, filling part of the gap between studies of recurrent miscarriage. Methods: A search in PubMed, Scientific Electronic Library Online (SCIELO), Latin American and Caribbean Literature in Health Sciences (LILACS), and Portal de CAPES/MEC databases for relevant published articles was conducted using the following controlled search terms: “copy number variation”, “cnv”, “miscarriage”, “recurrent miscarriage”, “spontaneous abortion”, “loss pregnancy”, “couple”, “microarray analysis”, “comparative genomic array”, and “array CGH”. The Boolean operators AND and OR were used. The search captured studies published up to October 2020. Results: A total of five studies were extracted for the present analysis. Sixteen CNVs involving the PDZD2, GOLPH3, TIMP2, CTNNA3, STS, EGFL6, STX6, CETN2, CTDSPL, GSTT1, HLA, MSR1, NIPA1, NIPA2, CYFIP1 and TUBGCP5 genes on ten different chromosomes were considered at potential risk for pregnancy maintenance. Conclusion: The findings of the present study affirm the importance of investigating the role of CNVs in couples with recurrent miscarriage and not just products of conception, in addition contributing to more accurate medical diagnoses.


copy number variations, recurrent miscarriage, chromosomal rearrangement, abortions, pregnancy maintenance


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