Abstract

ObjectiveTo investigate whether miscarried embryo/fetal crown rump length (CRL) measurement may yield a practical application for predicting a conclusive result at the cytogenetic analysis of miscarriage tissue. Our study might help in improving the cytogenetic method, the results of which may be affected by maternal cell contamination (MCC). In particular, we aimed at establishing whether the miscarried embryo/fetal CRL measurement shows accuracy in predicting the possibility of MCC and the scan cut-off value useful to this purpose and, as a result, suggest a multi-step procedure for the genetic ascertainment.MethodsWomen experiencing at least two miscarriages of less than 20 weeks size at the Pregnancy Loss Unit at Fondazione Policlinico A. Gemelli underwent a scan before surgery. The CRL value was recorded. After the dilatation and courettage (D&C) procedure, miscarriage tissue was processed through the proposed multi-step procedure before performing oligo-nucleotide-based and SNP (single nucleotide polymorphisms)-based comparative genomic hybridization (CGH+SNP) microarray analysis.Results63 women and 63 miscarriages met the criteria. By using the Receiving Operator Characteristic (ROC) curves, CRL showed an AUC of 0.816 (95%CI:0.703–0.928,p<0.001). A CRL≥24.5 mm cut-off value showed a higher positive likelihood ratio (5.27) but, conversely, a higher negative likelihood ratio (0.64) in predicting the possibility of MCC. Microarray analysis was successful in the totality of cases in which the embryo/fetal origin of miscarriage tissues was proven.ConclusionsThe 24.5 mm CRL value emerges as the most suitable cut-off enabling the identification of cases in which the embryo-fetal component can be isolated in the absence of MCC and the chromosomal array provide informative results.

Highlights

  • Miscarriage, defined as the pregnancy loss before 20 weeks of gestation, represents a frequent obstetrical event affecting up to 15% of clinically diagnosed pregnancies, yet a failure in the reproductive history of couples hoping for children. [1,2] It is estimated that chromosomal abnormalities, in the majority of cases aneuploidies, account for 50–70% of miscarriages of less than 10 week’ gestation in the general reproductive population [3,4,5,6,7,8,9]

  • By using the Receiving Operator Characteristic (ROC) curves, crown rump length (CRL) showed an Area Under the Curve (AUC) of 0.816 (95%CI:0.703–0.928,p

  • The 24.5 mm CRL value emerges as the most suitable cut-off enabling the identification of cases in which the embryo-fetal component can be isolated in the absence of maternal cell contamination (MCC) and the chromosomal array provide informative results

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Summary

Objective

To investigate whether miscarried embryo/fetal crown rump length (CRL) measurement may yield a practical application for predicting a conclusive result at the cytogenetic analysis of miscarriage tissue. Our study might help in improving the cytogenetic method, the results of which may be affected by maternal cell contamination (MCC). We aimed at establishing whether the miscarried embryo/fetal CRL measurement shows accuracy in predicting the possibility of MCC and the scan cut-off value useful to this purpose and, as a result, suggest a multi-step procedure for the genetic ascertainment

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