Undetected Maternal Cell Contamination in Products of Conception Analysis May Mask Recurrence Risks for Future Pregnancies: A Case Report and Discussion [ID: 1377203

Abstract

INTRODUCTION: Maternal cell contamination (MCC) in products of conception (POC) tissue is common; some studies report 59% of 46,XX results represent MCC. METHODS: Products of conception tissue and maternal blood samples were shipped to a laboratory for genotyping using Illumina CytoSNP-12b microarrays and bioinformatics (IRB E&I 19040-03A). Patient informed consent was obtained for submission of a case report. RESULTS: A 25-year-old woman with a family history of recurrent pregnancy loss (RPL) was first offered POC analysis after her second loss. The result was normal female; however, MCC could not be ruled out because a maternal sample was not provided. Thus, the result was presumed normal, and the patient was informed her testing did not identify a genetic cause for her loss. The patient's third miscarriage was sent for POC analysis with a parental sample, which identified a maternally derived 26.8-Mb terminal deletion and 39.3-Mb terminal duplication of chromosome 4. The submitted maternal sample allowed for reanalysis of the second loss confirming MCC. Maternal karyotype analysis revealed an abnormal result: 46,XX,inv(4)(p15.2q31.3). The patient was referred to reproductive endocrinology for discussion of options, including in vitro fertilization with preimplantation genetic testing. CONCLUSION: Undetected MCC can lead to erroneous normal female results, masking fetal findings that could affect recurrence risks. Since 5% of couples with RPL have a balanced chromosome rearrangement, almost six couples for every 1,000 losses are at risk for undetected MCC masking recurrence risks (calculated using a 50% expected aneuploidy rate and 59% of 46,XX results actually representing MCC).