DNA Genotyping of Nonmolar Donor Egg Pregnancies With Abnormal Villous Morphology: Allele Zygosity Patterns Prevent Misinterpretation as Complete Hydatidiform Mole

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DNA genotyping is the gold standard diagnostic test to distinguish hydatidiform moles from nonmolar but morphologically abnormal products of conception (POC). The test is based on comparison of alleles at 15 short tandem repeat loci in the chorionic villi of the POC to those in the maternal decidual tissue. If alleles in the POC are not present in the decidua, then the most concerning interpretation is that the POC has a paternal uniparental genome diagnostic of a complete hydatidiform mole (CHM). However, a nonmolar pregnancy from a donated egg would also appear the same because the maternal genome of the POC would match that of the maternal donor, not that of the decidua of the individual carrying the pregnancy. Not surprisingly, 2 cases of potential misclassification of the genotype of a donor egg POC as CHM have been reported in the literature. We hypothesize that the ratio of heterozygous loci to homozygous loci (so-called allele zygosity ratio) distinguishes the genotype of a donor egg POC from CHM. We compared the allele zygosity ratio in 11 nonmolar donor egg POC, 5 dispermic (heterozygous) CHM and 31 monospermic (homozygous) CHM, without knowledge of the use of a donor egg, the histologic findings, or results of p57 immunohistochemical staining. In all 47 cases, the alleles from the chorionic villi did not match those in the decidua. The average ratio of heterozygous to homozygous loci was 4:1 in donor egg POC and 1:3 in dispermic CHM (P<0.0001). Monospermic CHM contained 100% homozygous loci. p57 staining was intact in all donor egg POC. We conclude that the allele zygosity ratio is important to evaluate when interpreting the genotype of morphologically abnormal POC that does not match the genotype of the decidua. A high heterozygous:homozygous ratio should raise concern for a nonmolar donor egg pregnancy. Correlation of this variable along with review of the histologic findings and p57 immunohistochemistry may prevent misclassification of the genotype of a donor egg POC with abnormal villous morphology as a dispermic (heterozygous) CHM.

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