Short Tandem Repeat (STR) Analysis in the Clinical Diagnosis of Molar Pregnancy

Summary: Molar pregnancy results from abnormal fertilization and overgrowth of placenta. In a complete hydatidiform mole (CHM), an empty ovum is fertilized by one sperm, followed by doubling of the sperm haploid genome that results in a diploid genome of paternal origin only. Partial hydatidiform mole (PHM) typically involves triploidy, with an extra haploid set of paternal genome (diandric triploidy). CHM and PHM may transform into gestational trophoblastic neoplasia, highlighting the importance of quick diagnosis to mitigate the risk of malignancy in the mother. Karyotype and FISH analysis can determine the ploidy but not the parental origin of the genome, limiting their applicability in detecting a molar pregnancy. Short tandem repeat (STR) analysis is an alternative tool that compares selected markers between the maternal and fetal DNA to identify the ploidy and parental origin of the fetal genome. In this study, we aimed to evaluate the utility of STR testing in diagnosis of molar pregnancy. Data from 265 suspected cases of molar pregnancy were reviewed that the UPMC Cytogenetics Laboratories processed from Oct. 2022-Feb. 2025. STR analysis revealed normal diploidy with biparental inheritance in 158 (53.9%) cases. Of the 80 cases with triploidy, PHM was detected in 64 conceptuses (21.8%), while 16 were non-molar with two haploid sets of maternal genomes (digynic triploid, 5.5%). As expected, CHM was detected in only 6 cases (2%) as it can generally be diagnosed by distinct histomorphology and characteristic P57 immunostaining pattern without a need for cytogenetic testing. STR analysis was inconclusive in 21 cases (7.2%) due to the admixture of maternal and fetal DNA. This study highlights the superior clinical utility of STR analysis as compared to FISH and karyotyping. STR analysis is a reliable technique for detecting molar pregnancy which can be associated with an increased risk of neoplastic transformation. Marwa Daghsni, Kanika Goel, Lauren Skvarca, and Mahmoud Aarabi