Repetitive complete hydatidiform mole can be biparental in origin and either male or female

Complete hydatidiform mole (CHM) is an abnormality in pregnancy due to a di ploid conception which is generally androgenetic in origin, i.e. all 46 chr omosomes are paternally derived. We have examined the genetic origin of rep etitive hydatidiform moles in a patient having three CHM by two different p artners, and no normal pregnancies. Using fluorescent microsatellite genoty ping, we have shown all three CHM to be biparental, rather than androgeneti c, in origin. Examination of informative markers for each homologous pair o f chromosomes, in two of the CHM, failed to reveal any evidence of unipater nal disomy, suggesting that the molar phenotype might result from disruptio n of normal imprinting patterns due to a defect in the maternal genome. It has been suggested that intracytoplasmic sperm injection (ICSI), followed b y selection of male embryos, can prevent repetitive CHM; but examination of sex chromosome-specific sequences in the three CHM described here, showed that, while two were female, the first CHM was male, Selection of male embr yos is therefore unlikely to prevent repetitive CHM in this patient. Our re sults suggest that the genetic origin of repetitive CHM should be determine d prior to in-vitro fertilization (IVF) and that current strategies for the prevention of repetitive CHM may not be appropriate where the CHM are of b iparental origin.