Complete hydatidiform mole (CHM) is an abnormality in pregnancy due to a diploid conception which is generally androgenetic in origin, i.e. all 46 chromosomes are paternally derived. We have examined the genetic origin of repetitive hydatidiform moles in a patient having three CHM by two different partners, and no normal pregnancies. Using fluorescent microsatellite genotyping, we have shown all three CHM to be biparental, rather than androgenetic, in origin. Examination of informative markers for each homologous pair of chromosomes, in two of the CHM, failed to reveal any evidence of unipaternal disomy, suggesting that the molar phenotype might result from disruption of normal imprinting patterns due to a defect in the maternal genome. It has been suggested that intracytoplasmic sperm injection (ICSI), followed by 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 embryos is therefore unlikely to prevent repetitive CHM in this patient. Our results suggest that the genetic origin of repetitive CHM should be determined 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 biparental origin. [ABSTRACT FROM PUBLISHER]