Mechanisms of twinning. VI. Genetics and the etiology of monozygotic twinning in in vitro fertilization.

OBJECTIVE

To examine the possible role of inheritance in monozygotic twinning.

STUDY DESIGN

Via public announcement in national media, volunteers were requested who had given birth to monozygotic (MZ) twins or triplets and who also had relatives with twins. From the data received, common factors in such sets were sought. Zygosity was confirmed with various combinations of placental pathology, sex, blood type, DNA analysis, fingerprints and physical appearance.

RESULTS

Among the 109 responses, 78 mothers of MZ multifetal pregnancies with twin relatives were identified. Of special interest were 13 cases of triplets that resulted from transfer of 2 viable embryos during in vitro fertilization (IVF). Each of these cohorts had twin relatives. They were compared to 33 cases of spontaneous MZ triplets, also with twin relatives. The familial clustering phenomenon appeared to be a function of maternal age, whereas the effect of zygosity or lineage (paternal versus maternal) of the related twins was nonspecific.

CONCLUSION

The findings are consistent with the suggested influence of genetics and familial clustering on the MZ twinning rate, especially in IVF procedures. The risk of unintended dizygotic triplet pregnancies could be reduced by limiting transfer to 1 embryo in cases of older women with a family history of multiple gestation. Roles of calcium and insulinlike growth factor in this phenomenon appear plausible.