Live births in women with recurrent hydatidiform mole and two NLRP7 mutations.

Hydatidiform mole (HM) is an aberrant human pregnancy with abnormal embryonic development and excessive proliferation of the trophoblast. Recessive mutations in NLRP7 are responsible for recurrent HM (RHM). Women with recessive NLRP7 mutations fail to have normal pregnancies from spontaneous conceptions with the exception of three out of 131 reported patients. Because there is no treatment for RHM and maternal-effect genes are needed in the oocytes to sustain normal embryonic development until the activation of the embryonic genome, one patient with recessive NLRP7 mutations tried ovum donation and achieved a successful pregnancy. This study reports three additional live births from donated ova to two patients with recessive NLRP7 mutations. The occurrence of two live births from spontaneous conceptions to two other patients is also reported. The reproductive outcomes and mutations of all reported patients were reviewed and it was found that live births are associated with some missense mutations expected to have mild functional consequences on the protein. The data support a previous observation that ovum donation appears the best management option for these patients to achieve normal pregnancies and provide an explanation for the rare occurrence of live births from natural spontaneous conceptions in patients with two NLRP7 mutations.