Is gestational trophoblastic neoplasia more common among women with recurrent hydatidiform moles and biallelic NLRP7 mutations? a 17-years prospective study from India

Abstract

Objective

Recurrent hydatidiform moles (RHM) is a rare entity defined by the occurrence of two or more hydatidiform moles (HM) in a woman. We present data of women with RHM from a tertiary care institute in North India with respect to the incidence of Gestational Trophoblastic Neoplasia (GTN), subsequent reproductive outcome and genetic analysis in this cohort.

Methods

Women who presented with RHM and no prior live birth were enrolled from 2005 to 2022 and analysed for the presence of pathogenic or likely pathogenic (P/LP) variants in genes responsible for RHM. They were followed-up for occurrence of post-molar GTN as per FIGO and WHO guidelines, and subsequent reproductive outcomes.

Results

Of the 23 women with RHM, 22 (95.6 %) had biallelic P/LP variants in three genes, 20 in NLRP7 (87 %), one in KHDC3L (4 %), and one in TOP6BL (4 %). Of the 20 women with NLRP7 variants, 10 (50 %) developed GTN, mostly low-risk, which is approximately 2 to 3 times higher than the rate of GTN among women with sporadic HM at similar ages. Three of these women had recurrent GTN. Among the 22 women with biallelic P/LP variants, only one had a spontaneous live birth, and four underwent IVF with donated ova, of whom three had live births. Only one woman was negative for recessive causative variants in the known genes or any novel gene and she subsequently had two spontaneous live births.

Conclusion

Our data indicate a high incidence of biallelic P/LP NLRP7 variants among Indian women with RHM and no live birth. These women appeared to be at a higher risk for developing GTN and had a very low chance of a spontaneous live birth, and these two concerns may be mitigated by avoiding a spontaneous pregnancy and having donor ovum IVF. All women with RHM should have genetic testing and counseling specifically due to their higher risk of GTN.