Hydatidiform mole (HM) is an aberrant human pregnancy characterized by excessive trophoblastic proliferation and abnormal embryonic development. HM have two morphological types, complete (CHM) and partial (PHM), and non-recurrent ones have three genotypic types, androgenetic monospermic, androgenetic dispermic, and triploid dispermic. Most available studies on risk factors predisposing to different types of HM and their malignant transformation mainly suffer from the lack of comprehensive genotypic analysis of large cohorts of molar tissues combined with accurate postmolar hCG follow-up. Moreover, 10-20% of patients with one HM have at least one non-molar miscarriage, which is higher than the frequency of two pregnancy losses in the general population (2-5%) suggesting a common genetic susceptibility to HM and miscarriages. However, the underlying causes of the miscarriages in these patients are unknown. Here, we comprehensively analyzed 204 HM, mostly from patients referred to the Quebec Registry of Trophoblastic Diseases and for which postmolar hCG monitoring are available, and 30 of their non-molar miscarriages. We revisited the risk of maternal age and neoplastic transformation across the different HM genotypic categories and investigated the presence of chromosomal abnormalities in their non-molar miscarriages. We confirm that androgenetic CHM are more prone to gestational trophoblastic neoplasia (GTN) than triploid dispermic PHM, and androgenetic dispermic CHM are more prone to high risk GTN and choriocarcinoma (CC) than androgenetic monospermic CHM. We also confirm the association between increased maternal age and androgenetic CHM and their malignancies. Most importantly, we demonstrate for the first time that patients with an HM and miscarriages are at higher risk for aneuploid miscarriages [83.3%, 95% confidence interval (CI) 0.653-0.944] than women with sporadic (51.5%, 95% CI 50.3-52.7%, p-value = 0.0003828) or recurrent miscarriages (43.8%, 95% CI 40.7-47.0%, p-value = 0.00002). Our data suggest common genetic female germline defects predisposing to HM and aneuploid non-molar miscarriages in some patients.

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subjects who did not have a semen analysis and had microdroplet fertilization due to a normal HEPT. There was no difference in mean fertilization rates between these groups (92.71, 88.42-97.01) vs. (92.47, 89.74-95.20) (p ¼ 0.9252). CONCLUSIONS: The HEPT is similar to WHO-V morphology in predicting successful microdroplet fertilization, while allowing decreased utilization of ICSI. In addition, it appears to be a reasonable additional test to determine which couples with an abnormal morphology might have a successful microdroplet fertilization. References: 1. Practice Committees of the American Society for Reproductive, M. and T. Society for Assisted Reproductive, Intracytoplasmic sperm injection (ICSI) for non-male factor infertility: a committee opinion.