H19 regulates angiogenic capacity of extravillous trophoblasts by H19/miR-106a-5p/VEGFA axis.

PURPOSE: To investigate the role and underlying mechanism of H19 in regulating angiogenic capacity of extravillous trophoblasts. METHODS: Gain and loss of function experiments were performed using a human first-trimester extravillous trophoblast (EVT) cell line, HTR-8/SVneo cells. H19 was overexpressed or knocked down in HTR-8 cells by transfecting plasmid harboring whole-length H19 sequence (pH19) or siRNA specially targeting H19, respectively (siH19). Cell migration and tube-formation assay were assessed in the indicated groups. Gene expression was detected by RT-qPCR, Western blot, and ELISA assay. RESULTS: Overexpression of H19 in EVT cells increased cell migration and tube formation, while downregulation of H19 in EVT cells decreased cell migration and tube formation. Furthermore, we found that H19 played its role by VEGFA. In addition, we demonstrated the H19/miR-106a-5p/VEGFA regulatory axis in EVT. Experiments of the clinical specimen showed that H19 was very abundantly expressed in human first-trimester trophoblasts, and we found that the expression of H19 and VEGFA were significantly downregulated in the villous tissues from idiopathic recurrent miscarriage (RM) patients; moreover, the expression of H19 and VEGFA was positively correlated. CONCLUSION: H19/miR-106a-5p/VEGFA axis plays a role in regulating the angiogenic capacity of EVT, which might contribute to idiopathic RM.

[Cumulative live birth rates after frozen embryo transfer and fresh embryo transfer with oocyte numbers more than 15].

OBJECTIVE: To compare the cumulative live birth rates (CLBR) and the incidence of ovarian hyperstimulation syndrome (OHSS) between fresh embryo transfer (ET) and frozen ET (the freeze-all policy), when oocyte numbers are more than 15 in the first treatment of in vitro fertilization or intracytoplasmic sperm injection, and to evaluate the benefits of the freeze-all policy.
 Methods: We retrospectively analyzed clinical data of 2 842 patients whose oocytes numbers were more than 15, including 1 095 frozen ET patients and 1 747 fresh ET patients. The patients general data, a baseline features, CLBR, and the incidence of OHSS were compared between the 2 groups.
 Results: There were 598 patients in the 2 groups after they experienced the propensity score matching. No significant differences were found in age, infertility causes, body mass index, basal follicle stimulating hormone level, the total days and total dose of using gonadotrophin (Gn) between the 2 groups (all P>0.05). The CLBR of the freeze-all cycles increased along with the number of oocytes (P>0.05), and the oocyte numbers were greater in freeze-all group than those of the fresh ET group (P<0.001). There was no significant difference in CLBR after one complete cycle between the 2 groups (P>0.05), but after the first embryo transfer cycle, the CLBR in freeze-all group was higher than that in the fresh ET cycle group (P<0.05). The incidence of OHSS in patients with freeze-all was significantly lower than that in the patiants with fresh ET (P<0.05).
 Conclusion: Patients with oocytes over 15 and OHSS tendency who accepted the freeze-all strategy can help them to prevent OHSS and they have a higher CLBR than fresh ET cycles.