Integrin β3 (ITGB3), which is the target gene of the miRNA let-7 that can be antagonized by long noncoding RNA (lncRNA) H19, is well known to have a critical role in endometrium receptivity. However, the regulation of ITGB3 in cell–cell or cell–extracellular matrix adhesion and invasion for the maintenance of early pregnancy remains unknown. This study aimed to explore the role of the H19/let-7/ITGB3 axis in regulating trophoblastic spheroid adhesion and in vitro invasion ability using the HTR-8/SVneo cell line and to investigate the expression levels of lncRNA H19 and ITGB3 in human products of conception. The in vitro knockdown of H19 resulted in decreased expression of ITGB3 at the mRNA and protein levels and reduced the adhesion and invasion ability. In the embryonic chorion tissue of spontaneous abortion (SA), the expressions of H19 and ITGB3 at both the mRNA and protein levels decreased. The results of quantitative RT-PCR, Western blot analysis, dual-luciferase report gene and functional miRNA let-7 rescue experiments, adhesion assay and in vitro transwell invasion assay confirmed that H19 regulated trophoblastic spheroid adhesion with endometrial stromal cells through the H19/let-7/ITGB3 axis, thereby providing an improved understanding of the molecular mechanism of SA.

Background: MicroRNAs (miRNAs) are small, non-coding RNAs that are dysregulated in many diseases and can act as biomarkers. Although well-studied in cancer, the role of miRNAs in embryo implantation is poorly understood. Approximately 70% of embryos fail to implant following in-vitro fertilization and embryo transfer, 10% of patients experienced recurrent implantation failure. However, there are no well-established biomarkers that can predict implantation failure. Our purpose is to investigate distinct miRNA profiles in plasma and plasma exosomes during the window of implantation between patients with failed implantation and successful implantation. Methods: We select a nested case-control population of 12 patients with implantation failure or successfully clinical pregnancy using propensity score matching. RNA was extracted from plasma and plasma exosomes collected during the window of implantation (WOI). MicroRNA expression in all samples was quantified using microRNA sequencing. The intersection of differently expressed miRNAs in plasma and exosomes were further validated in the GEO dataset. Significantly altered microRNAs in both plasma and plasma exosomes were then subjected to target prediction and KEGG pathway enrichment analyses to search for key signaling pathways. WGCNA analysis was performed to identify hub miRNAs associated with implantation. Results: 13 miRNAs were differentially expressed in both plasma and plasma exosomes in patients with implantation failure. Among them, miR-150-5p, miR-150-3p, miR-149-5p, and miR-146b-3p had consistent direction changes in endometrium of patients with recurrent implantation failure (RIF), miR-342-3p had consistent direction changes in blood samples of patients with RIF. Pathway enrichment analysis showed that the target genes of differentially expressed miRNAs are enriched in pathways related to embryo implantation. WGCNA analysis indicated that miR-150-5p, miR-150-3p, miR-146b-3p, and miR-342-3p are hub miRNAs. Conclusions: Implantation failure is associated with distinct miRNA profiles in plasma and plasma exosomes during WOI.

Recently, perinatal outcomes and cumulative live birth rate (CLBR) have widely been utilized to assess the fertility outcomes and safety of assisted reproductive technology (ART), but more robust research is needed to address the success rates of live-healthy births resulting from this procedure, particularly for patients with low prognosis. This study aims to assess and comparative perinatal outcomes and CLBR per cycle of in vitro fertilization/Intracytoplasmic sperm injection (IVF/ICSI) between four groups of low prognosis characterized by POSEIDON criteria. A retrospective assessment was done among infertile women with a low prognosis undergoing IVF/ICSI at a reproductive center in China. Data were collected between January 2011 and December 2015 with a follow-up of at least two years, and censoring was defined by three-cycle completion, discontinuation, or having a live birth. Participants were grouped into 4 groups according to the POSEIDON classification (POSEIDON1, POSEIDON2, POSEIDON3, and POSEIDON4). The main outcomes were perinatal and obstetric outcomes with CLBR per cycle after IVF/ICSI procedure. And IVF/ICSI-technique outcomes as a secondary outcome. Statistical analyses were performed by SPSS, and a p value of < 0.05 was considered significant. A total of 461 eligible participants underwent a total of 825 IVF/ICSI cycles. POSEIDON1 had the best perinatal outcomes in terms of live births (≥ 28w) (54.8%). POSEIDON4 had a higher risk for perinatal and obstetric complications with abortion rate (9.8%); LBW (11.7%), PTD (23.5%), PROM (11.7%), and gestational diabetes (17.6%). POSEIDON2 had a high rate for malpresentation (14.2%), and cesarean delivery(57.2%), while POSEIDON3 was much associated with the occurrences of placenta previa (9.3%) compared to other groups (p value = 0.001). After adjusting odds ratio by age and BMI, POSEIDON4 had the least odds for biochemical pregnancy (p value = 0.019); and the least odds for clinical pregnancy (p value = 0.001) of the four groups. CLBR per cycle was better in POSEIDON1 and increased with an increasing number of cycles in all groups during the three cycles. Conservative CLBR after three complete cycles were 77.27%, 42.52%, 51.4% and 22.34%, while optimistic CLBR were 79.01%, 51.19%, 58.59% and 34.46% in POSEIDON1 to POSEIDON4, respectively. Younger women with low prognosis and normal ovarian reserve have a higher probability for live births and better perinatal outcomes compared with older women with poor or normal ovarian reserve. Besides, young women with low prognosis, despite ovarian reserve status, can increase their probability of conception and get relatively higher CLBR by undergoing multiple cycles of IVF/ICSI. Age is therefore considered as a critical parameter in predicting the perinatal outcome and CLBR.