MIR193BHG inhibits the proliferation, migration and invasion of trophoblasts by upregulating p53.

Aberrant expression of long non-coding RNAs (lncRNAs) serves a crucial role in the biological function of trophoblasts and contributes to preeclampsia (PE). lncRNA MIR193BHG expression is increased in PE placental tissues. In the present study, the effects of MIR193BHG on the function of trophoblasts were assessed to elucidate its underlying molecular mechanisms. The subcellular localization of MIR193BHG in HTR-8/SVneo human first-trimester extravillous trophoblast cells was determined using a fluorescent in situ hybridization assay and by conducting nucleocytoplasmic separation. The effect of MIR193BHG knockdown or overexpression on proliferation, migration, invasion and apoptosis was evaluated in vitro using Cell Counting Kit-8, wound healing, Transwell and flow cytometry assays. RNA-sequencing, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and protein-protein interaction network construction were subsequently performed to screen the downstream molecules regulated by MIR193BHG. Finally, rescue experiments were conducted to ascertain whether MIR193BHG influenced the biological function of trophoblasts via p53. MIR193BHG was predominantly localized in the nucleus of HTR-8/SVneo cells and overexpression of MIR193BHG significantly inhibited proliferation, migration and invasion, while increasing the rate of apoptosis of HTR-8/SVneo cells. Knockdown of MIR193BHG had the opposite effect. Furthermore, overexpression of MIR193BHG led to increases in both mRNA and protein levels of p53 compared with the control group, and knockdown of p53 rescued the effects induced by overexpression of MIR193BHG on cell proliferation, migration and invasion, while partially counteracting its effects on apoptosis of HTR-8/SVneo cells. In conclusion, the findings of the present study suggested that MIR193BHG served a critical role in progression of PE by regulating the expression of p53, and may be a novel therapeutic target for PE.

Regorafenib compared to nivolumab after sorafenib failure in patients with hepatocellular carcinoma: A systematic review and meta-analysis.

Which systemic therapy should be administered following sorafenib failure for patients with advanced hepatocellular carcinoma (HCC) is still a debated issue in clinical practice. This study aimed to compare regorafenib with nivolumab after sorafenib failure in patients with HCC. MEDLINE via PubMed, Scopus and Embase databases were searched for studies published until December 2021. The risk of bias (RoB) was evaluated using the Cochrane Collaboration tool for assessing risk of bias in randomized trials. From a total of 2120 articles, 3 papers were included in this meta-analysis. We found a statistically significant difference in the patient's objective response rate between the regorafenib and nivolumab groups (odds ratio (OR): 0.296, 95% confidence interval (95% CI): 0.161-0.544, p = 0.000). A statistically significant difference between regorafenib and nivolumab was not found for disease control rate after sorafenib failure in patients with advanced HCC (OR: 1.111, 95% CI: 0.793-1.557, p = 0.541) nor the number of progressive disease events (OR: 0.972, 95% CI: 0.693-1.362, p = 0.867). Overall survival (OS) and progression-free survival (PFS) were not calculable. The heterogeneity of the included data was low. Nivolumab monotherapy appears superior to regorafenib after sorafenib failure in patients with advanced HCC.

Effect of a 60-day weight reduction intervention prior to IVF/ICSI on perinatal outcomes in overweight or obese infertile women.

Purpose: The aim of this study was to determine whether a 60-day weight reduction intervention prior to in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and a higher weight loss ratio effectively improved perinatal outcomes for infertile overweight or obese women. Methods: This was a retrospective cohort study conducted at a university-affiliated fertility center. Two thousand three hundred and eighty-one overweight or obese infertile women who underwent or did not undergo a 60-day weight reduction intervention prior to IVF/ICSI between February 27, 2017 and November 11, 2020 were included in this study. All of these women achieved clinical pregnancy and delivered a single child after assisted reproductive technology (ART). Primary outcomes included neonatal birth weight and the incidence of pregnancy complications, premature delivery, and low birth weight. Results: The body mass index (BMI), blood glucose concentration, serum insulin level, and homeostasis model assessment of insulin resistance (HOMA-IR) of the intervention group decreased significantly after the weight reduction intervention. Neonatal birth weight was significantly higher in the intervention group (3519.6 g ±484.8 g) than the control group (3406.8 g ± 554.2 g; P < 0.001). There was no significant difference in the incidence of pregnancy complications between the two groups. Linear regression analysis found that the weight reduction intervention prior to IVF/ICSI and lower HOMA-IR at ovulation induction were associated with increased birth weight. As the weight loss ratio increased, the incidence of hypertensive disorders of pregnancy, premature membrane rupture, premature delivery, stillbirth, and low birth weight showed a downward trend. Conclusions: A 60-day weight reduction intervention prior to IVF/ICSI may increase neonatal birth weight, reduce maternal blood glucose concentration, and improve maternal insulin resistance in infertile overweight or obese women. This results require to be further verified by prospective randomized controlled trials with a larger sample size.

Perinatal outcomes of singleton live births after late moderate-to-severe ovarian hyperstimulation syndrome: A propensity score-matched study.

Objective: To evaluate whether singleton live births achieved following in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in women with late moderate-to-severe ovarian hyperstimulation syndrome (OHSS) is associated with adverse perinatal outcomes. Methods: This was a single-center retrospective cohort study conducted from January 2016 to June 2021. A total of 4,012 IVF/ICSI-fresh embryo transfer cycles that achieved singleton live births were included. According to the diagnosis of OHSS, the cycles were divided into two groups: late moderate-to-severe OHSS (MS-OHSS) group (n = 114) and non-OHSS group (n = 3,898). Multiple baseline covariates were controlled by propensity score matching, yielding 114 late MS-OHSS singleton live births matched to 337 non-OHSS singleton live births. The primary outcome of the study was normal term infant. The secondary outcomes were perinatal complications, gestational age at birth, birth weight, and birth height. Results: Before propensity score matching, no significant difference in perinatal outcomes was identified between late MS-OHSS group and non-OHSS group. After matching maternal age, BMI, basal serum FSH level, basal serum AMH level, basal antral follicle count, type of stimulation protocol, day of embryo development for embryo transfer, number of embryo transfer, and number of oocytes retrieved, there was still no significant difference in obstetric outcomes and neonatal outcomes between the two groups. Conclusions: The findings demonstrate that the perinatal outcomes were similar between the two groups. However, because the sample size of patients with late MS-OHSS was limited in this study, further investigations are warranted using a larger sample size.

Perinatal Outcomes of Singleton Live Births Following Preimplantation Genetic Testing for Chromosomal Structural Rearrangements in Single Frozen-Thawed Blastocyst Transfer Cycles: a Retrospective Cohort Study.

This study investigated whether singleton pregnancies conceived after preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) are associated with a higher risk of adverse perinatal outcomes than singleton pregnancies conceived after intracytoplasmic sperm injection (ICSI). We collected data on singleton live births after PGT-SR (n = 107) and ICSI (n = 585) in our hospital from January 2017 to August 2020. Multivariable analyses were used to adjust for maternal age, body mass index, gravidity and parity, paternal age, ovulatory disorder, and recurrent spontaneous abortion. The unadjusted results showed a significantly higher risk of hypertensive disorders of pregnancy (HDP) (odds ratio (OR) = 2.47; 95% confidence interval (CI): 1.10-5.54; P = 0.029) associated with PGT-SR singleton pregnancies than with ICSI singleton pregnancies. However, after adjusting for potential confounders, there were no longer any significant differences in the risk of HDP (adjusted OR = 2.24; 95% CI: 0.92-5.48; P = 0.077) between PGT-SR and ICSI singleton pregnancies. There were no significant differences between PGT-SR and ICSI singleton pregnancies in terms of gestational diabetes, preterm premature rupture of membranes, placenta previa, cesarean delivery, gestational age (weeks), preterm delivery (< 37 weeks), very preterm delivery (≥ 28 weeks and < 32 weeks), birth weight (g), low birth weight (< 2500 g), very low birth weight (< 1500 g), birth height (cm), birth defects, and 1-min and 5-min Apgar scores. In conclusion, for single frozen-thawed blastocyst cycles, there were no significant differences in adverse perinatal outcomes between PGT-SR and ICSI singleton pregnancies. However, due to the limited sample size, these conclusions need to be confirmed by further studies.

Integrated Analysis of Hub Genes and MicroRNAs in Human Placental Tissues from In Vitro Fertilization-Embryo Transfer.

Objective: Supraphysiological hormone exposure, in vitro culture and embryo transfer throughout the in vitro fertilization-embryo transfer (IVF-ET) procedures may affect placental development. The present study aimed to identify differences in genomic expression profiles between IVF-ET and naturally conceived placentals and to use this as a basis for understanding the underlying effects of IVF-ET on placental function. Methods: Full-term human placental tissues were subjected to next-generation sequencing to determine differentially expressed miRNAs (DEmiRs) and genes (DEGs) between uncomplicated IVF-ET assisted and naturally conceived pregnancies. Gene ontology (GO) enrichment analysis and transcription factor enrichment analysis were used for DEmiRs. MiRNA-mRNA interaction and protein-protein interaction (PPI) networks were constructed. In addition, hub genes were obtained by using the STRING database and Cytoscape. DEGs were analyzed using GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Differentially expressed miRNAs were validated through qRT-PCR. Results: Compared against natural pregnancies, 12 DEmiRs and 258 DEGs were identified in IVF-ET placental tissues. In a validation cohort, it was confirmed that hsa-miR-204-5p, hsa-miR-1269a, and hsa-miR-941 were downregulation, while hsa-miR-4286, hsa-miR-31-5p and hsa-miR-125b-5p were upregulation in IVF-ET placentas. Functional analysis suggested that these differentially expressed genes were significantly enriched in angiogenesis, pregnancy, PI3K-Akt and Ras signaling pathways. The miRNA-mRNA regulatory network revealed the contribution of 10 miRNAs and 109 mRNAs while EGFR was the most highly connected gene among ten hub genes in the PPI network. Conclusion: Even in uncomplicated IVF-ET pregnancies, differences exist in the placental transcriptome relative to natural pregnancies. Many of the differentially expressed genes in IVF-ET are involved in essential placental functions, and moreover, they provide a ready resource of molecular markers to assess the association between placental function and safety in IVF-ET offspring.

Obstetric and neonatal outcomes of pregnancies resulting from preimplantation genetic testing: a systematic review and meta-analysis.

BACKGROUND: Preimplantation genetic testing (PGT) includes methods that allow embryos to be tested for severe inherited diseases or chromosomal abnormalities. In addition to IVF/ICSI and repeated freezing and thawing of the embryos, PGT requires a biopsy to obtain embryonic genetic material for analysis. However, the potential effects of PGT on obstetric and neonatal outcomes are currently uncertain. OBJECTIVE AND RATIONALE: This study aimed to investigate whether pregnancies conceived after PGT were associated with a higher risk of adverse obstetric and neonatal outcomes compared with spontaneously conceived (SC) pregnancies or pregnancies conceived after IVF/ICSI. SEARCH METHODS: PubMed, EMBASE, MEDLINE, Web of Science and The Cochrane Library entries from January 1990 to January 2021 were searched. The primary outcomes in this study were low birth weight (LBW) and congenital malformations (CMs), and the secondary outcomes included gestational age, preterm delivery (PTD), very preterm delivery (VPTD), birth weight (BW), very low birth weight (VLBW), neonatal intensive care unit (NICU) admission, hypertensive disorders of pregnancy (HDP), gestational diabetes, placenta previa and preterm premature rupture of membranes (PROM). We further pooled the results of PGT singleton pregnancies. Subgroup analyses included preimplantation genetic diagnosis (PGD), preimplantation genetic screening (PGS), cleavage-stage biopsy combined with fresh embryo transfer (CB-ET) and blastocyst biopsy combined with frozen-thawed embryo transfer (BB-FET). OUTCOMES: This meta-analysis included 15 studies involving 3682 babies born from PGT pregnancies, 127 719 babies born from IVF/ICSI pregnancies and 915 222 babies born from SC pregnancies. The relative risk (RR) of LBW was higher in PGT pregnancies compared with SC pregnancies (RR = 3.95, 95% confidence interval [CI]: 2.32-6.72), but the risk of CMs was not different between the two groups. The pooled results for the risks of LBW and CMs were similar in PGT and IVF/ICSI pregnancies. The risks of PTD (RR = 3.12, 95% CI: 2.67-3.64) and HDP (RR = 3.12, 95% CI: 2.18-4.47) were significantly higher in PGT pregnancies compared with SC pregnancies. Lower gestational age (mean difference [MD] = -0.76 weeks, 95% CI -1.17 to -0.34) and BW (MD = -163.80 g, 95% CI: -299.35 to -28.24) were also noted for PGT pregnancies compared with SC pregnancies. Nevertheless, compared with IVF/ICSI pregnancies, the risks of VPTD and VLBW in PGT pregnancies were significantly decreased by 41% and 30%, respectively, although the risk of HDP was still significantly increased by 50% in PGT pregnancies compared with IVF/ICSI pregnancies. The combined results of obstetric and neonatal outcomes of PGT and IVF/ICSI singleton pregnancies were consistent with the overall results. Further subgroup analyses indicated that both PGD and PGS pregnancies were associated with a higher risk of PTD and a lower gestational age compared with SC pregnancies. WIDER IMPLICATIONS: This meta-analysis showed that PGT pregnancies may be associated with increased risks of LBW, PTD and HDP compared with SC pregnancies. The overall obstetric and neonatal outcomes of PGT pregnancies are favourable compared with those of IVF/ICSI pregnancies, although PGT pregnancies were associated with a higher risk of HDP. However, because the number of studies that could be included was limited, more randomised controlled trials and prospective cohort studies are needed to confirm these conclusions.