Luteal Phase Ovarian Stimulation versus Follicular Phase Ovarian Stimulation results in different Human Cumulus cell genes expression: A pilot study.

Background: Luteal-phase ovarian stimulation (LPOS) is an alternative in vitro fertilization (IVF) protocol. However, limited data showed the genes expression of cumulus cells (CCs) in LPOS. Therefore, this study aimed to investigate CC genes expression between LPOS and follicular-phase ovarian stimulation (FPOS) in poor ovarian responders (PORs) undergoing IVF cycles. Methods: This was a prospective non-randomized trial (ClinicalTrials.gov Identifier: NCT03238833). A total of 36 PORs who met the Bologna criteria and underwent IVF cycles were enrolled. Fifteen PORs were allocated to the LPOS group, and 21 PORs were allocated to the FPOS group. The levels of CC genes involved in inflammation (CXCL1, CXCL3, TNF, PTGES), oxidative phosphorylation (NDUFB7, NDUFA4L2, SLC25A27), apoptosis (DAPK3, BCL6B) and metabolism (PCK1, LDHC) were analyzed using real-time quantitative PCR and compared between the two groups. Results: The number of retrieved oocytes, metaphase II oocytes, fertilized oocytes, day-3 embryos and top-quality day-3 embryos, clinical pregnancy rates and live birth rates were similar between the two groups except for significantly high progesterone levels in the LPOS group. The mRNA expression levels of CXCL1 (0.51 vs 1.00, p < 0.001) and PTGES (0.30 vs 1.00, p < 0.01) were significantly lower in the LPOS group than in the FPOS group. The LPOS group had significantly lower mRNA expression of NDUFB7 (0.12 vs 1.00, p < 0.001) and NDUFA4L2 (0.33 vs 1.00, p < 0.01) than the FPOS group. DAPK3 (3.81 vs 1.00, p < 0.05) and BCL6B (2.59 vs 1.00, p < 0.01) mRNA expression was significantly higher in the LPOS group than in the FPOS group. Increased expression of PCK1 (3.13 vs. 1.00, p < 0.001) and decreased expression of LDHC (0.12 vs. 1.00, p < 0.001) were observed in the LPOS group compared to the FPOS group. Conclusions: Our data revealed different CC genes expression involving in inflammation, oxidative phosphorylation, apoptosis and metabolism between LPOS and FPOS in PORs. However, the results are non-conclusive; further large-scale randomized controlled trials are needed to validate the results.

Multi-Omics Analysis Identifying Key Biomarkers in Ovarian Cancer.

Ovarian cancer is one of the most common malignant tumors. Here, we aimed to study the expression and function of the CREB1 gene in ovarian cancer via the bioinformatic analyses of multiple databases. Previously, the prognosis of ovarian cancer was based on single-factor or single-gene studies. In this study, different bioinformatics tools (such as TCGA, GEPIA, UALCAN, MEXPRESS, and Metascape) have been used to assess the expression and prognostic value of the CREB1 gene. We used the Reactome and cBioPortal databases to identify and analyze CREB1 mutations, copy number changes, expression changes, and protein-protein interactions. By analyzing data on the CREB1 differential expression in ovarian cancer tissues and normal tissues from 12 studies collected from the "Human Protein Atlas" database, we found a significantly higher expression of CREB1 in normal ovarian tissues. Using this database, we collected information on the expression of 25 different CREB-related proteins, including TP53, AKT1, and AKT3. The enrichment of these factors depended on tumor metabolism, invasion, proliferation, and survival. Individualized tumors based on gene therapy related to prognosis have become a new possibility. In summary, we established a new type of prognostic gene profile for ovarian cancer using the tools of bioinformatics.

Dual-trigger improves the outcomes of in vitro fertilization cycles in older patients with diminished ovarian reserve: A retrospective cohort study.

BACKGROUND: Dual-trigger for final oocyte maturation has been applied on the women with poor ovarian response or diminished ovarian reserve. However, the results were controversial. The Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) stratification is a set of newly established criteria for low prognosis patients. The aim of this study was to examine the effectiveness of dual-trigger for final oocyte maturation on the in vitro fertilization (IVF) outcomes of patients who fulfill the POSEIDON group 4 criteria. METHODS: This retrospective cohort study investigated 384 cycles fulfilling the POSEIDON group 4 criteria. The patients underwent IVF treatment using the gonadotropin-releasing hormone (GnRH) antagonist protocol. The study group contained 194 cycles that received dual-trigger (human chorionic gonadotropin [hCG] plus GnRH-agonist) for final oocyte maturation. The control group included 114 cycles where final oocyte maturation was performed with only hCG. Baseline characteristics and cycle parameters, as well as IVF outcomes of both groups were compared. RESULTS: Baseline characteristics were similar between the dual trigger group and the control group. In terms of IVF outcomes, the dual trigger group demonstrated significantly higher number of retrieved oocytes, metaphase II oocytes, fertilized oocytes, day-3 embryos, and top-quality day-3 embryos. A statistically significant improvement in clinical pregnancy rate and live birth rate was also observed in the dual trigger group. CONCLUSIONS: Our data suggests that dual trigger for final oocyte maturation might improve clinical pregnancy rates and live birth rates of IVF cycles in patients fulfilling the POSEIDON group 4 criteria.

Pregnancy-induced hypertension is an independent risk factor for meconium aspiration syndrome: A retrospective population based cohort study.

OBJECTIVE: Meconium aspiration syndrome (MAS), possibly resulting from fetal hypoxia, is a respiratory distress disorder in the infant. Pregnancy-induced hypertension (PIH) can cause placental dysfunction and lead to fetal hypoxia, which may induce the development of MAS. Therefore, the aim of this study was to determine the association between PIH and MAS and to identify the predictive risk factors. MATERIALS AND METHODS: This was a retrospective cohort study. We selected patients with newly diagnosed PIH and a matched cohort group from the Taiwan National Health Insurance Research Database (NHIRD), from January 1, 2000 till December 31, 2013. For each patient in the PIH cohort, 4 subjects without PIH, matched for age and year of delivery, were randomly selected as the comparison cohort. The incidence of meconium aspiration syndrome was assessed in both groups. RESULTS: Among the 23.3 million individuals registered in the NHIRD, 29,013 patients with PIH and 116,052 matched controls were identified. Patients who experienced PIH had a higher incidence of MAS than did those without PIH. According to a multivariate analysis, PIH (odds ratio [OR] = 1.70, 95% confidence interval [CI] = 1.49-1.93, p < 0.0001) was independently associated with increased risk of MAS. Additionally, age ≥30 years (OR = 1.26, 95% CI = 1.12-1.42, p = 0.0001), nulliparity (OR = 1.13, 95% CI = 1.01-1.27, p = 0.0367) and patients with diabetes mellitus (OR = 3.09, 95% CI = 1.35-7.09, p = 0.0078) were also independent risk factors of MAS. CONCLUSION: Patients with PIH obtained higher subsequent risk for the development of MAS than those without PIH. Besides, age ≥30 years, nulliparity and patients with diabetes mellitus are the independent risk factors of developing MAS.

Kinome-Wide siRNA Screening Identifies Src-Enhanced Resistance of Chemotherapeutic Drugs in Triple-Negative Breast Cancer Cells.

Background: Chemotherapy is the main treatment for triple-negative breast cancer (TNBC), which lack molecular markers for diagnosis and therapy. Cancer cells activate chemoresistant pathways and lead to therapeutic failure for patients with TNBC. Several kinases have been identified as chemoresistant genes. However, the involvement of kinases in the chemoresistance in TNBC cells is not fully understood. Methods: We employed a kinome siRNA library to screen whether targeting any kinases could increase the chemosensitivity of TNBC cell lines. The effects of kinase on cell viability in various breast cancer cells were validated with ATP level and colony formation. Protein expression and phosphorylation were determined by immunoblotting. The Cancer Genome Atlas (TCGA) dataset was collected to analyze the correlation of Src expression with prognosis of TNBC patients. Results: Primary screening and validation for the initial hits showed that Src kinase was a potential doxorubicin-resistant kinase in the TNBC cell lines MDA-MB-231 and Hs578T. Both siRNA against Src and the Src inhibitor dasatinib enhanced the cytotoxic effects of doxorubicin in TNBC cells. Moreover, phosphorylation of AKT and signal transducer and activator of transcription 3 (STAT3), downstream effectors of Src, were accordingly decreased in Src-silenced or -inhibited TNBC cells. Additionally, TCGA data analysis indicated that Src expression levels in tumor tissues were higher than those in tumor-adjacent normal tissues in patients with TNBC. High co-expression level of Src and STAT3 was also significantly correlated with poor prognosis in patients. Conclusion: Our results showed that Src-STAT3 axis might be involved in chemoresistance of TNBC cells.

Complete resolution of diffuse placenta increta in a primigravida with twin pregnancy: sonographic monitoring.

We report a case of timely diagnosis of placenta increta by sonography during the third stage of labor, which avoided any attempt at manual removal of a retained placenta and thus prevented additional postpartum bleeding. The use of intra-cervical injection of vasopressin and methotrexate and application of transcatheter arterial embolization of bilateral uterine arteries and right internal iliac arteries resulted in a good outcome.

Prominent decidual vasculature overlying the internal cervical os: an entity potentially leading to acute life-threatening antepartum hemorrhage.

We report a new entity of prominent decidual vasculature overlying the internal cervical os which caused life-threatening antepartum uterine bleeding in a rhesus (Rh) D-negative patient at 32(+5) weeks' gestation. Cesarean hysterectomy was performed because of diffuse placenta increta. Early hospitalization, advanced preparation for emergency cesarean section, and timely blood transfusion, including 2L of RhD-positive packed red blood cells, aided in saving the lives of the patient and her baby. To the best of our knowledge, the ultrasound findings of this condition have never been reported. This condition could be considered as an independent sign for identification of a patient who is potentially at risk of acute massive antepartum hemorrhage. It deserves early accurate diagnosis by obstetricians using transvaginal sonography with color Doppler analysis.

Adynamic ileus and acute colonic pseudo-obstruction occurring after cesarean section in patients with massive peripartum hemorrhage.

The clinical histories (including radiographs) of 4 patients who suffered from significant adynamic ileus or acute colonic pseudo-obstruction after cesarean section are presented. The main manifestations were vomiting, severe colicky pain, and abdominal distension. These can occur immediately after or within 2 days of the operation. Based on our experience, the risk factors for the development of adynamic ileus are significant peripartum hemorrhage leading to unstable hemodynamic status, severe constipation, use of meperidine for pain relief, and overt bowel manipulation. Mild enema and metoclopramide seem to be helpful in facilitating its resolution. Here, we examine how to differentiate mechanical bowel obstruction from adynamic ileus and look at how to prevent the occurrence of adynamic ileus while minimizing its severity and shortening its clinical course.