Fixation in Form-Acetic allows hyaluronic acid detection in mouse ovaries

Lay summary To visualise tissues to determine the presence of disease or simply to understand anatomy, it is important to preserve fresh tissue. Fixatives are chemical solutions that preserve tissues to enable microscopic evaluation. However, some fixatives introduce artefact such as shrinkage of cells. Recently, a new fixative, Form-Acetic, was developed that is superior for preserving the structure of ovary tissue and allows investigation of ovary composition. One component of the ovary is hyaluronic acid (HA), which plays a crucial role in normal ovary function and fertility. Importantly, HA is sensitive to different fixative solutions. Therefore, it is meaningful to verify whether Form-Acetic is suitable for detecting HA. In this study, adult mouse ovaries were fixed in Form-Acetic and HA was detected. All HA-containing structures in the ovary were clearly distinguished which proves that the novel fixative allows the detection of HA.

A Case of Torsion in an Otherwise-Normal Ovary with a Giant Hematosalpinx Larger than Enlarged Ovary: Utilization of Diagnostic Laparoscopy for the Accurate Diagnosis

We report a case of torsion in an otherwise-normal ovary with a giant hematosalpinx. A 23-year-old woman presented with complaints of abdominal pain and nausea. At initial visit, there was few abnormal findings of imaging tests, and we made a diagnosis of ovarian hemorrhage. Three days later, she came back with increased symptoms, and we detected the mass of a complex solid cystic structure with a unilocular cyst much larger than solid component. A diagnostic laparoscopy was performed immediately, and we could make a diagnosis of torsion in an otherwise-normal ovary with a giant hematosalpinx. We performed a salpingectomy and could preserve her ovary. This is the first case of torsion in an otherwise-normal ovary with a giant hematosalpinx which enlarged to a greater extent than the ovary.

Clinicopathologic significance and race-specific prognostic association of MYB overexpression in ovarian cancer

Late diagnosis, unreliable prognostic assessment, and poorly-guided therapeutic planning result in dismal survival of ovarian cancer (OC) patients. Therefore, identifying novel functional biomarker(s) is highly desired for improved clinical management. MYB is an oncogenic transcription factor with emerging functional significance in OC. Here we examined its clinicopathologic significance by immunohistochemistry and TCGA/GTex data analyses. Aberrant MYB expression was detected in 94% of OC cases (n = 373), but not in the normal ovarian tissues (n = 23). MYB was overexpressed in all major epithelial OC histological subtypes exhibiting the highest incidence (~ 97%) and overall expression in serous and mucinous carcinomas. MYB expression correlated positively with tumor grades and stages. Moreover, MYB exhibited race-specific prognostic association. Moderate-to-high MYB levels were significantly associated with both poor overall- (p = 0.02) and progression-free (p = 0.02) survival in African American (AA), but not in the Caucasian American (CA) patients. Consistent with immunohistochemistry data, we observed significantly higher MYB transcripts in OC cases (n = 426) than normal ovary (n = 88). MYB transcripts were significantly higher in all epithelial OC subtypes, compared to normal, and its greater levels predicted poor survival in AA OC, but not CA OC, patients. Thus, MYB appears to be a useful clinical biomarker for prognostication, especially in AA patients.

Melatonin supplementation and outcomes after assisted reproductive technology: A systematic review and meta-analyses

To assess the effect of melatonin (MT) supplementation on the outcomes of ART. A meta-analysis and systematic review was conducted. Eleven studies were included in this meta-analysis. Clinical pregnancy rate (CPR), live birth rate (LBR), Miscarriage rate (MR), fertilization rate (FR), Number of oocyte, MII oocyte, top-quality embryo were reported in 10, 3, 6, 7, 9, 8, and 6 studies, respectively. MT supplementation significantly increased the CPR, the No. of MII oocyte, the No. of top-quality embryo, and the FR. However, there was no significant difference in LBR, No. of oocyte, and the MR. When studies were sub-grouped by the interventions, no matter the control group is MI+FA or placebo/none, MT supplementation increased No. of MII oocyte and No. of top embryo, whereas showed similar CPR. When studies were sub-grouped according to women’s characteristic, MT supplementation showed no significant benefit on CPR in women with PCOS, with normal ovary function, and with previous low fertilization or poor-quality embryo. However, MT supplementation increased the No of MII in women with PCOS, but did not show benefit in women with normal ovary function. MT supplementation may not improve the CPR and LBR of ART. But MT seems be beneficial to the quality of oocyte and embryo, especially for women with PCOS and DOR. Further well-designed studies are needed before the recommendation of its clinical use.

Prepronociceptin is differentially expressed in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We sought to identify genes associated with epithelial ovarian cancer and the high-grade serous ovarian cancer (HGSC) subtype by comparing global gene expression profiles of normal ovary with that of primary tumors from women diagnosed with epithelial cancer and HGSC in specific using published microarray data (2, 3). We identified the gene encoding prepronociceptin, PNOC, as among the genes whose expression was most different in epithelial ovarian cancer and in HGSC ovarian tumors. PNOC expression was significantly higher in high-grade serous ovarian tumors relative to normal ovary. PNOC expression correlated with overall survival in patients with ovarian cancer. These data indicate that expression of PNOC is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. PNOC may be relevant to pathways underlying ovarian cancer progression.

BIRC5 is differentially expressed in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We sought to identify genes associated with epithelial ovarian cancer and the high-grade serous ovarian cancer (HGSC) subtype by comparing global gene expression profiles of normal ovary with that of primary tumors from women diagnosed with epithelial cancer and HGSC in specific using published microarray data (2, 3). We identified the gene encoding the baculoviral inhibitor of apoptosis repeat (IAP) containing 5, BIRC5 as among the genes whose expression was most different in epithelial ovarian cancer and in HGSC ovarian tumors. BIRC5 expression was significantly higher in ovarian tumors relative to normal ovary. Correlation of BIRC5 expression with survival outcomes in patients with ovarian cancer was complex, with low expression favorable early in disease and high expression favorable later in disease. These data indicate that expression of BIRC5 is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. BIRC5 may be relevant to pathways underlying ovarian cancer progression.

Melatonin Supplementation and Outcomes After Assisted Reproductive Technology: A Systematic Review and Meta-analyses

Melatonin (MT) regulates a variety of important actions related to reproduction. Many studies have investigated the effect of MT application on the outcome after assisted reproductive technology (ART), with controversial results. The aim of this systematic review was to synthesize evidence from clinical studies that examine the effect of MT on the main outcomes of ART. PubMed, Embase, Web of Science, and Google scholar were searched. Clinical trials, which studied the effect of MT supplementation on outcome after ART and published in English from inception to April 2020, were included. One author assessed the risk of bias in the studies using the Cochrane Collaboration checklist. Dichotomous outcomes were analyzed as risk ratios (RR) using the Mantel-Haenszel statistical method and a random/fixed effect model. Continuous outcomes were analyzed as Mean Difference (MD) using the Inverse Variance statistical method. Eleven studies performed between 2008 and 2019 were included in this meta-analysis. Clinical pregnancy rate (CPR), live birth rate (LBR), Miscarriage rate (MR), fertilization rate (FR), Number of oocyte retrieved, MII oocyte, top-quality embryo were reported in 10, 3, 6, 7, 9, 8, and 6 studies, respectively. MT supplementation significantly increased the CPR (RR, 1.24; 95% confidence interval [CI], 1.04, 1.47), the No. of MII oocyte (MD, 1.39; 95% CI, 0.74, 2.04), the No. of top-quality embryo (MD, 0.56; 95% CI, 0.24, 0.88), and the FR (4 studies with RR, 1.10; 95% CI, 1.03, 1.17; 3 studies with MD, 0.13; 95% CI, 0.01, 0.24). However, there was no significant difference in LBR (RR, 1.23; 95% CI, 0.85, 1.80), No. of oocyte retrieved (MD, 0.58; 95% CI, -0.12, 1.27), and the MR (RR, 0.96; 95% CI, 0.50, 1.82). When studies were sub-grouped by the interventions, no matter the control group is MI+FA or placebo/none, MT supplementation increased No. of MII oocyte (MT+MI+FA vs. MI+FA MD, 0.91; 95% CI, 0.40, 1.41; MT vs. Placebo/none MD, 2.06; 95% CI, 0.73, 3.39) and No. of top embryo (MT+MI+FA vs. MI+FA MD, 0.70; 95% CI, 0.24, 1.16; MT vs. Placebo/none MD, 0.33; 95% CI, 0.11, 0.54), whereas showed similar CPR (MT+MI+FA vs. MI+FA RR, 1.22; 95% CI, 0.96, 1.54; MT vs. Placebo/None RR, 1.26; 95% CI, 0.97, 1.62). When studies were sub-grouped according to women’s characteristic, MT supplementation showed no significant beneficial effect on CPR in women with PCOS (RR, 1.18; 95% CI, 0.92, 1.52), with normal ovary function (RR, 1.15; 95% CI, 0.87, 1.53), and women with previous low fertilization or poor-quality embryo (RR, 1.71; 95% CI, 0.95, 3.07). However, MT supplementation increased the No of MII in women with PCOS (MD, 0.97; 95% CI, 0.22, 1.73), but did not show such benefit in women with normal ovary function (MD, 1.49; 95% CI, -0.33, 3.31). In conclusion, MT supplementation may not improve the clinical pregnancy and live birth of ART. But MT seems to be beneficial to the quality of oocyte and embryo, especially for women with PCOS and DOR, at least to some extent. Further well-designed studies are needed before recommendation of its use in clinical practice.

The progesterone receptor is differentially expressed in epithelial ovarian cancer and its expression correlates with patient survival.

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We sought to identify genes associated with high-grade serous ovarian cancer (HGSC), the most common type of EOC by comparing global gene expression profiles of normal ovary with that of primary tumors from women diagnosed with HGSC using published microarray data (2, 3). We found significant differential expression of the gene encoding the progesterone receptor, PGR, in high-grade serous ovarian tumors and in epithelial ovarian cancer broadly. PGR was expressed at lower levels in tumors from patients with high-grade serous ovarian cancer as compared to the normal ovary, and EOC patients whose tumors expressed low levels of PGR possessed significantly shorter progression-free survival than did those whose tumors expressed high levels of PGR. Multiple studies have described potential roles for the progesterone receptor in ovarian cancer, but our analysis is the first to demonstrate differential, decreased expression of PGR in tumors from patients with ovarian cancer and specifically in HGSC, in conjunction with unfavorable progression-free survival outcomes for ovarian cancer patients with low tumor expression of PGR.

MIR503HG is differentially expressed in high-grade serous ovarian cancers.

Ovarian cancer is the most lethal gynecologic cancer (1). We sought to identify genes associated with high-grade serous ovarian cancer (HGSC) by comparing global gene expression profiles of normal ovary with that of primary tumors from women diagnosed with HGSC using published microarray data (2, 3). We found significant differential expression of MIR503HG in high-grade serous ovarian tumors.

RBPMS is differentially expressed in high-grade serous ovarian cancers.

Ovarian cancer is the most lethal gynecologic cancer (1). We sought to identify genes associated with high-grade serous ovarian cancer (HGSC) by comparing global gene expression profiles of normal ovary with that of primary tumors from women diagnosed with HGSC using published microarray data (2, 3). We found significant differential expression of RBPMS in high-grade serous ovarian tumors.