Glycemic control and neonatal outcomes in women with gestational diabetes mellitus treated using glyburide, metformin, or insulin: a pairwise and network meta-analysis.

AIMS: We aimed to assess the comparative efficiency and safety of the use of glyburide, metformin, and insulin in gestational diabetes mellitus (GDM). METHODS: We searched for randomized controlled trials that compared glyburide, metformin, and insulin in GDM. Data regarding glycemic control and neonatal safety were collected and analyzed in pairwise and network meta-analyses. RESULTS: A total of 4533 individuals from 23 trials were included. Compared with glyburide, metformin reduced 2-h postprandial blood glucose (2HPG) to a greater extent (standard mean difference (SMD) 0.18; 95% credible interval (CI) 0.01, 0.34). There were significantly lower prevalence of neonatal hypoglycemia (risk difference (RD) - 0.07; 95%CI - 0.11, - 0.02) and preeclampsia (RD - 0.03; 95%CI - 0.06, 0) in the metformin group than in the insulin group. The metformin group had significantly lower birth weight (SMD - 0.17; 95%CI - 0.25, - 0.08) and maternal weight gain (SMD - 0.61; 95%CI - 0.86,- 0.35) compared with the insulin group. Network meta-analysis suggested that metformin had the highest probability of successfully controlling glycemia and preventing neonatal complications. CONCLUSIONS: The present meta-analysis suggests that metformin may be as effective as insulin for glycemic control and is the most promising drug for the prevention of neonatal and maternal complications.

Secretions released from mesenchymal stem cells improve spermatogenesis restoration of cytotoxic treatment with busulfan in azoospermia mice.

This study aimed at the efficacy of sequential treatment of bone marrow-derived mesenchymal stem cell secretion for busulfan-treated azoospermia in mice. The conditioned media (CM) was obtained from bone marrow mesenchymal stem cells (MSCs) or 293 cells. Chemically induced azoospermia mice received 200 µl MSC-CM or 293-CM twice a week intravenously for three consecutive weeks. The histological assessment of spermatogenic recovery quantifying the expression of meiosis-associated genes, and Sertoli cell barrier functional factors were assessed. The characteristics of TM4 cells (Sertoli cell line) after pre-incubation of MSC-CM in vitro were also obtained. The MSC-CM group had the most spermatogenic colonies among the three groups (p < .05), but no spermatids were seen. Expressions of the meiosis-associated genes Dazl, Vasa, Miwi, Stra8, CyclinA1, Pgk2 and Scp3 in MSC-CM testis were remarkably higher compared with 293-CM and busulfan groups respectively (p < .05). The levels of Sertoli cell barrier functional factors, for example ICAM-1 and N-cadherin, were significantly increased during MSC-CM treatment (p < .05). Moreover, pre-incubation of MSC-CM particularly accelerated the CD54 (ICAM-1) and CD44 expressions of TM4 cells and promoted cell inherent adhesion. MSC-CM treatment can significantly improve the short-term restoration of spermatogonial structures of chemically induced azoospermia related to facilitating Sertoli cell adhesion integrity.

Role of anti-Müllerian hormone and testosterone in follicular growth: a cross-sectional study.

BACKGROUND: Anti-Müllerian hormone (AMH) is now considered the best serum biomarker of ovarian reserve, while basal sex hormones are classic markers used for assessing ovarian reserve. The interaction between AMH and sex hormones are complicated and not sufficiently addressed. In this study, we took diminished ovarian reserve (DOR) and polycystic ovarian syndrome (PCOS) as two extremes of ovarian reserve (deficient and excessive respectively) to investigate the role of AMH and sex hormones in follicular growth. METHODS: A retrospective cross-sectional survey was performed. The patients assessed AMH and basal sex hormones in the Second Hospital of Zhejiang University from April 2016 to March 2019 were involved in this study. Serum AMH and sex hormone concentrations were tested with electrochemiluminescence method. Stepwise linear regression and binary logistic regression was used to determine the predictors of AMH level and to explore the involved factors determining DOR and PCOS. RESULTS: In the present study, we found that age and follicle-stimulating hormone (FSH) were main negative correlation factors, and luteinizing hormone (LH) and testosterone (T) were main positive factors of AMH. In DOR group, age, FSH and estradiol (E2) increased and T decreased, while in PCOS group, LH and T increased. Binary logistic regression found that age, weight, FSH, E2, and T were the significant factors which independently predicted the likelihood of DOR, and that age, body mass index (BMI), AMH, LH, and T predicted the likelihood of PCOS. CONCLUSIONS: Our study demonstrated that age, FSH, and T were factors that most closely correlated with AMH level, and T was involved in both DOR and PCOS. Since DOR and PCOS are manifested with insufficient AMH and excessive AMH respectively, it is suggested that total testosterone correlated with AMH closely and plays an important role in follicular growth. More attention should be given to testosterone level during controlled ovarian hyperstimulation (COH) process.

Mesenchymal stem cell-secreted factors delayed spermatogenesis injuries induced by busulfan involving intercellular adhesion molecule regulation.

The present study was designed to investigate the therapeutic effect of bone marrow MSC-derived factors on gonadotropic toxicity induced by busulfan in vivo. The conditioned media (CM) was obtained from MSCs in serum-free incubation for 48 hr and concentrated ~25-fold by ultrafiltration. The CM of HEK 293 cells was treated as control (293-CM). MSC-CM was injected into busulfan mice via caudal veins after 1 day of busulfan treatment for 2 weeks (200 µl per dose/twice weekly）. Compared to the 293-CM group, testicular injury was delayed in MSC-CM group, including reduced vacuolations of cells in the basal compartment of the seminiferous epithelium and detachment of cells from basement membrane. Apoptotic spermatogenic cells were significantly decreased in MSC-CM group (p ï¼œ 0.05). Interesting N-cadherin，ICAM-1 and P-cadherin expressions significantly increased in MSC-CM group, while occludin, ZO-1 and connexin 43 expressions showed no difference among MSC-CM, 293-CM and busulfan groups. Present results suggest MSC-secreted factors protect spermatogenesis impairment after busulfan treatment by reducing the apoptosis of spermatogenic cells and enhancing intercellular adhesion molecule expressions.

Construction of implantation failure related lncRNA-mRNA network and identification of lncRNA biomarkers for predicting endometrial receptivity.

Insufficient endometrial receptivity is a major factor leading to implantation failure (IF), and the traditional way of morphological observation of endometrium cannot determine the condition of receptivity sufficiently. Considering that long-noncoding RNAs (lncRNAs) regulate endometrial receptivity and competing endogenous RNA (ceRNA) mechanism works in plenty of biological processes, ceRNA is likely to function in the pathology of IF. In the present study, we aim to construct an implantation failure related lncRNA-mRNA network (IFLMN), and to identify the key lncRNAs as the candidates for predicting endometrial receptivity. The global background network was constructed based on the presumed lncRNA-miRNA and miRNA-mRNA pairs obtained from lncRNASNP and miRTarBase. Differentially expressed genes (DEGs) of IF were calculated using the data of GSE26787, and then re-annotated as differentially expressed mRNAs (DEMs) and lncRNAs (DELs). IFLMN was constructed by hypergeometric test, including 255 lncRNA-mRNA pairs, 10 lncRNAs, and 212 mRNAs. Topological analysis determined the key lncRNAs with the highest centroid. Functional enrichment analyses were performed by unsupervised clustering, GO classification, KEGG pathway, and co-expression module analyses, achieving six key lncRNAs and their ceRNA sub-networks, which were involved in immunological activity, growth factor binding, vascular proliferation, apoptosis, and steroid biosynthesis in uterus and prepared endometrium for embryo implantation. Sixteen endometrial samples were collected during mid-luteal phase, including 8 recurrent implantation failure (RIF) or recurrent miscarriage (RM) women and 8 controls who conceived successfully. Quantitative real-time PCR was performed to compare the expression of the above six lncRNAs, which validated that the expression of all these lncRNAs was significantly elevated in endometrium of RIF/RM patients. Further studies are needed to investigate the underlying mechanism, and the lncRNAs may be developed into predictive biomarkers for endometrial receptivity.