Key Points Question Is metformin associated with improved outcomes among women with polycystic ovarian syndrome undergoing in vitro fertilization? Findings This meta-analysis of 12 randomized clinical trials, which collectively included 1123 women, found that metformin treatment was associated with a decreased risk of ovarian hyperstimulation syndrome among women with polycystic ovarian syndrome undergoing in vitro fertilization but had no association with clinical pregnancy or live birth rates in the total population studied. However, among women with a body mass index of 26 or greater, metformin treatment was associated with an improved clinical pregnancy rate. Meaning The findings of this study suggest that metformin treatment should be carefully considered for women with polycystic ovarian syndrome undergoing in vitro fertilization and may be more preferred among women with a body mass index of 26 or greater.
Background Genetic, environmental and epigenetical factors may play important roles in the pathogenesis of polycystic ovary syndrome (PCOS), however the etiology of PCOS remains unclear. Studies indicated that non-coding RNAs (ncRNAs) were involved in the occurrence and development of PCOS. Thus, we aim to perform a systematic review and meta-analysis to investigate the presence and dysregulated expression of ncRNAs in human PCOS. Methods We searched in PubMed, Medline, Web of Science and Embase until July 2019 and summarized all eligible publications focusing on microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and small interfering RNAs (siRNAs) in PCOS. Results Sixty-seven articles were included in our systematic review and 9 articles were included in meta-analysis. There is little overlap between studies when comparing miRNA profiles. Sensitivity analysis showed that the expression of miR-93 was upregulated in PCOS patients (WMD 0.75, P < 0.00001), without heterogeneity among remaining studies (I2 = 0%). Conclusion A large number of ncRNAs with altered levels were observed in plasma, serum, follicular fluid, granulosa cells or other issues from PCOS patients. Aberrant ncRNAs expression in PCOS may lead to aberrant steroidogenesis, adipocyte dysfunction, altered ovarian cell proliferation and/or apoptosis and have the potential to be used as diagnostic biomarkers.
Background Thin endometrium is a primary cause of defective endometrial receptivity, resulting in infertility or recurrent miscarriage. Much effort has been devoted toward regenerating thin endometrium by stem cell-based therapies. The human placenta-derived mesenchymal stem cells (HP-MSCs) are emerging alternative sources of MSCs with various advantages. To maximize their retention inside the uterus, we loaded HP-MSCs with cross-linked hyaluronic acid hydrogel (HA hydrogel) to investigate their therapeutic efficacy and possible underlying mechanisms. Methods Ethanol was injected into the mice uterus to establish the endometrium-injured model. The retention time of HP-MSCs and HA hydrogel was detected by in vivo imaging, while the distribution of HP-MSCs was detected by immunofluorescence staining. Functional restoration of the uterus was assessed by testing embryo implantation rates. The endometrial morphological alteration was observed by H&E staining, Masson staining, and immunohistochemistry. In vitro studies were further conducted using EdU, transwell, tube formation, and western blot assays. Results Instilled HP-MSCs with HA hydrogel (HP-MSCs-HA) exhibited a prolonged retention time in mouse uteri than normal HP-MSCs. In vivo studies showed that the HP-MSCs-HA could significantly increase the gland number and endometrial thickness (P < 0.001, P < 0.05), decrease fibrous area (P < 0.0001), and promote the proliferation and angiogenesis of endometrial cells (as indicated by Ki67 and VEGF, P < 0.05, P < 0.05, respectively) in mice injured endometrium. HP-MSCs-HA could also significantly improve the embryo implantation rate (P < 0.01) compared with the ethanol group. Further mechanistic study showed the paracrine effects of HP-MSCs. They could not only promote the proliferation and migration of human endometrial stromal cells via the JNK/Erk1/2-Stat3-VEGF pathway but also facilitate the proliferation of glandular cells via Jak2-Stat5 and c-Fos-VEGF pathway. In turn, the increased VEGF in the endometrium promoted the angiogenesis of endothelial cells. Conclusion Our study suggested the potential therapeutic effects and the underlying mechanisms of HP-MSCs-HA on treating thin endometrium. HA hydrogel could be a preferable delivery method for HP-MSCs, and the strategy represents a promising therapeutic approach against endometrial injury in clinical settings. Graphical abstract
A receptive endometrium with proper thickness is essential for successful embryo implantation. However, endometrial injury caused by intrauterine procedures often leads to pathophysiological changes in its environment, resulting in subsequent female infertility. Among diverse treatment methods of endometrial injury, hydrogels are a class of hydrophilic threedimensional polymeric network with biocompatibility as well as the capability of absorbing water and encapsulation, which have potential applications as a promising intrauterine controlled-release delivery system. This review summarizes recent advances in the approaches of endometrial repair and further focuses on the application of a hydrogel-based delivery system in endometrial repair, including its preparation, therapeutic loading considerations, clinical applications, as well as working mechanisms.
Long non-coding RNAs (lncRNAs) are a class of transcripts (>200 nucleotides) lacking proteincoding capacity. Based on the complex three-dimensional structure, lncRNAs are involved in many biological processes and can regulate the expression of target genes at chromatin modification, transcriptional and post-transcriptional levels. LncRNAs have been studied in multiple diseases but little is known about their role(s) in polycystic ovary syndrome (PCOS), the most common endocrinological disorder in reproductiveaged women around the world. In this review, we characterized and explored the potential mechanisms of lncRNAs in the pathogenesis of PCOS. We found that lncRNAs play a molecular role in PCOS mainly by functioning as the competitive endogenous RNA (ceRNA) and are significantly correlated with some clinical phenotypes. We summarized in detail regarding aberrant lncRNAs in different specimens of women with PCOS [i.e., granulosa cells (GCs), cumulus cells (CCs), follicular fluid (FF), peripheral blood] and various PCOS rodent models [i.e., dehydroepiandrosterone (DHEA) and letrozole induced models]. In clinical practice, detection of lncRNAs in serum might enable early diagnosis. Furthermore, new lncRNAbased classifications might be emerging as potent predictors of a particular phenotype in PCOS. Overall, we proposed new insights for the application of precision medicine approaches to the management of PCOS.
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