Objective To evaluate the effects of body mass index (BMI) in patients with polycystic ovary syndrome (PCOS) undergoing controlled ovarian stimulation (COS) with intrauterine insemination (IUI). Methods This retrospective study evaluated couples with PCOS undergoing COS and IUI. The relationship between cumulative IUI pregnancy outcomes and BMI, treatment cycles, treatment schemes, number of dominant follicles, endometrial thickness, infertility duration and type of infertility was analysed. Results The study evaluated 831 IUI cycles in 451 couples with PCOS. Compared with normoweight women, overweight and obese women required more human menopausal gonadotropin (hMG) doses and more days of COS. Gestational diabetes mellitus occurred more frequently in the obese group than in the other BMI groups. The clinical pregnancy and live birth rates in the hMG, clomiphene citrate (CC) + hMG and letrozole (LE) + hMG groups were significantly higher than those in the CC and LE groups. The clinical pregnancy rate was higher in the secondary infertility group compared with the primary infertility group. Conclusion Obese women might require more hMG doses and more days of COS to overcome the effects of weight. As BMI increases, the incidence of gestational diabetes might also increase. The number of cycles and type of infertility may have a predictive value for pregnancy outcomes.
Background: Polycystic ovarian syndrome (PCOS) is a multi-gene hereditary disorder caused by the interaction of certain gene variation with environmental factors. Previous studies have shown that vascular endothelial growth factor (VEGF) gene polymorphisms are associated with the risk of polycystic ovarian syndrome. However, the results of these studies remain controversial. We performed the present meta-analysis aiming to further investigate the potential relationship between VEGF polymorphisms and susceptibility to PCOS. Methods: The following databases were systematically searched: PubMed, EMBASE, Web of Science (WOS), China National Knowledge Infrastructure (CNKI), and Wanfang Databases. The correlation between VEGF polymorphisms and PCOS risk was assessed by calculating pooled odds ratios (ORs) and their 95% confidence intervals (95% CIs). Subgroup analyses stratified by ethnicity and source of control were also conducted. Besides, trial sequential analysis (TSA) was done to verify the reliability of the pooled results. Results: 10 relevant case-control studies were incorporated in this meta-analysis, involving 1347 PCOS cases and 1378 controls. The VEGF rs2010963 polymorphism was associated with decreased PCOS risk in the whole population and the Asian populations. The VEGF rs3025039 polymorphism was associated with decreased PCOS susceptibility and the Asian populations, but increased risk of PCOS was observed among the Caucasian populations. In addition, the results of trial sequential analysis (TSA) showed the negative correlation between rs2010963 and PCOS risk, obtained by our meta-analysis, was stable and reliable. Conclusion: Overall, different VEGF gene polymorphisms may exert different effects on PCOS susceptibility. The VEGF rs2010963 polymorphism decreases PCOS susceptibility in both the whole population and the Asian populations, and VEGF rs3025039 polymorphism causes lower PCOS susceptibility in the whole population and the Asian populations but higher in the Caucasian populations.
Background
The pathophysiological mechanism of recurrent miscarriage (RM) is unclear. The goals of this study were to determine the role of microRNA-4497 overexpression in placental villus tissues in early RM; To identify the potential target mRNAs of miRNA-4497; And to investigate the microRNA-4497-mediated regulatory mechanisms in placental trophoblasts.
Methods
Bioinformatics analysis was performed to identify the candidate target genes of miRNA-4497. The protein expression of Sp1 transcription factor (SP1), chemokine (C-X-C motif) receptor 5 (CXCR5) and bone morphogenetic protein 8a (BMP8A) were determined in the villus tissues of the RM and normal groups by Western blotting and immunohistochemistry. Cultured 293T cells were co-transfected with the miRNA-4497 agomir or luciferase reporter vectors containing the wild-type or mutant 3’-UTRs of the target mRNAs to verify the regulatory role of miRNA-4497.
Results
Bioinformatics analysis suggested that SP1, CXCR5 and BMP8A mRNAs are potential targets of miRNA-4497. The expression of SP1, CXCR5 and BMP8A proteins in the chorionic villus tissues of RM placentas were significantly decreased compared to those in the normal controls. Moreover, SP1 protein levels were inversely correlated with the levels of miRNA-4497 in the placentas of RM patients and normal controls. The expression of SP1 mRNA and protein were down-regulated in HTR-8/SVneo cells after forced overexpression of the miRNA-4497 agomir. The results of the co-transfection assay showed that mutation of the miRNA-4497-binding sites in the 3’-untranslated region (3’-UTR) of SP1 led to a recovery of luciferase activity upon overexpression of miRNA-4497, suggesting that SP1 could be a direct target of miRNA-4497.
Conclusions
An increased miRNA-4497 level in the placental villus tissues associated with recurrent miscarriage may down-regulate SP1 expression. The negative regulation of SP1 by miRNA-4497 may potentially contribute to the pathogenesis of recurrent miscarriage through promotion of trophoblast apoptosis. These findings provide novel information on the regulation of placental trophoblast apoptosis, and could be useful for the development of new therapeutic strategies for better management of recurrent miscarriage.
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