| Objective: Ovarian hyper-stimulation syndrome(OHSS)is an iatrogenic complication of ovulation induction in assisted reproductive technologies(ART).which is rarely seen in people who without the aid of gonadotrophin.OHSS is an exaggerated response to gonadotrophin,leading to multiple follicle development which secrete high level of estrogen.Since the use of in vitro fertilization and embryo transfer(IVF)has risen dramatically over the past several years,ovarian hyper-stimulation syndrome has been one of the most frequent and most serious,potentially lethal,complications of controlled ovarian stimulation as part of assisted reproductive technologies(ART).Polycystic ovary syndrome(PCOS)is a heterogeneous endocrine disorder,affecting 5-10% women at reproductive age and 75% of them characterized by anovulation and infertility.Polycystic ovary syndrome is defined by ovulatory dysfunction,hyperandrogenism,and polycystic ovaries.New data suggest that ovulation induction followed by intra-uterus insemination(IUI)should be considered as the first-line medical treatment of anovulatory infertility in PCOS.When polycystic ovarian syndrome(PCOS)is accompanied by ovuduct obstruction,pelvic peritoneal adhesions,endometriosis and seminal abnormality,in vitro fertilization and embryo transfer(IVF-ET)is a very effective treatment.Polycystic ovarian syndrome(PCOS)is easy to cause a signifiantly increased risk of ovarian hyper-stimulation syndrome(OHSS)during controlled ovarian hyper-stimulation(COH)used in assisted reproduction treatment(ART).MicroRNAs(miRNAs)are a class of small non-coding RNAs that function as translational repressors and are involved in many important biological processes,such as.A recent study found an abundance of miRNAs in human serum/plasma;these miRNAs have attracted considerable attention because they possess unique features such as stability,easy detection,and disease specificity.Plasma/serum miRNAs have been verified to be an independent predictive system for different diseases.Here,we discuss that if serum miRNA could serve as a biomarker for predicting OHSS in women with PCOS before controlled ovarian hyper-stimulation(COH)is initiated.Materials and Methods and Results(1)Patients with PCOS undergoing IVF or IVF/intracytoplasmic sperm injection(ICSI)from February 2010 to July 2013 were recruited to this study.Patients were divided into two groups based on the possible severity of OHSS: those who would suffer from severe OHSS were placed in the OHSS group,and those without or with only mild signs of OHSS were placed in the control group.We randomly pooled the sera of ten women from the OHSS group and those of ten matched controls,and used the samples to identify the differential miRNA expression profile by TLDA chip assays between the two groups.By comparing the relative expression level of serum miRNAs,preliminary screening revealed that three miRNAs(miR-146 a,miR-30 c,and miR-191)were upregulated and five(miR-16,miR-223,mi R-212,miR-451,and miR-92a)were downregulated.(2)We carried out qRT-PCR on 30 and 70 samples from the OHSS and control groups,respectively,to validate the putative markers identified in the discovery phase.our data demonstrated that two of the eight serum miRNAs(miR-16 and mi R-223)were significantly downregulated in the women of the OHSS group than controls(P = 0.000 and P = 0.012,respectively).(3)To evaluate the sensitivity and specificity of the basal LH,basal LH/FSH,and BMI for the prediction of OHSS,we established ROC curves and calculated the AUC in each case,the AUC of the basal LH,basal LH/FSH,and BMI were 0.712,0.772 and 0.702,respectively.The results indicated that basal LH/FSH,which yielded the largest AUC,could adequately serve as a better biomarker for the prediction of OHSS.(4)To evaluate the sensitivity and specificity of the serum miRNA signature individually and in combination for the prediction of OHSS,we further established ROC curves and calculated the AUC in each case,the AUC of miR-16、miR-223,and miR-16/miR-223 were 0.848,0.801 and 0.836,respectively.The results indicated that miR-16,which yielded the largest AUC,could adequately serve as a biomarker for the prediction of OHSS.(5)Enrichment of biological processes in terms of Gene Ontology categories with respect to the target genes was determined using the DAVID Bioinformatics Resources and we used DIANA-miRRath,to analyze some of the common signaling pathways.Our data demonstrated that genes targeted by miR-16 were found to be involved in the vascular endothelial growth factor(VEGF),hypoxia,and angiogenesis pathways.And the gene targets of mi R-223 were involved in the many biological processes such as the insulin receptor signaling pathway,regulation of body size,and positive regulation of glucose import.(6)Spearman’s analysis was used to evaluate the association between miR-223 and BMI.The results revealed that the miR-223 level was strongly and positively associated with the BMI(R = 0.83;P = 0.000).ConciusionsPatients with PCOS undergoing IVF or IVF/intracytoplasmic sperm injection(ICSI)from February 2010 to July 2013 were recruited to this study.This is the first study comparing the expression patterns of serum miRNAs in PCOS women who have or will develop severe OHSS and in women with negligible or mild symptoms of the disease.Our findings indicate that there are potential candidate mi RNAs that are differentially expressed in the two study samples which can serve as predictors for severe OHSS.Our findings aiso indicate that the candidate serum miRNA-16 and miRNA-223 levels prior to gonadotropin administration could provide useful information to to avoid moderate and severe OHSS in PCOS patients.AND our data demonstrated that genes targeted by miR-16 and miRNA-223 were found to be involved in the developing of severe OHSS. |
