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Zhang B.,Shandong University | Zhang B.,National Research Center for Assisted Reproductive Technology and Reproductive Genetics | Zhang B.,The Key laboratory for Reproductive Endocrinology of Ministry of Education | Zhang B.,Shandong Provincial Key Laboratory of Reproductive Medicine | And 16 more authors.
Gynecology and Minimally Invasive Therapy | Year: 2017

Objective: To evaluate the effects of different treatment methods for previous ectopic pregnancies (EP) on cryopreserved embryo transfer (CET) outcomes. Materials and Methods: This was a retrospective cohort study. Patients with EP histories were divided into four groups based on their previous EP treatments: Group 1-unilateral tubal removal; Group 2-bilateral tubal removal or unilateral tubal removal with contralateral tubal ligation; Group 3-conservative surgery group; and Group 4-conservative medication group. A total of 1333 women with previous histories of being admitted to the hospital for CET treatment were consecutively enrolled between January 2009 and December 2014. Results: Patients who underwent bilateral tubal ligation or removal had a lower miscarriage rate [8.88% vs. 3.46%, p =0.006, odds ratio=2.718, 95% confidence interval (CI)=1.301-5.677] than those who underwent unilateral tubal removal. No significant difference was observed in the rate of EP after CET in the four groups in women with EP histories. (p 1 =0.258, 95%CI=0.113-1.836; p 2 =0.137, 95%CI=0.975-0.997; p 3 =0.314, 95%CI=0.987-1.001; p 4 =0.198, 95%CI=0.987-1.001). The groups were not different with regard to other pregnancy outcomes. Conclusion: There was no significant difference among EP treatment methods with regard to their impacts on CET outcomes in women with EP histories. Bilateral tubal ligation or removal surgery can decrease the miscarriage rate after CET. © 2017.


Li X.,Shandong University | Li X.,National Research Center for Assisted Reproductive Technology and Reproductive Genetics | Li X.,The Key Laboratory for Reproductive Endocrinology of Ministry of Education | Wang H.,Shandong University | And 6 more authors.
Mechanisms of Development | Year: 2017

MicroRNAs (miRNAs) have been improved to regulate oocyte development in a cell- or stage-specific manner. In this study, we aimed to clarify microRNA-224′s (miR-224) role in cumulus cells (CCs), to find out whether a change level of miR-224 in CCs could influence the maturation of oocyte. We found that overexpression of miR-224 of CCs led to the impairment of cell expansion, along with a decrease in the gene expression associated with cell expansion and maturation of oocyte. The increased expression of miR-224 in CC interrupted oocyte cell cycle at the GV stage. The GDF9, BMP15 and ZP3 of the oocytes were also down-regulated. The following in vitro fertilization had yielded a lower number of oocytes from cumulus-oocyte complexes (COCs) overexpressing miR-224 when reaching the blastocyst stage. The suppressive effect of miR-224 in the maturation of COC is validated by the miR-224 knockdown model, where the expansion of cumulus cell was increased and oocyte was developed to MII stage. In addition, the expression of aromatase in CCs was down-regulated by miR-224, resulting in a decreased level of estradiol (E2). A further investigation found that miR-224 down-regulated the expression of protein and mRNA of Ptx3 by targeting its 3’UTR. Our study revealed that miR-224 regulates the gene expression and function of CCs, which influences the maturation of oocyte, at least in part, via targeting Ptx3. © 2016 Elsevier Ireland Ltd


Zhai J.,Shanghai JiaoTong University | Zhai J.,Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics | Ding L.,Shandong University | Zhao S.,Shandong University | And 12 more authors.
Gynecological Endocrinology | Year: 2017

Kisspeptin is a polypeptide that plays an important role in reproductive endocrine regulation. The aim of present study was to investigate the dynamic trend of kisspeptin levels during the menstrual cycle and to elucidate the relationship between kisspeptin ovulation. First, 15 female volunteers with regular menstrual cycles were recruited to detect the change in serum and urine kisspeptin levels over one menstrual cycle within each individual. Subsequently, 114 serum samples and 79 urine samples from 114 individuals were randomly collected at the outpatient department to better ascertain the results. Kisspeptin levels showed a distinctive stage-specific pattern during the normal menstrual cycle in both serum and urine. It was low during the first 5 days, while the first surge appeared on the 11th day (the diameter of the dominant follicle was approximately 1.2 cm). Later, a second smaller surge appeared around the 14th day and the same changes were identified in serum and urine. Furthermore, serum kisspeptin levels were positively related to 17-β estradiol (E2) level increase. Thus, kisspeptin surge in serum and urine may be used as a marker for dominant follicle development and pre-ovulation. Moreover, kisspeptin may also play a vital role in female reproduction through regulating hormonal state. © 2017 Informa UK Limited, trading as Taylor & Francis Group.


Xue H.,Shandong University | Xue H.,Rizhao City Hospital of Traditional Chinese Medicine | Xue H.,National Research Center for Assisted Reproductive Technology and Reproductive Genetics | Xue H.,The Key Laboratory for Reproductive Endocrinology of Ministry of Education | And 15 more authors.
Journal of Assisted Reproduction and Genetics | Year: 2016

Purpose: The objective of this study was to evaluate the association between single-nucleotide polymorphisms (SNPs) rs2197076 and rs2241883 in fatty acid-binding protein 1 (FABP1) gene and polycystic ovary syndrome (PCOS). Methods: The two alleles rs2197076 and rs2241883 in FABP1 gene in 221 PCOS women and 198 normal women were amplified and sequenced. Allele frequency comparison was performed between the PCOS and control groups, and genotype-phenotype correlation analysis was performed using dominant and recessive models to assess the association of FABP1 and the main features of PCOS. Results: Allele frequency analyses showed a strong association of SNPs rs2197076 and rs2241883 of FABP1 gene with PCOS (P < 0.001). The additive, dominant, and recessive genotype model analyses further supported this association even after adjusting for age and body mass index (BMI). The minor allele frequency (MAF) of rs2241883 in obese PCOS women was less than that in obese control women. Further genotype-phenotype correlation analysis showed that SNP rs2197076 had a stronger association with the main features of PCOS than SNP rs2241883. Conclusion: In the association of SNPs in FABP1 gene with PCOS, rs2197076 was more closely associated with its main features than rs2241883 and seemed to play a more important role in the pathogenesis of PCOS. © 2015, Springer Science+Business Media New York.


Li T.,Shandong University | Li T.,National Research Center for Assisted Reproductive Technology and Reproductive Genetics | Wu K.,Shandong University | Wu K.,National Research Center for Assisted Reproductive Technology and Reproductive Genetics | And 36 more authors.
PLoS ONE | Year: 2013

Background:Fat mass and obesity-associated gene (FTO) has been associated with obesity, especially the common variant rs9939609. Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disorder and over 50% of patients are overweight/obese. Thus FTO is a potential candidate gene for PCOS but their relationship is confusing and remains to be clarified in different population with a large sample size. Method:This study was performed adopting a two-stage design by genotyping SNP rs9939609. The first set comprise of 741 PCOS and 704 control subjects, with data from our previous GWAS. The second phase of replication study was performed among another independent group of 2858 PCOS and 2358 control subjects using TaqMan-MGB probe assay. All subjects are from Han Chinese.Results:The less meaningful association of FTO rs9939609 and PCOS discovered in GWAS (P = 2.47E-03), was further confirmed in the replication study (P = 1.86E-09). Using meta-analysis, the P-meta value has reached 6.89E-12, over-exceeding the genome-wide association level of 5.00E-8. By combination, the P value was 1.26E-11 and after BMI adjustment it remained significant(P = 1.82E-06). To further elucidate whether this association is resulted from obesity or PCOS per se, the samples were divided into two groups-obese and non-obese PCOS, and the results were still positive in obese group (P obese = 5.81E-05, OR = 1.55), as well as in non-obese PCOS group (P non-obese = 7.06E-04, OR = 1.28).Conclusion:Variant rs9939609 in FTO is associated with PCOS in Chinese women, not only in obese PCOS subjects, but also in non-obese cases. © 2013 Li et al.


Zhao H.,Shandong University | Zhao H.,National Research Center for Assisted Reproductive Technology | Zhao H.,The Key laboratory for Reproductive Endocrinology of Ministry of Education | Zhao H.,Shandong Provincial Key Laboratory of Reproductive Medicine | And 5 more authors.
Molecular Human Reproduction | Year: 2013

Many genetic association studies have been performed to investigate disorders of female reproduction, such as polycystic ovary syndrome, premature ovarian failure and endometriosis. These disorders typically manifest heterogeneously, and their pathogeneses are influenced by polygenic and environmental factors. Researchers evaluating these genetic associations have chosen candidate genes related to hormone action, steroid biosynthesis, inflammatory cytokines and autoimmune factors. Several of these genes have yielded statistically significant associations with female reproductive disorders; however, few associations have been robust and reproducible. Whole-genome association studies generate more reliable and unbiased results and represent a breakthrough in genetic studies of female reproduction. Nevertheless, to date only a very small fraction of the overall heritability has been identified and so further studies are needed. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Guo T.,Shandong University | Guo T.,National Research Center for Assisted Reproductive Technology | Guo T.,The Key Laboratory for Reproductive Endocrinology of Ministry of Education | Qin Y.,Shandong University | And 17 more authors.
International Journal of Andrology | Year: 2012

Chromosomal polymorphism has been reported to be associated with infertility, but its effect on IVF/ICSI-ET outcome is still controversial. To evaluate whether or not chromosomal polymorphism in men plays a role in spermatogenesis and the outcome of IVF/ICSI-ET, we retrospectively analysed 281 infertile couples. Measures included fertilization rate, implantation rate, pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate, early miscarriage rate and preterm rate. Men with chromosomal polymorphism had significantly higher frequencies of severe oligozoospermia and azoospermia than those without (37.12% vs. 16.11%, p<0.001; 27.27% vs. 10.74%, p<0.001; respectively). Significantly, lower fertilization rate (68.02% vs. 78.00%, p<0.001) and clinical pregnancy rate (45.00% vs. 66.67%, p=0.031) were observed in polymorphism-carrying men with severe oligozoospermia compared with non-carriers with severe oligozoospermia. This suggests that chromosomal polymorphism has adverse effects on spermatogenesis, negatively influencing the outcome of IVF/ICSI-ET treatment. Polymorphic variations on the Y chromosome have been found to be the most prevalent polymorphism in infertile men, most frequently occurring in patients with severe oligozoospermia. © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.


Zhao H.,Shandong University | Zhao H.,National Research Center for Assisted Reproductive Technology and Reproductive Genetics | Zhao H.,The Key Laboratory for Reproductive Endocrinology of Ministry of Education | Lv Y.,Shandong University | And 10 more authors.
Best Practice and Research: Clinical Obstetrics and Gynaecology | Year: 2016

Polycystic ovary syndrome (PCOS) is a highly heterogeneous reproductive system disorder of which the aetiology is not fully understood. Previous association studies have been conducted on >100 candidate genes, which principally related to reproductive hormones, cellular metabolism and chronic inflammation. Heritable tendencies have long been recognized for pathogeneses of PCOS, and recently a genome-wide association study (GWAS) in PCOS provides new clues to understand the genetic components and pathways in PCOS physiology. However, the current knowledge of the pathogenesis of PCOS is still in its infancy. Further studies using new technologies such as next-generation sequencing (NGS) shall be useful to understand more causal variants for PCOS. © 2016.


Zhang Q.,Shandong University | Zhang Q.,National Research Center for Assisted Reproductive Technology and Reproductive Genetics | Zhang Q.,The Key Laboratory for Reproductive Endocrinology of Ministry of Education | Zhang Q.,Shandong Provincial Key Laboratory of Reproductive Medicine | And 4 more authors.
Reproductive Medicine and Biology | Year: 2015

Embryonic development into an implantation-competent blastocyst, synchronized uterine transformation into a receptive stage, and an intimate cross-talk between the activated blastocyst and the receptive uterus are essential for successful implantation, and therefore for subsequent pregnancy outcome. Evidence accumulating during recent years has underlined the importance of the Wnt signaling pathway in mammalian implantation and decidualization. Herein, this review focuses on the current state of knowledge regarding Wnt signaling in multiple implantation and decidualization events: pre-implantation embryo development, blastocyst activation for implantation, uterine development, and decidualization. © 2015 Japan Society for Reproductive Medicine


Shanshan G.,Shandong University | Shanshan G.,National Research Center for Assisted Reproductive Technology and Reproductive Genetics | Shanshan G.,The Key Laboratory for Reproductive Endocrinology of Ministry of Education | Shanshan G.,Shandong Provincial Key Laboratory of Reproductive Medicine | And 20 more authors.
Journal of Assisted Reproduction and Genetics | Year: 2015

Purpose: To evaluate the effect of different exposure temperatures during the dilution process on the survival rate of vitrified oocytes and following development. Methods: Patients were divided at random into two groups for different dilution temperature (20–22 °C, RT group; 37 °C,37 °C group) according to computer-generated random numbers on the day of oocyte warming. The survival and fertilization rates of vitrified oocytes as well as the implantation and clinical pregnancy rates of the resulting embryos were recorded. Results: A total of 662 and 676 oocytes were warmed in the 37 °C group and RT group, respectively, and significant difference was observed in the survival rate between 37 °C group (88.37 %) and RT group (79.88 %) (P = 0.0000). There was significant difference between the survival rate of 37 °Cgroup (87.27 %) and RT group (75.64 %) in nondonor patients (P = 0.0001). Multiple linear regression analysis showed that dilution temperature (β = 0.079, P = 0.017) and clinical outcomes of fresh cycles (β = 0.063, P = 0.001) were significantly and independently associated with survival rate. No significant difference was found between the 37 °C group and RT group in: fertilization rate (66.67 versus 65.37 %), implantation rate (20.0 versus19.46 %), clinical pregnancy rate (37.5 versus 35.0 %). Conclusions: In conclusion, the results of this study give supportive evidence of the application of 37 °C in the dilution process, especially for oocytes of poor quality. Further studies with well-controlled experimental groups are needed to optimize protocols for human oocyte vitrification. © 2015, Springer Science+Business Media New York.

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