Hua Duan

The impact of preoperative gonadotropin-releasing hormone agonist treatment on women with uterine fibroids: a meta-analysis.

Aim The objectives of this study were to evaluate the efficacy of gonadotropin-releasing hormone agonist (GnRHa) treatment before surgery for women with uterine fibroids and to explore potential factors predicting the pooled effect sizes. Methods A meta-analysis was performed from published randomized controlled trials using the random-effects model. The efficacy of preoperative treatment with GnRHa was investigated according to volume measurements of fibroid tumors, postoperative complications, myoma recurrence, and changes in fertility. Metaregression and subgroup analysis were used to identify potential predictors of the effect sizes. Results A total of 26 studies were selected for the meta-analysis. Preoperative GnRHa therapy for women with uterine fibroids was associated with a smaller preoperative volume of fibroid tumors, increased hemoglobin and hematocrit levels, reductions in preoperative pelvic symptoms and the vertical incision rate, and a higher proportion of patients undergoing a vaginal procedure. No differences were observed in postoperative complications, myoma recurrence, and changes in fertility in the GnRHa-treated patients compared with patients treated with placebo or alternative clinical agents. The metaregression suggested that age, the duration of GnRHa treatment, the type of control group, and the type of surgery were important predictors of the efficacy of preoperative GnRHa treatment. Conclusions Preoperative GnRHa treatment for women with uterine fibroids reduces preoperative fibroid size and increases hemoglobin and hematocrit levels. Gonadotropin-releasing hormone agonist pretreatment reduces preoperative pelvic symptoms and the rate of vertical incision and results in a higher chance of patients to receive a vaginal procedure, without significant difference in postoperative complications when comparing with other preoperative treatments. The patients’ age, duration of GnRHa treatment, agents selected as control, and types of surgical procedures serve as predictors of the efficacy of preoperative GnRHa treatment. Target Audience Obstetricians and gynecologists, family physicians Learning Objectives After completing this CME activity, physicians should be better able to evaluate the efficacy of gonadotropin-releasing hormone agonist treatment before surgery for women with uterine fibroids.

Salpingectomy and proximal tubal occlusion for hydrosalpinx prior to in vitro fertilization: a meta-analysis of randomized controlled trials.

Objective The objective of this study was to conduct a systematic review of studies comparing the pregnancy outcomes in hydrosalpinx patients treated with salpingectomy versus those treated with proximal tubal occlusion prior to in vitro fertilization (IVF). Data Sources An extensive PubMed literature search was performed for the period from 1980 to December 2013 using combinations of the following keywords: “hydrosalpinx,” “salpingectomy,” and “tubal occlusion.” Methods of the Study Selection Initially, 204 relevant studies were identified from MEDLINE and screened for retrieval. All of the randomized controlled trials comparing ovarian response and the pregnancy outcome of salpingectomy and proximal tubal occlusion for hydrosalpinx patients prior to IVF were considered eligible for analysis. Tabulation, Integration, and Results Two investigators independently reviewed the studies. The data were pooled, and the mean standard difference (SD) was calculated. Eligible randomized controlled trials were selected for this meta-analysis. There were no differences in the response days to controlled ovarian hyperstimulation (SD = −1.112, SE = 0.973, Z = −1.14, P = 0.253), number of oocytes retrieved (SD = 0.404, SE = 0.311, Z = 1.300, P = 0.194), embryos transferred per cycle (SD = −0.757, SE = 0.568, Z = −1.332, P = 0.183), and fertilized oocytes (SD = −0.006, SE = 0.130, Z = −0.045, P = 0.964) between the patients receiving salpingectomy and proximal tubal occlusion. The pooled rates for clinical pregnancy (odds ratio, 0.864; 95% confidence interval, 0.534–1.398; Z = −0.596, P = 0.551) and implantation (odds ratio, 1.558; 95% confidence interval, 0.809–3.003; Z = 1.325, P = 0.185) were not significantly different between the hydrosalpinx patients with salpingectomy versus proximal tubal occlusion. Conclusions Similar responses to controlled ovarian hyperstimulation and pregnancy outcome were observed in patients treated with salpingectomy or proximal tubal occlusion. Target Audience Obstetricians and gynecologists, family physicians Learning Objectives After completing this CME activity, physicians should be better able to evaluate the efficacy of salpingectomy versus proximal tubal occlusion treatment prior to IVF for hydrosalpinx patients.

Treatment Options To Terminate Persistent Cesarean Scar Pregnancy

Aims: Persistent Cesarean scar pregnancy (PCSP) is a rare and special type of Cesarean scar pregnancy (CSP) which is resistant to conservative treatment. The treatment option is challenging. We report a case series to provide indications for further treatment. Methods: Ten women diagnosed as having a PCSP, seeking better treatment because of primary treatment failure, were admitted to a gynecologic minimally invasive center. Ultrasound combined with office hysteroscopy was used for preoperative evaluation, and then a further surgical strategy was selected. Clinical data were retrospectively studied. Results: Among ten PCSP patients, 4 were type I and 6 were type II. In the 4 type I cases, 2 were treated by laparoscopy and the other 2 by hysteroscopy; to stop bleeding in 1 of them, the uterine artery was occluded laparoscopically. All type II cases were successfully treated by laparoscopic excision. The mean operating time was 61.5 min. The mean blood loss was 83.5 ml. No complications occurred except one intraoperative hemorrage. Conclusions: Experience from this case series indicates that an individualized surgical plan based on a full preoperative evaluation provides useful information for choosing a suitable treatment for PCSP. Endoscopically guided surgical excision with experienced hands may be considered the most useful treatment.

Expression of oxytocin receptors in the uterine junctional zone in women with adenomyosis

To compare the expression of oxytocin receptor in the uterine junctional zone of the fundus and isthmus in the proliferative and secretory phases in women with and without adenomyosis.

Human amniotic mesenchymal stromal cell transplantation improves endometrial regeneration in rodent models of intrauterine adhesions

BACKGROUND AIMS Intrauterine adhesion (IUA) is a common uterine cavity disease characterized by the unsatisfactory regeneration of damaged endometria. Recently, stem cell transplantation has been proposed to promote the recovery process. Here we investigated whether human amniotic mesenchymal stromal cells (hAMSCs), a valuable resource for transplantation therapy, could improve endometrial regeneration in rodent IUA models. METHODS Forty female Sprague-Dawley rats were randomly assigned to five groups: normal, sham-operated, mechanical injury, hAMSC transplantation, and negative control group. One week after intervention and transplantation, histological analyses were performed, and immunofluorescent and immunohistochemical expression of cell-specific markers and messenger RNA expression of cytokines were measured. RESULTS Thicker endometria, increased gland numbers and fewer fibrotic areas were found in the hAMSC transplantation group compared with the mechanical injury group. Engraftment of hAMSCs was detected by the presence of anti-human nuclear antigen-positive cells in the endometrial glands of the transplantation uteri. Transplantation of hAMSCs significantly decreased messenger RNA levels of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1β), and increased those of anti-inflammatory cytokines (basic fibroblast growth factor, and interleukin-6) compared with the injured uterine horns. Immunohistochemical expression of endometrial epithelial cells was revealed in specimens after hAMSC transplantation, whereas it was absent in the mechanically injured uteri. CONCLUSIONS hAMSC transplantation promotes endometrial regeneration after injury in IUA rat models, possibly due to immunomodulatory properties. These cells provide a more easily accessible source of stem cells for future research into the impact of cell transplantation on damaged endometria.

Efficacy of freeze‐dried amnion graft following hysteroscopic adhesiolysis of severe intrauterine adhesions

To evaluate the efficacy of freeze‐dried amnion graft for prevention of intrauterine adhesion (IUA) reformation after hysteroscopic adhesiolysis.

17β-Estradiol Induces Overproliferation in Adenomyotic Human Uterine Smooth Muscle Cells of the Junctional Zone Through Hyperactivation of the Estrogen Receptor-Enhanced RhoA/ROCK Signaling Pathway.

Adenomyosis (ADS) is a common estrogen-dependent gynecological disease with unknown etiology. Recent models favor abnormal thickening of the junctional zone (JZ) may be the causative factor in the development of ADS. RhoA, a small guanosine triphosphatase which controls multiple cellular processes, is involved in the control of cell proliferation. Here we demonstrate that treatment of human uterine smooth muscle cells (SMCs) of the JZ with 17β-estradiol (E2) increased expression of RhoA and its downstream effectors (-associated coiled coil containing protein kinase [ROCK] 1 and ROCK2). Compared with non-ADS cells, RhoA, ROCK1, and ROCK2 were overexpressed and hyperactivated in ADS cells. These effects were suppressed in the presence of ICI 182,780, supporting an estrogen receptor (ER)-dependent mechanism. Hyperactivation of ER-enhanced RhoA/ROCK signaling was associated with overproliferation in ADS human uterine SMCs of the JZ. Moreover, E2-induced overproliferation was accompanied by downregulation of cyclin-dependent kinases inhibitors (CKIs; p21Waf1/Cip1 and p27Kip1) and upregulation of cyclin-dependent kinases (CDKs) and cyclins (cyclin D1, cyclin E1, CDK2, CDK4, and CDK6).

Integrated Data Set of microRNAs and mRNAs Involved in Severe Intrauterine Adhesion

Background: Adhesion tissue is formed following injury to the uterine basal layer. Currently, there is no effective treatment for severe intrauterine adhesion (IUA), which causes loss of reproductive function. Enhanced understanding of the molecular mechanisms driving severe IUA would be beneficial for the treatment. Methods: Differentially expressed microRNAs (miRNAs) and messenger RNAs (mRNAs) in severe IUA (n = 3) and normal (n = 3) endometrium were analyzed by high-throughput microarray analysis. Subsequently, the target genes of the differentially expressed miRNAs were predicted and found to overlap with the differentially expressed mRNAs. Gene Ontology and pathway analyses were performed for the intersecting genes. Three of the significantly dysregulated miRNAs and 4 of their target mRNAs were further assessed using quantitative real-time polymerase chain reaction (PCR) in 10 severe IUA and 10 normal endometrium samples. Results: Microarray analysis indicated that 26 miRNAs and 1180 mRNAs were significantly different between the 2 groups. Of these, 16 miRNAs and 54 mRNAs overlapped with putative miRNA target genes and prediction of target gene. Real-time PCR revealed upregulation of hsa-miR-513a-5p and has-miR-135a-3p and downregulation of hsa-miR-543 and their corresponding target genes, plus downregulation of ADAM9 (a disintegrin-containing and metalloproteinases) and lysyl oxidase and upregulation of CDH2 (N-cadherin) and COL16A1 (collagen 16A1). Both CDH2 and COL16A1 were bioinformatically predicted and confirmed in vitro as target genes of miR-543. Conclusion: This study provides an integrated data set of the miRNA and mRNA profiles in severe IUA, showing involvement of many miRNAs and their target genes. Further analysis of these genes will help in understanding of the molecular mechanism of IUA formation.

MicroRNA-1291 promotes endometrial fibrosis by regulating the ArhGAP29-RhoA/ROCK1 signaling pathway in a murine model

Intrauterine adhesions (IUAs) are caused by endometrial damage and are associated with a poor pregnancy prognosis including infertility, oligomenorrhea and recurrent pregnancy loss. Understanding the pathogenesis of IUAs may help prevent and treat this condition more effectively. The aim of the current study was to investigate the function of microRNA-1291 (miR-1291) during the development of IUAs following endometrial damage and elucidate the potential molecular mechanisms involved. The expression of Rho GTPase activating protein 29 (ArhGAP29), a putative target mRNA of miR-1291, was determined by immunohistochemical staining of human endometrial tissue from patients with IUAs and compared with normal endometrial tissues. ArhGAP29 expression was significantly decreased in endometrial tissues with IUAs compared with normal endometrium. Additionally, a murine IUAs model was developed and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) demonstrated that miR-1291 levels were significantly increased in the uterine tissue and plasma of the IUAs group compared with the normal mice. Furthermore, an miR-1291 antagomir was injected into the uterine cavity of experimental IUAs mice to block miR-1291. Hematoxylin and eosin and Massons stain revealed that blocking miR-1291 significantly ameliorated endometrial fibrosis. Furthermore, levels of epithelial mesenchymal transition (EMT)-associated proteins, and ArhGAP29-RhoA/Rho-associated coiled coil containing protein kinase 1 (ROCK1) were measured in uterine tissue by western blot, RT-qPCR analysis and immunofluorescence staining. Levels of the mesenchymal marker proteins, vimentin and N-cadherin, were increased in the IUAs group mice, accompanied by a relative decrease in the epithelial marker proteins, cytokeratin and E-cadherin compared with normal murine endometrium. miR-1291 inhibition decreased RhoA/ROCK1 expression in the EMT pathway, but increased ArhGAP29 expression. Taken together, the findings indicate that miR-1291 acts upstream of ArhGAP29 to negatively regulate the RhoA/ROCK1 EMT pathway, ultimately leading to endometrial fibrosis. These studies may provide new potential therapeutic options and pave the way to use circulating miR-1291 as a clinical biomarker of endometrial fibrosis.

FAK regulates epithelial‑mesenchymal transition in adenomyosis

Epithelial-mesenchymal transition (EMT) has been associated with the pathogenesis of adenomyosis; focal adhesion kinase (FAK) serves an important role in the EMT process. The aim of the present study was to determine whether FAK regulates EMT in adenomyosis and to investigate the potential pathway in this process. The expression of FAK and EMT-associated molecules in adenomyosis and control cells were determined by immunohistochemical staining and immunofluorescence at the protein level, and at the mRNA level by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Small interfering RNAs were designed to knock down FAK expression. Subsequently, molecular expression was detected by immunofluorescence, RT-qPCR and western blotting; cell migration was investigated via Transwell assays. In addition, the expression levels of members of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway was also analyzed by RT-qPCR and western blotting to determine the association between these members and EMT in adenomyosis. The results of the present study revealed that FAK was upregulated and the expression levels of EMT-associated molecules were altered in adenomyosis. Silencing FAK expression inhibited adenomyosis cell migration in vitro and the expression of EMT-promoting molecules, suggesting that the FAK/PI3K/AKT signaling pathway may participate in the EMT of endometrial cells in adenomyosis. In conclusion, FAK may regulate EMT in adenomyosis, and this process may be associated with the PI3K/AKT signaling pathway.