How to boost an obstetrician's confidence in vaginal delivery after high-intensity focused ultrasound: a comparison study on delivery outcomes.

OBJECTIVE: To assess the feasibility of vaginal delivery after HIFU. METHODS: A total of 37 women who met the trial of labor after HIFU (TOLAH) inclusion criteria and 368 women who met the trial of labor after cesarean delivery (TOLAC) inclusion criteria gave birth at Shanghai First Maternity and Infant Hospital between 14th June 2018 and 24th September 2021. The delivery outcomes of the two groups were compared. Multivariable logistic regression analysis was used to estimate the adjusted risk of postpartum hemorrhage (PPH). RESULTS: In the Qualified Candidates for TOLAH group, vaginal delivery is substantially less common (p = 0.000). The prevalence of PPH in the Qualified Candidates for TOLAH group is lower than in the Candidates for TOLAC group (8.82% vs 10.51%, p = 0.534; 0% vs 2.51%, p = 0.418). Hemoglobin drop in the Qualified Candidates for TOLAH group is also lower (7.03 ± 7.39vs 12.11 ± 12.62, p = 0.001). The rate of using more than two types of uterotonic medications to promote contraction is significantly lower in the Qualified Candidates for TOLAH group (54.05% vs 69.84%, p = 0.04), and the percentage of abnormal uterine contraction is lower in the Qualified Candidates for TOLAH group (35.14% vs 49.18%, p = 0.072). PPH is strongly predicted by abnormal uterine contraction (aOR: 17.177, 95% CI:5.046 ∼ 58.472, p = 0.000), but not by HIFU (aOR:1.105; 95% CI:0.240 ∼ 5.087, p = 0.898). No uterine rupture occurred in the cases after HIFU. CONCLUSIONS: No uterine rupture occurred in our study group after HIFU. HIFU is not a risk for PPH. It is promising for those after HIFU to choose vaginal delivery.

High intensity focused ultrasound treatment for diffuse uterine leiomyomatosis: a feasibility study.

OBJECTIVE: To investigate the safety and efficacy of high-intensity focused ultrasound (HIFU) treatment for diffuse uterine leiomyomatosis (DUL). METHODS: Eight patients with DUL were admitted to the Department of Gynecology of Shanghai First Maternity and Infant Hospital and underwent HIFU treatment. MRI was performed before and one day after HIFU treatment for the evaluation of lesion ablation. The uterine size was measured at 3-8 months after HIFU ablation. The menstrual volume score and serum levels of hemoglobin and CA-125 were measured pre-HIFU ablation and 12-36 months post-HIFU ablation. RESULTS: After an average of 5.9 months of follow-up after HIFU treatment, an average uterine volume reduction of 67.6% was observed. Menstruation returned to normal in all patients, and their serum HGB and CA-125 levels also returned to normal after an average of 19.1 months of clinical follow-up. The quality of life of all patients improved significantly. CONCLUSION: HIFU treatment is safe and effective in the treatment of patients with DUL.

Combined therapeutic effects of HIFU, GnRH-a and LNG-IUS for the treatment of severe adenomyosis.

OBJECTIVE: To evaluate the combined efficacy of high-intensity focused ultrasound (HIFU), gonadotropin-releasing hormone agonist (GnRH-a) and the levonorgestrel-releasing intrauterine system (LNG-IUS) for the treatment of severe adenomyosis. METHOD: Four hundred and sixty-six patients with adenomyosis admitted to the Department of Gynecology of Shanghai First Maternity and Infant Hospital underwent HIFU treatment, and then were consecutively administered with GnRH-a 1 d, 1 month and 3 months after HIFU treatment. The uterine size was then measured with ultrasound or MRI 2-4 weeks after three cycles of GnRH-a injection. The LNG-IUS was then inserted when the uterine length less than 9 cm. The visual analog scale (VAS), verbal rating scale (VRS), menstrual volume score, uterus volume, MRI, serum levels of hemoglobin and CA125 were measured at pre and 3-, 6-, 12-month post-HIFU. RESULTS: Dysmenorrhea and menorrhagia significantly relieved after combined treatment with HIFU, GnRH-a and the LNS-IUS. The uterine volume shrank and returned to its normal size. The serum CA-125 level was reduced to the normal level after the combined treatment. CONCLUSIONS: The combined therapeutic regimen of HIFU, GnRH-a and LNS-IUS is safe, effective and efficient for curing severe adenomyosis.

Aberrant endometrial DNA methylome of homeobox A10 and catechol-O-methyltransferase in endometriosis.

PURPOSE: Differential methylation of both HOXA10 and catechol-O-methyltransferase (COMT) has been reported in different endometrium disorders, and the two genes are linked through the estrogen pathway. The current study investigates the DNA methylation of HOXA10 and COMT in ectopic and eutopic endometrial tissues and its correlation with and the occurrence of endometriosis in women from Xinjiang province in China. METHODS: In the current study, 120 patients with endometriosis were recruited from our hospital between January 2011 and June 2014. The DNA methylation sites of HOXA10 and COMT were detected using a DNA methylation array. The methylation levels of specific sites were compared between ectopic and eutopic endometrial tissues via pyrosequencing. RESULTS: Five differentially expressed CpGs were localized in the promoter region of the COMT gene and expressed significantly higher in the ectopic endometrium than the eutopic endometrium (P < 0.001). Two out of the five differentially expressed CpGs in the HOXA10 gene located in the promoter region were both significantly lower (nearly half) in the ectopic endometrium than the eutopic endometrium (P < 0.001). CONCLUSIONS: To summarize, significant differential methylation of HOXA10 and COMT promoter regions was found between the ectopic and eutopic endometrial tissues. This is the first study investigating the methylation of HOXA10 and COMT genes and their linkage to endometriosis in Chinese patients.

Management of long-term and reversible hysteroscopic sterilization: a novel device with nickel-titanium shape memory alloy.

BACKGROUND: Female sterilization is the second most commonly used method of contraception in the United States. Female sterilization can now be performed through laparoscopic, abdominal, or hysteroscopic approaches. The hysteroscopic sterilization may be a safer option than sterilization through laparoscopy or laparotomy because it avoids invading the abdominal cavity and undergoing general anaesthesia. Hysteroscopic sterilization mainly includes chemical agents and mechanical devices. Common issues related to the toxicity of the chemical agents used have raised concerns regarding this kind of contraception. The difficulty of the transcervical insertion of such mechanical devices into the fallopian tubes has increased the high incidence of device displacement or dislodgment. At present, Essure® is the only commercially available hysteroscopic sterilization device being used clinically. The system is irreversible and is not effective immediately. PRESENTATION OF THE HYPOTHESIS: Our new hysteroscopic sterility system consists of nickel-titanium (NiTi) shape memory alloy and a waterproof membrane. The NiTi alloy is covered with two coatings to avoid toxic Ni release and to prevent stimulation of epithelial tissue growth around the oviducts. Because of the shape memory effect of the NiTi alloy, the device works like an umbrella: it stays collapsed at low temperature before placement and opens by the force of shape memory activated by the body temperature after it is inserted hysteroscopically into the interstitial tubal lumen. The rim of the open device will incise into interstitial myometrium during the process of unfolding. Once the device is fixed, it blocks the tube completely. When the patient no longer wishes for sterilization, the device can be closed by perfusing liquid with low temperature into the uterine cavity, followed by prospective hysteroscopic removal. After the device removal, the fallopian tube will revert to its physiological functions. TESTING THE HYPOTHESIS: Currently, experimental and clinical studies are needed to attest the safety, efficiency and reversibility of the novel sterilization device. IMPLICATIONS OF THE HYPOTHESIS: If our hypothesis is confirmed, appropriate and reversible contraceptive can be achieved with the device we have designed, which may have significant repercussions for numerous women worldwide.

Effects of laparoscopic ovarian endometriosis cystectomy combined with postoperative GnRH-a therapy on ovarian reserve, pregnancy, and outcome recurrence.

OBJECTIVE: The aim of this study was to investigate the impacts of laparoscopic ovarian endometriosis cystectomy combined with postoperative GnRH-a therapy on ovarian reserve, pregnancy outcome and recurrence. MATERIALS AND METHODS: This was a prospective control study. The experimental group: 63 patients with combinations of laparoscopic bilateral ovarian endometrial cystectomies and gonadotropin-releasing hormone agonist (GnRH-a) treatment for three months. CONTROL GROUP: 62 patients with laparoscopic bilateral ovarian endometrial cystectomies. Benchmarks: the changes of follicle stimulating hormone (FSH) and FSH/luteinizing hormone (LH), etradiol (E2) in preoperative and postoperative three months or menstrual two to three days, menstrual two to three days after surgery, natural pregnancy, and cyst recurrence in 18th month during postoperative follow-up. RESULTS: In experimental group after six months, the percentage of returned FSH accounted for 95.3% of normal range, in the control group it was 82.2%, and the difference was significant (p < 0.05). The natural pregnancy rate of preoperative infertility patients (57.1%) was higher than the control (36.8%) (p < 0.05). The recurrence rate of preoperative infertility patients (12.7%) was lower than the control (27.4%) (p < 0.05). CONCLUSION: After bilateral laparoscopic ovarian endometrial cystectomy, an implement of GnRH-a therapy can improve the postoperative pregnancy rate, which changes with clinical stage and patient age, reduces ovarian recurrence, and its influence on ovarian reserve is lesser.

Plasma-free amino acid profiling of cervical cancer and cervical intraepithelial neoplasia patients and its application for early detection.

In this study, plasma-free amino acid profiles were used to investigate pre-cancerous cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) metabolic signatures in plasma. Additionally, the diagnostic potential of these profiles was assessed, as well as their ability to provide novel insight into CSCC metabolism and systemic effects. Plasma samples from CIN patients (n = 26), CSCC patients (n = 22), and a control healthy group (n = 35) were analyzed by high-performance liquid chromatography, and their spectral profiles were subjected to the t test for statistical significance. Potential metabolic biomarkers were identified using database comparisons that examine the significance of metabolites. Compared with healthy controls, patients with CIN and CSCC demonstrated lower levels of plasma amino acids; plasma levels of arginine and threonine were increased in CIN patients but were decreased in cervical cancer patients. Additionally, the levels of a larger group of amino acids (aspartate, glutamate, asparagine, serine, glycine, histidine, taurine, tyrosine, valine, methionine, lysine, isoleucine, leucine, and phenylalanine) were gradually reduced from CIN to invasive cancer. These findings suggest that plasma-free amino acid profiling has great potential for improving cancer screening and diagnosis and for understanding disease pathogenesis. Plasma-free amino acid profiles may have the potential be used to determine cancer diagnoses in the early stage from a single blood sample and may enhance our understanding of its mechanisms.

Combination of curcumin and ginkgolide B inhibits cystogenesis by regulating multiple signaling pathways.

Autosomal dominant polycystic kidney disease (ADPKD), a common disease with a high incidence ratio of between 1/400 and 1/1,000 individuals, often results in kidney failure and even mortality. However, there are relatively few effective treatments available, and treatment is limited to lifelong hemodialysis or kidney transplant. Our previous studies have reported that curcumin (Cur) and ginkgolide B (GB) inhibited cystogenesis by regulating the Ras/ERK MAPK signaling pathway. In the present study, it was hypothesized that Cur and GB may have a synergistic effect on the inhibition of cystogenesis, and their synergistic effect may be the result of regulation of multiple signaling pathways. To assess this hypothesis, an in vitro Madin­Darby canine kidney (MDCK) cyst model and an in vivo kidney­specific polycystin 1 transient receptor potential channel interacting (Pkd1) knockout mouse model were established to observe the effects of the combination of Cur and GB. The cysts exposed to Cur, GB and Cur combined with GB became small thick­walled cysts, small thin­walled cysts and round shaped cell colonies, respectively. The combination of Cur and GB was more effective compared with either treatment alone in inhibiting cystogenesis. Additionally, to the best of our knowledge, the present study was the first to demonstrate the synergistic effect of Cur and GB on the inhibition of cystogenesis in Pkd1 knockout mice. Cur may have mediated its anti­cyst effects by blocking EGFR/ERK1/2, JNK and PI3K/mTOR signaling pathways, while GB may have inhibited cystogenesis via the downregulation of the EGFR/ERK1/2, JNK and p38 signaling pathways. These results provide a proof­of­concept for application of the combination of Cur and GB in inhibiting cystogenesis in ADPKD.

Analysis of differences in the transcriptomic profiles of eutopic and ectopic endometriums in women with ovarian endometriosis.

BACKGROUND: Endometriosis is a common gynecological disease among women in their reproductive years. Although much effort has been made, the pathogenesis of this disease and the detailed differences between eutopic endometrial cells and ectopic endometrial cells are still unclear. METHODS: In this study, eutopic and ectopic endometrial cells were collected from patients with and without endometriosis and RNA sequencing was performed. The gene expression patterns and differentially expressed genes (DEGs) in eutopic and ectopic endometrial cells, as well as control endometrial cells, were analyzed using a weighted gene co-expression network analysis (WGCNA) and the DESeq2 package. The functions of significant genes were detected using Gene ontology (GO) enrichment analysis, and qRT-PCR validation was performed. RESULTS: The results indicated that eight gene modules were found among these three groups. They also indicated that the gene module, which is highly related to eutopic endometrial cells, was mainly enriched in cell adhesion, embryo implantation, etc., while the gene module related to ectopic endometrial cells was mainly enriched in cell migration, etc. The results of differential expression analysis were generally consistent with the WGCNA results through identified significant DEGs between different groups. These DEGs may play an important role in the occurrence of endometriosis, including the infertility associated gene ARNTL and PIWIL2, tissue remodeling gene MMP11, cell survival and migration gene FLT1, inflammatory response gene GNLY, the tumor suppressor genes PLCD1, etc. Further analysis suggested the function of adhesion is stronger in ectopic endometrial cells than in eutopic endometrial cells, while the ectopic endometrium may have a higher potential risk of malignant transformation than eutopic endometrium. CONCLUSIONS: Overall, these data provide a reference for understanding the pathogenesis of endometriosis and its relationship with malignant transformation.

High intensity focused ultrasound treatment of adenomyosis: The relationship between the features of magnetic resonance imaging on T2 weighted images and the therapeutic efficacy.

OBJECTIVES: To investigate the relationship between the features of magnetic resonance imaging (MRI) on T2 weighted images (T2WI) and the therapeutic efficacy of high intensity focused ultrasound (HIFU) on adenomyosis. MATERIALS AND METHODS: From January 2011 to November 2015, four hundred and twenty-eight patients with symptomatic adenomyosis were treated with HIFU. Based on the signal intensity and the number of hyperintense foci in the adenomyotic lesions on T2WI, the patients were classified into groups. The day after HIFU ablation patients underwent contrast-enhanced MRI and a comparison was made of non-perfused volume (NPV) ratio, energy efficiency factor (EEF), treatment time, sonication time, and adverse effects. RESULTS: No significant difference in terms of HIFU treatment settings and results was observed between the group of patients with hypointense adenomyotic lesions and the group with isointense adenomyotic lesions (P>0.05). However, the sonication time and EEF were significantly higher in the group with multiple hyperintense foci compared to the group with few hyperintense foci. The NPV ratio achieved in the lesions with multiple hyperintenese foci was significantly lower than that in the lesions with few hyperintense foci (P<0.05). No significant difference was observed in the rate of adverse effects between the two groups. CONCLUSIONS: Based on our results, the response of the adenomyotic lesions to HIFU treatment is not related to the signal intensity of adenomyotic lesions on T2WI. However, the number of the high signal intensity foci in the adenomyotic lesions on T2WI can be considered as a predictive factor to help select patients for HIFU treatment.

[Clinical study of different forms of hysteroscopic surgery for endometrial polyps].

OBJECTIVE: To investigate the curative effects of different types of hysteroscopic surgery for endometrial polyps. METHODS: A total of 327 cases by different ways of hysteroscopic surgery for endometrial polyps from Nov 1999 to Nov 2004 were followed up. The mean age was (40 +/- 6) years. The mean follow-up was (3.0 +/- 0.6) years. Among 228 polyps patients in sexual maturity without desire of maintaining fertility, 53 (group A) underwent polypectomy with electrosurgical vaporization, and 175 cases (group B) did polypectomy with endometrial resection. Fifty-four (group C) cases (19 cases of infertility), who desired future childbearing, did polypectomy with endometrial resection of superficial layer near the polyps. Forty-five postmenopausal patients (group D) did polypectomy with endometrial coagulation. RESULTS: The time of operation: group A (15.1 +/- 0.8) second, group B (19.7 +/- 0.7) second, group C (20.9 +/- 0.7) second, and group D (22.1 +/- 0.8) second. None of the polyps recurred for the patients of groups A and D after operation, and the recurrent rate of groups B and C was 1.7% and 7.4%. There were no cases with amenorrhea in group C, who hoped to keep the function of fertility, but the recurrent rate of polyps was higher than other three groups. Of 19 cases of infertility, 14 cases became pregnant after the surgery. CONCLUSION: It is feasible to select different hysteroscopic surgery for endometrial polyps, according to different ages and the desire of childbearing of the patients.

Use of hysteroscope for vaginoscopy or hysteroscopy in adolescents for the diagnosis and therapeutic management of gynecologic disorders: a systematic review.

STUDY OBJECTIVE: The purpose of this article is to review the published literature and perform a systematic review to evaluate the effectiveness and feasibility of the use of a hysteroscope for vaginoscopy or hysteroscopy in diagnosing and establishing therapeutic management of adolescent patients with gynecologic problems. DESIGN: A systematic review. SETTING: PubMed, Web of science, and Scopus searches were performed for the period up to September 2013 to identify all the eligible studies. Additional relevant articles were identified using citations within these publications. PARTICIPANTS: Female adolescents aged 10 to 18 years. RESULTS: A total of 19 studies were included in the systematic review. We identified 19 case reports that described the application of a hysteroscope as treatment modality for some gynecologic conditions or diseases in adolescents. No original study was found matching the age of this specific population. CONCLUSIONS: A hysteroscope is a useful substitute for vaginoscopy or hysteroscopy for the exploration of the immature genital tract and may help in the diagnosis and treatment of gynecologic disorders in adolescent patients with an intact hymen, limited vaginal access, or a narrow vagina.

Application of two-dimensional electrophoresis and mass spectrometry to screen endometriosis-related proteins.

The aim of the present study was to detect the differences in the protein expression between Uyghur females with or without endometriosis (EM). The two dimensional (2D) gel images of proteins extracted from the serum of Uyghur and Han females with EM and the controls were analyzed using Phoretix 2D software, and the differentially expressed proteins were identified primarily by database query. Having compared the reproducible 2D gel images of proteins from the serum of Uihgur and Han females with and without EM, 13 differentially expressed proteins were obtained from Uyghur females and eight differentially expressed proteins were obtained from Han females. The present study demonstrated ethnic differences in gene and protein expression between Uyghur and Han females with EM.

Association of the plasma and tissue riboflavin levels with C20orf54 expression in cervical lesions and its relationship to HPV16 infection.

Riboflavin deficiency can cause a variety of metabolic problems that lead to skin and mucosal disorders. Limited evidence suggests that high intake of riboflavin may reduce overall risks of cancer. However, association of this deficiency with cervical cancer and precancerous lesions are still not definitively known. In this study, we characterized the relationship between plasma and tissue riboflavin levels and C20orf54 protein expression in patients with cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) as well as the relationship of these levels with human papillomavirus virus 16, 18 (HPV16/18) infections. High-performance liquid chromatography (HPLC) was used to measure blood riboflavin levels in patients with CIN and CSCC, and an enzyme-linked immunosorbent assay (ELISA) was used to determine tissue riboflavin levels in patients with CSCC and matched normal mucous epithelia. The expression of C20orf54 in fresh CSCC and matched tissues were detected by qRT-PCR and western blot, respectively. And it was further confirmed by immunohistochemistry (IHC) with formalin-fixed, paraffin-embedded CIN and CSCC. An HPV genotyping chip was used to analyze HPV infection and typing. The results showed that patients with CIN and CSCC had decreased plasma riboflavin levels as compared with normal controls. There was also significantly decreased riboflavin in tissues from CSCC patients, when compared with normal cervical epithelia. C20orf54 expression were significantly up-regulated in CSCC compared to matched control on both mRNA and protein level. Tissue riboflavin levels were significantly lower in HPV16/18 positive tissue compared with HPV16/18-negative tissue, and an inverse association was found between tissue riboflavin levels and C20orf54 mRNA and protein expression in CSCC. Additionally, C20orf54 was significantly correlated with tumor stages. In conclusion, C20orf54 tend to play a protective role in Uyghur cervical carcinogenesis of which modulating riboflavin absorption, and it is also related with HPV infection.