Maximize the safety and efficacy of fertility preservation by random start/dual ovarian stimulation for early breast cancer patients.

OBJECTIVE: What is the more efficient and safer protocol during controlled ovarian hyperstimulation (COH) for early-stage breast cancer patients seeking emergency fertility preservation before adjuvant chemo/radiotherapy? MATERIALS AND METHODS: This retrospective, case-series study involved two early-stage (Ia) breast cancer patients that requested for fertility preservation within 3 weeks. Random start/dual stimulation protocols with aromatase inhibitor (AI) were used to maximize oocyte yield and suppress serum estradiol (E2) level. RESULTS: E2 levels on trigger day during dual COH were between 112.0 and 407.0 pg/mL. Duration of COH could be shortened to only 17 days, and up to 41 oocytes were successfully retrieved with two retrievals. CONCLUSION: This remarkable efficient and safe protocol involves the combination of random start/dual stimulation with step-up AI dosage beforehand which not only maximize oocyte yield within the shortest possible timeframe, but also to maintain the low level of E2 to avoid over-stimulating estrogen-sensitive cancer cells and to decrease the risk of developing ovarian hyperstimulation syndrome (OHSS).

The debated role of bariatric surgery in improving in-vitro fertilization outcomes in morbidly-obese infertile women-a case report and brief overview.

OBJECTIVE: Obesity has a negative impact on in-vitro fertilization (IVF) outcomes, and obese women who plan IVF treatments are often encouraged to pursue weight reduction. Bariatric surgery is an effective strategy for the treatment of morbidly obese women. The current case report is to investigate the impact of bariatric surgery on IVF outcome in a morbidly obese woman with subfertility. CASE REPORT: A 37-year-old, morbidly obese woman with subfertility was indicated for IVF treatment. Due to her high body mass index (47.9 kg/m2), she was advised to lose weight; initial failure at conservative measures of weight loss prompted her to undergo bariatric surgery, combined with post-operative lifestyle change, prior to receiving IVF treatment. The woman successfully conceived at the second cycle and delivered twins by cesarean section smoothly at 36 + 3/7 weeks of gestation. Both twins have normal development up to two years of age. CONCLUSIONS: Weight reduction mediated by bariatric surgery in subfertile and morbidly obese women can be considered before IVF treatment.

Probing coordinated co-culture cancer related motility through differential micro-compartmentalized elastic substrates.

Cell development and behavior are driven by internal genetic programming, but the external microenvironment is increasingly recognized as a significant factor in cell differentiation, migration, and in the case of cancer, metastatic progression. Yet it remains unclear how the microenvironment influences cell processes, especially when examining cell motility. One factor that affects cell motility is cell mechanics, which is known to be related to substrate stiffness. Examining how cells interact with each other in response to mechanically differential substrates would allow an increased understanding of their coordinated cell motility. In order to probe the effect of substrate stiffness on tumor related cells in greater detail, we created hard-soft-hard (HSH) polydimethylsiloxane (PDMS) substrates with alternating regions of different stiffness (200 and 800 kPa). We then cultured WI-38 fibroblasts and A549 epithelial cells to probe their motile response to the substrates. We found that when the 2 cell types were exposed simultaneously to the same substrate, fibroblasts moved at an increased speed over epithelial cells. Furthermore, the HSH substrate allowed us to physically guide and separate the different cell types based on their relative motile speed. We believe that this method and results will be important in a diversity of areas including mechanical microenvironment, cell motility, and cancer biology.

Evaluation of adenomyosis after gonadotrophin-releasing hormone agonist therapy using ultrasound post-processing imaging: a pilot study.

OBJECTIVE: We explored a method for the quantitative sonographic analysis of myometrial texture using computer-aided image analysis software to assess outcomes following treatment with gonadotrophin-releasing hormone (GnRH) agonist for adenomyosis in women with infertility. METHOD: Data for patients with ultrasound images of the myometrium obtained at Taipei Medical University Hospital from 1 September 2018 to 5 April 5 2019 were analyzed. Only 10 patients with 20 ultrasound images matched the eligibility criteria. The images were divided into pre-treatment (n = 10) and post-treatment images (n = 10) and quantitative grayscale histograms were obtained from the ultrasound images using publicly available ImageJ computer-aided image analysis software. We analyzed the differences between the pre- and post-treatment images using the Mann-Whitney test and compared the results with outcomes assessed by serum CA-125 levels. RESULTS: Image analysis of the grayscale histograms revealed significant differences between before and after treatment. The classification of the myometrium pre-treatment and post-treatment was similar using CA-125 and histogram grayscale analysis. CONCLUSION: Computer-aided image analysis of grayscale histograms of the myometrium obtained from ultrasound images is an alternative method for assessing myometrial conditions after GnRH agonist treatment in patients with adenomyosis.

Mature cystic teratoma arising from the fimbrial end of the left fallopian tube. a case report.

We present a rare case of a woman with a mass containing soft tissue, fat, and calcified components attached to the fimbrial end of the left fallopian tube. A 38-year-old nulligravida woman who visited our clinic for infertility counseling had mild abdominal discomfort and a palpable mass in the lower abdomen. Multiple examinations were performed. Preoperatively, we considered that the patient had teratoma or teratocarcinoma of the left ovary. On exploratory laparotomy, we found that she had a mass with protuberances and a bulbous projection at one surface that was attached to the fimbrial end of the left fallopian tube. A histopathological examination showed a mature cystic teratoma that arose from the fimbrial end of the fallopian tube. Obstetricians should be aware of this abnormality. Early detection of this abnormality is advantageous for infertility counseling and planning of less invasive surgery in the hospital.

Mosaic ring chromosome 21, monosomy 21, and isodicentric ring chromosome 21: prenatal diagnosis, molecular cytogenetic characterization, and association with 2-Mb deletion of 21q21.1-q21.2 and 5-Mb deletion of 21q22.3.

OBJECTIVE: To present the perinatal findings and molecular cytogenetic characterization of prenatally detected mosaic r(21). MATERIALS, METHODS, AND RESULTS: A 29-year-old primigravid woman underwent amniocentesis at 22 weeks' gestation because of hyperechogenic cardiac foci and intrauterine growth restriction. Amniocentesis revealed a karyotype of 46,XY,r(21)[15]/45,XY,-21[5]. The parental karyotypes were normal. The woman requested repeat amniocentesis. Oligonucleotide-based array comparative genomic hybridization was applied to the uncultured amniocytes, rapidly detecting a 2.09-Mb deletion of 21q21.1-q21.2 (21,495,262-23,580,815 bp) and a 5.03-Mb deletion of 21q22.3-q22.3 (41,887,412-46,914,715 bp). Cytogenetic analysis revealed a karyotype of 46,XY,r(21)[8]/45,XY,-21[3]/46,XY,idic r(21)[1]. The pregnancy was terminated, and a malformed fetus was delivered with clinodactyly, short big toes, separation between the first and second toes, prominent nasal bridge, downward slanting palpebral fissures, protuberant occiput, prominent forehead, broad anteverted nasal tip, long philtrum, thin upper lip, small mouth, and micrognathia. The placenta had a karyotype of 46,XY,r(21)[83]/45,XY,-21[11]/46,XY,idic r(21)[6], and the cord blood lymphocytes had a karyotype of 46,XY,r(21)[88]/45,XY,-21[9]/46,XY,idic r(21)[3]. Polymorphic DNA marker analysis determined a maternal origin for the deletion. CONCLUSION: An extra interstitial 21q deletion can be associated with mosaic r(21) in addition to a terminal 21q deletion. aCGH is useful in determining the breakpoints and associated subtle structural abnormalities in cases of prenatally detected ring chromosome in order to facilitate genetic counseling.

Ultrasonographic quantification of the endometrium during the menstrual cycle using computer-assisted analysis.

OBJECTIVE: Sonographic gray-scale histogram is used to assess the endometrial changes in the different phases of the menstrual cycle. The objective was to examine the usefulness of a gray-scale histogram and computer-assisted image analysis software in assessing normal physiologic states of the endometrium with sonography. MATERIALS AND METHODS: Thirty-eight patients, who visited the Taipei Medical University-Wan Fang Hospital and matched the eligibility criteria, were categorized into one of three groups: (1) menstrual phase; (2) follicular phase; and (3) luteal phase of the menstrual cycle. Ultrasonography of the uterus was performed on each patient and the endometrium was analyzed with ImageJ image analysis software. RESULTS: A statistically significant difference in signal intensity scores of the gray-level histogram, represented as m(j), was found among the three groups. CONCLUSION: Sonographic images analyzed by using computer-assisted image analysis software and gray-level histogram are proven to be useful in assessing the physiological state of the endometrium.

Evaluation of placental maturity by the sonographic textures.

PURPOSE: Routine ultrasound screening to predict gestational age is important for risk assessment of pregnancy complications among pregnant women. We explored a quantitative method for sonographic analysis of placental texture, with the objective of reproducible measurement. METHODS: We studied 151 pregnant women; the gestational ages of their fetuses ranged from 10 to 38 weeks. Three experienced sonographers delineated the placental contour to define the region of interest (ROI). From these sonograms, 72 texture features were derived from the spatial gray-level dependence matrices and gray-level difference matrices. We used these as input variables in a multiple linear regression analysis. RESULTS: A significant positive correlation (P < 0.01) was found between the multiple linear regression results and the corresponding gestation ages by the three assessors (r (A) = 0.755, r (B) = 0.851, and r (C) = 0.832). We also found good agreement between multiple linear regression results for the three observers. Their κ statistic values were 0.685 between assessors A and B, 0.679 between A and C, and 0.804 between B and C. CONCLUSION: Quantitative sonography using texture analysis of the placenta was useful in practice to determine gestational age.

Polycystic ovary syndrome or hyperprolactinaemia: a study of mild hyperprolactinaemia.

Polycystic ovary syndrome (PCOS) and hyperprolactinaemia are both common causes of secondary amenorrhoea in reproductive women. The relationship between PCOS and hyperprolactinaemia has been reported with controversial results. To evaluate the clinical and laboratory features of women with mild hyperprolactinaemia and PCOS, we studied 474 Taiwan Chinese women: 101 had mild hyperprolactinaemia, 266 had PCOS and 107 were the control group. In this study, we found that 64% of the women with mild hyperprolactinaemia fulfilled the PCOS diagnostic criteria, regardless of their prolactin levels. Obese women with PCOS had significantly lower luteinising hormone (LH) and LH-to-FSH ratios than non-obese women with PCOS. Obese hyperprolactinaemic women had significantly lower follicle-stimulating hormone (FSH), but higher LH-to-FSH ratios than the non-obese hyperprolactinaemic women. For women with PCOS, the BMIs were significantly negative with LH (γ = -0.253, p < 0.001), but not with FSH (γ = -0.061, p = 0.319). For the hyperprolactinaemic women, the BMIs were significantly negative with FSH (γ = -0.353, p < 0.001), but not with LH (γ = -0.021, p = 0.837). Although PCOS-related syndrome was very prevalent in women with hyperprolactinaemia, the patterns of disturbance in gonadotropin secretion were different between the PCOS and the hyperprolactinaemia patients.

Ultrasonographic evaluation of endometrial changes using computer assisted image analysis.

AIM: To examine the usefulness of a gray scale histogram and computer assisted image analysis software in assessing physiologic states of the endometrium with ultrasonography. METHODS: Seventy patients at the Taipei Medical University-Wan Fang Hospital who matched eligibility criteria were categorized into one of three groups: (i) normal menstrual cycle, (ii) postmenopausal, and (iii) post incomplete abortion. Ultrasonography of the uterus was performed on each patient and the endometrium was analyzed with ImageJ image analysis software. RESULTS: A statistically significant difference in signal intensity scores of the gray level histogram, represented as m(j), was found between the groups. CONCLUSION: Ultrasonographic images analyzed using computer assisted image analysis software and gray level histogram are useful in assessing the physiological state of the endometrium.

A comparative study of cutaneous manifestations of hyperandrogenism in obese and non-obese Taiwanese women.

PURPOSE: The aim of the study was to investigate the impact of obesity on cutaneous manifestations of clinical hyperandrogenism. METHODS: A total of 627 Taiwanese women of reproductive age were included. RESULTS: Women with acne had a greater incidence of PCOS, hyperandrogenemia and hirsutism, and had higher serum total testosterone than women without acne. Obese women, even with significantly higher serum total testosterone levels, had lower incidence of acne than non-obese women, and this was found uniformly across the hyperandrogenemia and the non-hyperandrogenemia groups. Although BMI had a significantly positive correlation with serum total testosterone in the studied women, obese women presented less acne than the non-obese subjects. CONCLUSIONS: Obese women, regardless of having higher serum testosterone levels, had a lower incidence of acne than non-obese women; however, the factuality was not found in hirsutism.

Sonographic quantification of endometrial changes after abortion with computer-assisted image analysis.

OBJECTIVE: To examine the diagnostic feasibility of sonographic gray scale histograms to assess changes in the endometrium following abortion induced by mifepristone and misoprostol. DESIGN: Retrospective study. SETTING: Taipei Medical University-Wan Fang academic medical center. POPULATION OR SAMPLE: A total of 109 patients who matched eligibility criteria were divided into three groups: (a) complete abortion, (b) normal menstrual cycles, and (c) incomplete abortion. METHODS: Ultrasonographic examination of the uterus with fixed settings on each patient and sonographic gray scale histograms with image analysis software, using multivariate analysis by the partial least square model. MAIN OUTCOME MEASURES: Thickness, brightness, area and distribution of pixels of the endometrium and its contents. RESULTS: The groups could be discriminated (p < 0.01, Kruskal-Wallis test) using the analyzed gray scale histograms. The classification between complete and incomplete abortion reached 97% sensitivity and 100% specificity. CONCLUSIONS: Partial least square analysis of gray scale histograms of the endometrium in ultrasonographic images is useful in assessing endometrial changes.

Effects of different arginine concentrations on angiogenic protein production induced by HeLa cells.

OBJECTIVES: This in vitro study investigated the effects of different arginine (Arg) concentrations on angiogenic protein expressions of HeLa cells and endothelial cells (ECs) after stimulation. In addition, an inducible nitric oxide (iNO) synthase inhibitor (1400W) was used to investigate the possible role of iNO in angiogenesis. METHODS: Endothelial cells and HeLa cells were treated with different concentrations of Arg and 1400W: Arg 0, 50, 100, and 1000 micromol/L; Arg 100 micromol/L+1400W 10 micromol/L; and Arg 1000 micromol/L+1400W 10 micromol/L for 24 h. Then, ECs and HeLa cells were cocultured for 2 h, and the supernatant in the transwell was collected for analysis of angiogenic protein secreted. The expression of CD51/CD61 by ECs was also analyzed. RESULTS: The productions of vascular endothelial growth factor, basic fibroblast growth factor, prostaglandin E(2), and matrix metalloproteinase-2 were higher with Arg 100 and 1000 micromol/L than with Arg 0 and 50 micromol/L Arg, and this was consistent with the expression of CD51/CD61 by ECs. Inhibition of iNO production resulted in lower angiogenic protein expressions comparable with groups with low Arg administration. CONCLUSION: The findings of this study suggest that Arg administration at levels similar to or higher than physiologic concentrations enhance the production of angiogenic protein and iNO may partly play a role in promoting angiogenesis in the presence of HeLa cells.

Computer-aided diagnosis of soft-tissue tumors using sonographic morphologic and texture features.

RATIONALE AND OBJECTIVES: The aim of this study was to develop a computer-aided diagnosis (CAD) system in assessing the sonographic morphologic and texture features of soft-tissue tumors. MATERIALS AND METHODS: The retrospective study involved 114 pathology proven cases including 73 benign and 41 malignant soft-tissue tumors. The tumor regions were delineated by an experienced radiologist who was unknown to the pathologic result. Then, we applied 10 morphologic features and 6 gray-level co-occurrence matrix texture features to analyze the tumor regions. To classify the tumors as benign or malignant, we used two methods, a linear discriminant analysis with stepwise feature selection and a multilayer neural network with the back-propagation algorithm as classifiers. The classification performances are evaluated by the area A(z) under the receiver operating characteristic. Furthermore, four radiologists provided malignancy grades for all tumors in the comparison of the CAD system. RESULTS: In this analysis, the CAD system based on the combination of morphologic and texture feature sets can give the optimal CAD result by LDA with an accuracy of 89.5%, a sensitivity of 90.2%, a specificity of 89.0%, a positive predictive value (PPV) of 82.2%, negative predictive value (NPV) of 94.2%, and A(z) value of 0.96, and by the multilayer perception with an accuracy of 88.6%, a sensitivity of 90.2%, a specificity of 87.5%, a positive predictive value of 80.4%, negative predictive value of 94.2%, and A(z) value of 0.95. The A(z) values of the four radiologists were ranged between 0.74 and 0.86, and the optimal CAD results were shown the highest A(z) values than the four radiologists' rankings. CONCLUSIONS: This study has shown that performing the CAD system with both morphologic and texture features on sonography, can successfully distinguish between benign and malignant soft-tissue tumors. Moreover, it can also provide a second opinion for the tumor diagnosis and avert unnecessary biopsy.

Effect of lower extremity bypass surgery on inflammatory reaction and endothelial dysfunction in type 2 diabetic patients.

Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia and dyslipidemia. The abnormalities in nutrient metabolism and elevated inflammatory mediators resulting from DM lead to impairment of wound healing and vulnerability to infection and foot ulcers. Diabetic lower limb ischemia often leads to limb necrosis. Lower extremity bypass surgery (LEBS) is indicated to prevent limb loss in patients with critical leg ischemia. This study investigated the alteration of inflammatory and endothelium dysfunction markers before and after LEBS in DM patients. Twenty one type 2 DM patients with LEBS were included. Blood was drawn before and at 1 day and 7 days after surgery in the patients. Plasma soluble cellular adhesion molecule levels and blood leukocyte integrin expressions were measured. Also, plasma concentrations of endothelin-1 and nitric oxide were analyzed to evaluate the vascular endothelial function. The results showed that there were no significant differences in plasma cellular adhesion molecules, endothelin-1 and nitric oxide levels, nor did any differences in leukocyte integrin expressions before and after the operation. These results suggest that the efficacy of LEBS on alleviating inflammatory reaction and improving endothelial function in DM patients was not obvious.

Computer-aided diagnosis of soft tissue tumors on high-resolution ultrasonography with geometrical and morphological features.

RATIONALE AND OBJECTIVES: The aim of this study was to develop a semi-automated computer-aided diagnosis (CAD) system based on high-resolution ultrasonography for classifying benign and malignant soft tissue tumors (STTs). MATERIALS AND METHODS: One hundred seven patients with STTs (70 benign and 37 malignant) were enrolled, and regions of interest were manually delineated for analysis. Sixteen tumor shape features, including five geometric features and 11 morphologic features (six old and five new normalized radial length [NRL] features) were individually evaluated using Student's t test and the area under the receiver-operating characteristic curve (A(z)). Then linear discriminant analysis with stepwise feature selection was used to construct a semi-automated CAD system with old NRL features, new NRL features, and all features combined. Additionally, two experienced radiologists participated in malignancy grading of tumors. To investigate the associations among CAD results, pathologic results, and radiologists' rankings, Spearman's rank correlation coefficient was used in the statistical analysis. RESULTS: The results showed that 11 features had P values < .05, and five of the proposed features were significant. The optimal CAD system achieved accuracy of 87.9%, sensitivity of 89.2%, specificity of 87.1%, and an A(z) value of 0.93. Correlation between pathologic results and radiologists' rankings was obtained (radiologist A: r=0.62, P < .01; radiologist B: r=0.61, P < .01). In addition, a higher correlation between pathologic results and CAD results (r=0.73, P < .01) was demonstrated. CONCLUSION: This semi-automated CAD method based on tumor shape features can successfully distinguish between benign and malignant STTs. It can also provide a second opinion to ultrasound for the diagnosis of STTs.

Composite polymer systems with control of local substrate elasticity and their effect on cytoskeletal and morphological characteristics of adherent cells.

At the interface between extracellular substrates and biological materials, substrate elasticity strongly influences cell morphology and function. The associated biological ramifications comprise a diversity of critical responses including apoptosis, differentiation, and motility, which can affect medical devices such as stents. The interactions of the extracellular environment with the substrate are also affected by local properties wherein cells sense and respond to different physical inputs. To investigate the effects of having localized elasticity control of substrate microenvironments on cell response, we have developed a method to control material interface interactions with cells by dictating local substrate elasticity. This system is created by generating a composite material system with alternating, linear regions of polymers that have distinct stiffness characteristics. This approach was used to examine cytoskeletal and morphological changes in NIH 3T3 fibroblasts with emphasis on both local and global properties, noting that cells sense and respond to distinct material elasticities. Isolated cells sense and respond to these local differences in substrate elasticity by extending processes along the interface. Also, cells grown on softer elastic regions at higher densities (in contact with each other) have a higher projected area than isolated cells. Furthermore, when using chemical agents such as cytochalasin-D to disrupt the actin cytoskeleton, there is a significant increase in projected area for cells cultured on softer elastic regions This method has the potential to promote understanding of biomaterial-affected responses in a diversity of areas including morphogenesis, mechanotransduction, stents, and stem cell differentiation.

Effects of parenteral glutamine supplementation on modulating the immune response in rats undergoing a total gastrectomy.

The present study investigated the effect of parenteral glutamine (Gln) supplementation on cellular adhesion molecule expression and release of chemokines responsible for inflammatory cell recruitment in rats undergoing a total gastrectomy. Normal rats with internal jugular catheters were assigned to one control group and two experimental groups and received total parenteral nutrition (TPN). A total gastrectomy was performed in the experimental groups, whereas the control group received a sham operation (Sham). The TPN solutions were isonitrogenous and identical in nutrient composition except that the Sham group and one of the experimental group received conventional (Conv) TPN solution, whereas the other experimental group received 25% of the amino acid nitrogen as Gln. Half of the rats in each group were killed 1 or 3 d after surgery or the Sham to examine their immune response. The results showed that the surgery produced higher polymorphonuclear leucocyte CD11b/CD18 expressions, and Gln supplementation lowered CD11b/CD18 expressions compared with the Conv group post-operatively. The levels of monocyte chemotactic protein-1 and macrophage inflammatory protein-2 in peritoneal lavage fluid were higher in the Gln group than those in the Conv group 1 d post-operatively; these chemotactic proteins had returned to the levels comparable with those in the Sham group on post-operative day 3. These results suggest that Gln supplementation attenuated polymorphonuclear leucocyte integrin expression. In addition, Gln-enriched parenteral nutrition induced an earlier more intensive and rapid immune response to injury than the Conv parenteral nutrition after a total gastrectomy.