The Value of Anti-Müllerian Hormone in Predicting Ovulation Induced by Aromatase Inhibitors in Women With Polycystic Ovary Syndrome.

OBJECTIVES: This study aimed to evaluate the value of anti-Müllerian hormone (AMH) in predicting ovulation induced by aromatase inhibitors (AI) and pregnancy outcomes in women with polycystic ovary syndrome (PCOS). METHODS: From January 2018 to December 2020, this prospective cohort study enrolled women with PCOS aged between 18 and 45 years who underwent ovulation induction using AI protocol and intrauterine insemination (IUI) for infertility at a Center for Reproductive Endocrinology and Infertility, University Hospital. Receiver operating characteristic curves were used to estimate the chance of ovulation responses and pregnancy outcomes. RESULTS: In total, 64% of 65 women with PCOS were recruited following AI treatment, and the clinical pregnancy rate was 19.4% following IUI. Patients who experienced ovulation had a lower mean serum AMH concentration than non-responders (7.11 ng/mL vs. 8.95 ng/mL, respectively), but the difference was not statistically significant. Between the pregnancy and non-pregnancy groups, statistically significant differences in AMH concentrations were observed (8.71 ng/mL vs. 6.73 ng/mL, respectively, P = 0.040). The area under the curve of the receiver operating characteristic for non-ovulation prediction was 0.445, 95% CI (0.284-0.606) with P = 0.467, and for clinical pregnancy was 0.735, 95% CI (0.561-0.910) with P = 0.104. CONCLUSIONS: In women with PCOS, the AMH level does not predict ovarian responsiveness to AI treatment, but it does predict the success of IUI cycles.

Copenhagen Index versus ROMA in preoperative ovarian malignancy risk stratification: Result from the first Vietnamese prospective cohort study.

OBJECTIVES: This study aimed to evaluate the diagnostic performances of the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA) in the preoperative prediction of ovarian cancer. METHODS: In a prospective cohort study, data were collected from 475 patients with ovarian masses diagnosed by gynecologic examination / ultrasound who were hospitalized at the Departments of Obstetrics and Gynecology, Hue University of Medicine and Pharmacy Hospital and Hue Central Hospital, Vietnam, between January 2018 and June 2020. ROMA and CPH-I were calculated based on measurements of serum carbohydrate antigen (CA-125) and human epididymis protein (HE4). The final diagnosis was based on clinical features, radiologic and histologic findings, and the International Federation of Gynecology and Obstetrics (FIGO) 2014 stages of ovarian cancer were recorded. Matching the values of ROMA and CPH-I to postoperative histopathology reports resulted in the preoperative prediction values. RESULTS: Among the 475 women, 408 had benign tumors, 5 had borderline tumors and 62 had malignant tumors. The two indices showed similar discriminatory performances with no significant differences (p > 0.05). At an optimal cut-off, the sensitivities/specificities of ROMA and CPH-I for ovarian cancer diagnosis were 74.2% and 91.8%, 87.1% and 78.5%, respectively. The optimal cut-off for CPH-I was 1.89%. The areas under the ROC curves (AUCs) of ROMA and CPH-I were 0.882 (95% CI: 0.849-0.909) and 0.898 (95% CI: 0.867-0.924), respectively. CONCLUSIONS: The introduction of the Copenhagen Index to help stratify the malignancy risk of ovarian tumors, irrespective of menopausal status, might be applied as a simple alternative with a similar efficacy to ROMA in clinical practice.

HER2Ile655Val Single Nucleotide Polymorphism Associated with Early-Onset Breast Cancer Susceptibility: A Systematic Review and Meta-Analysis.

ackground: Human epidermal growth factor receptor 2 (HER2) plays an important role in the development and progression of breast cancer. To understand the precise association, this meta-analysis was conducted to estimate the association between HER2Ile655Val single nucleotide polymorphism (SNP) and susceptibility to early-onset breast cancer. METHODS: A comprehensive database retrieval from PubMed, Embase, Web of Science and Google Scholar was pooled to investigate links between the HER2Ile655Val SNP and risk of breast cancer. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to appraise the association under the additive model (Ile vs. Val), dominant model (Val/Val + Ile/Val vs. Ile/Ile), and recessive model (Val/Val vs. Ile/Val + Ile/Ile). RESULTS: Seventeen relevant studies with 11,749 cases and 8,105 controls were finally included. We found that HER2Ile655Val SNP is associated with an increased risk of breast cancer in an additive and dominant model. In the subgroup analysis with age stratification, a significant association between the HER2 codon 655 SNP and the risk of breast cancer was found in young women in an additive, dominant, and recessive model; conversely, no significant associations were indicated in older women. In the breast cancer subgroup, HER2Ile655Val SNP was significantly associated with younger age women with breast cancer in the dominant model. In contrast, no association between the HER2 codon 655 SNP and age was found in control populations. CONCLUSION: Our findings suggest that the Val allele in HER2 codon 655 SNP is strongly associated with breast cancer susceptibility in the young female population and is also significantly associated with younger age in women with breast cancer. HER2Ile655Val SNP might be a susceptibility factor that favours early-onset breast cancer.
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Should Scrotal Color Doppler Ultrasound Be Routinely Indicated in Fertility Evaluation of Non-Azoospermic Men?

OBJECTIVE: Scrotal ultrasound is not a routine investigation in the clinical approach to male infertility analysis. This study aims to identify the role of testicular Doppler ultrasound in male infertility assessment and its relation to semen parameters in non-azoospermic men. METHODS: Cross-sectional descriptive analysis of 558 men from infertile couples were examined at the Hue Center for Reproductive Endocrinology and Infertility, Hue University Hospital from June 2016 to May 2018. Some cohort characteristics, semen analysis and testicular Doppler ultrasound were analyzed. Men with acute systemic diseases, acute urinary tract infection, hepatic dysfunction, malignant diseases, retrograde ejaculation, cryptorchidism or azoospermia were excluded. RESULTS: The mean volumes of the right and left testicles were 8.87 and 8.77 ml, respectively. The total volume of the 2 sides was 17.63 ± 4.34 ml (95% confidence interval 17.27-18.00 ml). The mean right resistive index (RI) was 0.61 ± 0.23, and the mean left RI was 0.59 ± 0.01. The rate of normal semen quality was 23.2% in group with varicocele and 30.6% in group with non-varicocele. The ultrasound results from the normal semen group were much different from those of the abnormal semen group regarding testicular volume: mean right testis volume: 9.67 ± 1.88 vs. 8.75 ± 2.34 ml, p = 0.0096; mean left testis volume: 9.54 ± 1.78 vs. 8.51 ± 2.44 ml, p = 0.0047; mean total volume of 2 sides: 19.21 ± 3.60 vs. 17.26 ± 4.59 ml, p = 0.005 (varicocele group); mean right testis volume: 9.21 ± 2.21 vs. 8.63 ± 2.21 ml, p = 0.029 (non-varicocele group). The other indexes of color Doppler ultrasound (peak systolic velocity, end diastolic velocity, RI) were not found to correlate with semen quality. CONCLUSIONS: Testicular volume which has a close relation to the semen parameters could be used as a clinical prediction factor for the quality of semen.

Does sperm DNA fragmentation correlate with semen parameters?

PURPOSE: This study aimed to investigate the association between sperm quality assessed by routine semen analysis and sperm DNA integrity assay. METHODS: In our cross-sectional study, a total of 318 men from the infertile couples were enrolled from December 2017 to March 2019 at the Hue Center for Reproductive Endocrinology and Infertility, Vietnam. General characteristics and semen parameters were detected. The sperm DNA fragmentation index (DFI) was estimated by the sperm chromatin dispersion (SCD) assay. A threshold of DFI 30% was applied to classify normal (DFI < 30%) or abnormal (DFI ≥ 30%) groups. The correlations between DFI and semen parameters were analyzed by Spearman's rank correlation coefficient. RESULTS: In the correlation analysis, DFI was significantly correlated with abnormal head and progressive motility, with a positive correlation with abnormal head (ρ = .202, P = .0003) and a weak negative correlation with progressive motility (ρ = -.168, P = .0027), respectively. In the bivariate analysis, DFI was associated with male age, smoking, and alcohol consumption with P < .05. CONCLUSIONS: The sperm DFI was not strongly correlated with conventional semen parameters. Therefore, a sperm DNA fragmentation assay should be performed as an additional step in the investigation of male fertility.

Defining polycystic ovary syndrome phenotype in Vietnamese women.

AIM: This study aimed to evaluate the unique phenotype of the Vietnamese polycystic ovarian syndrome (PCOS) population. METHODS: In this multicenter cross-sectional descriptive study, a total of 901 reproductive-age women were recruited at three medical centers in Vietnam from June 2016 to May 2018. Group I included 479 patients with PCOS (Rotterdam 2003 consensus) and Group II included 422 non-PCOS women, consisted of women with regular menstrual cycle, collected at the same time of PCOS recruitment, without ovarian disease or ovarian failure. Main outcome measures were anthropomorphic, serum hormone, ultrasound and physical characteristics of PCOS. RESULTS: The Vietnamese PCOS population was lean, but with a higher weight and body mass index compared to controls. About 34.4% of PCOS subjects had hirsutism, primarily confined to the leg, arm and pubis. The PCOS population had higher serum luteinizing hormone (LH), LH : follicle stimulating hormone ratio, anti-Mullerian hormone and testosterone. The PCOS population had double the ovarian volume compared to controls. PCOS subjects had no increase in metabolic disease history and had on average optimal serum markers for low metabolic disease risk. Group D (O + polycystic ovary morphology [PCOM]) was the most prevalent phenotype noted in our Vietnamese PCOS cohort (67.6%). Modified Ferriman-Gallwey, levels of LH, testosterone and anti-Mullerian hormone were highest in Group A (O + H + PCOM) and lowest in Group D (O + PCOM). CONCLUSION: The Vietnamese PCOS population is characterized by a lean body type, nonfacial hirsutism, anovulatory, enlarged ovaries and typical PCOS serum hormone markers, low risk factors for metabolic syndrome. Nonclassical phenotypes for PCOS were more frequent than the classic phenotype.

Exploration of the role of anti-Mullerian hormone and LH/FSH ratio in diagnosis of polycystic ovary syndrome.

OBJECTIVE: This study explores the role of anti-Mullerian hormone (AMH) and LH/FSH ratio in diagnosis of polycystic ovary syndrome (PCOS). METHODS: In this multicentre cross-sectional descriptive study, a total of 863 infertile women between 18 and 45 years were evaluated at three infertility centres in Vietnam and were recruited from June 2016 to June 2017. The patients were classified into two groups: Group I included 441 patients with PCOS (based on Rotterdam criteria consensus) and Group II included 422 non-PCOS women. Diagnosis of PCOS was established based on Rotterdam 2003 consensus, and exclusion criteria were ovarian disease (ovary cyst/tumour), history of ovarian surgery and ovarian failure. RESULTS: At an optimum cut-off level of 32.79 pmol/L, AMH showed sensitivity and specificity of 78.50% and 75.83%, respectively, with the AUC 0.852 (95% CI: 0.826-0.875). The LH/FSH ratio had a similar AUC at the optimum cut-off of 1.33 (AUC = 0.867, 95% CI 0.842-0.889), which demonstrated a similar diagnosis value to AMH (P = 0.340). By using multiple logistic regression analysis, 1 ng/mL increase in AMH levels was associated with an increased risk of PCOS (OR = 1.63, 95% CI: 1.506-1.764; P < 0.001). Similarly, one unit increase in LH/FSH ratio was associated with 14.433 times increased (95% CI: 9.302-22.395; P < 0.001) risk of PCOS. There were no significant differences between values of AMH and LH/FSH ratio in PCOS diagnosis, as the difference between the two AUCs was 0.013, 95% CI: -0.024 to 0.028 and P = 0.897. CONCLUSION: The value of serum AMH concentration has been found not significantly superior to LH/FSH ratio in PCOS diagnosis. Although these biomarkers separately are not adequate for PCOS diagnosis based on their own value, the combination of different endocrine factors including AMH, LH and LH/FSH ratio together with BMI and other anthropometric and clinical characteristics may offer extra value to establish the diagnosis of PCOS.

Community-based prevalence versus hospital-based incidence of genital Human Papillomavirus infection in Central Vietnam.

INTRODUCTION: This study aims to determine the genital HPV prevalence in reproductive-age women in Thua Thien Hue Province and comparison with HPV incidence in Hue University Hospital, Vietnam. METHODOLOGY: Cross-sectional study on 1,034 women of reproductive age from 11 communes/wards of three districts representing three different geographic areas of Thua Thien Hue Province, Vietnam. The hospital-based group included 102 women with cervicitis and/or abnormal Pap smear result coming to Hue University Hospital. Extracting DNA from cervical samples, performing the real-time PCR for detecting HPV and the reverse dot-blot assay for HPV typing in HPV positive cases. RESULTS: In community, HPV prevalence was 0.9%. Mean-age of HPV positive group was 37.9 ± 6.2 years. The detected low-risk types were 6 and 11; high-risk types include 16, 18, 33, 45, 52, and 58. Single-type infection was found in 66.7% of cases. In hospital-based group, 41.2% of women have been infected with HPV, 6 different HPV types were detected. HPV18 was the most frequent high-risk type (33.3%), followed by HPV16 (15.1%); HPV6 was the most frequent among low-risk HPV types (31.2%). Single-type infection rate was 33,3%; 2 and 3 types co-infections were 28,6% and 38.1%, respectively. CONCLUSIONS: Routine screening of high-risk HPV infection in women with symptomatic gynecologic infection and/or abnormal Pap smear appears to be benefit in early detection and prevention of cervical cancer, due to the high incidence of HPV infection.

Enantiomeric 3-chloromandelic acid system: binary melting point phase diagram, ternary solubility phase diagrams and polymorphism.

A systematic study of binary melting point and ternary solubility phase diagrams of the enantiomeric 3-chloromandelic acid (3-ClMA) system was performed under consideration of polymorphism. The melting point phase diagram was measured by means of thermal analysis, that is, using heat-flux differential scanning calorimetry (DSC). The results reveal that 3-ClMA belongs to the racemic compound-forming systems. Polymorphism was found for both the enantiomer and the racemate as confirmed by X-ray powder diffraction analysis. The ternary solubility phase diagram of 3-ClMA in water was determined between 5 and 50 degrees C by the classical isothermal technique. The solubilities of the pure enantiomers are extremely temperature-dependent. The solid-liquid equilibria of racemic 3-ClMA are not trivial due to the existence of polymorphism. The eutectic composition in the chiral system changes as a function of temperature. Further, solubility data in the alternative solvent toluene are also presented.

A novel semi-automatic image processing approach to determine Plasmodium falciparum parasitemia in Giemsa-stained thin blood smears.

BACKGROUND: Malaria parasitemia is commonly used as a measurement of the amount of parasites in the patient's blood and a crucial indicator for the degree of infection. Manual evaluation of Giemsa-stained thin blood smears under the microscope is onerous, time consuming and subject to human error. Although automatic assessments can overcome some of these problems the available methods are currently limited by their inability to evaluate cases that deviate from a chosen "standard" model. RESULTS: In this study reliable parasitemia counts were achieved even for sub-standard smear and image quality. The outcome was assessed through comparisons with manual evaluations of more than 200 sample smears and related to the complexity of cell overlaps. On average an estimation error of less than 1% with respect to the average of manually obtained parasitemia counts was achieved. In particular the results from the proposed approach are generally within one standard deviation of the counts provided by a comparison group of malariologists yielding a correlation of 0.97. Variations occur mainly for blurred out-of-focus imagery exhibiting larger degrees of cell overlaps in clusters of erythrocytes. The assessment was also carried out in terms of precision and recall and combined in the F-measure providing results generally in the range of 92% to 97% for a variety of smears. In this context the observed trade-off relation between precision and recall guaranteed stable results. Finally, relating the F-measure with the degree of cell overlaps, showed that up to 50% total cell overlap can be tolerated if the smear image is well-focused and the smear itself adequately stained. CONCLUSION: The automatic analysis has proven to be comparable with manual evaluations in terms of accuracy. Moreover, the test results have shown that the proposed comparison-based approach, by exploiting the interrelation between different images and color channels, has successfully overcome most of the inherent limitations possibly occurring during the sample preparation and image acquisition phase. Eventually, this can be seen as an opportunity for developing low-cost solutions for mass screening.

Angiotensin AT4 receptor ligand interaction with cystinyl aminopeptidase and aminopeptidase N: [125I]Angiotensin IV only binds to the cystinyl aminopeptidase apo-enzyme.

Due to its high affinity for [(125)I]Angiotensin IV, cystinyl aminopeptidase (CAP) has recently been assigned as the 'angiotensin AT(4) receptor'. Since the aminopeptidase N (AP-N) activity is also susceptible to inhibition by Angiotensin IV, it might represent an additional target for this peptide. Based on [(125)I]Angiotensin IV binding and catalytic activity measurements, we compared the ligand interaction properties of recombinant human CAP and human AP-N. Both enzymes displayed distinct pharmacological profiles. Although their activity is inhibited by Angiotensin IV and LVV-hemorphin 7, both peptides are more potent CAP-inhibitors. On the other hand, substance P and l-methionine have a higher potency for AP-N. High affinity binding of [(125)I]Angiotensin IV to CAP occurs in the presence of chelators but not to AP-N in either the absence or presence of chelators. These differences were exploited to determine whether CAP and/or AP-N are present in different cell lines (CHO-K1, COS-7, HEK293, SK-N-MC and MDBK). We provide evidence that CAP predominates in these cell lines and that, comparatively, CHO-K1 cells display the highest level of this enzyme.

Synergistic modulation of cystinyl aminopeptidase by divalent cation chelators.

Membranes of Chinese hamster ovary (CHO-K1) cells were used to study the opposite modulation of enzyme activity and [125I]Ang IV binding to cystinyl aminopeptidase (EC 3.4.11.3) by divalent cation chelators. Whereas ethylene diamine tetraacetic acid (EDTA) or ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA) alone only slightly affected the enzyme activity, 1,10-phenanthrolin (1,10-PHE) produced a complete and concentration-dependent inhibition. Interestingly EDTA (> or =0.05 mM) or EGTA (> or =0.15 mM) enhanced the inhibitory effect of 1,10-PHE. Two-site analysis of the corresponding inhibition curves revealed that EDTA and EGTA converted enzymes with low sensitivity towards 1,10-PHE into enzymes with high sensitivity. The combined inhibition by EDTA (0.1 mM) and 1,10-PHE (0.1 mM) could be prevented and reversed by addition of Zn2+ (at about 0.04-0.1 mM). In contrast, specific binding of [125I]Ang IV was enhanced in the presence of 1,10-PHE. Binding was only slightly affected by EDTA or EGTA alone. Furthermore, the stimulatory effect of 1,10-PHE was potentiated by EDTA (> or =0.05 mM) as well as EGTA (> or =0.15 mM). In the presence of EDTA (0.1 mM) and 1,10-PHE (0.1 mM), specific [125I]Ang IV binding was completely inhibited by Zn2+ (IC50= 39.7 +/- 6.2 microM). The present data show that divalent cations such as Zn2+ are essential for the enzyme activity of cystinyl aminopeptidase and inhibitory for [125I]Ang IV binding. Modulation of the effects of 1,10-PHE by other chelators such as EDTA or EGTA, suggests that, in addition to the binding site for zinc in the catalytic site, cystinyl aminopeptidase also bears a regulatory divalent cation binding site.

Endogenous cystinyl aminopeptidase in Chinese hamster ovary cells: characterization by [125I]Ang IV binding and catalytic activity.

The angiotensin II C-terminal hexapeptide fragment angiotensin IV (Ang IV) exerts central and cardiovascular effects. Cystinyl aminopeptidase (EC 3.4.11.3), a membrane-associated zinc-dependent metallopeptidase of the M1 family, has recently been found to display high affinity for Ang IV and it was proposed to represent the AT4 receptor. We present evidence for the presence of endogenous cystinyl aminopeptidase in membranes from Chinese hamster ovary (CHO-K1) cells by binding studies with [125I]Ang IV and by measuring the cleavage of L-leucine-p-nitroanilide. The equilibrium dissociation constant of [125I]Ang IV in saturation binding studies (KD= 0.90 nM) was similar to the value (KD= 0.70 nM) calculated from the association and dissociation rates. Binding was displaced with high potency by the "AT4 receptor" ligands (Ang IV > divalinal1-Ang IV approximately LVV-hemorphin-7 approximately LVV-hemorphin-6 > Ang (3-7) > Ang III > Ang (4-8)) but not by AT1/AT2 receptor antagonists. Enzymatic activity in CHO-K1 cell membranes was competitively inhibited upto 94% by Ang IV and other "AT4 receptor" ligands (Ang IV > Ang III approximately divalinal1-Ang IV approximately Ang (3-7) approximately LVV-hemorphin-7 > Ang (4-8) approximately LVV-hemorphin-6). High affinity binding of [125I]Ang IV required the presence of metal chelators and the ligands such as Ang IV and LVV-hemorphin-7 displayed higher potency in the binding studies as in the enzyme assay. This difference in potency varied from one peptide to another. These pharmacological properties match those previously reported for the recombinantly-expressed human cystinyl aminopeptidase in embryonal kidney cells.