A specific controlled ovarian stimulation (COS) protocol for fertility preservation in women with breast cancer undergoing neoadjuvant chemotherapy.

AIM OF THE STUDY: The authors present a novel and specific controlled ovarian stimulation protocol for fertility preservation in women with estrogen-positive receptor breast cancer undergoing neoadjuvant chemotherapy. The protocol foresees random start ovarian stimulation and the use of letrozole associated to tamoxifen. MATERIAL AND METHODS: Forty breast cancer patients were included in the study. COS was performed either with recombinant FSH or hMG. Concomitantly with COS, letrozole in a dose of 5 mg and tamoxifen in a dose of 20 mg were given orally on a daily basis. The trigger was performed with 0.2 mg of triptorelin, in the presence of follicles ≥ 19 mm. Oocyte retrieval was scheduled 35-36 hours after triptorelin injection. Our main outcome measures were the number of oocytes collected and number of oocytes vitrified, the length of ovarian stimulation, total dose of gonadotropins administered, and levels of estradiol on the day of the trigger. RESULTS: The mean age of patients was 30.43 ±4.25 years. Nineteen women commenced COS in the luteal phase, eleven in the early follicular phase and ten in the late follicular phase. The mean number of collected oocytes was 11.78 ±9.12 and the mean number of vitrified oocytes was 9.72 ±7.36. The mean duration of COS was 10.03 ±1.33 days. The mean estradiol concentrations on the triggering day was 623.10 ±441.27, and the mean dose of gonadotropins administered was 2540 ±713.10. CONCLUSIONS: The authors suggest that the protocol is efficient and may be a safe option for oocyte vitrification in these patients.

Cervicovaginal levels of proinflammatory cytokines are increased during chlamydial infection in bacterial vaginosis but not in lactobacilli-dominated flora.

OBJECTIVE: The purpose of this study was to assess the cervicovaginal levels of proinflammatory cytokines in women with Chlamydia trachomatis (CT) infection in the presence of bacterial vaginosis (BV) and normal flora and to compare with those negative for CT. MATERIALS AND METHODS: In this cross-sectional study, nonpregnant women were enrolled at 2 outpatient clinics and at 1 primary medical care unit in São Paulo State, Brazil. Cervicovaginal samples from 256 women with BV, of which 68 (26.6%) had concomitant CT infection and 188 (73.4%) were CT-negative, were measured for interleukin-1ß (IL-1ß), IL-6, and IL-8 by enzyme-linked immunosorbent assay. A matching number of samples from women with normal flora, CT-positive (n = 68) and negative (n = 188), were evaluated as control. Cytokine levels were compared by Mann-Whitney test and differences were considered significant at p < .05. RESULTS: In CT-negative women, IL-1ß was increased in BV (p < .001) when compared to normal flora, while the levels of IL-6 and IL8 were unchanged. The presence of CT infection was not associated with differences on cytokine levels in women with normal flora. However, women with BV had higher levels of IL-1ß (p = .02), IL-6 (p = .02), and IL-8 (p = .03) in the presence of CT when compared to those who tested negative for CT. CONCLUSIONS: Detection of endocervical CT is associated with increased cervicovaginal IL-1ß, IL-6, and IL-8 levels in women with concomitant BV but not in those with normal flora.

Efficacy of sperm motility after processing and incubation to predict pregnancy after intrauterine insemination in normospermic individuals.

BACKGROUND: Intrauterine insemination (IUI) is widely used to treat infertility, and its adequate indication is important to obtain good pregnancy rates. To assess which couples could benefit from IUI, this study aimed to evaluate whether sperm motility using a discontinuous gradient of different densities and incubation in CO2 in normospermic individuals is able to predict pregnancy. METHODS: A total of 175 couples underwent 175 IUI cycles. The inclusion criteria for women were as follows: 35 years old or younger (age range: from 27 to 35 years) with normal fallopian tubes; endometriosis grades I-II; unexplained infertility; nonhyperandrogenic ovulatory dysfunction. Men with normal seminal parameters were also included. All patients underwent ovarian stimulation with clomiphene citrate and human hMG or r-FSH. When one or (at most) three follicles measuring 18 to 20 mm were observed, hCG (5000 UI) or r-hCG (250 mcg) was administered and IUI performed 36-40 h after hCG. Sperm processing was performed using a discontinuous concentration gradient. A 20 microliters aliquot was incubated for 24 h at 37 degrees C in 5% CO2 following a total progressive motility analysis. The Mann-Whitney and Chi-square tests, as well as a ROC curve were used to determine the cutoff value for motility. RESULTS: Of the 175 couples, 52 (in 52 IUI cycles) achieved clinical pregnancies (CP rate per cycle: 29.7%). The analysis of age, duration and causes of infertility did not indicate any statistical significance between pregnancy and no pregnancy groups, similar to the results for total sperm count and morphology analyses, excluding progressive motility (p < 0.0001). The comparison of progressive motility after processing and 24 h after incubation between these two groups indicated that progressive motility 24 h after incubation was higher in the pregnancy group. The analysis of the progressive motility of the pregnancy group after processing and 24 h after incubation has not shown any motility difference at 24 h after incubation; additionally, in couples who did not obtain pregnancy, there was a statistically significant decrease in progressive motility 24 h after incubation (p < 0.0001). The ROC curve analysis generated a cutoff value of 56.5% for progressive motility at 24 h after incubation and this cutoff value produced 96.1% sensitivity, 92.7% specificity, 84.7% positive predictive value and 98.3% negative predictive value. CONCLUSIONS: We concluded that the sperm motility of normospermic individuals 24 h after incubation at 37 degrees C in 5% CO2, with a cutoff value of 56.5%, is predictive of IUI success.

Genetic polymorphisms associated with steroids metabolism and insulin action in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is an endocrinopathy associated with infertility, diabetes and cardiovascular events. This study aimed to correlate polymorphisms of genes involved in the biosynthesis and metabolism of steroids and insulin action (CYP17A1, CYP19A1, AR, ESR1, ESR2, INSR, IGF2 and PAI1) with clinical and biochemical parameters of PCOS. DNA was extracted from peripheral blood samples obtained from 117 PCOS and 105 healthy women. The PAI1 insertion/deletion (-675 ins/delG) polymorphism (rs1799768) was genotyped by PCR-SSCP. CYP19A1 [TTTA](n), AR [CAG](n), ESR1 [TA](n), and ESR2 [CA](n) genes were evaluated by PCR-based GeneScan analysis, while CYP17A1 5'UTR (rs743572), INSR 1058 CT (rs1799817), and IGF2 3'UTR GA (rs680) polymorphisms were evaluated by PCR-RFLP. The results showed a prevalence of PAI1 4G5G+4G4G genotypes in PCOS (p = 0.025). Younger PCOS women showed a predominance of CT+TT, GA+AA and 4G5G+4G4G genotypes of INSR, IGF2, and PAI1 (p = 0.0499, p = 0.0300, p = 0.0350, respectively). AR shorter alleles (≤ 20 repeats) were significantly associated with higher serum levels of total testosterone (TT, p = 0.0086). In conclusion, PAI1 polymorphism seems to be associated with the risk of PCOS development. Younger PCOS women had specific genotypes of INSR, IGF2 and PAI1 genes. AR shorter alleles can be associated with higher serum levels of TT in PCOS patients.

Evaluation of N-acetilglucosaminidase and myeloperoxidase activity in patients with endometriosis-related infertility undergoing intracytoplasmic sperm injection.

AIM: Inflammation is as an important factor in ovulation with the active participation of leucocytes and their inflammatory mediators. The present study was performed to compare the activity of the inflammatory enzymes myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) in patients with endometriosis-related infertility and in normally ovulating women undergoing intracytoplasmic sperm injection (ICSI). MATERIAL AND METHODS: This prospective study included infertile women undergoing ICSI treatment. These women were divided into two groups: endometriosis anovulation (n = 18) and normally ovulating (n = 20). NAG and MPO activity was evaluated colorimetrically in serum and in follicular fluids obtained at the time of oocyte retrieval. RESULTS: There was a significant correlation between the serum and follicular fluid activities of NAG and MPO (τ = 0.256, P = 0.025; and τ = -0.234, P = 0.041; respectively). Both serum and follicular fluid NAG activities were higher in patients with endometriosis compared to the control group (P < 0.001). MPO follicular fluid activity was lower in patients with endometriosis compared to normally ovulating women (P = 0.016). CONCLUSION: Infertile patients with endometriosis show a distinct pattern of serum and follicular fluid macrophage/neutrophil activation compared to normally ovulating women undergoing ICSI, which may reflect the role of immune and inflammatory alterations in endometriosis-related infertility.

Single-embryo transfer reduces clinical pregnancy rates and live births in fresh IVF and Intracytoplasmic Sperm Injection (ICSI) cycles: a meta-analysis.

BACKGROUND: It has become an accepted procedure to transfer more than one embryo to the patient to achieve acceptable ongoing pregnancy rates. However, transfers of more than a single embryo increase the probability of establishing a multiple gestation. Single-embryo transfer can minimize twin pregnancies but may also lower live birth rates. This meta-analysis aimed to compare current data on single-embryo versus double-embryo transfer in fresh IVF/ICSI cycles with respect to implantation, ongoing pregnancy and live birth rates. METHODS: Search strategies included on-line surveys of databases from 1995 to 2008. Data management and analysis were conducted using the Stats Direct statistical software. The fixed-effect model was used for odds ratio (OR). Fixed-effect effectiveness was evaluated by the Mantel Haenszel method. Seven trials fulfilled the inclusion criteria. RESULTS: When pooling results under the fixed-effect model, the implantation rate was not significantly different between double-embryo transfer (34.5%) and single-embryo transfer group (34.7%) (P = 0.96; OR = 0.99, 95% CI 0.78, 1.25). On the other hand, double-embryo transfer produced a statistically significantly higher ongoing clinical pregnancy rate (44.5%) than single-embryo transfer (28.3%) (P < 0.0001; OR:2.06, 95% CI = 1.64,2.60). At the same time, pooling results presented a significantly higher live birth rate when double-embryo transfer (42.5%) (P < 0.001; OR: 1.87, 95% CI = 1.44,2.42) was compared with single-embryo transfer (28.4%). CONCLUSION: Meta-analysis with 95% confidence showed that, despite similar implantation rates, fresh double-embryo transfer had a 1.64 to 2.60 times greater ongoing pregnancy rate and 1.44 to 2.42 times greater live birth rate than single-embryo transfer in a population suitable for ART treatment.

Atendendo mulheres com cariótipo 46, XY / Attending women with 46, XY karyotype

As diferenças ou distúrbios do desenvolvimento sexual (DDS) compreendem um grupo heterogêneo de condições congênitas que resultam na discordância entre os cromossomos sexuais, as gônadas e/ou o sexo anatômico de um indivíduo. A classificação desses distúrbios é baseada no cariótipo conforme o Consenso de Chicago de 2006 e substitui os termos pseudo-hermafroditismo, hermafroditismo e intersexo. O objetivo desta revisão é fornecer ao ginecologista conhecimentos básicos sobre a etiologia, fisiopatologia e orientações das principais anormalidades de DDS para uma avaliação diagnóstica e terapêutica no atendimento de mulheres na infância, adolescência e em idade adulta com cariótipo 46,XY. O diagnóstico deve ser realizado pela interação entre o exame clínico as dosagens hormonais, os exames de imagem e a análise genética, desde o cariótipo até o estudo de alterações dos genes por técnicas de biologia molecular. O tratamento é realizado de acordo com a etiologia e inclui intervenções cirúrgicas como a gonadectomia e plásticas sobre a genitália externa, terapia de reposição hormonal e apoio psicológico. São necessárias a individualização dos casos e uma equipe interdisciplinar, para um atendimento adequado às mulheres com cariótipo 46,XY.(AU)

Differences or disorders of sexual development (DSDs) comprise a heterogeneous group of congenital conditions that result in the disagreement between an individual's sex chromosomes, gonads and/or anatomic sex. The classification of these disorders is based on the karyotype according to the 2006 Chicago Consensus and replaces the terms pseudohermaphroditism, hermaphroditism and intersex. The aim of this review is to provide the gynecologist with basic knowledge about the etiology, pathophysiology and guidelines of the main abnormalities of DDS for a diagnostic and therapeutic evaluation in the care of women in childhood, adolescence and adulthood with a karyotype 46,XY. The diagnosis must be made by the interaction between clinical examination hormonal measurements, imaging and genetic analysis from the karyotype to the study of gene alterations by molecular biology techniques. Treatment is carried out according to the etiology and includes surgical interventions such as gonadectomy and plastic surgery on the external genitalia, hormone replacement therapy and psychological support. Individualization of cases and an interdisciplinary team are required to provide adequate care for women 46,XY karyotype.(AU)

Efficacy of hormone therapy with and without methyltestosterone augmentation of venlafaxine in the treatment of postmenopausal depression: a double-blind controlled pilot study.

OBJECTIVE: This study evaluated the augmentation of venlafaxine with hormone therapy in the treatment of postmenopausal depression. The hormones evaluated were estrogen (0.625 mg) in combination with medroxyprogesterone acetate (2.5 mg) and methyltestosterone (2.5 mg). DESIGN: Seventy-two menopausal women (mean age: 53.6 +/- 4.27 years) diagnosed with depression (Montgomery-Asberg Depression Rating Scale [MADRS] scores > or = 20) were treated with venlafaxine and one of the following hormone therapy combinations, in a double-blind regimen: estrogen + medroxyprogesterone + methyltestosterone (group 1, n = 20); estrogen + medroxyprogesterone acetate (group 2, n = 20); methyltestosterone only (group 3, n = 16); and no hormone therapy (group 4, n = 16). Study duration was 24 weeks. Primary efficacy outcome was remission according to the MADRS, whereas secondary efficacy measures included the Clinical Global Impression (CGI), Blatt-Kupperman Index, and Women's Health Questionnaire (WHQ). RESULTS: Forty-eight patients completed the study. All groups showed significant improvement from baseline. Group 3 demonstrated significant improvement on the MADRS compared with placebo (group 4) at weeks 20 (P = 0.048) and 24 (P = 0.030); effect size 8.04 (0.83; 15.26) (P = 0.029), but also had the highest dropout rate. Groups 1 and 3 had significant CGI improvement rates compared with placebo: 42.23% (P = 0.012) and 44.45% (P = 0.08), respectively. There were no differences in the WHQ or BKI scores among the groups. CONCLUSIONS: Methyltestosterone 2.5 mg had the highest effect size compared with placebo, but the high dropout rate prevented its efficacy from being determined. Estrogen plus medroxyprogesterone, combined with methyltestosterone or otherwise, demonstrated a trend toward increased efficacy of venlafaxine. Further larger-scale clinical trials are needed to elucidate the findings of this pilot study.

Independent clonal origin of multiple uterine leiomyomas that was determined by X chromosome inactivation and microsatellite analysis.

OBJECTIVE: In an attempt to clarify the clonality and genetic relationships that are involved in the tumorigenesis of uterine leiomyomas, we used a total of 43 multiple leiomyomas from 14 patients and analyzed the allelic status with 15 microsatellite markers and X chromosome inactivation analysis. STUDY DESIGN: We have used a set of 15 microsatellite polymorphism markers mapped on 3q, 7p, 11, and 15q by automated analysis. The X chromosome inactivation was evaluated by the methylation status of the X-linked androgen receptor gene. RESULTS: Loss of heterozygosity analysis showed a different pattern in 7 of the 8 cases with allelic loss for at least 1 of 15 microsatellite markers that were analyzed. A similar loss of heterozygosity findings at 7p22-15 was detected in 3 samples from the same patient. X chromosome inactivation analysis demonstrated the same inactivated allele in all tumors of the 9 of 12 informative patients; different inactivation patterns were observed in 3 cases. CONCLUSION: Our data support the concept that uterine leiomyomas are derived from a single cell but are generated independently in the uterus. Loss of heterozygosity findings at 7p22-15 are consistent with previous data that suggested the relevance of chromosomal aberrations at 7p that were involved in individual uterine leiomyomas.

Benefits of soy germ isoflavones in postmenopausal women with contraindication for conventional hormone replacement therapy.

OBJECTIVE: To evaluate the effects of isoflavones on vasomotor symptoms and blood lipids in postmenopausal women with contraindication for conventional hormone replacement therapy (HRT). METHODS: This prospective, double-blind and placebo-controlled study included 50 postmenopausal women randomly divided into two groups: 25 women on soy germ isoflavones (60 mg per day, capsules) and 25 women on placebo. Inclusion criteria included: non-vegetarian, non-asian women whose last menstruation dated at least 12 months prior to the beginning of the study, with FSH > 40 mIU/ml, hot flushes and contraindication for HRT, not using tamoxifen or antibiotic and no disease of the gastrointestinal tract. For 6 months, the Kupperman menopausal index (KMI), the vaginal cytological maturation value (MV) and both hormonal and lipid profiles were assessed. The t-test and analysis of variance (ANOVA) were employed to compare the two groups. RESULTS: In both groups, a decreased KI rate was observed. However, isoflavone was significantly superior to placebo in reducing hot flushes (44% versus 10%, respectively) (P < 0.05). After 6 months, the isoflavone group showed increased estradiol levels with unchanged FSH, LH, and vaginal cytology, and a reduction of 11.8% in LDL and an increase of 27.3% in HDL (P < 0.05 ). In the placebo group, just a reduction in MV was observed after 6 months (P < 0.05 ). CONCLUSIONS: Soy germ isoflavone exerted favorable effects on vasomotor symptoms and lipid profile, showing itself to be an interesting alternative therapy for the postmenopausal women with contraindication for conventional HRT.

[Contribution of hyperandrogenism to the development of metabolic syndrome in obese women with polycystic ovary syndrome]. / Contribuição do hiperandrogenismo para o desenvolvimento de síndrome metabólica em mulheres obesas com síndrome dos ovários policísticos.

PURPOSE: To assess the contribution of hyperandrogenism to the development of metabolic syndrome (MetS) in obese women with polycystic ovary syndrome (PCOS). METHODS: Retrospective cross-sectional study conducted on 60 obese women with classic PCOS phenotype - Rotterdam Consensus - and 70 non-PCOS obese women. MetS was diagnosed by the NCEP-ATP III criteria and obesity was defined by body mass index. The Ferriman-Gallwey score (mFG) was used to evaluate hirsutism. The following measurements were performed: total testosterone, dehydroepiandrosterone sulfate (DHEA-S), glucose and insulin, total cholesterol, HDL, and triglycerides. Insulin resistance was measured using the HOMA-IR and insulin sensitivity index of Matsuda and De Fronzo (ISI). Statistical analysis was performed using the Student's t-test, χ² test and multivariate logistic regression analysis (p<0.05). RESULTS: Obese women with PCOS had significantly higher mFG (15.4 ± 6.1), waist circunference (105.6 ± 11.4 cm), DHEA-S (200.8 ± 109.2 µg/dL), testosterone (135.8 ± 71.4 ng/dL), and HOMA-IR (8.4 ± 8.5) values and lower ISI values (2.0 ± 1.8) than non-obese PCOS women (3.2 ± 2.1; 101.4 ± 9.2 cm; 155.0 ± 92.7 µg/dL; 50.0 ± 18.2 ng/dL; 5.1 ± 4.7 and 3.3 ± 2.7, respectively) (p<0.05). The frequency of MetS was higher in PCOS obese (75%) than non-PCOS obese (52.8%) women (p=0.015). Multivariate analysis did not reveal the contribution of the variables IFG, testosterone, and DHEAS to the development of MetS (p>0.05). CONCLUSION: Obese women with PCOS have a higher frequency of metabolic syndrome than non-PCOS obese women, and hyperandrogenism does not contribute to the development of metabolic syndrome in this group of women.

[Clinical manifestations, biochemical, ultrasonographic and metabolic of polycystic ovary syndrome in adolescents]. / Manifestações clínicas, bioquímicas, ultrassonográficas e metabólicas da síndrome dos ovários policísticos em adolescentes.

PURPOSE: To evaluate the clinical, ultrasonographic, biochemical and metabolic alterations of adolescents with polycystic ovary syndrome (PCOS). METHODS: Retrospective observational study conducted on 44 adolescents aged 12 to 19 years, diagnosed with PCOS according to the Rotterdam Consensus. Metabolic changes were assessed according to the recommendations of the International Diabetes Federation, considering: waist circumference (WC) >90th percentile (10-15 years of age) or >80 cm (age >16 years), fasting glucose >100 mg/dL, triglycerides >150 mg/dL, HDL <40 mg/dL, and blood pressure >Hg 130/85 mm. RESULTS: Mean age was 16.7 ± 2.2 years and age at menarche was 11.8 ± 1.4 years. The menstrual irregularity most frequently observed was amenorrhea (72.7%) followed by oligomenorrhea (27.3%); hirsutism was observed in 86.4% and acne in 56.8%. Polycystic ovaries were observed by ultrasound only in 27.3%. Mean BMI was 30.3 ± 6.6 kg/m². According to BMI, 52.3% of adolescents were obese, 13.6% were overweight and 6.8% had a healthy weight. Increased waist circumference (63.6%, 28/44) and the reduction of HDL-C (34.1%, 15/44) were the metabolic changes most frequently observed. Increased triglycerides were observed in 27.3% (12/44) and increased blood pressure and impaired fasting glucose were found in 9.1% (4/44) and 4.5% (2/44) of cases, respectively. Acanthosis nigricans was observed in 52.3% and insulin resistance in 62.8% of the adolescents with PCOS. Metabolic syndrome was identified in six children (13.6%), all of them obese or overweight. CONCLUSION: In the adolescents with PCOS studied here, menstrual irregularity and hirsutism were the most common clinical manifestations, while the sonographic findings consistent with polycystic ovaries were less prevalent. Obesity associated with insulin resistance predisposes these adolescents to a higher frequency of metabolic disorders.

An integrative genomic and transcriptomic analysis reveals potential targets associated with cell proliferation in uterine leiomyomas.

BACKGROUND: Uterine Leiomyomas (ULs) are the most common benign tumours affecting women of reproductive age. ULs represent a major problem in public health, as they are the main indication for hysterectomy. Approximately 40-50% of ULs have non-random cytogenetic abnormalities, and half of ULs may have copy number alterations (CNAs). Gene expression microarrays studies have demonstrated that cell proliferation genes act in response to growth factors and steroids. However, only a few genes mapping to CNAs regions were found to be associated with ULs. METHODOLOGY: We applied an integrative analysis using genomic and transcriptomic data to identify the pathways and molecular markers associated with ULs. Fifty-one fresh frozen specimens were evaluated by array CGH (JISTIC) and gene expression microarrays (SAM). The CONEXIC algorithm was applied to integrate the data. PRINCIPAL FINDINGS: The integrated analysis identified the top 30 significant genes (P<0.01), which comprised genes associated with cancer, whereas the protein-protein interaction analysis indicated a strong association between FANCA and BRCA1. Functional in silico analysis revealed target molecules for drugs involved in cell proliferation, including FGFR1 and IGFBP5. Transcriptional and protein analyses showed that FGFR1 (P = 0.006 and P<0.01, respectively) and IGFBP5 (P = 0.0002 and P = 0.006, respectively) were up-regulated in the tumours when compared with the adjacent normal myometrium. CONCLUSIONS: The integrative genomic and transcriptomic approach indicated that FGFR1 and IGFBP5 amplification, as well as the consequent up-regulation of the protein products, plays an important role in the aetiology of ULs and thus provides data for potential drug therapies development to target genes associated with cellular proliferation in ULs.

[Sonohysterography accuracy versus transvaginal ultrasound in infertile women candidate to assisted reproduction techniques]. / Acurácia da histerossonografia versus ultrassonografia transvaginal em mulheres inférteis candidatas às técnicas de reprodução assistida.

PURPOSE: To compare the diagnostic accuracy of sonohysterography (HSN) and conventional transvaginal ultrasound (USG) in assessing the uterine cavity of infertile women candidate to assisted reproduction techniques (ART). METHODS: Comparative cross-sectional study with 120 infertile women candidate to ART, assisted at Centro de Reprodução Assistida (CRA) of Hospital Regional da Asa Sul (HRAS), Brasília - DF, from August 2009 to November 2010. Sonohysterography was performed with saline solution infusion in a close system. The sonohysterography finding was compared to previous USG results. The uterine cavity was considered abnormal when the endometrium was found to be thicker than expected during the menstrual cycle and when an endometrial polyp, a submucous myoma and an abnormal shape of the uterine cavity were observed. The statistical analysis was done using absolute frequencies, percentage values and the χ², with the level of significance set at 5%. RESULTS: HSN revealed that 92 (76.7%) infertile women candidate to ART had a normal uterine cavity, while 28 (23.3%) had the following abnormalities: 15 polyps (12.5%), 9 cases of abnormal shape of the uterine cavity (7.5%), 6 submucous myomas (5%), 4 cases of inadequate endometrial thickness for the menstrual cycle phase (3.3%), and 2 cases of uterine septum (1.7%); 5 women presented more than one abnormality (4.2%). While USG showed alteration in the cavity only in 5 (4.2%) women, the sonohysterography confirmed 4 out of the 5 abnormalities shown by USG and detected an abnormal uterine cavity in 24 other women, who had not been detected by USG. This means that sonohysterography was able to detect more abnormalities in the uterine cavity than USG, with a statistically significant difference (p=0.002). CONCLUSION: The sonohysterography was more accurate than USG in the assessment of the uterine cavity of this cohort of infertile women candidate to ART. The sonohysterography can be easily incorporated into the investigation of these women and contribute to reducing embryo implantation failures.

Inflammatory response patterns in ICSI patients: a comparative study between chronic anovulating and normally ovulating women.

The aim of this study was to evaluate inflammatory response in chronic anovulating infertility women undergoing intracytoplasmic sperm injection. Thirteen infertile women with chronic anovulation and 23 normally ovulating women were prospectively evaluated. N-acetylglucosaminidase (NAG), myeloperoxidase (MPO), monocyte chemoattractant protein 1 (MCP-1), and C-reactive protein (CRP) concentrations were evaluated in serum and follicular fluid. Women with chronic anovulation presented higher NAG and MPO activity in follicular fluid when compared with normally ovulating women. Serum MPO activity was higher in the control group compared to the chronic anovulation group. Both serum and follicular fluid CRP concentrations were higher in women with chronic anovulation in comparison with the control group. Higher MCP-1 follicular fluid concentrations and serum levels of CRP were associated with the occurrence of ovarian hyperstimulation syndrome. Patients with chronic anovulation exhibited significantly higher follicle macrophage/neutrophil activation as well as unspecific inflammatory response by comparison with normally ovulating women.

[The importance of oral glucose tolerance test in diagnosis of glucose intolerance and type 2 diabetes mellitus in women with polycystic ovary syndrome]. / A importância do teste de tolerância à glicose oral no diagnóstico da intolerância à glicose e diabetes mellitus do tipo 2 em mulheres com síndrome dos ovários policísticos.

PURPOSE: To evaluate the importance of the oral glucose tolerance test for the diagnosis of glucose intolerance (GI) and type 2 diabetes mellitus (DM-2) in women with PCOS. METHODS: A retrospective study was conducted on 247 patients with PCOS selected at random. The diagnosis of GI was obtained from the two-hour oral glucose tolerance test with 75 g of glucose according to the criteria of the World Health Organization (WHO) (GI: 120 minutes for plasma glucose >140 mg/dL and <200 mg/dL), and the diagnosis of DM-2 was obtained by both the oral glucose tolerance test (DM: 120 minutes for plasma glucose >200 mg/dL) and fasting glucose using the criteria of the American Diabetes Association (impaired fasting glucose: fasting plasma glucose >100 and <126 mg/dL; DM: fasting glucose >126 mg/dL). A logistic regression model for repeated measures was applied to compare the oral glucose tolerance test with fasting plasma glucose. ANOVA followed by the Tukey test was used for the analysis of the clinical and biochemical characteristics of patients with and without GI and/or DM-2. A p<0.05 was considered statistically significant. RESULTS: PCOS patients had a mean age of 24.8±6.3, and body mass index (BMI) of 18.3 to 54.9 kg/m² (32.5±7.6). The percentage of obese patients was 64%, the percentage of overweight patients was 18.6% and 17.4% had healthy weight. The oral glucose tolerance test identified 14 cases of DM-2 (5.7%), while fasting glucose detected only three cases (1.2%), and the frequency of these disorders was higher with increasing age and BMI. CONCLUSIONS: The results of this study demonstrate the superiority of the oral glucose tolerance test in relation to fasting glucose in diagnosing DM-2 in young women with PCOS and should be performed in these patients.

[Insulin resistance in women with polycystic ovary syndrome: relationship with anthropometric and biochemical variables]. / Resistência à insulina em mulheres com síndrome dos ovários policísticos: relação com as variáveis antropométricas e bioquímicas.

PURPOSE: To analyze the prevalence of insulin resistance, according to different biochemical and anthropometric measurements in women with polycystic ovary syndrome. METHODS: A total of 189 patients with polycystic ovary syndrome were retrospectively analyzed. Insulin resistance diagnosis was performed using fasting insulin, HOMA-IR, QUICKI, insulin sensibility index and glucose/fasting insulin ratio. Body mass index and lipid accumulation product were used. Data were analyzed statistically by descriptive statistics, ANOVA, Tukey post-test, and Pearson's correlation. RESULTS: The polycystic ovary syndrome patients had a mean age of 24.9 ± 5.2 and a mean body mass index of 31.8 ± 7.6. The percentage of obese patients was 57.14%. Among the methods of insulin resistance investigation, the insulin sensibility index was the technique that most detected (56.4%) the presence of insulin resistance in women with polycystic ovary syndrome. The insulin resistance was detected in 87% of obese patients. The fasting glucose/fasting insulin ratio and insulin sensibility index were strongly correlated with lipid accumulation product. CONCLUSION: The prevalence of insulin resistance varied according to the method used, and it was greater the higher the body mass index. Lipid accumulation product was also related to insulin resistance.

Manifestações clínicas, bioquímicas, ultrassonográficas e metabólicas da síndrome dos ovários policísticos em adolescentes / Clinical manifestations, biochemical, ultrasonographic and metabolic of polycystic ovary syndrome in adolescents

OBJETIVO: Avaliar os parâmetros clínicos, ultrassonográficos, bioquímicos e as alterações metabólicas em adolescentes com síndrome dos ovários policísticos (SOP). MÉTODOS: Estudo retrospectivo realizado com 44 adolescentes entre 12 e 19 anos, com diagnóstico de SOP pelo Consenso de Rotterdam. As alterações metabólicas foram avaliadas de acordo com as recomendações da Federação Internacional de Diabetes, sendo consideradas: circunferência da cintura (CC) >percentil 90 (10-15 anos de idade) ou >80 cm (idade >16 anos); glicemia de jejum >100 mg/dL; triglicerídios >150 mg/dL; HDL <40 mg/dL, e pressão arterial >Hg 130/85 mm. RESULTADOS: A média de idade foi de 16,7±2,2 anos e da idade da menarca 11,8±1,4 anos. A irregularidade menstrual mais observada foi amenorreia (72,7%) seguida de oligomenorréia (27,3%); hirsutismo foi observado em 86,4% e acne em 56,8%. Ovários policisticos ao ultrassom observados apenas em 27,3%. A média do IMC foi de 30,3±6,6 kg/m². De acordo com o IMC, 52,3% das adolescentes eram obesas, 13,6% estavam com sobrepeso e 6,8% eram eutróficas. O aumento da circunferência da cintura (63,6%, 28/44) e a redução do HDL-C (34,1%, 15/44) foram as alterações metabólicas mais observadas. Triglicerídios aumentados foram observados em 27,3% (12/44), pressão arterial e aumento da glicemia de jejum alterada foram encontrados em 9,1% (4/44) e 4,5% (2/44) dos casos, respectivamente. Acantosis nigricans foi observada em 52,3% das adolescentes com SOP e a resistência insulinica encontrada em 62,8%. A sindrome metabólica foi identificada em seis adolescentes (13,6%), sendo todas obesas ou com sobrepeso. CONCLUSÃO: Entre as adolescentes com SOP do estudo, a irregularidade menstrual e o hirsutismo são as manifestações clínicas mais frequentes, enquanto os achados ultrassonográficos compatíveis com ovários policísticos são os menos prevalentes. A obesidade associada à resistência à insulina predispõe estas adolescentes à maior frequência de alterações metabólicas.

PURPOSE: To evaluate the clinical, ultrasonographic, biochemical and metabolic alterations of adolescents with polycystic ovary syndrome (PCOS). METHODS: Retrospective observational study conducted on 44 adolescents aged 12 to 19 years, diagnosed with PCOS according to the Rotterdam Consensus. Metabolic changes were assessed according to the recommendations of the International Diabetes Federation, considering: waist circumference (WC) >90th percentile (10-15 years of age) or >80 cm (age >16 years), fasting glucose >100 mg/dL, triglycerides >150 mg/dL, HDL <40 mg/dL, and blood pressure >Hg 130/85 mm. RESULTS: Mean age was 16.7±2.2 years and age at menarche was 11.8±1.4 years. The menstrual irregularity most frequently observed was amenorrhea (72.7%) followed by oligomenorrhea (27.3%); hirsutism was observed in 86.4% and acne in 56.8%. Polycystic ovaries were observed by ultrasound only in 27.3%. Mean BMI was 30.3±6.6 kg/m². According to BMI, 52.3% of adolescents were obese, 13.6% were overweight and 6.8% had a healthy weight. Increased waist circumference (63.6%, 28/44) and the reduction of HDL-C (34.1%, 15/44) were the metabolic changes most frequently observed. Increased triglycerides were observed in 27.3% (12/44) and increased blood pressure and impaired fasting glucose were found in 9.1% (4/44) and 4.5% (2/44) of cases, respectively. Acanthosis nigricans was observed in 52.3% and insulin resistance in 62.8% of the adolescents with PCOS. Metabolic syndrome was identified in six children (13.6%), all of them obese or overweight. CONCLUSION: In the adolescents with PCOS studied here, menstrual irregularity and hirsutism were the most common clinical manifestations, while the sonographic findings consistent with polycystic ovaries were less prevalent. Obesity associated with insulin resistance predisposes these adolescents to a higher frequency of metabolic disorders.

Contribuição do hiperandrogenismo para o desenvolvimento de síndrome metabólica em mulheres obesas com síndrome dos ovários policísticos / Contribution of hyperandrogenism to the development of metabolic syndrome in obese women with polycystic ovary syndrome

OBJETIVO: Avaliar a contribuição do hiperandrogenismo para o desenvolvimento da síndrome metabólica (SM) em mulheres obesas com ou sem Síndrome dos Ovários Policísticos (SOP). MÉTODOS: Estudo transversal retrospectivo no qual foram incluídas 60 mulheres obesas com fenótipo clássico da SOP - Consenso de Rotterdam - e 70 obesas sem SOP. A SM foi diagnosticada pelos critérios do NCEP-ATP III. A obesidade foi definida pelo índice de massa corpórea e o hirsutismo, pelo Índice de Ferriman-Gallwey (IFG). As dosagens realizadas foram: testosterona total, sulfato de dehidroepiandrosterona (SDHEA), insulina e glicose, colesterol total, HDL e triglicerídios. A resistência insulínica (RI) foi avaliada pelo HOMA-IR e pelo índice de sensibilidade à insulina de Matsuda e De Fronzo. A analise estatística foi realizada com o teste t de Student, teste do χ² e análise de regressão logística multivariada (p<0,05). RESULTADOS: As obesas com SOP apresentaram significativamente maiores valores de IFG (15,4±6,1), circunferência da cintura (105,6±11,4 cm), testosterona (135,8±71,4 ng/dL), SDHEA (200,8±109,2 µg/dL), HOMA-IR (8,4±8,5) e menores valores de ISI (2,0±1,8) quando comparadas às obesas não SOP (3,2±2,1; 101,4±9,2 cm; 50,0±18,2 ng/dL; 155,0±92,7 µg/dL; 5,1±4,7; 3,3±2,7, respectivamente) (p<0,05). A frequência de SM foi significativamente maior nas obesas com SOP (75%) do que nas obesas não SOP (52,8%) (p=0,01). A análise multivariada não demonstrou contribuição das variávies IFG, testoterona total e SDHEA para o desenvolvimento da SM (p>0,05). CONCLUSÃO: Mulheres obesas com SOP apresentam maior frequência de SM quando comparadas às obesas não SOP. O hiperandrogenismo não mostrou influência nesse grupo de mulheres estudadas.

PURPOSE: To assess the contribution of hyperandrogenism to the development of metabolic syndrome (MetS) in obese women with polycystic ovary syndrome (PCOS). METHODS: Retrospective cross-sectional study conducted on 60 obese women with classic PCOS phenotype - Rotterdam Consensus - and 70 non-PCOS obese women. MetS was diagnosed by the NCEP-ATP III criteria and obesity was defined by body mass index. The Ferriman-Gallwey score (mFG) was used to evaluate hirsutism. The following measurements were performed: total testosterone, dehydroepiandrosterone sulfate (DHEA-S), glucose and insulin, total cholesterol, HDL, and triglycerides. Insulin resistance was measured using the HOMA-IR and insulin sensitivity index of Matsuda and De Fronzo (ISI). Statistical analysis was performed using the Student's t-test, χ² test and multivariate logistic regression analysis (p<0.05). RESULTS: Obese women with PCOS had significantly higher mFG (15.4±6.1), waist circunference (105.6±11.4 cm), DHEA-S (200.8±109.2 µg/dL), testosterone (135.8±71.4 ng/dL), and HOMA-IR (8.4±8.5) values and lower ISI values (2.0±1.8) than non-obese PCOS women (3.2±2.1; 101.4±9.2 cm; 155.0±92.7 µg/dL; 50.0±18.2 ng/dL; 5.1±4.7 and 3.3±2.7, respectively) (p<0.05). The frequency of MetS was higher in PCOS obese (75%) than non-PCOS obese (52.8%) women (p=0.015). Multivariate analysis did not reveal the contribution of the variables IFG, testosterone, and DHEAS to the development of MetS (p>0.05). CONCLUSION: Obese women with PCOS have a higher frequency of metabolic syndrome than non-PCOS obese women, and hyperandrogenism does not contribute to the development of metabolic syndrome in this group of women.

Polymorphisms of CYP17A1, CYP19, and androgen in Brazilian women with uterine leiomyomas.

BACKGROUND: Uterine leiomyomas are common, benign, smooth muscle tumors representing a significant public health problem. The aim of this study was to investigate CYP17A1, CYP19, and androgen (AR) polymorphisms, their relative risks for uterine leiomyomas and possible associations with clinical parameters. METHODS: Uterine leiomyoma tissues and blood samples were obtained from 87 patients, as were peripheral blood samples from 68 control women. Clinical data were recorded in both groups. The CYP17A1 (rs743572) polymorphism was analyzed by PCR-RFLP, and the CYP19 [TTTA](n) repeat and AR [CAG](n) repeat were analyzed using PCR-based GeneScan analysis. AR loss of heterozygosity (LOH) and microsatellite instability were also evaluated, while samples exhibiting LOH were analyzed for X inactivation. RESULTS: Clinical parameters related to disease development did not differ between cases and controls. CYP17A1 A2/A2 genotype was prevalent in non-white women. CYP17A1, CYP19, and AR genotypes and alleles did not differ between groups. However, alleles presenting [TTTA](7) repeats in intron 4 of CYP19 were more frequent in the control group (p=0.0550). Shorter and longer [CAG](n) repeat alleles of AR were exclusive to the leiomyoma group. The LOH assay showed allele losses at AR locus in four informative tumors and X chromosome inactivation analysis revealed that these tumors retained the active allele. CONCLUSIONS: The overall lack of association between uterine leiomyomas with polymorphisms involved in steroidogenesis or steroid metabolism is consistent with the hypothesis that these polymorphisms do not substantially contribute to the development of these tumors.