Edison Capp

The degree of cycle irregularity correlates with the grade of endocrine and metabolic disorders in PCOS patients

OBJECTIVE PCOS (polycystic ovarian syndrome) is a clinically heterogeneous endocrine disorder which affects up to 4-10% of women of reproductive age. A standardized definition is still difficult because of a huge variety of different phenotypes. The aim of this study was to evaluate possible correlations between the degree of cycle irregularity and the grade of endocrine and metabolic abnormalities. STUDY DESIGN A cross-sectional study was carried out. Hyperandrogenic and/or hirsute women with regular menstrual cycles and polycystic ovaries on ultrasound (PCOS eumenorr, n=45), PCOS patients with oligomenorrhea (PCOS oligo, n=42) and PCOS patients with amenorrhea (PCOS amenorr, n=31) were recruited from the Department of Gynecological Endocrinology and Reproductive Medicine of the Womens University Hospital Heidelberg (Heidelberg, Germany). RESULTS Normocyclic patients demonstrated significantly better metabolic parameters (BMI, fasting insulin, HOMA-IR) than patients with oligo/amenorrhea. Hormonal parameters (LH, FSH, FAI and testosterone) were significantly different between patients with different menstrual patterns and patients with regular cycles. CONCLUSION Determining the degree of cycle irregularity as a simple clinical parameter might be a valuable instrument to estimate the degree of metabolic and endocrine disorders. Emphasis should be given to those parameters as a first step to characterize PCOS patients with a risk of endocrine and metabolic disorders leading to consequent detailed examination.

Metformin modulates IL-8, IL-1β, ICAM and IGFBP-1 expression in human endometrial stromal cells.

To evaluate the effects of metformin on endometrial stromal cell gene expression and on the decidualization process, endometrial biopsies were collected from five healthy, regularly cycling women. Stromal cell culture was performed and decidualized with oestrogen/progesterone in the presence or absence of metformin and thereafter stimulated with insulin. The effect of metformin on decidualization was analysed by prolactin determination in the cell culture supernatant. Gene expression of insulin-like growth factor binding protein 1 (IGFBP-1), interleukin (IL) 8 and 1β and intercellular adhesion molecule (ICAM) was analysed by real-time PCR. Decidualization was significantly diminished in cells incubated with metformin (P<0.05) accompanied by a significant reduction of prolactin secretion in the supernatant (day 10: 2.2 fold, P<0.05; day 15: 3.1 fold, P<0.05). IGFBP-1 gene expression was reduced after long-term metformin exposure (7.7 fold, P<0.05). The negative effect of insulin on IL-8 (4.8 fold) and IL-1β (9.3 fold) gene expression was similarly found in cells incubated with metformin. As far as is known, this is the first demonstration of a change in endometrial gene and protein expression after in-vitro stimulation with metformin, including a diminished decidualization process and changes in genes relevant to implantation.

Transvaginal ultrasound ovarian diathermy: sheep as an experimental model

BackgroundSome techniques of transvaginal ovarian drilling have been previously described. Nevertheless a monopolar transvaginal ovarian cauterization, that use the expertise and safety of transvaginal puncture for oocyte captation seems to be an easier and feasible approach. The aim of this study was to develop a minimally invasive ovarian cauterization technique under transvaginal ultrasound control, and to evaluate the safety of the transvaginal ovarian monopolar cauterization, female sheep at reproductive age were used as an experimental model.FindingsAn experimental study was performed in a university research center. Seventeen female sheep (15 Corriedale e 2 Suffolk) in reproductive age were submitted to transvaginal ovarian cauterization with a monopolar Valleylab Force 2 electrocautery. Macroscopic and microscopic lesions were assessed. Ovarian size were 1.31 cm2 ± 0,43 (Corriedale) and 3.41 cm2 ± 0,64 (Suffolk). From 30 ovaries from Corriedale sheep punctured, only 3 were cauterized, presenting macroscopic and typical microscopic lesion. In the Suffolk sheep group, only one ovary was cauterized. No lesion could be found in the needle path.ConclusionsThis is the first experimental animal model described for ovarian cauterization needle guided by transvaginal ultrasound. The sheep does not seem to be the ideal animal model to study this technique. Another animal model, whose ovaries are better identified by transvaginal ultrasound should be sought for this technique, theoretically less invasive, before it could be offered safely to women with polycystic ovary syndrome.

Timing of ovarian stimulation in patients prior to gonadotoxic therapy: an analysis of 684 stimulations

OBJECTIVE Time to therapy initiation in patients requiring gonadotoxic therapy is crucial. This article evaluates the efficiency of random start ovarian stimulation in affected women. STUDY DESIGN Retrospective anonymous registry data analysis from 85 university and non-university fertility centres participating in the international network FertiPROTEKT. The study comprised 684 women undergoing ovarian stimulation for fertility preservation from 2007 to 2013. According to the time of stimulation initiation, days of ovarian stimulation, total dose of gonadotropins used, gonadotropin dose used per day, number of oocytes retrieved and incidence of ovarian hyperstimulation syndrome were analysed. Statistical analysis was performed using analysis of variance in case of continuous outcome variables and chi-square tests in case of categorical variables. RESULTS Among 684 women who underwent ovarian stimulation prior to gonadotoxic therapy 472 (69.0%) started ovarian stimulation between menstrual cycle day 1-5 (group A), 109 (15.9%) between day 6-14 (group B) and 103 (15.1%) after day 14 (group C). The days of stimulation (A: 10.8±2.4, B: 10.6±2.7, C: 11.5±2.2) and total dose of gonadotropins (A: 2496IU±980, B: 2529IU±940, C: 2970IU±1145) were significantly increased in group C. Numbers of obtained oocytes (Group A: 11.6±7.7, B: 13.9±9.1, C: 13.6±7.9) were significantly increased in group B and C, while the overall incidence of ovarian hyperstimulation syndrome III° was 0.15%. CONCLUSION The outcome of ovarian stimulation is similar after stimulation initiation during any phase of the menstrual cycles, supporting the concept of random-start ovarian stimulation before gonadotoxic therapy without disadvantage for the patient concerning later fertility preservation.

Risk factors for cardiovascular disease ten years after preeclampsia

CONTEXT AND OBJECTIVE Preeclampsia is a gestational disease that occurs mainly among nulliparous women after the 20th week of gestation, and frequently close to delivery. The effects of preeclampsia on womens blood pressure over the long term are still controversial. Patients with recurrent preeclampsia or preeclampsia in the early stages of pregnancy appear to present higher risk of hypertension. The aim of this study was to determine the risk factors for cardiovascular disease among women with preeclampsia 10 years earlier. DESIGN AND SETTING Cross-sectional study at Hospital de Clínicas de Porto Alegre (HCPA). METHODS Forty women with preeclampsia and 14 normotensive pregnant women followed up 10 or more years earlier at HCPA underwent clinical and laboratory examinations. Spearmans correlation coefficient was used to correlate body mass index (BMI) and systolic and diastolic pressures. The risk of developing hypertension was measured using the chi-square test. P < 0.05 was considered significant. RESULTS The patients with preeclampsia 10 or more years earlier had significantly higher diastolic blood pressure (P = 0.047), BMI (P = 0.019) and abdominal circumference (P = 0.026). They presented positive correlations between BMI and diastolic blood pressure (0.341; P = 0.031) and between BMI and systolic blood pressure (0.407; P = 0.009). CONCLUSION The patients with preeclampsia 10 or more years earlier had significantly higher diastolic blood pressure, BMI and abdominal circumference than did the control group. This emphasizes the importance of long-term follow-up assessment for cardiovascular risk factors among patients with preeclampsia.

Sexual Function in Women from Infertile Couples and in Women Seeking Surgical Sterilization

The purpose of this study was to compare sexual function between women of infertile couples (AR) and women seeking tubal ligation (TL). Women who attended Setor de Infertilidade do Serviço de Ginecologia e Obstetrícia do Hospital de Clinicas de Porto Alegre (HCPA) or the Serviço de Orientação e Planejamento Familiar (SERPLAN) completed the Female Sexual Function Index, a questionnaire about sexual activity in the last 4 weeks. Scored data were collected on six different domains: desire, arousal, lubrication, orgasm, satisfaction, and discomfort/pain. The greatest positive correlation in the TL group was between orgasm and sexual satisfaction (0.798), and in group AR between desire and arousal (0.627). Infertile women and fertile women who want to undergo surgical sterilization have similar sexual satisfaction scores.

Protein Expression of Estrogen Receptors α and β and Aromatase in Myometrium and Uterine Leiomyoma

Background: Leiomyomas are the most common tumors of the female reproductive tract and a major public health problem. The mechanism of tumorigenesis is unknown, but evidence suggests that estrogens regulate cell proliferation and myoma growth. This effect might be due to different amounts of estrogen receptors (ERα and ERβ) in normal and myoma tissues and overexpression of aromatase P450 in myomas. Purpose: To assess protein expression of ERs and aromatase in leiomyomas and normal adjacent myometrium of premenopausal women. Methods: Samples were collected from 12 premenopausal women admitted for abdominal hysterectomy due to fibroids. Results: The protein expression of ERα, ERβ and aromatase was similar in leiomyoma and normal myometrium (p = 0.239, p = 0.695 and p = 0.203, respectively). Conclusions: In this analysis of 12 matched leiomyoma and myometrial samples, the data do not support the theory that overexpression ERα, ERβ and aromatase in uterine leiomyomas compared to adjacent myometrium are the cause of tumor growth. The estrogens may exert their growth-stimulatory effects on leiomyomas intermediated by other elements, such as cytokines and growth or apoptosis factors. The effect of estrogen on the growth and development of fibroids is complex and far from being completely understood.

Insulin-Like Growth Factor 1 Receptor mRNA Expression and Autophosphorylation in Human Myometrium and Leiomyoma

Uterine leiomyomas are the most common tumors of the genital tract. Growth factors seem to be implicated in the development of leiomyoma. The aim of this study was to determine insulin-like growth factor 1 receptor (IGF-1-R) mRNA levels and IGF-1-R tyrosine kinase activity in normal myometrium and leiomyoma. Plasma membranes of myometrium and leiomyoma of 14 women subjected to hysterectomy were prepared, and samples were incubated in the absence or presence of recombinant human IGF-1 to assess the tyrosine kinase activity (Western blot). Reverse-transcriptase polymerase chain reaction with specific primers for IGF-1-R was used to determine IGF-1-R mRNA levels. IGF-1-R mRNA levels in myometrium (0.8216 ± 0.096) and in leiomyoma (0.7905 ± 0.136) were not statistically significantly different (p = 0.648). The degree of IGF-1-R autophosphorylation stimulated by recombinant IGF-1 was not different in myometrium (1.020 ± 0.120) and leiomyoma (1.620 ± 0.656) either (p = 0.075). There was no difference in IGF-1-R expression and IGF-1-R autophosphorylation between normal myometrium and leiomyoma.

Expression of glucose transporter 1 in human endometrial and decidual tissue

Regulation of endometrial glucose transport is important for the decidualization process. Therefore ,we have examined the expression of the glucose transporter protein isoform 1 (GLUT1) in endometrial samples during the menstrual cycle and in decidual tissue by immunohistochemistry ,and GLUT1 mRNA by RNase protection assays. GLUT1 protein was not detected in proliferative endometrial samples ,but was highly expressed in decidual tissue. Placental tissue was highly positive. GLUT1 mRNA could be detected in endometrial samples with an increase in endometria of the late secretory phase (day 25–28) and maximum concentration in the decidua of the 9th–10th week of gestation. Our results show that GLUT1 is differentially expressed in the different phases of the human endometrium with a maximum in the human decidua. Therefore ,GLUT1 may be an important marker for endometrial differentiation.

Biologia molecular do câncer cervical

Carcinogenesis involves several steps. Disorders of the cytogenetic balance occur during the evolution from normal epithelium to cervical cancer. Several studies support the hypothesis that the Human Papiloma Virus (HPV) infection is associated to development of premalignant and malignant lesions of cervical cancer. In this review we show the basis to understand cervical oncogenesis. The cell cycle is controlled by protooncogenes and supressive genes. This orchestrated cell cycle can be affected by virus such as HPV. Of special interest in the cervical carcinogenesis are the HPV subtypes 16 and 18. How HPV immortalizes cervical cells is not fully understood. Advances have been made in the application of molecular biology techniques in the understanding of this mechanism. Once established, these techniques will lead to a better assessment of cervical neoplasias and help the development of new therapies, hopefully less invasive and more effective.