Anderson Sanches de Melo

High prevalence of polycystic ovary syndrome in women born small for gestational age

BACKGROUND There is evidence that intrauterine growth restriction, resulting in newborn girls that are small for gestational age (SGA), may be related to the onset of polycystic ovary syndrome (PCOS). Thus, we studied whether women born SGA have a higher prevalence of PCOS than women born appropriate for gestational age (AGA). METHODS This was a prospective birth cohort study of 384 women born at term between June 1, 1978, and May 31, 1979, in Ribeirão Preto, Brazil. After exclusion, 165 women effectively participated in this study, of whom 43 were SGA and 122 were AGA. The prevalence of PCOS was analysed. At a mean age of 29 years, the women agreed to follow the study protocol, which included: anamnesis, physical examination, serum tests [follicle stimulating hormone, luteinizing hormone, total and free testosterone, dehydroepiandrostenedione sulphate, 17-OH-progesterone, fasting insulin, sex steroid-binding globulin (SHBG) and fasting glucose] and pelvic ultrasound. Data regarding gestational age, birthweight, age at menarche and maternal data were obtained from the files of the cohort. The adjusted relative risk (RR) values of the SGA, insulin resistance, body mass index, maternal smoking and parity variables were analysed using Poisson regression with robust adjustment of variance for the prediction of PCOS. RESULTS The prevalence of PCOS was higher in the SGA group than in the AGA group [adjusted RR = 2.44, 95% CI (1.39-4.28)]. Hyperandrogenism was more prevalent in the SGA women than in the AGA women (P = 0.011). Circulating SHBG was lower in the SGA women than in the AGA women (P = 0.041), but fasting insulinemia was similar in both groups. CONCLUSIONS The prevalence of PCOS in SGA women was twice as high as in AGA women in our study population.

Unfavorable lipid profile in women with endometriosis

Similar to dyslipidemia, the oxidative stress and intrinsic inflammatory status may be associated with the development of endometriosis. Thus, we performed a cross-sectional study and found that women with endometriosis had an increased low-density lipoprotein (LDL) and non-high-density lipoprotein (HDL) cholesterol levels compared with controls presumably without endometriosis.

The Frequency of Metabolic Syndrome is Higher Among PCOS Brazilian Women With Menstrual Irregularity Plus Hyperandrogenism

Polycystic ovary syndrome (PCOS) has a heterogeneous phenotypic distribution that can potentially lead to variations in metabolic repercussions. A cross-sectional study was conducted with 372 women of reproductive age (146 of whom were ovulatory and 226 with PCOS) divided into groups according to PCOS phenotype: (i) complete phenotype involving menstrual irregularity (MI), hyperandrogenism (H), and ultrasound (US) findings of polycystic ovaries (132 patients); (ii) MI + H (18 patients); (iii) MI + US (51 patients); and (iv) H + US (25 patients). The frequencies of metabolic syndrome (MetS) were 45.4%, 38.9%, 33.3%, 36%, and 8.2% for the MI + H + US, MI + H, MI + US, H + US, and control groups (P < .01), respectively. In logistic regression, body mass index ([BMI] odds ratio [OR]: 1.1, 95% confidence interval [CI] 1.1-1.2) and the association of the complete phenotype with MI + H (OR: 5.8 CI95% [2.2-15.8) were independent predictors of the occurrence of MetS. The defining characteristics of MetS were more frequently found in women with PCOS than in controls, regardless of the phenotype (P < .01 for each variable). In conclusion, the frequency of MetS is similar for various PCOS phenotypes among young Brazilian women from the Southeast region of the country, although only BMI and the presence of MI + H, regardless of the presence of US findings, were more predictive of the development of MetS.

Resistance Exercise Impacts Lean Muscle Mass in Women with Polycystic Ovary Syndrome

PURPOSE This study investigated the effects of progressive resistance training (PRT) on lean muscle mass (LMM) in women with or without polycystic ovary syndrome (PCOS) and its effects on metabolic factors and concentrations of related steroid hormones. DESIGN This was a nonrandomized, therapeutic, open, single-arm study. PARTICIPANTS All in all, 45 sedentary women with PCOS and 52 without (non-PCOS), 18-37 yr of age, with body mass indexes (BMI) of 18-39.9 kg·m(-2) of all races and social status, performed PRT three times a week for 4 months. Before and after PRT, the concentrations of hormones and metabolic factors and waist circumference were measured. LMM and total body fat percentage were determined using dual-energy x-ray absorptiometry. Clinical characteristics, LMM, and fasting glucose were adjusted for confounding covariables and compared using general linear mixed models. Each patients menstrual history was taken before study enrollment and after PRT. RESULTS PRT resulted in reduced plasma testosterone and fasting glucose levels. After PRT, the androstenedione concentration increased and the sex hormone-binding globulin concentration decreased in women with PCOS. The waist circumference was reduced (P < 0.01) and the muscle mass index, lean mass (LM)/height2, increased in women with PCOS (P = 0.04). Women with PCOS showed increased muscle mass indexes of appendicular LM/height2 (P = 0.03) and LM/height2 (P < 0.01) compared with the baseline. Total LM and trunk LM were elevated in women with PCOS (P = 0.01) at the baseline and after PRT. CONCLUSION To our knowledge, this is the first report to show that resistance exercise alone can improve hyperandrogenism, reproductive function, and body composition by decreasing visceral fat and increasing LMM, but it has no metabolic impact on women with PCOS.

Oocyte diameter as a predictor of fertilization and embryo quality in assisted reproduction cycles

OBJECTIVE To assess the impact of the mean oocyte diameter (MOD) on occurrence of fertilization and embryo quality in assisted reproduction cycles. DESIGN Prospective observational study. SETTING Sector of Human Reproduction of the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo (HCFMRP-USP). PATIENT(S) Thirty-five women undergoing intracytoplasmic sperm injection (ICSI) at the University Hospital of Ribeirão Preto from May to October 2007. INTERVENTION(S) MOD assessment. MAIN OUTCOME MEASURE(S) Occurrence of fertilization and qualitative embryo classification on 2nd and 3rd day after ICSI. RESULT(S) We divided 160 metaphase II oocytes according to MOD into groups A (MOD below the 25th percentile), B (MOD between 25th and 75th percentile), and C (MOD above the 75th percentile). There was no statistically significant association between MOD and the occurrence of fertilization or the qualitative embryo classification on days 2 and 3. There was no statistically significant difference between groups regarding number of cells or the qualitative embryo classification on days 2 and 3. CONCLUSION(S) The MOD of mature oocytes does not seem to be related to the occurrence of fertilization or to the developmental quality of human embryos on days 2 and 3 after ICSI.

Anormalidades metabólicas em mulheres com síndrome dos ovários policísticos: obesas e não obesas

OBJETIVO: Comparar as caracteristicas metabolicas de mulheres jovens do sudeste brasileiro, obesas e nao obesas com sindrome dos ovarios policisticos (SOP). METODOS: Estudo transversal que incluiu 218 mulheres de idade reprodutiva com diagnostico de SOP - 90 mulheres nao obesas (IMC entre 18,5 e 29,9 kg/m2) e 128 pacientes obesas (IMC >30 kg/m2), selecionadas no momento do diagnostico. Foram comparadas as frequencias de resistencia insulinica (RI), intolerância a glicose (IG), sindrome metabolica (MetS) e diabetes mellitus tipo 2 (DM2) e os valores medios de colesterol total (CT), triglicerides (TG), lipoproteinas de alta (LDL) e baixa densidade (HDL), entre as pacientes obesas e nao obesas com SOP. Foram comparadas tambem as caracteristicas clinicas e hormonais (hormonio foliculo estimulante, luteinizante, prolactina, hormonio tireoestimulante, testosterona total, sulfato de dehidroepiandrostenediona e 17-hidroxiprogesterona) nos dois grupos. A analise estatistica foi realizada com o auxilio do software SAS 9.0. Para analise das variaveis com distribuicao normal, utilizou-se o teste t de Student nao pareado; na ausencia desta caracteristica, o teste utilizado foi Mann-Whitney bicaudal. Para as variaveis qualitativas utilizou-se o teste Exato de Fisher. Em todas as analises, foi considerado o nivel de significância de 5% (p<0,05). RESULTADOS: As frequencias de RI, IG e MetS foram significativamente mais elevadas em pacientes com SOP obesas do que nao obesas (66,7, 29,9 e 63% versus 24,7, 12,2 e 16.4%, respectivamente). As pacientes obesas apresentaram maiores niveis de CT e TG (189,8±35.8 mg/dL e 145.4±71.1 mg/dL, respectivamente) do que as nao obesas (172,1±38.4 mg/dL e 99,3±54 mg/dL, respectivamente). Ambos os grupos apresentaram niveis medios de HDL abaixo de 50 mg/dL. CONCLUSOES: Mulheres obesas jovens com SOP apresentam maior frequencia de RI, IG e SM do que as nao obesas. Todavia, a ocorrencia dos disturbios metabolicos e elevada tambem na pacientes nao obesas, sugerindo que a presenca da sindrome favoreca o desenvolvimento de comorbidades metabolicas, com potenciais repercussoes a medio e longo prazos.

Pathogenesis of polycystic ovary syndrome: multifactorial assessment from the foetal stage to menopause.

Polycystic ovary syndrome (PCOS) is a multifactorial disorder that arises from interactions between genetic, environmental and intra-uterine factors. Small-for-gestational-age (SGA) babies and the daughters of mothers with PCOS represent possible postnatal clinical targets for developmental programming by steroid excess. The presence of excess glucocorticoids and/or androgens during foetal organogenesis and growth might promote changes in gene expression, and these changes might be related to an increase in the risk of PCOS-like reproductive and metabolic disorders in postnatal life, such as rapid growth and weight gain during the first 2 years of life (only in SGA babies), hyperinsulinaemia, adipocyte dysfunction and childhood visceral obesity, premature pubarche and adrenarche (only in SGA babies) and PCOS. In the fourth decade of life, women who have PCOS may be at higher risk for type 2 diabetes mellitus, dyslipidaemia and systemic arterial hypertension, which suggests that these women are also at higher risk for cardiovascular disease during menopause. However, PCOS can also occur in women who were born at appropriate weight for GA or in newborns of women without PCOS, which suggests that genetic variation and environmental factors play important roles in the development and maintenance of PCOS in a population. Genome-wide association studies based on adequate population samples have shown a higher frequency of genetic polymorphisms of the LHCGR, THADA and DENND1A genes in women with PCOS. Genetic studies of PCOS have also included analyses of structural changes in the chromosome based on an assessment of telomere length in single, cross-sectional evaluations, and these studies have produced controversial results. The present narrative review assesses the multifactorial origins of PCOS (including environmental, genetic and intra-uterine factors) and the development of conditions associated with this disorder. It is concluded that although PCOS might originate in the intra-uterine environment through developmental programming by steroid excess, the interaction between genetic and environmental factors is crucial for its appearance. Follow-up studies should be conducted to assess the same populations over their entire lifespans while taking into account different aspects of the pathogenesis of PCOS.

Treatment of infertility in women with polycystic ovary syndrome: approach to clinical practice

Polycystic ovary syndrome represents 80% of anovulatory infertility cases. Treatment initially includes preconception guidelines, such as lifestyle changes (weight loss), folic acid therapy to prevent the risk of fetal neural tube defects and halting the consumption of tobacco and alcohol. The first-line pharmacological treatment for inducing ovulation consists of a clomiphene citrate treatment for timed intercourse. The second-line pharmacological treatment includes the administration of exogenous gonadotropins or laparoscopic ovarian surgery (ovarian drilling). Ovulation induction using clomiphene citrate or gonadotropins is effective with cumulative live birth rates of approximately 70%. Ovarian drilling should be performed when laparoscopy is indicated; this procedure is typically effective in approximately 50% of cases. Finally, a high-complexity reproduction treatment (in vitro fertilization or intracytoplasmic sperm injection) is the third-line treatment and is recommended when the previous interventions fail. This option is also the first choice in cases of bilateral tubal occlusion or semen alterations that impair the occurrence of natural pregnancy. Evidence for the routine use of metformin in infertility treatment of anovulatory women with polycystic ovary syndrome is not available. Aromatase inhibitors are promising and longer term studies are necessary to prove their safety.

Small for gestational age babies are not related to changes in markers of adipose tissue dysfunction during reproductive age

BACKGROUND Small for gestational age (SGA) birth has been associated with adipocyte dysfunction during later phases of life. Because SGA women are at a higher risk of developing polycystic ovary syndrome (PCOS), adipocyte dysfunction detected in patients with PCOS may be associated with SGA birth. AIMS To determine whether SGA birth is related to altered serum markers of adipose tissue dysfunction during the third decade of life in Brazilian women. A secondary objective was to relate the presence of PCOS with serum markers of adipose tissue dysfunction. STUDY DESIGN Prospective cohort observational study. SUBJECTS A total of 384 women born at 37 to 42weeks of gestation from June 1, 1978 to May 31, 1979 in Ribeirão Preto, State of São Paulo, Brazil. After exclusion, 165 women participated in the study. Of these women, 43 were in the SGA group and 122 were in the adequate for gestational age group based on birth weight determined from cohort files. OUTCOME MEASURES Body mass index (BMI), arterial systolic and diastolic pressures, abdominal circumference and serum concentrations of total testosterone, fasting glucose and insulin, lipid profile, adiponectin, leptin and necrosis factor alpha tumor (TNFα). RESULTS BMI was an independent predictor of lower adiponectin (adjusted coefficient=-0.02, p=0.01) and higher leptin (adjusted coefficient=0.06, p=0.01) concentrations. The serum insulin concentration was associated with higher leptin (adjusted coefficient=0.03, p=0.02) and TNF-α (adjusted coefficient=0.01, p=0.03) concentrations. Having PCOS or being born SGA did not predict any markers of adipocyte dysfunction.

Oxidative stress and polycystic ovary syndrome: an evaluation during ovarian stimulation for intracytoplasmic sperm injection

Oxidative stress (OS) may affect natural fertility and the results of assisted reproduction techniques (ARTs). Subfertility associated with polycystic ovary syndrome (PCOS) may be related to OS. This process may intensify during controlled ovarian stimulation (COS) for ARTs because of increased ovarian metabolic activity and hypoestrogenism with the use of gonadotropin-releasing hormone agonists (GnRHas). The objective of this study was to investigate the presence of systemic OS in non-stimulated cycles and to determine OS markers (malondialdehyde [MDA], advanced oxidation protein products [AOPP], hydroperoxides [FOX], glutathione [GSH], and vitamin E) during COS in non-obese infertile women with and without PCOS who were subjected to ARTs. A prospective cohort study was conducted on non-obese women (16 with PCOS, and 60 ovulatory patients with infertility due to male and/or tubal factors). The OS markers were determined during the following time-points: the follicular phase of the natural cycle (D1), after pituitary downregulation with GnRHa and before the use of gonadotropins (D2), on the day of administration of human chorionic gonadotropin (D3), and at oocyte retrieval (D4). Intergroup analysis showed that serum MDA concentrations were higher in the PCOS group at D3 (P=0.048) and D4 (P=0.002). On an intragroup analysis, the control group had higher MDA concentrations at D2 than at D1 (P=0.01) or D4 (P=0.004). The AOPP concentrations were higher at D2 (P<0.0001), D3 (P<0.001) and D4 (P<0.0001) compared to D1. The FOX concentrations were lower at D2 (P<0.0001), D3 (P<0.0001), and D4 (P<0.001) than at D1. Serum GSH concentrations were significantly higher at D4 than at D1 (P=0.02). An intragroup analysis of the PCOS subjects showed that the five OS markers did not differ significantly among the four time-points when they were analyzed (D1, D2, D3 and D4). In conclusion, non-obese infertile women with PCOS showed evidence of systemic OS after COS with gonadotropins for ICSI. On the other hand, non-obese ovulatory infertile women, and women with infertility due to male and/or tubal factors showed a possible systemic oxidative balance until the final of COS.