MIR146A and ADIPOQ genetic variants are associated with birth weight in relation to gestational age: a cohort study.

PURPOSE: To evaluate the genetic variants related to polycystic ovary syndrome (PCOS) and its metabolic complications in girls born small for gestational age (SGA). DESIGN: Retrospective birth cohort study. MATERIALS AND METHODS: We evaluated 66 women of reproductive age born at term (37-42 weeks of gestational age) according to the birth weight in relation to gestational age: 26 SGA and 40 AGA (Adequate for gestational age). Anthropometric and biochemical characteristics were measured, as well as the PCOS prevalence. We analyzed 48 single nucleotide polymorphisms (SNPs) previously associated with PCOS and its comorbidities using TaqMan Low-Density Array (TLDA). miRNet and STRING databases were used to predict target and disease networks. RESULTS: Anthropometric and biochemical characteristics did not differ between the SGA and AGA groups, as well as insulin resistance and PCOS prevalence. Two SNPs were not in Hardy-Weinberg equilibrium, the rs2910164 (MIR146A C > G) and rs182052 (ADIPOQ G > A). The rs2910164 minor allele frequency (MAF) was increased in SGA (OR, 2.77; 95%; CI, 1.22-6.29), while the rs182052 was increased AGA (OR, 0.34; 95%; CI, 0.13 - 0.88). The alleles related to reduced miRNA-146a (C) and ADIPOQ (A) activity showed increased frequency in SGA. The mature miR-146a targets 319 genes, been the CXCR4, TMEM167A and IF144L common targets and contributes to PCOS. The ADIPOQ main protein interactions were ERP44, PPARGCIA and CDH13. CONCLUSIONS: The miR-146a (rs2910164) and ADIPOQ (rs182052) allelic variants are related to birth weight in SGA and may predict health-related outcomes, such as PCOS and obesity risk.

Corifollitropin alpha, clomiphene citrate and dydrogesterone without daily gonadotrophin: a new option of a friendly protocol for high-responder oocyte donors.

OBJECTIVE: To compare the number of oocytes obtained in the follicular puncture of high- responder oocyte donors, submitted to ovarian stimulation for in vitro fertilization (IVF) in two different protocols: Friendly and Conventional. METHODS: There were one hundred-and-eight infertile egg-donor women, aged between 21 and 35 years, undergoing IVF in this retrospective cohort study. The women were divided into two groups: 1) Friendly protocol: controlled ovarian stimulation (COS) with corifollitropin alpha, clomiphene citrate and dydrogesterone without daily rFSH (n=52) and 2) In the Conventional protocol, we had COS with menotropin daily and ganirelix (n=66). We assessed age, body mass index, time and cause of infertility, antral follicle count (AFC) by three-dimensional ultrasound, number of visits to the clinic, COS duration, number of follicles ≥14mm on the trigger day, early ovulation frequency, number of mature oocytes, number of cryopreserved embryos, clinical pregnancy rate, frequency of OHSS. RESULTS: The ovulatory factor was higher in women in the Conventional protocol (p=0.03), and the tubal factor (p=0.02) was higher in the Friendly protocol group. The number of visits to the clinic was lower among women in the Friendly protocol (p=0.04). The number of mature eggs, the clinical pregnancy rate and the frequency of OHSS were similar between the groups. The number of frozen embryos was higher in the Friendly group (p=0.02). The regression model demonstrated that the ovulatory factor, the tubal factor and the number of visits to the clinic were not predictors of the number of mature oocytes. Only AFC was an independent predictor of the number of meiosis II oocytes (p<0.01). CONCLUSIONS: The Friendly protocol seems to be as safe and effective as the Conventional protocol for infertile high-responder oocyte donors, resulting in a similar number of mature oocytes and OHSS incidence.

Continuous versus intermittent aerobic exercise in the improvement of quality of life for women with polycystic ovary syndrome: A randomized controlled trial.

Polycystic ovary syndrome predisposes alterations which contribute to the reduction of quality of life. This randomized controlled clinical trial study was to evaluate the effect of two protocols of aerobic exercise on quality of life in women with polycystic ovary syndrome. Women were allocated to three groups: continuous aerobic training (n = 28), intermittent aerobic training (n = 29), and control group (no training; n = 30). Testosterone levels, body composition indices, and quality of life were assessed at baseline and after 16 weeks of intervention. Both protocols were effective to improve testosterone levels, anthropometric indices, and quality of life in polycystic ovary syndrome women. Thus, these protocols should be included in the clinical environment to improve clinical parameters psychological, biological and social health to this population.

Fertility optimization in women with cancer: from preservation to contraception.

Advances in the early diagnosis and treatment of cancer have reduced mortality rates and improved patient survival. For this reason, professionals from different areas have strived to implement actions to increase patient quality-of-life during and after cancer treatment. Among these measures, integral attention in reproductive health is one of the main points for the inclusion, safety, and autonomy of female patients. The approach to fertility in these cases should include counseling on fertility preservation and contraceptive options. Oocyte/embryo freezing is an effective technique that does not delay the start of cancer treatment, since controlled ovarian stimulation can be initiated at any stage of the menstrual cycle. At the same time, contraceptive counseling should be conducted based on the eligibility criteria established by the World Health Organization and the Centers for Disease Control and Prevention. However, there is still a lack of studies on (i) the suitability of contraceptives to patients of reproductive age with relatively frequent tumors (lymphoma, leukemia, bone cancer), and (ii) the use of contraceptive concurrently with chemotherapeutic agents. Therefore, the choice of contraceptive method should consider other factors such as tumor type, thrombogenic risk factors linked to cancer/chemotherapy, immunosuppression, blood disorders (thrombocytopenia/anemia), bone mass reduction, metabolic/cardiovascular effects, and drug interaction.

Cardiovascular risk markers among obese women using the levonorgestrel-releasing intrauterine system: A randomised controlled trial.

According to international guidelines, women with obesity without other comorbidities can safely use any hormonal contraceptive (HC). However, limited information is available about contraceptive safety for women with obesity since obesity is an exclusion criterion of most contraceptive clinical trials. As such little is known about the possible risks of HC exposure for women with obesity without comorbidities. One way to assess possible long-term risks in this population, even prior to the development of any clinical disease, is to measure alterations in subclinical atherosclerosis markers. We evaluated the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) on subclinical markers of cardiovascular risk in women with obesity. This is a randomised clinical trial in which 106 women with obesity [body mass index (BMI)≥30kg/m2] were randomised to the LNG-IUS (n=53) or to non-hormonal methods (n=53) and followed for 12 months. We evaluated waist circumference (WC), blood pressure, blood glucose, insulin, lipid profile, and endothelial function markers (carotid intima-media thickness, brachial artery flow-mediated dilation, and carotid arterial stiffness). At 12 months, BMI (p=0.005), WC (p=0.045), and glucose levels (p=0.015) were significantly lower in the LNG-IUS group than in the control group. We did not find any clinically relevant changes in subclinical markers of cardiovascular risk among with obesity women at 12 months after LNG-IUS placement compared to users of non-hormonal contraceptive methods.

Hormonal contraception in women with polycystic ovary syndrome: choices, challenges, and noncontraceptive benefits.

Polycystic ovary syndrome (PCOS) is an endocrine disorder among women of reproductive age characterized by chronic anovulation and polycystic ovary morphology and/or hyperandrogenism. Management of clinical manifestations of PCOS, such as menstrual irregularities and hyperandrogenism symptoms, includes lifestyle changes and combined hormonal contraceptives (CHCs). CHCs contain estrogen that exerts antiandrogenic properties by triggering the hepatic synthesis of sex hormone-binding globulin that reduces the free testosterone levels. Moreover, the progestogen present in CHCs and in progestogen-only contraceptives suppresses luteinizing hormone secretion. In addition, some types of progestogens directly antagonize the effects of androgens on their receptor and also reduce the activity of the 5α reductase enzyme. However, PCOS is related to clinical and metabolic comorbidities that may limit the prescription of CHCs. Clinicians should be aware of risk factors, such as age, smoking, obesity, diabetes, systemic arterial hypertension, dyslipidemia, and a personal or family history, of a venous thromboembolic event or thrombophilia. This article reports a narrative review of the available evidence of the safety of hormonal contraceptives in women with PCOS. Considerations are made for the possible impact of hormonal contraceptives on endocrine, metabolic, and cardiovascular health.

The telomere attrition rate is not accelerated in women born small for gestational age: A birth cohort study.

BACKGROUND: Physiologically, a reduction in telomere length (LTL) occurs with aging, but epigenetic changes may accelerate telomere shortening and also facilitate the onset of oxidative/inflammatory stress and the development of clinical/metabolic comorbidities in life spam. Although individuals born small for gestational age (SGA) may be related to those epigenetic changes, the assessment of LTL in individuals born SGA has yielded conflicting results (only cross-sectional studies) and has not been carried out in longitudinal studies. We performed a birth cohort study to evaluate the rate of telomere erosion in women born SGA in comparison to women born appropriate for gestational age (AGA) assessed at two different time points during the third decade of life. In our research, born SGA or AGA showed no difference in LTL shortening during a period of five years in the third decade of life. Our finding may have implications for understanding the natural history of diseases in lifespan because the same women (under the influence of similar environmental factors) may be accessed in different phases of life. Thus, the analysis of the present cohort population at a more advanced age may reveal a dynamics of telomere shortening different from here and its possible relation with onset of age-related diseases.

Oxidative stress and polycystic ovary syndrome: evaluation during ovarian stimulation for ICSI.

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.

Subclinical Hypothyroidism and Intracytoplasmic Sperm Injection Outcomes.

Purpose Whether preconception elevated concentrations of thyroid-stimulating hormone (TSH) compromises reproductive outcomes in patients undergoing assisted reproduction techniques (ARTs) remains unclear. This study therefore compared the reproductive outcomes in patients with TSH concentrations of < 2.5 mIU/L, 2.5-4.0 mIU/L, and 4.0-10.0 mIU/L undergoing controlled ovarian stimulation (COS) for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Methods This retrospective cohort study evaluated the medical records of all women with measured TSH concentrations who underwent IVF/ICSI between January 2011 and December 2012. The patients were divided into three groups: TSH < 2.5 mIU/L (group 1); THS ≥2.5 and < 4.0 mIU/L (group 2); and THS ≥4 mIU/L and < 10.0 mIU/L (group 3). Patients who were administered levothyroxine for treating hypothyroidism were excluded from the analysis. The primary endpoints were clinical pregnancy, miscarriage, live birth and multiple pregnancy rates. Results During the study period, 787 women underwent IVF/ICSI. Sixty were excluded because their TSH concentrations were unavailable, and 77 were excluded due to their use of levothyroxine. The prevalence of patients presenting elevated concentrations of TSH was of 5.07% (using a TSH threshold of 4.0 mIU/L) and of 29.99% (using a TSH threshold of 2.5 mIU/L). Patient characteristics, type of COS, and response to COS did not differ among the three groups, and there were no differences in clinical pregnancy (24.4% versus 25.9% versus 24.2%, p = 0.93); miscarriage (17.1% versus 14.3% versus 12.5%, p = 0.93); live birth (20.2% versus 22.2% versus 21.2%, p = 0.86); and multiple pregnancy rates (27.0% versus 21.4% versus 25.0%, p = 0.90) respectively. Conclusion Response to COS, live birth, and miscarriage rates were not altered in women with elevated concentrations of TSH undergoing IVF/ICSI, regardless of using a TSH threshold of 2.5 mIU/L or 4.0 mIU/L. These findings reinforce the uncertainties related to the impact of subclinical hypothyroidism on reproductive outcomes in women undergoing COS for ARTs.

Subclinical Hypothyroidism and Intracytoplasmic Sperm Injection Outcomes / Hipotireoidismo subclínico e resultados de Injeção intracitoplasmática de espermatozoide

Abstract Purpose Whether preconception elevated concentrations of thyroid-stimulating hormone (TSH) compromises reproductive outcomes in patients undergoing assisted reproduction techniques (ARTs) remains unclear. This study therefore compared the reproductive outcomes in patients with TSH concentrations of < 2.5 mIU/L, 2.5-4.0 mIU/L, and 4.0-10.0mIU/L undergoing controlled ovarian stimulation (COS) for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Methods This retrospective cohort study evaluated the medical records of all women with measured TSH concentrations who underwent IVF/ICSI between January 2011 and December 2012. The patients were divided into three groups: TSH < 2.5mIU/L (group 1); THS ≥2.5 and < 4.0 mIU/L (group 2); and THS ≥4 mIU/L and < 10.0 mIU/L (group 3). Patients who were administered levothyroxine for treating hypothyroidism were excluded from the analysis. The primary endpoints were clinical pregnancy,miscarriage, live birth and multiple pregnancy rates. Results During the study period, 787 women underwent IVF/ICSI. Sixty were excluded because their TSH concentrations were unavailable, and 77 were excluded due to their use of levothyroxine. The prevalence of patients presenting elevated concentrations of TSHwas of 5.07% (using a TSH threshold of 4.0 mIU/L) and of 29.99% (using a TSH threshold of 2.5 mIU/L). Patient characteristics, type of COS, and response to COS did not differ among the three groups, and there were no differences in clinical pregnancy (24.4% versus 25.9% versus 24.2%, p = 0.93); miscarriage (17.1% versus 14.3% versus 12.5%, p = 0.93); live birth (20.2% versus 22.2% versus 21.2%, p = 0.86); and multiple pregnancy rates (27.0% versus 21.4% versus 25.0%, p = 0.90) respectively. Conclusion Response to COS, live birth, and miscarriage rates were not altered in women with elevated concentrations of TSH undergoing IVF/ICSI, regardless of using a TSH threshold of 2.5mIU/L or 4.0mIU/L. These findings reinforce the uncertainties related to the impact of subclinical hypothyroidism on reproductive outcomes in women undergoing COS for ARTs.

Resumo Objetivos Se concentrações elevadas de hormônio estimulante da tireoide (TSH) antes do parto comprometem resultados reprodutivos em pacientes submetidas a técnicas de reprodução assistida (TRA) é incerto. Este estudo comparou resultados reprodutivos de pacientes com concentrações de TSH < 2,5 mIU/L; 2,5-4,0 mIU/L e 4,0-10,0 mIU/L submetidas a estimulação ovariana controlada (EOC) para fertilização in vitro (FIV)/injeção intracitoplasmática de espermatozoide (ICSI). Métodos Este estudo de coorte retrospectiva avaliou prontuários médicos de todas as pacientes que tinham registro de concentrações de TSH submetidas a FIV/ICSI entre janeiro de 2011 e dezembro de 2012. As pacientes foram divididas em três grupos: aquelas com TSH < 2,5 mIU/L (grupo 1); entre 2,5 e 4,0 mIU/L (grupo 2) e entre 4,0 mIU/L e 10,0 mIU/L (grupo 3). As pacientes que estavam em uso de levotiroxina para tratamento de hipotireoidismo foram excluídas da análise. Os desfechos primários foram taxas de gravidez clínica, de abortamento, de nascido vivo e de gravidez múltipla. Resultados Durante o período do estudo, 787 mulheres foramsubmetidas a FIV/ICSI. Sessenta foram excluídas por causa da indisponibilidade das concentrações de TSH, e 77 foram excluídas porque estavam usando levotiroxina. A prevalência de pacientes apresentando elevação das concentrações de TSH foi de 5,07% (usando um limite de TSH de 4,0 mIU/L) e 29,99% (usando um limite de TSH de 2,5 mIU/L). As características das pacientes, tipo de EOC e reposta à EOC não diferiram entre os três grupos, nem houve diferenças nas taxas de gravidez clínica (24,4% versus 25,9% versus 24,2%, p = 0,93); abortamento (17,1% versus 14,3% versus 12,5%, p = 0,93); nascido vivo (20,2% versus 22,2% versus 21,2%, p = 0,86); e taxas de gestação múltipla (27,0% versus 21,4% versus 25,0%, p = 0,90), respectivamente. Conclusão Resposta à EOC, taxa de nascido vivo e de abortamento não foram alteradas em mulheres submetidas a FIV/ICSI com concentrações elevadas de TSH independente de usar um limite de 2,5 ou 4,0 mIU/L. Estes achados reforçam as incertezas relacionadas ao impacto do hipotireoidismo subclínico nos resultados reprodutivos de mulheres submetidas a EOC para TRA.

Levonorgestrel-Releasing Intrauterine System for Women With Polycystic Ovary Syndrome: Metabolic and Clinical Effects.

Polycystic ovary syndrome (PCOS) is related to clinical and metabolic comorbidities that may limit the prescription of combined hormonal contraceptives, with consequent need to use progestogen-only contraceptives (POCs). Thus, the objective of the present study was to evaluate the clinical and metabolic effects of a POC, the levonorgestrel-releasing intrauterine system (LNG-IUS), in women with PCOS followed up over a period of 6 months compared to baseline and to women without PCOS. Thus, an observational, prospective, controlled study was conducted on 30 women with a diagnosis of PCOS who presented adverse effect secondary to the use of combined oral contraceptives (nausea, headache, mastalgia or vomiting; PCOS group) paired with 30 ovulatory women without PCOS (control group), both groups being free of comorbidities and having chosen the LNG-IUS as contraceptive. Clinical, laboratory, and ultrasonographic variables were evaluated immediately before LNG-IUS insertion and 6 months after the use of this method. Before LNG-IUS insertion, the PCOS group had higher total testosterone levels (P = .04), lower HDL levels (P = .04), and greater ovarian volume (P < .01) than the control group. Six months after LNG-IUS insertion, there was a 2.3% increase in abdominal circumference (P = .04) and a 3.4% increase in fasting glycemia (P = .02). On the other hand, mean ovarian volume was 10% smaller compared to the volume found before LNG-IUS insertion (P = .04), LDL levels were reduced by 5.2% (P = .03), and total cholesterol levels were reduced by 6.7% (P < .01) compared to baseline evaluation in the PCOS group. The remaining variables did not differ significantly during the 6 months of observation. The control group did not show significant changes compared to the period before LNG-IUS insertion. When the groups were compared after the 6-month follow-up, only glycemia showed a statistically significant variation between the groups, with glycemia levels increasing by 3.4% in the PCOS group and decreasing by 2.6% in the control group (P = .008). In conclusion, the use of the LNG-IUS for 6 months was not associated with relevant changes in clinical or metabolic variables of women with no comorbidities regardless of the presence of PCOS.

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 patient's 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.

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.

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.

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.

Tratamento com andrógenos como possibilidade de melhoria do prognóstico reprodutivo em mulheres com envelhecimento ovariano / Treatment with androgens as a possibility to improve the reproductive outcome of women with ovarian aging

Justificativa: A resposta ao estímulo ovariano é uma peça-chave na reprodução assistida. Apesar dos recentes avanços das técnicas, pacientes com baixa reserva ovariana apresentam mau prognóstico e representam um desafio na medicina reprodutiva. Objetivo: Propor estratégia de melhoria do prognóstico reprodutivo em mulheres com idades superiores a 38 anos ou jovens com baixa contagem de folículos antrais, por meio do uso de testosterona previamente ao estímulo ovariano. Material e métodos: Levantamento de dados da literatura científica na área da medicina reprodutiva. Resultados e conclusões: O uso de androgênios em fases que antecedem a estimulação ovariana em ciclos de fertilização in vitro parece ser ótima ferramenta de melhoria da resposta à estimulação oocitária controlada em pacientes com mais de 38 anos ou com reserva ovariana diminuída. Melhora tanto a quantidade quanto a qualidade oocitária e aumenta as taxas de gestação e de nascido vivos.

Justification: The response to ovarian stimulation is a keyelement in assisted reproduction (AR). Despite recent advances in the techniques, patients with low ovarian reserve havepoor prognosis and represent a challenge in reproductive medicine.Objective: To propose a strategy to improve reproductive prognosis of women older than 38years or young women with low antral follicle count, through the use of testosterone prior to ovarian stimulus.Material and methods: Survey data from the scientific literature in the field of reproductive medicine. Results and conclusions: The use of androgens in stages preceding ovarian stimulation in IVF cycles seems to be great tool for improving oocyte response in oocyte controlled stimulation of patients older than 38 years or with diminished ovarian reserve, improving both quantityand quality of oocytes and increasing rates of pregnancy and live-born.

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.

[Frequency and risk factors for metabolic syndrome in adolescents and adults women with polycystic ovary syndrome]. / Frequência e fatores de risco para síndrome metabólica em mulheres adolescentes e adultas com síndrome dos ovários policísticos.

PURPOSE: To compare the frequency of metabolic syndrome (MetS) and the risk factors associated with this syndrome in women from the Brazilian Southeast with polycystic ovary syndrome (POS) evaluated during adolescence and adult age. METHODS: This was a cross-sectional study conducted on 147 patients with a diagnosis of POS who were divided into two groups: Adolescents, 42 adolescents aged 13 to 19 years, and Adults, 105 women aged 20 to 40 years. The following factors were evaluated: clinical characteristics (body mass index - BMI, Ferriman index, abdominal circumference - AC, and systemic arterial pressure), mean ovarian volume, laboratory variables (serum androgen profile, lipid profile, glycemia, and fasting insulin), and frequency of MetS. The results were expressed as mean±standard deviation. We used multiple logistic regression with the response variable being the presence of MetS and the predictor variables the levels of total testosterone, insulin and BMI. RESULTS: The frequency of MetS was approximately twice higher in the group of adult women compared to the adolescents with POS (Adolescents: 23.8 vs. Adults: 42.9%, p=0.04). Among the defining criteria of MetS, only the qualitative variable of systemic arterial pressure ≥130/85 mmHg was more frequent among the adult women (p=0,01). The BMI was an independent predictor of MetS among the adolescent (p=0.03) and adult women (p<0.01) with POS. Serum insulin level was a predictor of MetS only among adult women with POS (p<0.01). AC was greater among adult women (p=0.04). CONCLUSION: Adult women with POS have a twice higher frequency of MetS than adolescents with POS from the Brazilian Southeast. Although the BMI is associated with the development of MetS in any phase of life in women with POS, serum insulin level was an independent predictor of MetS only among adult women with this disorder.

Frequência e fatores de risco para síndrome metabólica em mulheres adolescentes e adultas com síndrome dos ovários policísticos / Frequency and risk factors for metabolic syndrome in adolescents and adults women with polycystic ovary syndrome

OBJETIVOS: Comparar a frequência de síndrome metabólica (SMet) e dos fatores de risco para esta síndrome em mulheres adultas e adolescentes do sudeste brasileiro com síndrome dos ovários policísticos (SOP). MÉTODOS: Estudo transversal, realizado com 147 pacientes que apresentavam diagnóstico de SOP e que foram divididas em dois grupos: Adolescência, constituído por 42 adolescentes com 13 a 19 anos e Adultas, composto por 105 mulheres com idade entre 20 e 40 anos. Foram avaliadas características clínicas (índice de massa corporal - IMC, índice de Ferriman, circunferência abdominal - CA e pressão arterial sistêmica), o volume ovariano médio, variáveis laboratoriais (perfil androgênico sérico, lipidograma, glicemia e insulina de jejum) e frequência da SMet. Os resultados foram expressos em média±desvio padrão. Utilizou-se regressão logística múltipla tendo como variável resposta a presença de SMet e como variáveis preditoras para SMet os níveis de testosterona total, insulina e IMC. RESULTADOS: A frequência de SMet foi aproximadamente duas vezes maior no grupo de mulheres adultas em relação às adolescentes com SOP (Adolescência: 23,8 versus Adultas: 42,9%, p=0,04). Entre os critérios definidores da SMet, apenas a variável qualitativa da pressão arterial sistêmica ≥130/85 mmHg foi mais frequente nas adultas (p=0,01). O IMC foi preditor independente para SMet em mulheres adolescentes (p=0,03) e adultas (p<0,01) com SOP; o nível sérico de insulina foi preditor para SMet apenas para o grupo de mulheres com SOP adultas (p<0,01). A média das CA foi maior nas mulheres de idade adulta (p=0,04). CONCLUSÃO: Mulheres com SOP adultas apresentam frequência de SMet duas vezes maior do que adolescentes com SOP do sudeste brasileiro. Embora o IMC esteja associado com a SMet em qualquer fase da vida da mulher com SOP, o nível sérico de insulina foi preditor independente apenas da SMet em pacientes com esse distúrbio na idade adulta.

PURPOSE: To compare the frequency of metabolic syndrome (MetS) and the risk factors associated with this syndrome in women from the Brazilian Southeast with polycystic ovary syndrome (POS) evaluated during adolescence and adult age. METHODS: This was a cross-sectional study conducted on 147 patients with a diagnosis of POS who were divided into two groups: Adolescents, 42 adolescents aged 13 to 19 years, and Adults, 105 women aged 20 to 40 years. The following factors were evaluated: clinical characteristics (body mass index - BMI, Ferriman index, abdominal circumference - AC, and systemic arterial pressure), mean ovarian volume, laboratory variables (serum androgen profile, lipid profile, glycemia, and fasting insulin), and frequency of MetS. The results were expressed as mean±standard deviation. We used multiple logistic regression with the response variable being the presence of MetS and the predictor variables the levels of total testosterone, insulin and BMI. RESULTS: The frequency of MetS was approximately twice higher in the group of adult women compared to the adolescents with POS (Adolescents: 23.8 vs. Adults: 42.9%, p=0.04). Among the defining criteria of MetS, only the qualitative variable of systemic arterial pressure ≥130/85 mmHg was more frequent among the adult women (p=0,01). The BMI was an independent predictor of MetS among the adolescent (p=0.03) and adult women (p<0.01) with POS. Serum insulin level was a predictor of MetS only among adult women with POS (p<0.01). AC was greater among adult women (p=0.04). CONCLUSION: Adult women with POS have a twice higher frequency of MetS than adolescents with POS from the Brazilian Southeast. Although the BMI is associated with the development of MetS in any phase of life in women with POS, serum insulin level was an independent predictor of MetS only among adult women with this disorder.

[Women with polycystric ovary syndrome have a higher frequency of metabolic syndrome regardless of body mass index]. / Mulheres com síndrome dos ovários policísticos apresentam maior frequência de síndrome metabólica independentemente do índice de massa corpóreo.

PURPOSE: To assess the prevalence of metabolic syndrome and of its defining criteria in women with polycystic ovary syndrome from the Brazilian Southeast, who were stratified according to body mass index and compared to ovulatory controls. METHODS: This was a cross-sectional study conducted on 332 women of reproductive age, who were divided into two groups: Control, consisting of 186 women with regular menstrual cycles and ovulatory symptoms and without a diagnosis of polycystic ovary syndrome or other type of chronic anovulation, and the Polycystic ovary syndrome,Group, consisting of 146 women with a diagnosis of polycystic ovary syndrome (Rotterdam Consensus ASRM/ESHRE). Each group was stratified according to the body mass index, as follows: body mass index ( < 25 ≥25 and <30, and ≥ 30 kg/m²). The frequencies of metabolic syndrome and of its defining criteria and the clinical and hormonal characteristics (follicle stimulating hormone, total testosterone, dehydroepiandrostenedione sulfate) were analyzed. RESULTS: The frequency of metabolic syndrome was six times higher in the obese Polycystic ovary syndrome Group than among control women with the same body mass index (Control with 10.5 versus Polycystic ovary syndrome with 67.9%, p<0.01); twice higher in the Polycystic ovary syndrome Group with body mass index ≥ 25 and <30 kg/m² (Control with 13.2 versus Polycystic ovary syndrome with 22.7%, p<0.01), and three times higher in the Polycystic ovary syndrome Group with body mass index <25 kg/m² (Control with 7.9 versus Polycystic ovary syndrome with 2.5%, p<0.01), compared to control women paired for the same body mass index. Regardless of the body mass index, women with polycystic ovary syndrome had a higher frequency of all the criteria defining metabolic syndrome. CONCLUSION: Women with polycystic ovary syndrome have higher frequency of metabolic syndrome and of its defining criteria regardless of the body mass index. Hyperinsulinemia and hyperandrogenism are important characteristics of the origin of these alterations, especially in obese women with polycystic ovary syndrome.