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.

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.

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.

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.

A importância da via de administração na terapia hormonal do climatério / The importance of route administration in hormonal therapy of climacteric

Quanto à via de administração, a terapia hormonal (TH) apresenta aspectos específicos que podem potencializar o benefício de sua utilização em várias situações clínico-metabólicas. O efeito de primeira passagem hepática do metabolismo estrogênico promove alteração na produção de diversos tipos de proteínas, característica que pode influenciar no nível de lipoproteínas plasmáticas e no equilíbrio entre os processos de coagulação e fibrinólise. Assim, a TH oral é a mais adequada na presença da hipercolesterolemia. Por outro lado, mulheres hipertensas ou com risco de trombose venosa ou, ainda, com níveis elevados de triglicérides podem se beneficiar do uso da via transdérmica. Apesar disso, independentemente da via, não se deve prescrever TH para prevenção primária de doença cardiovascular (DCV)

In relation to the route of administration, hormonal therapy (HT) presents specific aspects that may increase the benefits of its use in different clinical and metabolic situations. The estrogen hepatic first-pass effect promotes alterations to the production of several types of proteins, characteristic that may influence the plasmatic lipoprotein level and the balance between the processes of coagulation and fibrinolysis. Therefore, in the presence of hypercholesterolemia, oral HT is the most appropriate route. Nonetheless, women with hypertension or with risk for venous thrombosis or with hypertriglyceridemy may benefit from transdermal route. However, regardless the administration route, one should not prescribe HT in primary prevention of cardiovascular disease (CVD)