Chronic administration of sildenafil improves endothelial function in spontaneously hypertensive rats by decreasing COX-2 expression and oxidative stress.

AIMS: Spontaneously hypertensive rats (SHR) exhibit impaired endothelial vasodilation and enhanced vasoconstriction. The phosphodiesterase 5 (PDE5) inhibitor sildenafil (Sild) potentiates the nitric oxide (NO)-mediated effects exerting antioxidative and anti-inflammatory actions. In the present study, we hypothesized that Sild could improve endothelial function in SHR. MATERIALS AND METHODS: Male rats were treated daily for 60 days by oral gavage with Sild (45 mg/kg) before the onset of the hypertensive state (pre-hypertensive protocol). The aortic relaxation to acetylcholine (ACh), sodium nitroprusside (SNP) and the phenylephrine (Phe)-induced contraction was evaluated in SHR. Protein expression of eNOS, p-eNOS, caveolin, COX-1, COX-2, ERK and p-ERK was measured by Western blot. KEY FINDINGS: Resting blood pressure was not modified by Sild administration. Treatment with Sild did not alter the relaxation response to SNP but improved the ACh-induced relaxation and reduced Phe-induced contraction in aortic rings from SHR. This protective effect of Sild could be attributed to reduced superoxide anions (O2-) generation, cyclooxygenase type 2 (COX-2) protein downregulation and increased NO bioavailability. SIGNIFICANCE: Sild improves endothelial function in SHR aorta without affecting resting blood pressure values. These results indicate that PDE5 inhibition has a potential role in the improvement of vascular function and could be an adjuvant in the treatment of essential hypertension.

Clinical outcomes after preimplantation genetic diagnosis of patients with Corino de Andrade disease (familial amyloid polyneuropathy).

The aim of this study was to determine whether patients with transthyretin-related hereditary amyloidosis (V30M), after transplantation or under tafamidis treatment, have normal gamete reproductive capacity. A retrospective analysis was carried out of all preimplantation genetic diagnosis (PGD) cycles performed in patients with the V30M mutation. The groups analysed were: total cases with V30M, female cases with V30M and male cases with V30M. Detailed demographic, stimulation, embryological, clinical and newborn outcomes were evaluated. Comparisons revealed that patients have a high likelihood of achieving a live birth per PGD treatment cycle (48%). This is the first large report on patients with the V30M mutation treated with PGD. The high rate of live birth obtained should represent a strong stimulus for patients to use PGD as it proved to be effective and safe. As a neurodegenerative disease that leads to death, it is of maximum importance that it could be eradicated using PGD in order to definitively avoid the transmission of the disease.

Ovarian hyperstimulation syndrome: a clinical report on 4894 consecutive ART treatment cycles.

BACKGROUND: Although a large number of studies have been dedicated to ovarian hyperstimulation syndrome (OHSS) none gave full embryological and clinical outcomes comparing oocyte trigger with human chorionic gonadotrophin (HCG) versus with a gonadotrophin-releasing hormone (GnRH) agonist (Buserelin) in cases with suspicious OHSS. The aim of the present study was thus to analyze 4894 consecutive assisted reproductive treatment cycles to undercover associated risk factors for development of OHSS, and the effects of the use of Buserelin as ovulation trigger on embryological and clinical outcomes. METHODS: In the 51 cases that developed OHSS, ovulation trigger was performed with HCG as indicators were not suspicious for OHSS. These were compared against two types of groups: 71 cases where Buserelin was used for ovulation induction due to suspicious development of OHSS; and those remaining 4772 cases where ovulation trigger was currently performed with HCG (control). RESULTS: Of the cases treated with Buserelin the oocyte maturation rate and the ongoing pregnancy rate were significantly lower, with higher rates of ectopic pregnancy and newborn malformations, but none developed OHSS. Of the OHSS cases, 23 needed hospitalization, with no major complications. CONCLUSIONS: Young age, lower time of infertility, lower basal follicle stimulating hormone levels, higher number of cases with female factor and polycystic ovarian syndrome, high number of follicles and higher estradiol concentrations were the risk factors found associated with OHSS. Cases with OHSS also presented higher follicle count but the estradiol levels were within the normal range. It thus remains to develop more strict criteria to avoid all cases with OHSS.

[Ovarian hyperstimulation syndrome: experience of a reproductive medicine center 2005-2011]. / Síndrome de Hiperestimulação Ovárica: experiência de um Centro de Medicina da Reprodução 2005-2011.

INTRODUCTION: Ovarian Hyperstimulation Syndrome is a complication of controlled ovarian hyperstimulation during cycles of Assisted Medical Reproduction. The objective of this work was to analyze those cycles to achieve a better knowledge of this pathology, namely risk factors and strategies for prevention and treatment of Ovarian Hyperstimulation Syndrome. MATERIALS AND METHODS: Retrospective analysis of 4870 ART cycles (2005 - 2011), with moderate (27) and severe (24) Ovarian Hyperstimulation Syndrome. Data was analyzed for patients' characteristics, stimulation protocol, embryologic and clinical outcomes, and treatment performed. RESULTS: In Ovarian Hyperstimulation Syndrome groups the mean ages and the doses of rFSH + HMG were lower, and the serum E2 levels, doses of HCG, number of oocytes retrieved as well as the rates of blastocyst, biochemical and clinical pregnancy, implantation, newborns, very preterm birth and newborns with low and very low weight were significantly higher. Patients with severe Ovarian Hyperstimulation Syndrome were hospitalized and received only support measures with no complications. DISCUSSION: Ovarian Hyperstimulation Syndrome is associated with conditions that can bring risk to the fetus, namely prematurity and low birth weight, so the pregnancy should be carefully monitored in these cases. CONCLUSIONS: Young age is a risk factor for Ovarian Hyperstimulation Syndrome and high serum E2 levels may predict a higher risk too and thus should induce the adoption of prevention strategies.

Introdução: A Síndrome de Hiperestimulação Ovárica é uma complicação da hiperestimulação controlada do ovário realizada nos ciclos de reprodução medicamente assistida . O objetivo deste trabalho foi efetuar uma análise desses ciclos, para melhor compreensão daquela patologia, nomeadamente fatores de risco, formas de prevenção e tratamento da mesma e suas consequências. Materiais e Métodos: Análise retrospetiva de 4870 ciclos de reprodução medicamente assistida (2005 - 2011) com Síndrome de Hiperestimulação moderado (27) e grave (24). Foram estudados, os dados das características dos doentes, protocolos de estimulação, resultados embriológicos e clínicos, e tratamento efetuado. Resultados: No grupo com Síndrome de Hiperestimulação Ovárica a idade média foi inferior, a dose de rFSH + HMG foi mais baixa e os níveis de estradiol foram mais elevados. Nos grupos com Síndrome de Hiperestimulação, as taxas foram significativamente superiores para o número médio de ovócitos e blastocistos obtidos, de gravidez bioquímica e clínica, de implantação e de recém-nascidos. O parto muito pré-termo e a proporção de recém-nascidos com peso baixo e muito baixo foram superiores no grupo com Síndrome de Hiperestimulação Ovárica. As doentes com Síndrome de Hiperestimulação Ovárica grave foram hospitalizadas tendo apenas sido necessária medicação de suporte. Discussão: A Síndrome de Hiperestimulação Ovárica foi associada a condições de risco para o feto, nomeadamente prematuridade e baixo peso ao nascimento, devendo manter-se uma vigilância apertada da gravidez nestes casos. Conclusão: A idade jovem constitui um fator de risco de Síndrome de Hiperestimulação Ovárica e o nível de estradiol elevado foi preditor do mesmo, devendo levar à adoção de estratégias de prevenção.

Ultrastructure of tubular smooth endoplasmic reticulum aggregates in human metaphase II oocytes and clinical implications.

OBJECTIVE: To compare demographic, embryologic, pregnancy, and newborn outcomes after intracytoplasmic sperm injection (ICSI) cycles with or without mature oocytes (metaphase II [MII]) showing visible aggregates of tubular smooth endoplasmic reticulum (aSERT) and to describe the ultrastructure of this dysmorphism. DESIGN: Retrospective study. SETTING: Private fertility center and university cell biology and genetics departments. PATIENT(S): There were 721 ICSI cycles, 520 carrying morphologically normal MII (control group) and 60 containing aSERT-MII (study group). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Embryologic and clinical and live birth outcomes, including malformations and ultrastructural characterization of aSERT-MII. RESULT(S): Compared with the control group there was a significant decrease in the fertilization, embryo cleavage, and blastocyst rates in the study group. The only child born after transfer of embryos derived from aSERT-MII presented a major cardiovascular malformation. Ultrastructurally, large aSERT were surrounded by abnormal-shaped mitochondria and clusters of small dense bodies formed by very small vesicles, and they had curvilinear dense tubules in the interior. The same pathology was observed in small peripheral aSERT. CONCLUSION(S): The presence of large aSERT, showing attainment of the periphery, demonstrated that the cytoplasm is pathologic. The compromised embryo development and implantation was associated with decreased clinical outcomes and newborn malformations. Therefore, oocytes with large aSERT should not be used for embryo transfer.

Impact of GnRH ovarian stimulation protocols on intracytoplasmic sperm injection outcomes.

BACKGROUND: Although a large number of studies have been conducted in relation to ovarian response and pregnancy after GnRH agonist and GnRH antagonist controlled ovarian hyperstimulation protocols, most of them used single or combinations of a few predictive factors, and none included the stimulation protocol in the multivariable analysis. The present study was thus primarily designed to investigate the predictive value of the stimulation protocol and to analyze the possible relationships between stimulation protocols and treatment outcomes after adjusting for a large set of variables that potentially affect reproductive outcomes. Factors related to pregnancy achievement and predictive of the number of oocytes retrieved and high quality of the embryos obtained were also analyzed. METHODS: To analyze the impact of GnRH ovarian stimulation protocols on the independent predictors of ovarian response, high quality embryos and clinical pregnancy, two groups out of 278 ICSI treatment cycles were compared prospectively, 123 with a GnRH agonist and 155 with a GnRH antagonist, with multivariable analysis assessing outcomes after adjusting for a large set of variables. RESULTS: Antagonists were significantly associated with lower length and total dose of GnRH, lower length of rFSH, and higher numbers of oocytes and high quality embryos, whereas the agonist presented a higher fertilization rate and probability of pregnancy. Significant predictors of retrieved oocytes and high quality embryos were the antagonist protocol, lower female age, lower serum levels of basal FSH and higher total number of antral follicles. Significant predictors of clinical pregnancy were the agonist protocol, reduced number of attempts, increased endometrial thickness and lower female age. The probability of pregnancy increased until 30 years-old, with a decline after that age and with a sharp decline after 40 years-old. CONCLUSION: The models found suggest that not only the protocol but also factors as female age, basal FSH, antral follicles, number of attempts and endometrial thickness should be analyzed for counselling patients undergoing an ICSI treatment.