Effects of recombinant LH supplementation to recombinant FSH during induced ovarian stimulation in the GnRH-agonist protocol: a matched case-control study

<p>Abstract</p> <p>Background</p> <p>Some studies have suggested that the suppression of endogenous LH secretion does not seem to affect the majority of patients who are undergoing assisted reproduction and stimulation with recombinant FSH (r-FSH). Other studies have indicated that a group of normogonadotrophic women down-regulated and stimulated with pure FSH preparations may experience low LH concentrations that compromise the IVF parameters. The present study aimed to compare the efficacy of recombinant LH (r-LH) supplementation for controlled ovarian stimulation in r-FSH and GnRH-agonist (GnRH-a) protocol in ICSI cycles.</p> <p>Methods</p> <p>A total of 244 patients without ovulatory dysfunction, aged <40 years and at the first ICSI cycle were divided into two groups matched by age according to an ovarian stimulation scheme: Group I (n = 122): Down-regulation with GnRH-a + r-FSH and Group II (n = 122): Down-regulation with GnRH-a + r-FSH and r-LH (beginning simultaneously).</p> <p>Result(s)</p> <p>The number of oocytes collected, the number of oocytes in metaphase II and fertilization rate were significantly lower in the Group I than in Group II (<it>P </it>= 0.036, <it>P </it>= 0.0014 and <it>P </it>= 0.017, respectively). In addition, the mean number of embryos produced per cycle and the mean number of frozen embryos per cycle were statistically lower (<it>P </it>= 0.0092 and <it>P </it>= 0.0008, respectively) in Group I than in Group II. Finally the cumulative implantation rate (fresh+thaw ed embryos) was significantly lower (<it>P </it>= 0.04) in Group I than in Group II. The other clinical and laboratory results analyzed did not show difference between groups.</p> <p>Conclusion</p> <p>These data support r-LH supplementation in ovarian stimulation protocols with r-FSH and GnRH-a for assisted reproduction treatment.</p

Relaxin: Review of Biology and Potential Role in Treating Heart Failure

Relaxin is a naturally occurring human peptide initially identified as a reproductive hormone. More recently, relaxin has been shown to play a key role in the maternal hemodynamic and renal adjustments that accommodate pregnancy. An understanding of these physiologic effects has led to the evaluation of relaxin as a pharmacologic agent for the treatment of patients with acute heart failure. Preliminary results have been encouraging. In addition, the other known biologic properties of relaxin, including anti-inflammatory effects, extracellular matrix remodeling effects, and angiogenic and anti-ischemic effects, all may play a role in potential benefits of relaxin therapy. Ongoing, large-scale clinical testing will provide additional insights into the potential role of relaxin in the treatment of heart failure

Relaxin, a pleiotropic vasodilator for the treatment of heart failure

Relaxin is a naturally occurring peptide hormone that plays a central role in the hemodynamic and renovascular adaptive changes that occur during pregnancy. Triggering similar changes could potentially be beneficial in the treatment of patients with heart failure. The effects of relaxin include the production of nitric oxide, inhibition of endothelin, inhibition of angiotensin II, production of VEGF, and production of matrix metalloproteinases. These effects lead to systemic and renal vasodilation, increased arterial compliance, and other vascular changes. The recognition of this has led to the study of relaxin for the treatment of heart failure. An initial pilot study has shown favorable hemodynamic effects in patients with heart failure, including reduction in ventricular filling pressures and increased cardiac output. The ongoing RELAX-AHF clinical program is designed to evaluate the effects of relaxin on the symptoms and outcomes in a large group of patients admitted to hospital for acute heart failure. This review will summarize both the biology of relaxin and the data supporting its potential efficacy in human heart failure

Expression and function of G-protein-coupled receptorsin the male reproductive tract

This review focuses on the expression and function of muscarinic acetylcholine receptors (mAChRs), α1-adrenoceptors and relaxin receptors in the male reproductive tract. The localization and differential expression of mAChR and α1-adrenoceptor subtypes in specific compartments of the efferent ductules, epididymis, vas deferens, seminal vesicle and prostate of various species indicate a role for these receptors in the modulation of luminal fluid composition and smooth muscle contraction, including effects on male fertility. Furthermore, the activation of mAChRs induces transactivation of the epidermal growth factor receptor (EGFR) and the Sertoli cell proliferation. The relaxin receptors are present in the testis, RXFP1 in elongated spermatids and Sertoli cells from rat, and RXFP2 in Leydig and germ cells from rat and human, suggesting a role for these receptors in the spermatogenic process. The localization of both receptors in the apical portion of epithelial cells and smooth muscle layers of the vas deferens suggests an involvement of these receptors in the contraction and regulation of secretion.Esta revisão enfatiza a expressão e a função dos receptores muscarínicos, adrenoceptores α1 e receptores para relaxina no sistema reprodutor masculino. A expressão dos receptores muscarínicos e adrenoceptores α1 em compartimentos específicos de dúctulos eferentes, epidídimo, ductos deferentes, vesícula seminal e próstata de várias espécies indica o envolvimento destes receptores na modulação da composição do fluido luminal e na contração do músculo liso, incluindo efeitos na fertilidade masculina. Além disso, a ativação dos receptores muscarínicos leva à transativação do receptor para o fator crescimento epidermal e proliferação das células de Sertoli. Os receptores para relaxina estão presentes no testículo, RXFP1 nas espermátides alongadas e células de Sertoli de rato e RXFP2 nas células de Leydig e germinativas de ratos e humano, sugerindo o envolvimento destes receptores no processo espermatogênico. A localização de ambos os receptores na porção apical das células epiteliais e no músculo liso dos ductos deferentes de rato sugere um papel na contração e na regulação da secreção.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de FarmacologiaUNIFESP, EPM, Depto. de FarmacologiaSciEL

Biological versus chronological ovarian age:implications for assisted reproductive technology

<p>Abstract</p> <p>Background</p> <p>Women have been able to delay childbearing since effective contraception became available in the 1960s. However, fertility decreases with increasing maternal age. A slow but steady decrease in fertility is observed in women aged between 30 and 35 years, which is followed by an accelerated decline among women aged over 35 years. A combination of delayed childbearing and reduced fecundity with increasing age has resulted in an increased number and proportion of women of greater than or equal to 35 years of age seeking assisted reproductive technology (ART) treatment.</p> <p>Methods</p> <p>Literature searches supplemented with the authors' knowledge.</p> <p>Results</p> <p>Despite major advances in medical technology, there is currently no ART treatment strategy that can fully compensate for the natural decline in fertility with increasing female age. Although chronological age is the most important predictor of ovarian response to follicle-stimulating hormone, the rate of reproductive ageing and ovarian sensitivity to gonadotrophins varies considerably among individuals. Both environmental and genetic factors contribute to depletion of the ovarian oocyte pool and reduction in oocyte quality. Thus, biological and chronological ovarian age are not always equivalent. Furthermore, biological age is more important than chronological age in predicting the outcome of ART. As older patients present increasingly for ART treatment, it will become more important to critically assess prognosis, counsel appropriately and optimize treatment strategies. Several genetic markers and biomarkers (such as anti-Müllerian hormone and the antral follicle count) are emerging that can identify women with accelerated biological ovarian ageing. Potential strategies for improving ovarian response include the use of luteinizing hormone (LH) and growth hormone (GH). When endogenous LH levels are heavily suppressed by gonadotrophin-releasing hormone analogues, LH supplementation may help to optimize treatment outcomes for women with biologically older ovaries. Exogenous GH may improve oocyte development and counteract the age-related decline of oocyte quality. The effects of GH may be mediated by insulin-like growth factor-I, which works synergistically with follicle-stimulating hormone on granulosa and theca cells.</p> <p>Conclusion</p> <p>Patients with biologically older ovaries may benefit from a tailored approach based on individual patient characteristics. Among the most promising adjuvant therapies for improving ART outcomes in women of advanced reproductive age are the administration of exogenous LH or GH.</p