Individualised controlled ovarian stimulation (iCOS): maximising success rates for assisted reproductive technology patients

<p>Abstract</p> <p>Background</p> <p>In the last two decades, pregnancy rates for patients undergoing in-vitro fertilisation (IVF) have significantly increased. Some of the major advances responsible for this improvement were the introduction of controlled ovarian stimulation (COS) for the induction of multiple follicle development, and the utilisation of mid-luteal gonadotropin-releasing hormone agonists to achieve pituitary down-regulation and full control of the cycle. As a result, a combination of a gonadotropin-releasing hormone agonist with high doses (150-450 IU/day) of recombinant follicle-stimulating hormone has become the current standard approach for ovarian stimulation. However, given the heterogeneity of patients embarking on IVF, and the fact that many different drugs can be used alone or in different combinations (generating multiple potential protocols of controlled ovarian stimulation), we consider the need to identify special populations of patients and adapt treatment protocols accordingly, and to implement a more individualised approach to COS.</p> <p>Discussion</p> <p>Studies on mild, minimal and natural IVF cycles have yielded promising results, but have focused on fresh embryo transfers and included relatively young patient populations who generally have the potential for more favourable outcomes. The efficacy of these protocols in patients with a poorer prognosis remains to be tested. When comparing protocols for COS, it is important to think beyond current primary endpoints, and to consider the ideal quality and quantity of oocytes and embryos being produced per stimulated patient, in order to achieve a pregnancy. We should also focus on the cumulative pregnancy rate, which is based on outcomes from fresh and frozen embryos from the same cycle of stimulation. Individualised COS (iCOS) determined by the use of biomarkers to test ovarian reserve has the potential to optimise outcomes and reduce safety issues by adapting treatment protocols according to each patient's specific characteristics. As new objective endocrine, paracrine, functional and/or genetic biomarkers of response are developed, iCOS can be refined further still, and this will be a significant step towards a personalised approach for IVF.</p> <p>Conclusions</p> <p>A variety of COS protocols have been adopted, with mixed success, but no single approach is appropriate for all patients within a given population. We suggest that treatment protocols should be adapted for individual patients through iCOS; this approach promises to be one of the first steps towards implementing personalised medicine in reproductive science.</p

Hormonal, functional and genetic biomarkers in controlled ovarian stimulation: tools for matching patients and protocols

Variability in the subfertile patient population excludes the possibility of a single approach to controlled ovarian stimulation (COS) covering all the requirements of a patient. Modern technology has led to the development of new drugs, treatment options and quantitative methods that can identify single patient characteristics. These could potentially be used to match patients with the right treatment options to optimise efficacy, safety and tolerability during COS. Currently, age and follicle-stimulating hormone (FSH) level remain the most commonly used single patient characteristics in clinical practice. These variables only provide a basic prognosis for success and indications for standard COS treatment based on gross patient categorisation. In contrast, the anti-Müllerian hormone level appears to be an accurate predictor of ovarian reserve and response to COS, and could be used successfully to guide COS. The antral follicle count is a functional biomarker that could be useful in determining the dose of FSH necessary during stimulation and the success of treatment. Finally, in the future, genetic screening may allow an individual patient's response to stimulation during COS to be predicted based on genotype. Unfortunately, despite the predictive power of these measures, no single biomarker can stand alone as a guide to determine the best treatment option. In the future, hormonal, functional and genetic biomarkers will be used together to personalise COS

Recombinant human follicle-stimulating hormone produces more oocytes with a lower total dose per cycle in assisted reproductive technologies compared with highly purified human menopausal gonadotrophin: a meta-analysis

<p>Abstract</p> <p>Background</p> <p>Human menopausal gonadotrophins and recombinant human follicle stimulating hormone are the two main gonadotrophin products utilized for controlled ovarian stimulation in assisted reproductive technologies. In this meta-analysis, the number of oocytes was designated as the most relevant endpoint directly resulting from ovarian stimulation, and therefore where the drug effect may be estimated with the best sensitivity.</p> <p>Methods</p> <p>All published randomized controlled trials on ovarian stimulation comparing the two gonadotrophin products were evaluated. Internal validity was determined using Chalmers' validated scale. If trials did not meet the established quality criteria, a sensitivity analysis assessed the stability of the results. The comparison of continuous variables was conducted following the weighted mean difference and the standardized mean difference (Cohen's effect size) with the random model. Given the known relationship of baseline conditions on treatment endpoints, results were adjusted for age, body mass index and type of infertility.</p> <p>Results</p> <p>Sixteen studies involving 4040 patients were included. Treatment with human menopausal gonadotrophins resulted in fewer oocytes (-1.54; 95% CI: -2.53 to -0.56; P < 0.0001) compared to recombinant human follicle-stimulating hormone. When adjusting for baseline conditions, the mean difference estimate was -2.10 (95% CI: -2.83 to -1.36; P < 0.001). A higher total dose of human menopausal gonadotrophin was necessary (mean difference, 235.46 IU [95% CI: 16.62 to 454.30; P = 0.03]; standardized mean difference, 0.33 [95% CI: 0.08 to 0.58; P = 0.01]). The pregnancy absolute risk difference (RD [hMG-r-hFSH]) for fresh transfers was 3% (P = 0.051), and the relative risk 1.10 (P = 0.06). When adjusted for baseline conditions, the relative risk was 1.04 (P = 0.49) and absolute difference was 0.01 (P = 0.34), respectively.</p> <p>Conclusions</p> <p>Because baseline conditions are predictive of outcome, meta-analytic results are more sensitive when these variables are considered. Using an endpoint closely associated with the stimulation period, sufficient sensitivity is achieved to compare gonadotrophin treatments. As the largest meta-analysis published to date on this subject, treatment with human menopausal gonadotrophins is characterized by fewer oocytes and a higher total dose. When considering only fresh transfers, pregnancy rates were similar.</p

Diseño cuasi experimental para el análisis de la decisión de compra del consumidor limeño ante los sistemas de rotulado frontal en abarrotes y lácteos

Esta investigación analiza la decisión de compra del consumidor limeño al momento de adquirir productos de la canasta básica familiar en la coyuntura de la implementación de los llamados octógonos nutricionales, rotulado frontal cuya finalidad es informar al consumidor. Este sistema consiste en la aplicación de etiquetas que indican si un producto es alto en “azúcar”, “sodio”, “grasas saturadas” o “grasas trans”, a fin de que el usuario disponga de más herramientas para elegir responsablemente sobre el consumo de diferentes productos. Es preciso indicar que en el Perú el rotulado se aplicó en cumplimiento del Decreto Legislativo N° 1304, Ley de Etiquetado y Verificación de los Reglamentos Técnicos de los Productos Industriales Manufacturados, cuya finalidad es establecer, de manera obligatoria, el etiquetado para los productos industriales manufacturados, para uso o consumo final, que sean comercializados en el territorio nacional (Decreto Legislativo N° 1304, 2016). La presente investigación aplica una metodología mixta, en la que destaca un cuasiexperimento a fin de identificar si la cantidad de octógonos nutricionales influye en la decisión de compra del consumidor. Para ello se realiza una simulación de compra online de dos productos de la canasta familiar: aceite y margarina. El usuario debe elegir entre dos marcas en diferentes escenarios: en uno de ellos, los productos tienen la misma cantidad de octógonos, y en el otro se muestra una cantidad diferente. Tras los resultados del estudio, se concluye que sí existen diferencias en la decisión de compra del consumidor de productos de la canasta familiar rotulados con octógonos nutricionales, lo cual muestra en el caso de los aceites y margarinas un comportamiento y toma de decisiones responsables respecto a la salud nutricional de las personas.Tesi

Untangling the dinosaur family tree

For over a century, the standard classification scheme has split dinosaurs into two fundamental groups: ‘lizard-hipped’ saurischians (including meat-eating theropods and long-necked sauropodomorphs) and ‘bird-hipped’ ornithischians (including a variety of herbivorous species).In a recent paper, Baron et al. challenged this paradigm with a new phylogenetic analysis that places theropods and ornithischians together in a group called Ornithoscelida, to the exclusion of sauropodomorphs, and used their phylogeny to argue that dinosaurs may have originated in northern Pangaea, not in the southern part of the supercontinent, as has more commonly been considered. Here we evaluate and reanalyse the morphological dataset underpinning the proposal by Baron et al. and provide quantitative biogeographic analyses, which challenge the key results of their study by recovering a classical monophyletic Saurischia and a Gondwanan origin for dinosaurs. This shows that the Ornithoscelida hypothesis is not the final word, and that there is still great uncertainty around the basic structure of the dinosaur family tree.Fil: Langer, Max C.. Universidade de Sao Paulo; BrasilFil: Ezcurra, Martin Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales “Bernardino Rivadavia”; ArgentinaFil: Rauhut, Oliver Walter Mischa. Ludwig Maximilians Universitat; AlemaniaFil: Benton, Michael J.. University of Bristol; Reino UnidoFil: Knoll, Fabien. University of Manchester; Reino UnidoFil: McPhee, Blair W.. Universidade de Sao Paulo; BrasilFil: Novas, Fernando Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales “Bernardino Rivadavia”; ArgentinaFil: Pol, Diego. Museo Paleontológico Egidio Feruglio; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Brusatte, Stephen L.. University of Edinburgh; Reino Unid

The Human Oocyte Preservation Experience (HOPE) a phase IV, prospective, multicenter, observational oocyte cryopreservation registry

<p>Abstract</p> <p>Background</p> <p>It has been recommended by the American Society of Clinical Oncology and the American Society of Reproductive Medicine that options to preserve fertility be presented at the outset of treatment for cancer. This recommendation may have arisen, in part, to the increasing survival of patients with cancer and the realization that certain forms of cancer treatment can lead to infertility. One option for these patients, particularly those with ethical or religious objections to freezing embryos is oocyte cryopreservation. However universal acceptance of these procedures has yet to be established, most likely due to a poor history of success and concerns that there has yet to be a comprehensive approach to evaluating these techniques. In light of this, a registry of patients undergoing oocyte cryopreservation, called the HOPE registry, is being implemented.</p> <p>Discussion</p> <p>The intent of the HOPE Registry is to enroll approximately 400 women of reproductive age who will undergo thawing/warming of oocytes and subsequent transfer. Data from the patients enrolled will be collected via a uniform, standardized form and will document important parameters such as demographics, laboratory procedures and outcomes, including following the outcomes of babies born for one year after birth. The results of the registry will be published on a yearly basis.</p> <p>Summary</p> <p>A patient registry has been established in order to systematically document the techniques and outcomes of oocyte cryopreservation procedures. The results will be published in order to provide a widely accessible resource that will allow patients who are considering these procedures validated information in order to make informed decisions as to how their treatment will proceed.</p

A New Basal Sauropodomorph (Dinosauria: Saurischia) from Quebrada del Barro Formation (Marayes-El Carrizal Basin), Northwestern Argentina

BACKGROUND: Argentinean basal sauropodomorphs are known by several specimens from different basins; Ischigualasto, El Tranquilo, and Mogna. The Argentinean record is diverse and includes some of the most primitive known sauropodomorphs such as Panphagia and Chromogisaurus, as well as more derived forms, including several massospondylids. Until now, the Massospondylidae were the group of basal sauropodomorphs most widely spread around Pangea with a record in almost all continents, mostly from the southern hemisphere, including the only record from Antarctica. METHODOLOGY/PRINCIPAL FINDING: We describe here a new basal sauropodomorph, Leyesaurus marayensis gen. et sp. nov., from the Quebrada del Barro Formation, an Upper Triassic-Lower Jurassic unit that crops out in northwestern Argentina. The new taxon is represented by a partial articulated skeleton that includes the skull, vertebral column, scapular and pelvic girdles, and hindlimb. Leyesaurus is diagnosed by a set of unique features, such as a sharply acute angle (50 degrees) formed by the ascending process of the maxilla and the alveolar margin, a straight ascending process of the maxilla with a longitudinal ridge on its lateral surface, noticeably bulging labial side of the maxillary teeth, greatly elongated cervical vertebrae, and proximal articular surface of metatarsal III that is shelf-like and medially deflected. Phylogenetic analysis recovers Leyesaurus as a basal sauropodomorph, sister taxon of Adeopapposaurus within the Massospondylidae. Moreover, the results suggest that massospondylids achieved a higher diversity than previously thought. CONCLUSIONS/SIGNIFICANCE: Our phylogenetic results differ with respect to previous analyses by rejecting the massospondylid affinities of some taxa from the northern hemisphere (e.g., Seitaad, Sarahsaurus). As a result, the new taxon Leyesaurus, coupled with other recent discoveries, suggests that the diversity of massospondylids in the southern hemisphere was higher than in other regions of Pangea. Finally, the close affinities of Leyesaurus with the Lower Jurassic Massospondylus suggest a younger age for the Quebrada del Barro Formation than previously postulated