04 July 2011
Vista completa||Volver a mensajesTaller women more likely to have twins
Taller women are more likely to have dizygotic (non-identical) twin pregnancies after double embryo transfer (DET), researchers from The Netherlands have found. Dr. Marieke Lambers, from VUMC, Gynaecology Obstetrics and Reproductive Medicine, Amsterdam, told the annual conference of the European Society of Human Reproduction and Embryology today (Monday) that the findings could help doctors decide whether to transfer one or two embryos in order to minimise multiple pregnancies without compromising pregnancy rates. “This is a further step towards the development of tailor-made personalised IVF treatment,” she said. The researchers say that this is the first time the effect of maternal height on multiple implantation has been shown. “In natural dizygotic twinning it is not possible to distinguish between multiple ovulation and implantation,” said Dr. Lambers “whereas by studying pregnancies in mothers who have undergone DET we know exactly how many embryos were transferred and can therefore draw firm conclusions about the factors that influence the development of twin pregnancies.” The researchers studied data from the 19840 women in The Netherlands who underwent IVF treatment between 1983 and 1995 (the OMEGA study group). They selected all first fresh (unfrozen) IVF and ICSI cycles using DET that resulted in the delivery of a single or twin baby, both living and stillborn. Excluded from the analysis were cases where there were insufficient data from medical files, patients who used donated oocytes or who had undertaken fertility treatment besides IVF and ICSI, those who had had an abortion, an ectopic pregnancy, or a miscarriage. The remaining group was analysed using a dependent variable – whether or not the pregnancy was single or multiple – and a number of independent variables: BMI, weight, height, maternal age, number of oocytes retrieved, use of alcohol, level of education and parity. Of the 6589 patients who completed their first IVF cycle, 2357 women had DET, resulting in 371 singleton and 125 twin pregnancies. “When we came to analyse the twin group, we found that a maternal height of over 1.74cm and more than 11 oocytes retrieved were independently associated with twin pregnancies,” said Dr. Lambers. “The positive relationship between a higher number of oocytes retrieved and a twin pregnancy probably reflects the fact that these women would have had a larger choice of good quality embryos. But the association between increased height and multiple pregnancy is more difficult to explain. Previous studies have shown that women who are prone to conceive twins after IVF have a higher level of vascular endothelial growth factor-A (VEGF-A), which promotes the growth of blood vessels at the site of implantation. Perhaps there is also an association between tall stature and increased VEGF-A levels,” she said. “Doctors working in IVF are faced with a constant balancing act between giving the best chance of achieving a pregnancy without incurring all the problems associated with multiple births,” said Dr. Lambers. “We hope that our work could be used in future as a basis for predictive models that assist in the choice between single and double embryo transfer. This is an important topic, since multiple pregnancies involve a higher risk of problems for the mother, such as pre-eclampsia, and also for the baby due to pre-term or immature delivery.”
03 July 2011
Treatment approach to human Usher syndrome: Small molecules ignore stop signals
Usher syndrome is the most common form of combined congenital deaf-blindness in humans and affects 1 in 6,000 of the population. It is a recessive inherited disease that is both clinically and genetically heterogeneous. In the most severe cases, patients are born deaf and begin to suffer from a degeneration of the retina in puberty, ultimately resulting in complete blindness. These patients experience major problems in their day-to-day life. While hearing loss can be compensated for with hearing aids and cochlea implants, it has not proven possible to develop a treatment for the associated sight loss to date. Researchers at Johannes Gutenberg University Mainz (JGU) in Germany have now developed a new treatment approach to this disease. In previously conducted research into this subject, the research team headed by Professor Uwe Wolfrum of the Institute of Zoology at Mainz University had already gained insight into of the fundamental molecular processes and mechanisms causing this debilitating syndrome. Using the results of this successful basic research, the Usher treatment team in Mainz headed by Dr Kerstin Nagel-Wolfrum has now evaluated potential ocular treatment options. Their attention was focused on a mutation identified in a specific German family known to develop the most severe form of Usher syndrome. This mutation is a so-called nonsense mutation in the USH1C gene, which leads to the generation of a stop signal in a DNA base, resulting in premature termination of protein synthesis.
The Mainz research team has now published its latest work on pharmacogenetic strategies for the treatment of Usher syndrome patients with nonsense mutations in the May edition of the journal Human Gene Therapy. The researchers were able to show that a small molecule known as PTC124 (Ataluren®) causes the stop signal in the mutated USH1C gene to be ignored, thus resulting in continuing protein synthesis and the formation of the functional genetic product in cell and organ cultures. In addition to its ability to cause readthrough of stop signals, the active agent PTC124 has also been demonstrated to be highly compatible with murine and human retina cultures. Moreover, the team managed for the first time to demonstrate readthrough of an eye mutation codon in vivo.
"PTC124 is already being tested in clinical trials for its efficacy in treating other diseases involving nonsense mutations, such as cystic fibrosis and Duchenne muscular dystrophy. We therefore hope that this treatment approach will soon be ready for use in Usher syndrome patients," explains Dr Kerstin Nagel-Wolfrum.
Currently putting the finishing touches on his doctoral thesis, Tobias Goldmann is comparing the efficiency of the readthrough rate and the biocompatibility of other molecules that induce the readthrough of nonsense mutations. The focus is particularly on modified aminoglycosides, i.e. derivatives of commercially available and clinically tested antibiotics. These are being designed and synthesized by an Israeli cooperation partner, Professor Timor Bassov of the Haifa Technicon, and have already been successfully used by researchers in Mainz for readthrough of nonsense mutations in Usher genes. In addition to conducting further preclinical studies of the ocular applications of these new substances, the Usher laboratory in Mainz is planning to use this new method of treating this specific form of Usher syndrome in hospital patients as soon as possible.
The translational biomedical research on readthrough of nonsense mutations aimed at developing a treatment for Usher syndrome is being funded by the FAUN foundation and the "Syscilia" project of the Seventh Framework Program of the European Union. It is part of the Research Training Group 1044 "Developmental and Disease-Induced Modifications of the Nervous System," funded by the German Research Foundation (DFG). The group has recently joined the Translational Neurosciences Research Focus of Johannes Gutenberg University Mainz.
**Source: Johannes Gutenberg Universitaet Mainz
The Mainz research team has now published its latest work on pharmacogenetic strategies for the treatment of Usher syndrome patients with nonsense mutations in the May edition of the journal Human Gene Therapy. The researchers were able to show that a small molecule known as PTC124 (Ataluren®) causes the stop signal in the mutated USH1C gene to be ignored, thus resulting in continuing protein synthesis and the formation of the functional genetic product in cell and organ cultures. In addition to its ability to cause readthrough of stop signals, the active agent PTC124 has also been demonstrated to be highly compatible with murine and human retina cultures. Moreover, the team managed for the first time to demonstrate readthrough of an eye mutation codon in vivo.
"PTC124 is already being tested in clinical trials for its efficacy in treating other diseases involving nonsense mutations, such as cystic fibrosis and Duchenne muscular dystrophy. We therefore hope that this treatment approach will soon be ready for use in Usher syndrome patients," explains Dr Kerstin Nagel-Wolfrum.
Currently putting the finishing touches on his doctoral thesis, Tobias Goldmann is comparing the efficiency of the readthrough rate and the biocompatibility of other molecules that induce the readthrough of nonsense mutations. The focus is particularly on modified aminoglycosides, i.e. derivatives of commercially available and clinically tested antibiotics. These are being designed and synthesized by an Israeli cooperation partner, Professor Timor Bassov of the Haifa Technicon, and have already been successfully used by researchers in Mainz for readthrough of nonsense mutations in Usher genes. In addition to conducting further preclinical studies of the ocular applications of these new substances, the Usher laboratory in Mainz is planning to use this new method of treating this specific form of Usher syndrome in hospital patients as soon as possible.
The translational biomedical research on readthrough of nonsense mutations aimed at developing a treatment for Usher syndrome is being funded by the FAUN foundation and the "Syscilia" project of the Seventh Framework Program of the European Union. It is part of the Research Training Group 1044 "Developmental and Disease-Induced Modifications of the Nervous System," funded by the German Research Foundation (DFG). The group has recently joined the Translational Neurosciences Research Focus of Johannes Gutenberg University Mainz.
**Source: Johannes Gutenberg Universitaet Mainz
Unos investigadores piden ciudades mejor adaptadas a la meteorología
Caminar media hora al día es uno de los mejores ejercicios, repiten continuamente los médicos. Bastan 30 minutos a buen paso para cuidar un poco la salud. Pero ¿qué hacer en verano, cuando las autoridades sanitarias recomiendan no salir -mucho menos andar- en las horas centrales del día, o en invierno cuando la nieve hace imposible este ejercicio? Unos investigadores de la Universidad McGill (Montreal, Canadá) han analizado cómo influye el clima en los paseos ciudadanos.
Desde noviembre hasta mayo observaron el gusto por las caminatas de los habitantes de nueve ciudades del hemisferio norte: Santa Cruz de La Palma en Gran Canaria, Kilmarnock y Glasgow en Escocia, Rousse en Bulgaria, Gliwice en Polonia, Oulu y Jakobstad en Finlandia, Sion en Suiza e Ítaca en EEUU. De las estudiadas, la ciudad española es la más pequeña, con 18.000 ciudadanos, mientras que Glasgow es la más numerosa, con una población de 1,2 millones de personas. Oulu es el lugar más frío de todos, con temperaturas por debajo de los 0ºC la mayoría de los días estudiados.
Los resultados del trabajo, publicados en 'Environment and Behavior' muestran que cuando hace frío, un aumento de 5ºC en la temperatura incrementa el número de peatones un 14% y cuando deja de nevar el incremento es del 23%. Y, lo que más desanima a quienes quieren pasear es la lluvia. En Rousse, en los días lluviosos, el número de caminantes descendía un 42%. El aire, sin embargo, tiene menos influencia que otros factores del clima.
Además de la alternativa de los gimnasios o, en el verano, aprovechar las primeras o las últimas horas del día, los investigadores afirman que "muchas más personas caminarían si quienes diseñan los planes urbanísticos de las ciudades tuvieran en cuenta el clima y utilizaran superficies que absobieran bien el agua, un sistema de alcantarillado que desagüe en condiciones o partes cubiertas en determinados tramos de la ciudad, así como servicios que retiren la nieve acumulada con rapidez".
"Nuestro estudio demuestra que la gente camina cuando está preparada para aguantar la temperatura . Es un ejercicio que no requiere un gran cambio de actitud, porque las personas están dispuestas, pero sí necesitan que el paisaje urbano ofrezca unas condiciones óptimas para hacerlo", indica Luc de Montigny, del Departamento de Epidemiología de la Universidad y principal firmante de la investigación. "Dada la epidemia de obesidad que afecta a todos los países, facilitar el paseo a sus ciudadanos es lo menos que las autoridades pueden hacer", concluye.
**Publicado en "EL MUNDO"
Desde noviembre hasta mayo observaron el gusto por las caminatas de los habitantes de nueve ciudades del hemisferio norte: Santa Cruz de La Palma en Gran Canaria, Kilmarnock y Glasgow en Escocia, Rousse en Bulgaria, Gliwice en Polonia, Oulu y Jakobstad en Finlandia, Sion en Suiza e Ítaca en EEUU. De las estudiadas, la ciudad española es la más pequeña, con 18.000 ciudadanos, mientras que Glasgow es la más numerosa, con una población de 1,2 millones de personas. Oulu es el lugar más frío de todos, con temperaturas por debajo de los 0ºC la mayoría de los días estudiados.
Los resultados del trabajo, publicados en 'Environment and Behavior' muestran que cuando hace frío, un aumento de 5ºC en la temperatura incrementa el número de peatones un 14% y cuando deja de nevar el incremento es del 23%. Y, lo que más desanima a quienes quieren pasear es la lluvia. En Rousse, en los días lluviosos, el número de caminantes descendía un 42%. El aire, sin embargo, tiene menos influencia que otros factores del clima.
Además de la alternativa de los gimnasios o, en el verano, aprovechar las primeras o las últimas horas del día, los investigadores afirman que "muchas más personas caminarían si quienes diseñan los planes urbanísticos de las ciudades tuvieran en cuenta el clima y utilizaran superficies que absobieran bien el agua, un sistema de alcantarillado que desagüe en condiciones o partes cubiertas en determinados tramos de la ciudad, así como servicios que retiren la nieve acumulada con rapidez".
"Nuestro estudio demuestra que la gente camina cuando está preparada para aguantar la temperatura . Es un ejercicio que no requiere un gran cambio de actitud, porque las personas están dispuestas, pero sí necesitan que el paisaje urbano ofrezca unas condiciones óptimas para hacerlo", indica Luc de Montigny, del Departamento de Epidemiología de la Universidad y principal firmante de la investigación. "Dada la epidemia de obesidad que afecta a todos los países, facilitar el paseo a sus ciudadanos es lo menos que las autoridades pueden hacer", concluye.
**Publicado en "EL MUNDO"
La comunicación y la rigurosidad científica, claves para la obtención de los claims de Salud
Se reunieron 60 personas en Barcelona en la I Jornada 'El Claim de Salud', organizada por Claimfoodcom, cuyo propósito ha sido el de debatir sobre los aspectos más importantes de las alegaciones o declaraciones nutricionales y de salud, comprender las claves para obtener su aprobación e identificar los beneficios que pueden suponer tanto para los consumidores como para la industria de la alimentación.
De izq. a dcha.: Abel Mariné, Ana Palencia, Xavier Lorenz y Andreu Palou.
Todos los ponentes han coincidido en destacar la relevancia de la base científica para sustentar estas alegaciones, teniendo como referencia el Reglamento europeo 1924/2006. Montserrat Prieto, Directora de Política Alimentaria de la Federación Española de Industria de Alimentación y Bebidas (FIAB), ha sintetizado que este Reglamento sirve “para gestionar la comunicación en nutrición y salud a escala europea y lograr mayor protección para el consumidor, garantizando la libre circulación de mercancías y aportando un alto valor a la base científica”. Este Reglamento y el trabajo que está llevando a cabo la EFSA (European Food Safety Authority) han estado presentes en todas las ponencias pero ha sido Carmen Arias, de la Subdirección General de Gestión de Riesgos Alimentarios (AESAN) quien ha centrado toda su presentación en revisar su aplicación y realizar una completa actualización: “La EFSA ha estado publicando opiniones durante todo el mes de junio (la última fue ayer mismo), a excepción de los botánicos”. También ha avanzado que están trabajando en una guía sobre el uso de declaraciones saludables.
De izq. a dcha.: Abel Mariné, Ana Palencia, Xavier Lorenz y Andreu Palou.
Todos los ponentes han coincidido en destacar la relevancia de la base científica para sustentar estas alegaciones, teniendo como referencia el Reglamento europeo 1924/2006. Montserrat Prieto, Directora de Política Alimentaria de la Federación Española de Industria de Alimentación y Bebidas (FIAB), ha sintetizado que este Reglamento sirve “para gestionar la comunicación en nutrición y salud a escala europea y lograr mayor protección para el consumidor, garantizando la libre circulación de mercancías y aportando un alto valor a la base científica”. Este Reglamento y el trabajo que está llevando a cabo la EFSA (European Food Safety Authority) han estado presentes en todas las ponencias pero ha sido Carmen Arias, de la Subdirección General de Gestión de Riesgos Alimentarios (AESAN) quien ha centrado toda su presentación en revisar su aplicación y realizar una completa actualización: “La EFSA ha estado publicando opiniones durante todo el mes de junio (la última fue ayer mismo), a excepción de los botánicos”. También ha avanzado que están trabajando en una guía sobre el uso de declaraciones saludables.
-Estudios clínicos siempre que se pueda
El profesor Francisco Pérez Jiménez, Catedrático y Jefe de Medicina Interna del Hospital Universitario Reina Sofía de Córdoba, ha basado su ponencia en la importancia de la investigación como base para el establecimiento de un claim de salud y ha concluído que siempre que se pueda deben llevarse a cabo estudios clínicos o en su defecto, estudios observacionales “muy potentes”. Asimismo, el profesor Pérez Jiménez ha recalcado la importancia de la publicación de estos trabajos en revistas de alto factor de impacto: “una evidencia científica que no se publica, no existe”.
El profesor Andreu Palou, Catedrático de Bioquímica y Biología Molecular de la Universitat de les Illes Balears, ha destacado que sólo podrán llevar claims los alimentos que tengan un perfil nutricional apropiado y la protección de la propiedad intelectual. Asimismo, ha advertido que “cada solicitud debe referirse sólo a una relación entre un alimento y un efecto, y para sustentarla, se requieren estudios en humanos. Si el claim hace referencia a un factor de riesgo, nuestro objetivo será buscar una efecto beneficioso; y si se trata de claims funcionales, deberemos buscar a través de la evidencia científica que se mantengan o se mejoren esas funciones”.
El profesor Andreu Palou, Catedrático de Bioquímica y Biología Molecular de la Universitat de les Illes Balears, ha destacado que sólo podrán llevar claims los alimentos que tengan un perfil nutricional apropiado y la protección de la propiedad intelectual. Asimismo, ha advertido que “cada solicitud debe referirse sólo a una relación entre un alimento y un efecto, y para sustentarla, se requieren estudios en humanos. Si el claim hace referencia a un factor de riesgo, nuestro objetivo será buscar una efecto beneficioso; y si se trata de claims funcionales, deberemos buscar a través de la evidencia científica que se mantengan o se mejoren esas funciones”.
-Comunicación en todo el proceso
Otro de los puntos clave en las alegaciones y declaraciones de salud para alimentos es la gestión de la comunicación para que al fin del proceso el consumidor medio comprenda los efectos beneficiosos tal y como se expresan en la declaración. Según Ana Palencia, Directora de Comunicación Corporativa de Unilever España, la comunicación debería ir más de la mano con la legislación para lograr una mejor comprensión final por parte del consumidor. Desde el punto de vista corporativo, Palencia ha destacado que para Unilever trabajar en los claims de salud implica dar “una respuesta a necesidades específicas de comunicación de las propiedades saludables bajo las mismas reglas” y ha puesto el ejemplo pionero de Flora pro.activ. Además, para una compañía aporta “diferenciación, competitividad y credibilidad”.
Xavier Lorenz, Director General de innuo, ha remarcado que la comunicación debe participar en todo el proceso de una alegación y debe estar “sustentada científicamente y acorde con la legislación vigente, además de avalada, aceptada y conocida por los profesionales de la salud y comprensible y atractiva para el consumidor final”. Lorenz ha dibujado las tendencias en los claims de salud a través de “las 3’s: sabor, salud y sostenibilidad” y ha finalizado con los nuevos escenarios que aporta la comunicación 2.0, que “acercan más las marcas, a los consumidores y a los profesionales de la salud”.
Xavier Lorenz, Director General de innuo, ha remarcado que la comunicación debe participar en todo el proceso de una alegación y debe estar “sustentada científicamente y acorde con la legislación vigente, además de avalada, aceptada y conocida por los profesionales de la salud y comprensible y atractiva para el consumidor final”. Lorenz ha dibujado las tendencias en los claims de salud a través de “las 3’s: sabor, salud y sostenibilidad” y ha finalizado con los nuevos escenarios que aporta la comunicación 2.0, que “acercan más las marcas, a los consumidores y a los profesionales de la salud”.
-Los alimentos funcionales
Abel Mariné, Catedrático de Nutrición del Departamento de Bromatología de la Facultad de Farmacia de la Universidad de Barcelona, se ha centrado en los alimentos funcionales, aquellos que además de aportar nutrientes, tienen algún componente, bien porque les es propio o porque se les ha añadido, que aporta algún efecto saludable que va más allá de la salud. Ha hablado de dianas terapéuticas en alimentación funcional y ha dicho que “todo alimento funcional se debe juzgar por sus efectos beneficiosos, porque ya los lleva o porque se han modificado”. Respecto a las nuevas técnicas aplicadas a la alimentación, como es el caso de la nanotecnología, se ha mostrado prudente: “todavía está cuestionada por su seguridad”.
-Más sobre los claims de salud y Claimfoodcom
Las alegaciones o declaraciones nutricionales y de salud están cada vez más presentes en el etiquetado y la publicidad de los alimentos comercializados. Están regulados por la Unión Europea desde 2006 mediante un Reglamento que se desarrolló para asegurar que las alegaciones o claims fueran claros, precisos y, sobre todo, basados en la evidencia científica.
Claimfoodcom nace en 2010 como la primera compañía especializada en el campo de las declaraciones nutricionales y de salud que reúne estrategia, ciencia y comunicación. Ofrece a las empresas del sector las máximas garantías de éxito en la obtención de alegaciones de salud para sus productos y la rentabilización de las mismas integrándolas en los planes de marketing y comunicación.
Claimfoodcom nace en 2010 como la primera compañía especializada en el campo de las declaraciones nutricionales y de salud que reúne estrategia, ciencia y comunicación. Ofrece a las empresas del sector las máximas garantías de éxito en la obtención de alegaciones de salud para sus productos y la rentabilización de las mismas integrándolas en los planes de marketing y comunicación.
**Publicado en "PM FARMA"
Aumentan los casos de sarampión en Europa
En toda Europa se está viviendo un importante brote de sarampión y España no es ajena a ello. En los datos del año 2010 afectó a 24 países de nuestro continente y en España se contabilizaron 264 casos, una cifra ya superada este año. Andalucía es la comunidad autónoma donde más han aumentado la incidencia.
Los datos fueron dados a conocer por el doctor José María Bayas( del Hospital Clínic de Barcelona y presidente de la Sociedad Española de Vacunología) durante el "I Foro de discusión y análisis sobre vacunas" celebrado en Alhama de Aragón( Zaragoza) con la presencia de los principales expertos españoles en el sector agrupados en el Observatorio para el estudio de las Vacunas.
Las vacunas evitan seis millones de muertes al año y ahorran la pérdida de 400.000.000 de años de vida solo en niños. En estos momentos 23´2 millones de niños no reciben las vacunas básicas en el mundo. Para el especialista, España es de los mejores países de vacunaciones de Europa, "pero no vamos tan bien del todo. Llegamos al 95´9% del total de vacunaciones y en la triple vírica se ha bajado algo. Pese a todo el descenso de la mortalidad en España a raíz de
las vacunas es grande en comparación con las últimas décadas". Y destacó que en Sudamérica existe cierto temor que puedan aparecer casos importados allí.
Las vacunas evitan seis millones de muertes al año y ahorran la pérdida de 400.000.000 de años de vida solo en niños. En estos momentos 23´2 millones de niños no reciben las vacunas básicas en el mundo. Para el especialista, España es de los mejores países de vacunaciones de Europa, "pero no vamos tan bien del todo. Llegamos al 95´9% del total de vacunaciones y en la triple vírica se ha bajado algo. Pese a todo el descenso de la mortalidad en España a raíz de
las vacunas es grande en comparación con las últimas décadas". Y destacó que en Sudamérica existe cierto temor que puedan aparecer casos importados allí.
Para José María Bayas "es preciso comunicar mejor el impacto de las vacunas en Salud Pública" y avanzó seis ideas de futuro que de avecinan:
-los mecansimos de autorización de vacunas hacen muy improbable el riesgo de reacciones adversas graves
-los sistemas de Farmacovigilancia son una garantía adicional
-el uso sistemático y generalizado de una vacuna requiere un análisis de eficiencia( desde la eficacia y la efectividad)
-los grupos detractores de la vacunación aumentarán su influencia
-las Autoridades Sanitarias deberían hacer algo más contra estos grupos y publicaciones antivacuna
-la mayoría de los médicos desconocen la realidad de las vacunas
-los mecansimos de autorización de vacunas hacen muy improbable el riesgo de reacciones adversas graves
-los sistemas de Farmacovigilancia son una garantía adicional
-el uso sistemático y generalizado de una vacuna requiere un análisis de eficiencia( desde la eficacia y la efectividad)
-los grupos detractores de la vacunación aumentarán su influencia
-las Autoridades Sanitarias deberían hacer algo más contra estos grupos y publicaciones antivacuna
-la mayoría de los médicos desconocen la realidad de las vacunas
ESHRE release: How many embryos to transfer?
Swedish researchers develop new method to avoid twins while maintaining high live birth rates Stockholm, Sweden: Swedish researchers have, for the first time, developed a reliable way of deciding whether one or two embryos should be transferred during fertility treatment; the method simultaneously maintains a high chance of women giving birth to a live baby, while reducing the risk of twins. Dr Jan Holte told the annual meeting of the European Society for Human Reproduction and Embryology, that if this model were to be applied in all fertility clinics, it had the potential to reduce the twin rates to the level of just under two percent seen in the normal population. Already, another four clinics have started to use the model.
Sweden leads the world in attempts to reduce multiple pregnancies by transferring only one embryo to a woman’s womb during fertility treatment whenever possible. In 2007 (the most recent year for which data are available*), 69.9% of embryo transfers were single embryos, 30.1% were double embryo transfers, and only 5.3% of deliveries after fertility treatment were multiple deliveries – the lowest multiple delivery rate in the world. “However, until now, evidence-based strategies have been lacking for guidance on when to perform single embryo transfer in order to achieve the best possible balance between maintaining a high level of live birth rates, but reducing twin implantation rates,” said Dr Holte, who is medical director, a senior consultant and responsible for research at the Carl Von Linnéklinikken, Uppsala Science Park (Uppsala, Sweden).
Over a four-year period between 1999-2002 Dr Holte and his colleagues analysed a series of 3223 embryo transfers and recorded 80 different factors that played a role in the success of fertility treatment. They found that four variables were significant in predicting pregnancy outcome: the quality of the embryo, the age of the woman, ovarian responsiveness (the number of eggs retrieved in relation to the dose of ovarian stimulating hormones), and information about whether the woman had had previous IVF attempts with either fresh or frozen-thawed embryos, how many, and whether or not they resulted in a pregnancy.
Using these four variables, they constructed a mathematical model that predicted the chances of pregnancy after the transfer of one or two embryos and of the risk of twins. Over a subsequent four-year period between 2004-2007, they applied the model in the clinic for 3410 embryo transfers. They aimed to achieve a risk of twins of no more than 15% and any women that had a higher risk had only one embryo transferred in one cycle. Transfers of embryos that had been frozen, stored and then thawed before implantation followed the same model. During this period the proportion of single embryo transfers increased to 76.2% (compared to 11.1% in the previous period between 1999-2002), and the rate of twin deliveries was reduced from 26.1% to 1.9%. Live birth rates per fresh embryo transfer fell from 29.1% to 24.6%, but when transfers of frozen-thawed embryos were included the live birth rate was similar during the two periods: 31.1% in the earlier period and 30.7% in the later period.
Dr Holte also made adjustments to take account of the fact that women in the later period tended to be older and have a less favourable prognosis than those in the earlier period and, therefore, would have a lower predicted live birth rate. Once he had done this, the live birth rate (including frozen-thawed embryos) in the later period was higher at 36% versus 31.1% in the earlier period. Just as significant as the dramatic drop in twin births were the outcomes for babies born between 2004-2007. Average birth weights increased from 3086g to 3412g; the frequencies of babies born prematurely (before week 33) and babies with birth weights below 2500g were reduced by two-thirds; the frequency of babies born small for gestational age was reduced by 26%; and deaths either just before, during or just after birth were reduced by 58%.
Dr Holte said: “These improved outcomes were entirely due to the lower rate of twins. There was no significant differences in outcomes between the two periods when comparing only babies born as a result of a single pregnancy.” The researchers found that their model correctly predicted the pregnancy rates that occurred in all women, regardless of their chances of becoming pregnant. Dr Holte explained: “The predicted chance of pregnancy for an individual couple ranged between around 5% up to around 60% per attempt. When the treatments were grouped according to their predicted chances into ‘stratas’ or groups of 0-10%, 10-20%, 20-30%, 30-40%, 40-50% and >50%, the corresponding observed clinical pregnancy rates were shown to fit very accurately with the predicted results. “To our knowledge, this is the first time that a model has been developed that successfully predicts pregnancy and the risk of twin implantation during fertility treatment.
The results suggest that application of the model may reduce twin rates to the desired level, in our case to that of the normal Swedish population, while totally preserving pregnancy rates and markedly reducing risks for the offspring.” Multiple pregnancies, where a woman becomes pregnant with two or more embryos, carry a high risk to both mothers and babies; complications can include miscarriage, premature birth, low birth weight, cerebral palsy and death. For this reason, fertility doctors increasingly try to find ways of avoiding them without jeopardising women’s chances of becoming pregnant. The model has been validated by another, independent Swedish clinic, with similarly good results over a five-year period, and now three other clinics (two in Sweden and one in Italy) have started to use it. Dr Holte and his colleagues are continuing to refine and test the model further.
Sweden leads the world in attempts to reduce multiple pregnancies by transferring only one embryo to a woman’s womb during fertility treatment whenever possible. In 2007 (the most recent year for which data are available*), 69.9% of embryo transfers were single embryos, 30.1% were double embryo transfers, and only 5.3% of deliveries after fertility treatment were multiple deliveries – the lowest multiple delivery rate in the world. “However, until now, evidence-based strategies have been lacking for guidance on when to perform single embryo transfer in order to achieve the best possible balance between maintaining a high level of live birth rates, but reducing twin implantation rates,” said Dr Holte, who is medical director, a senior consultant and responsible for research at the Carl Von Linnéklinikken, Uppsala Science Park (Uppsala, Sweden).
Over a four-year period between 1999-2002 Dr Holte and his colleagues analysed a series of 3223 embryo transfers and recorded 80 different factors that played a role in the success of fertility treatment. They found that four variables were significant in predicting pregnancy outcome: the quality of the embryo, the age of the woman, ovarian responsiveness (the number of eggs retrieved in relation to the dose of ovarian stimulating hormones), and information about whether the woman had had previous IVF attempts with either fresh or frozen-thawed embryos, how many, and whether or not they resulted in a pregnancy.
Using these four variables, they constructed a mathematical model that predicted the chances of pregnancy after the transfer of one or two embryos and of the risk of twins. Over a subsequent four-year period between 2004-2007, they applied the model in the clinic for 3410 embryo transfers. They aimed to achieve a risk of twins of no more than 15% and any women that had a higher risk had only one embryo transferred in one cycle. Transfers of embryos that had been frozen, stored and then thawed before implantation followed the same model. During this period the proportion of single embryo transfers increased to 76.2% (compared to 11.1% in the previous period between 1999-2002), and the rate of twin deliveries was reduced from 26.1% to 1.9%. Live birth rates per fresh embryo transfer fell from 29.1% to 24.6%, but when transfers of frozen-thawed embryos were included the live birth rate was similar during the two periods: 31.1% in the earlier period and 30.7% in the later period.
Dr Holte also made adjustments to take account of the fact that women in the later period tended to be older and have a less favourable prognosis than those in the earlier period and, therefore, would have a lower predicted live birth rate. Once he had done this, the live birth rate (including frozen-thawed embryos) in the later period was higher at 36% versus 31.1% in the earlier period. Just as significant as the dramatic drop in twin births were the outcomes for babies born between 2004-2007. Average birth weights increased from 3086g to 3412g; the frequencies of babies born prematurely (before week 33) and babies with birth weights below 2500g were reduced by two-thirds; the frequency of babies born small for gestational age was reduced by 26%; and deaths either just before, during or just after birth were reduced by 58%.
Dr Holte said: “These improved outcomes were entirely due to the lower rate of twins. There was no significant differences in outcomes between the two periods when comparing only babies born as a result of a single pregnancy.” The researchers found that their model correctly predicted the pregnancy rates that occurred in all women, regardless of their chances of becoming pregnant. Dr Holte explained: “The predicted chance of pregnancy for an individual couple ranged between around 5% up to around 60% per attempt. When the treatments were grouped according to their predicted chances into ‘stratas’ or groups of 0-10%, 10-20%, 20-30%, 30-40%, 40-50% and >50%, the corresponding observed clinical pregnancy rates were shown to fit very accurately with the predicted results. “To our knowledge, this is the first time that a model has been developed that successfully predicts pregnancy and the risk of twin implantation during fertility treatment.
The results suggest that application of the model may reduce twin rates to the desired level, in our case to that of the normal Swedish population, while totally preserving pregnancy rates and markedly reducing risks for the offspring.” Multiple pregnancies, where a woman becomes pregnant with two or more embryos, carry a high risk to both mothers and babies; complications can include miscarriage, premature birth, low birth weight, cerebral palsy and death. For this reason, fertility doctors increasingly try to find ways of avoiding them without jeopardising women’s chances of becoming pregnant. The model has been validated by another, independent Swedish clinic, with similarly good results over a five-year period, and now three other clinics (two in Sweden and one in Italy) have started to use it. Dr Holte and his colleagues are continuing to refine and test the model further.
Could ovarian stimulation cause an increase in chromosome copy number abnormalities in the oocytes of older mothers?ESHRE study may answer those
Ovarian stimulation undertaken by women of advanced maternal age (over 35 years) receiving fertility treatment may be disrupting the normal pattern of meiosis – a critical process of chromosome duplication followed by two specialised cell divisions in the production of oocytes and sperm – and leading to abnormalities of chromosome copy numbers (aneuploidy) that result in IVF failure, pregnancy loss or, more rarely, the birth of affected children with conditions such as Down’s syndrome, which is caused by the inheritance of three copies of chromosome 21 (trisomy 21).
Researchers involved in ESHRE’s polar body screening study (launched in 2009) will tell the annual conference of the European Society of Human Reproduction and Embryology today (Monday) that results from the study are leading to a new understanding about how such abnormalities are developing, and they believe that the ovarian stimulation a woman receives might be playing a part. Understanding the mechanisms involved could help older women who are trying to have a healthy baby with their own oocytes.Professor Alan Handyside, Director of The London Bridge Fertility, Gynaecology and Genetics Centre, London, UK, and colleagues from eight countries undertook a proof of principle study of a novel method of screening polar bodies, small cells that are the by-product of oocyte development, using the new technology of microarray comparative genomic hybridisation (array CGH) in order to find whether this was a reliable method of analysing the chromosomal status of an oocyte. This is because many more chromosome copy number abnormalities arise in the oocyte than in sperm.
"In doing so, we obtained a lot of data at the individual chromosome and chromatid level," says Professor Joep Geraedts, co-ordinator of the ESHRE Task Force on preimplantation genetic screening (PGS). (A chromatid is one of the two identical copies of DNA making up a duplicated chromosome). "So we decided to analyse these data separately to see whether they could provide us with information that could be useful in determining better treatment strategies for the future."
"In this unique study, we were able to use the new technology of array CGH to examine the copy number of all 23 pairs of chromosomes, in all three products of female meiosis in over 100 oocytes with abnormal numbers of chromosomes," says Professor Handyside. "What happens in female meiosis is that the 23 pairs of chromosomes duplicate and each pair of duplicated chromosomes comes together and the four single chromosomes, or ‘chromatids’, become ‘glued’ together along the whole length of each chromosome. This actually occurs before the woman is born and is the stage at which DNA is swapped between the grandparents’ chromosomes.
"Sometimes, decades later, just before ovulation, the glue ‘dissolves’ first between the two duplicated chromosomes and finally after fertilisation between the two individual chromosomes. This enables pairs of chromosomes to segregate in the first meiotic division producing the first polar body. In the second meiotic division the second polar body is produced, resulting in a single set of chromosomes in the fertilised oocyte or ‘zygote’, which, when combined with the single set in the fertilising sperm, restores the 23 pairs," he says.
The researchers believe that ovarian stimulation may be disturbing this process in older women because the chromosomes are becoming unglued prematurely, particularly the smaller ones like chromosome 21. Ovarian stimulation uses hormonal medication to stimulate the ovaries to release a larger number of oocytes than normal, in order to provide enough good quality oocytes for fertilisation in vitro.
Following natural conception in older mothers, Down’s pregnancies are predominantly caused by errors in the first female meiotic division. "Our evidence demonstrates that, following IVF, there are multiple chromosome errors in both meiotic divisions, suggesting more extensive premature separation of single chromosomes resulting in more random segregation, which in turn results in multiple chromosome copy number changes in individual oocytes," says Professor Handyside.
"We need to look further into the incidence and pattern of meiotic errors following different stimulation regimes including mild stimulation and natural cycle IVF, where one oocyte per cycle is removed, fertilised and transferred back to the woman. The results of such research should enable us to identify better clinical strategies to reduce the incidence of chromosome errors in older women undergoing IVF."
"We also believe that our research will help identify women who want to have their own offspring but have practically no chance of doing so that we can advise them to use donor oocytes," says Professor Geraedts. "This in itself is already a big step forward that will aid couples hoping for a healthy pregnancy and birth to be able to achieve one."
Researchers involved in ESHRE’s polar body screening study (launched in 2009) will tell the annual conference of the European Society of Human Reproduction and Embryology today (Monday) that results from the study are leading to a new understanding about how such abnormalities are developing, and they believe that the ovarian stimulation a woman receives might be playing a part. Understanding the mechanisms involved could help older women who are trying to have a healthy baby with their own oocytes.Professor Alan Handyside, Director of The London Bridge Fertility, Gynaecology and Genetics Centre, London, UK, and colleagues from eight countries undertook a proof of principle study of a novel method of screening polar bodies, small cells that are the by-product of oocyte development, using the new technology of microarray comparative genomic hybridisation (array CGH) in order to find whether this was a reliable method of analysing the chromosomal status of an oocyte. This is because many more chromosome copy number abnormalities arise in the oocyte than in sperm.
"In doing so, we obtained a lot of data at the individual chromosome and chromatid level," says Professor Joep Geraedts, co-ordinator of the ESHRE Task Force on preimplantation genetic screening (PGS). (A chromatid is one of the two identical copies of DNA making up a duplicated chromosome). "So we decided to analyse these data separately to see whether they could provide us with information that could be useful in determining better treatment strategies for the future."
"In this unique study, we were able to use the new technology of array CGH to examine the copy number of all 23 pairs of chromosomes, in all three products of female meiosis in over 100 oocytes with abnormal numbers of chromosomes," says Professor Handyside. "What happens in female meiosis is that the 23 pairs of chromosomes duplicate and each pair of duplicated chromosomes comes together and the four single chromosomes, or ‘chromatids’, become ‘glued’ together along the whole length of each chromosome. This actually occurs before the woman is born and is the stage at which DNA is swapped between the grandparents’ chromosomes.
"Sometimes, decades later, just before ovulation, the glue ‘dissolves’ first between the two duplicated chromosomes and finally after fertilisation between the two individual chromosomes. This enables pairs of chromosomes to segregate in the first meiotic division producing the first polar body. In the second meiotic division the second polar body is produced, resulting in a single set of chromosomes in the fertilised oocyte or ‘zygote’, which, when combined with the single set in the fertilising sperm, restores the 23 pairs," he says.
The researchers believe that ovarian stimulation may be disturbing this process in older women because the chromosomes are becoming unglued prematurely, particularly the smaller ones like chromosome 21. Ovarian stimulation uses hormonal medication to stimulate the ovaries to release a larger number of oocytes than normal, in order to provide enough good quality oocytes for fertilisation in vitro.
Following natural conception in older mothers, Down’s pregnancies are predominantly caused by errors in the first female meiotic division. "Our evidence demonstrates that, following IVF, there are multiple chromosome errors in both meiotic divisions, suggesting more extensive premature separation of single chromosomes resulting in more random segregation, which in turn results in multiple chromosome copy number changes in individual oocytes," says Professor Handyside.
"We need to look further into the incidence and pattern of meiotic errors following different stimulation regimes including mild stimulation and natural cycle IVF, where one oocyte per cycle is removed, fertilised and transferred back to the woman. The results of such research should enable us to identify better clinical strategies to reduce the incidence of chromosome errors in older women undergoing IVF."
"We also believe that our research will help identify women who want to have their own offspring but have practically no chance of doing so that we can advise them to use donor oocytes," says Professor Geraedts. "This in itself is already a big step forward that will aid couples hoping for a healthy pregnancy and birth to be able to achieve one."
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