An evaluation by potential IVF/Donor Oocyte patients of the Use and Handling of the Bemfola® Pen compared with the Gonal-f® Pen and Puregon Pen® / Evaluación del uso y manejo de la pluma Bemfola® en comparación con el de la pluma Gonal-f® y la pluma Puregon® en pacientes potenciales de FIV/ donantes de ovocitos

BACKGROUND: Since the 1990s recombinant human FSH (r-hFSH), such as Gonal-f® and Puregon®, have been in widespread use for fertility treatment [1]. More recently Bemfola®, biosimilar to r-hFSH, has been introduced with similar efficacy and safety to Gonal-f® [2], but delivered in a novel, innovative injector pen system (Reddot design award 2011). The Bemfola® pen (BP) is a single-use, disposable pen available in five different presentations (i.e., 75IU, 150IU, 225IU, 300IU and 450IU), each of which provides a range of doses that it can deliver. Non-compliance to hormonal treatment regimens might be a critical issue to reach therapeutic goals. The use of pens by patients is often limited by factors such as fear of injection, but can be also related to the device itself [3-6]. Therefore, easy-to-use devices may also positively influence physicians» hormonal prescribing habits and patient's compliance. Accordingly, this user acceptance study aimed to assess the use of the Bemfola® pen in a population of potential users with regard to the easiness and convenience of handling of the Bemfola® Pen in comparison to the Gonal-f® pen and Puregon® pen. Material and Methods Randomised and single-blind study with three-arm user test. The investigation was conducted in females who considered undergoing hormonal treatment for the first time (naïve) and who were considering to start an IVF or donor egg treatment cycle. A total of 10 centers from Spain participated in this investigation. This study of user acceptance included 460 females qualifying for potential patients considering a therapy with follicle stimulating hormone. Users received the three pens in a randomized, consecutive sequence, completed for each of the pen one questionnaire (same for all 3 pens) and thereafter completed a concluding questionnaire comparing the handling, convenience and indicating their preference among the 3 pens. No self-injections were performed and an application pad for injections was used. Results The Bemfola® pen showed the highest scorings and strong preferences in all pen features assessed and achieved the highest proportion of best choice compared to both the Gonal-f® and Puregon®. pen. Conclusions The results indicated significant preferences of women, who intended to undergo a hormonal treatment, for the Bemfola® pen compared to both the Puregon® pen and the Gonal-f® pen

ANTECEDENTES: Desde la década de los noventa, la hormona foliculoestimulante humana recombinante (hFSH-r) como Gonal-f® y Puregon®, se ha utilizado ampliamente en el tratamiento de la fertilidad [1]. Más recientemente se ha introducido Bemfola®, biosimilar de la hFSH-r con eficacia y seguridad similar a Gonal-f® [2], pero desarrollada con un innovador sistema de pluma inyectora (premio de diseño Reddot, 2011). Bemfola® es una pluma precargada desechable de un solo uso, disponible en cinco presentaciones diferentes (75 UI, 150 UI, 225 UI, 300 UI y 450 UI), cada una de las cuales proporciona un rango de dosis determinado. El no-cumplimiento de las pautas de tratamiento hormonal es un problema fundamental en la consecución de los objetivos terapéuticos. El uso de plumas por las pacientes se ve a menudo limitado por el miedo a la inyección e incluso relacionado con el propio dispositivo [3-6]. Por tanto, los dispositivos de fácil uso pueden influir positivamente tanto en los hábitos de prescripción de terapias hormonales de los médicos como en el cumplimiento del paciente. En consecuencia, el objetivo de este estudio consiste en evaluar el uso de Bemfola® en una población de usuarias potenciales con respecto a la facilidad, y conveniencia en su manejo en comparación con las plumas Gonal-f® y Puregon®. Material y Métodos Estudio aleatorizado y simple ciego de tres ramas de tratamiento. Esta investigación se llevó a cabo en mujeres sin tratamiento previo que estaban considerando bien iniciar un ciclo de FIV o bien ser donantes de ovocitos. En este estudio participaron 10 centros de fertilidad de España. Se incluyeron 460 mujeres cualificadas para ser «pacientes potenciales de terapia hormonal con hormona foliculoestimulante humana recombinante» Las usuarias recibieron las tres plumas (Bemfola®, Gonal-f® y Puregon®) en una secuencia aleatoria y consecutiva, y completaron un cuestionario idéntico por cada una de las plumas, y un cuestionario de conclusión con el fin de comparar el manejo, la comodidad y la preferencia de las tres plumas. En ningún caso se realizaron auto-inyecciones y en su lugar se utilizó una almohadilla de aplicación de inyecciones. Resultados La pluma Bemfola® mostró la mayor puntuación y elevadas preferencias en todas las características evaluadas, y alcanzó la mayor proporción de «mejor» opción en comparación con la pluma Gonal-f® y la pluma Puregon®. Conclusiones Los resultados mostraron preferencias significativas de mujeres que tenían la intención de someterse a un tratamiento hormonal, para la pluma Bemfola® en comparación con las plumas Gonal-f® y Puregon®

Anti-Müllerian hormone levels to predict oocyte maturity and embryo quality during controlled ovarian hyperstimulation.

BACKGROUND: The aim of this study was to assess the correlation between controlled ovarian hyperstimulation (COH) outcome parameters and anti-Müllerian hormone (AMH) serum levels during in vitro fertilization (IVF) treatment in women with varying ovarian reserve levels. METHODS: Prospective study of 46 women undergoing GnRH-antagonist short protocol for IVF. Participants included women with low ovarian reserve (N.=11), normoreserve (N.=16), and polycystic ovarian syndrome (PCOS; N.=19). AMH was measured on menstrual cycle day 1-3 (basal AMH), on the day of GnRH-antagonist administration (AMH-GnRH), on the day of hCG administration (AMH-hCG), and in follicular fluid on the day of oocyte retrieval (AMH-FF). RESULTS: Basal AMH was significantly correlated (P<0.001) with antral follicle count and number of follicles >11mm on hCG day (P<0.05). Both basal AMH and AMH-GnRH were significantly correlated (P<0.05) with the number of oocytes retrieved and metaphase II. AMH-hCG was correlated with top quality embryos (P=0.04). No correlations were found between COH outcome parameters and AMH-FF. CONCLUSIONS: Basal AMH serum concentration was the strongest predictor of oocyte yield. AMH concentration at the mid-follicular phase was also a good predictor of oocyte yield and this marker was the only useful ovarian reserve indicator during the follicle growth process to predict IVF outcomes. AMH-hCG levels appear to predict embryo quality. AMH levels during the COH can provide valuable data to help individualize treatment and predict COH results.

Anti-Müllerian hormone dynamics during GNRH-antagonist short protocol for IVF/ICSI in women with varying ovarian reserve levels.

BACKGROUND: Data on variations in anti-Müllerian hormone (AMH) levels according to ovarian reserve are scant. The aim of this study was to investigate changes in AMH levels during controlled ovarian hyperstimulation with a GnRH-antagonist protocol for in vitro fertilization (IVF). METHODS: Prospective, observational study of 46 women. The subjects were divided into three cohorts according to ovarian reserve levels: polycystic ovary syndrome (PCOS; N.=19), low ovarian reserve (LOR; N.=11), and normoreserve (NR; N.=16). Serum AMH concentration was measured at baseline (cycle day 2-3 before follicle stimulating hormone [FSH] administration) and just prior to GnRH-antagonist and human chorionic gonadotropin (hCG) administration. AMH concentration in follicular fluid (FF) was assessed on the day of oocyte retrieval. RESULTS: AMH serum concentration decreased significantly (P<0.001) and progressively in all three groups from baseline (initiation of stimulation) to all subsequent assessments. Serum AMH levels were significantly higher in the PCOS group at all determinations: (AMH1: 8.18±6.26ng/mL, AMH2: 5.3±3.97ng/mL, AMH3: 2.19±1.31ng/mL) versus the NR group (AMH1: 2.94±1.53ng/mL, AMH2: 1.44±0.77ng/mL, AMH3: 0.71±0.57ng/mL) and LOR group (AMH1: 0.63±0.42ng/mL, AMH2: 0.58±0.4ng/mL, AMH3: 0.31±0.2ng/mL). No significant between-group differences were observed for AMH levels in FF (PCOS: 3.56±3.19ng/mL, NR: 4.06±5.44ng/mL, LOR: 1.31±0.47ng/mL) nor for fertilization rate, number of top quality embryos, or clinical pregnancy rates. CONCLUSIONS: Serum AMH levels gradually decrease during GnRH-antagonist protocol for IVF. This decrease starts at the beginning of the follicular phase and continues up to the day of hCG administration. These results underscore the important role that AMH plays in the process of folliculogenesis and dominant follicle selection.

Evaluación del uso y manejo de la pluma Bemfola® en comparación con el de la pluma Gonal-f® y la pluma Puregon® en pacientes potenciales de FIV/ donantes de ovocitos / An evaluation by potential IVF/Donor Oocyte patients of the Use and Handling of the Bemfola® Pen compared with the Gonal-f® Pen and Puregon Pen®

ANTECEDENTES: Desde la década de los noventa, la hormona foliculoestimulante humana recombinante (hFSH-r) como Gonal-f® y Puregon®, se ha utilizado ampliamente en el tratamiento de la fertilidad [1]. Más recientemente se ha introducido Bemfola®, biosimilar de la hFSH-r con eficacia y seguridad similar a Gonal-f® [2], pero desarrollada con un innovador sistema de pluma inyectora (premio de diseño Reddot, 2011). Bemfola® es una pluma precargada desechable de un solo uso, disponible en cinco presentaciones diferentes (75 UI, 150 UI, 225 UI, 300 UI y 450 UI), cada una de las cuales proporciona un rango de dosis determinado. El no-cumplimiento de las pautas de tratamiento hormonal es un problema fundamental en la consecución de los objetivos terapéuticos. El uso de plumas por las pacientes se ve a menudo limitado por el miedo a la inyección e incluso relacionado con el propio dispositivo [3-6]. Por tanto, los dispositivos de fácil uso pueden influir positivamente tanto en los hábitos de prescripción de terapias hormonales de los médicos como en el cumplimiento del paciente. En consecuencia, el objetivo de este estudio consiste en evaluar el uso de Bemfola® en una población de usuarias potenciales con respecto a la facilidad, y conveniencia en su manejo en comparación con las plumas Gonal-f® y Puregon®. Material y MÉTODOS: Estudio aleatorizado y simple ciego de tres ramas de tratamiento. Esta investigación se llevó a cabo en mujeres sin tratamiento previo que estaban considerando bien iniciar un ciclo de FIV o bien ser donantes de ovocitos. En este estudio participaron 10 centros de fertilidad de España. Se incluyeron 460 mujeres cualificadas para ser «pacientes potenciales de terapia hormonal con hormona foliculoestimulante humana recombinante». Las usuarias recibieron las tres plumas (Bemfola®, Gonal-f® y Puregon®) en una secuencia aleatoria y consecutiva, y completaron un cuestionario idéntico por cada una de las plumas, y un cuestionario de conclusión con el fin de comparar el manejo, la comodidad y la preferencia de las tres plumas. En ningún caso se realizaron auto-inyecciones y en su lugar se utilizó una almohadilla de aplicación de inyecciones. RESULTADOS: La pluma Bemfola® mostró la mayor puntuación y elevadas preferencias en todas las características evaluadas, y alcanzó la mayor proporción de «mejor» opción en comparación con la pluma Gonal-f® y la pluma Puregon®. CONCLUSIONES: Los resultados mostraron preferencias significativas de mujeres que tenían la intención de someterse a un tratamiento hormonal, para la pluma Bemfola® en comparación con las plumas Gonal-f® y Puregon®

BACKGROUND: Since the 1990s recombinant human FSH (r-hFSH), such as Gonal-f® and Puregon®, have been in widespread use for fertility treatment [1]. More recently Bemfola® has been introduced with familiar efficacy and safety to Gonal-f® [2], but delivered in a novel, innovative injector pen system (Reddot design award 2011). The Bemfola® pen (BP) is a singleuse, disposable pen available in five different presentations (i.e., 75IU, 150IU, 225IU, 300IU and 450IU), each of which provides a range of doses that it can deliver. Non-compliance to hormonal treatment regimens might be a critical issue to reach therapeutic goals. The use of pens by patients is often limited by factors such as fear of injection, but can be also related to the device itself [3-6]. Therefore, easy-to-use devices may also positively influence physicians' hormonal prescribing habits and patient's compliance. Accordingly, this user acceptance study aimed to assess the use of the Bemfola® pen in a population of potential users with regard to the easiness and convenience of handling of the Bemfola® Pen in comparison to the Gonal-f® pen and Puregon® pen. Material and methods Randomised and single-blind study with three-arm user test. The investigation was conducted in females who considered undergoing hormonal treatment for the first time (naïve) and who were considering to start an IVF or donor egg treatment cycle. A total of two 10 centres from Spain participated in this investigation. This study of user acceptance included 460 females qualifying for potential patients considering a therapy with follicle stimulating hormone. Users received the three pens in a randomized, consecutive sequence, complete for each of the pen one questionnaire (same for all 3 pens) and thereafter complete a concluding questionnaire comparing the handling, convenience and indicating their preference among the 3 pens. No self-injections were performed and an application pad for injections was used. Results The Bemfola® pen showed the highest scorings and strong preferences in all pen features assessed and achieved the highest proportion of best choice compared to both, the Gonal-f® and Puregon® pen. Conclusions The results indicated significant preferences of women, who intended to undergo a hormonal treatment, for the Bemfola® pen compared to both the Puregon® pen and the Gonal-f® pen