Evidence-based clinical practice guidelines for the management of sedoanalgesia and delirium in critically ill adult patients. / Guías de práctica clínica basadas en la evidencia para el manejo de la sedoanalgesia y delirium en el paciente adulto críticamente enfermo.

Given the importance of the management of sedation, analgesia and delirium in Intensive Care Units, and in order to update the previously published guidelines, a new clinical practice guide is presented, addressing the most relevant management and intervention aspects based on the recent literature. A group of 24 intensivists from 9 countries of the Pan-American and Iberian Federation of Societies of Critical Medicine and Intensive Therapy met to develop the guidelines. Assessment of evidence quality and recommendations was made according to the Grading of Recommendations Assessment, Development and Evaluation Working Group. A systematic search of the literature was carried out using MEDLINE, Cochrane Library databases such as the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects, the National Health Service Economic Evaluation Database and the database of Latin American and Caribbean Literature in Health Sciences (LILACS). A total of 438 references were selected. After consensus, 47 strong recommendations with high and moderate quality evidence, 14 conditional recommendations with moderate quality evidence, and 65 conditional recommendations with low quality evidence were established. Finally, the importance of initial and multimodal pain management was underscored. Emphasis was placed on decreasing sedation levels and the use of deep sedation only in specific cases. The evidence and recommendations for the use of drugs such as dexmedetomidine, remifentanil, ketamine and others were incremented.

Uso de agonista de GnRH para inducir ovulación en ciclos de hiperestimulación ovárica controlada: experiencia de Clínica Monteblanco, Santiago, Chile / Use of GnRH agonist to induce ovulation cycles controlled ovarian hyperstimulation: experience of Monteblanco Clinic, Santiago, Chile

Objetivo: Presentar la experiencia de la Unidad de Medicina Reproductiva de Clínica Monteblanco con el uso de análogos GnRh para la inducción final de la maduración ovocitaria. Método: Se registraron los casos de IVF/ICSI durante el año 2012 en los que se indujo la maduración final ovocitaria con análogos GnRh (Lupron®). Todos los ciclos fueron estimulados con FSHr (Puregon®) y gonadotrofina urinaria altamente purificada (Menopur®), para la prevención del alza prematura de LH, el día 5° de estimulación se agregó diariamente antagonista de GnRh. La maduración ovocitaria final se realizó con 1,25 mg de acetato de leuprolide (Lupron®), posteriormente se realizó aspiración folicular bajo guía ecográfica. Todos los embriones obtenidos fueron vitrificados y transferidos en ciclos posteriores. Resultados: Entre enero y diciembre del año 2012 se registraron 110 pacientes cuya inducción de maduración final ovocitaria se realizó con acetato de leuprolide. El promedio de ovocitos recuperados fue de 21, la proporción de ovocitos maduros fue de 72 por ciento y la frecuencia de fecundación fue de 64 por ciento. No hubo ningún caso de síndrome de hiperestimulación ovárico severo. Conclusiones: En los casos presentados de inducción de la maduración ovocitaria final con acetato de leuprolida, los resultados obtenidos son óptimos en términos de número de ovocitos en metafase II recuperados y en frecuencia de fecundación, mostrando ser una alternativa eficiente en la prevención del síndrome de hiperestimulación ovárico severo, sin alterar el pronóstico de las pacientes.

Objective: To present the experience of the Reproductive Medicine Unit of Clinica Monteblanco inducing oocyte final maturation by GnRh analogue administration. Methods: We analysed all IVF/ICSI cases performed in 2012, in which final oocyte maturation was induced by administration of GnRH analogue (Lupron®). Controlled ovarian hyperstimulation was achieved bydaily rFSH (Puregon®) and highly purified urinary gonadotropin (Menopur®) administration. In order to prevent premature LH rise, on the 5th day of stimulation daily GnRH antagonist (Orgalutran®) was added. Final oocyte maturation was induced by the administration of 1.25 mg leuprolide acetate (Lupron®). Follicular aspiration was subsequently performed under ultrasound guidance. All embryos were vitrified and transferred in a subsequent cycle. Results: We registered 110 patients. The mean number of recovered oocytes was 21; the proportion of mature oocytes was 72 percent, and the fecundation rate reached was 64 percent. No case of severe ovarian hyperstimulation syndrome (OHSS) was recorded. Conclusions: In this cohort, the use of leuprolide acetate for induce final oocyte maturation demonstrated to be an efficient alternative to induce oocyte final maturation, while preventing OHSS.

Vitrificación ovocitaria para posponer fecundidad: experiencia de la Unidad de Medicina Reproductiva de Clínica Monteblanco / Oocyte vitrification to postponement of fertility

Antecedentes: Múltiples variables médicas y sociales han llevado al desarrollo de técnicas que permitan a la mujer posponer su fertilidad; dentro de ellas la vitrificación ovocitaria surge como una técnica relativamente sencilla y muy promisoria en este campo. Objetivo: Presentar la experiencia del Centro de Medicina Reproductiva de Clínica Monteblanco, en mujeres que han vitrificado sus ovocitos y posteriormente han intentado embarazarse con ellos. Método: Se revisaron todos los casos de vitrificación ovocitaria con posterior intento de embarazo, realizados desde el año 2007 a la fecha. Resultados: Del total de ciclos de vitrificación ovoci-taria, 22 mujeres han intentado un embarazo posterior al procedimiento. La mediana de edad al momento de la vitrificación fue de 36 años. En 10 pacientes no hubo transferencia embrionaria, ya fuera por no fecundación (4 casos) o por detención del desarrollo embrionario (6 casos); 12 pacientes fueron transferidas, la mitad de ellas lograron embarazo. Discusión: En este trabajo se presenta la primera serie nacional de casos de vitrificación de óvulos con posterior intento de embarazo; 12 de 20 pacientes lograron ser transferidas y 6 de ellas lograron el embarazo. Las mujeres más jóvenes vitrificaron un mayor número de ovocitos, tuvieron más embriones y tuvieron una mayor posibilidad de lograr embarazo. Conclusión: Pese a que la vitrificación ovocitaria no es una solución definitiva a la postergación de la fertilidad, representa en estos casos una alternativa válida.

Background: The postponement of pregnancy responds to several medical and social reassons. Oocy-te vitrification is a relatively simple and promising technique for this purpose. Objective: To illustrate the experience at the Reproductive Medicina Unit of Monteblanco of cases of women who underwent oocyte vitrification and attempted later to get pregnant. Methods: We reviewed all cases of oocyte vitrification with later attempt of pregnancy since 2007. Results: In the studied period, 20 cycles of oocyte vitrification were registered, thereof 22 women attempted a pregnancy after that. Median age at vitrification was 36 years old. Ten patient did not underwent embryo transfer, either by fertilization failure (4 patients) or detention of embryonic development (6 patients). Six of 12 patients that underwent embryo transfer, achieved pregnancy. Discussion: We report the first series of vitrification cases with posterior attempt of pregnancy in Chile; 12 of 20 women underwent embryo transfer and 6 of them got pregnant. Young women had a more oocytes, embryos and a better chance to achieve pregnancy. Conclusion: Despite the fact that vitrification is not the final solution for today's postponement of fertility, it represents a useful alternative for these cases.

Clinical pharmacology information in summaries of product characteristics and package inserts.

The aim of the study was to assess the clinical pharmacology information provided in the summaries of product characteristics (SPCs) of European drugs compared with their package inserts. A list of the 150 most prescribed drugs at the local Health Service was assessed. To analyze clinical pharmacology information contained in package inserts and SPCs, Spyker's systematized scoring approach was used (scoring from 0 to 2). Ninety-one SPCs (84.3%) and 108 package inserts were obtained. The mean score for core information provided in the package inserts was 7.94 (confidence interval (CI) 95 %: 7.34-8.53), whereas for the SPCs it was 17.62 (CI 95 %: 16.48-18.75; 35.2% of the maximum). One core information item and two extra credit items were not contained in any of the SPCs. In the European Union the clinical pharmacology information found in SPCs is clearly insufficient. An improved access to and regular review of the SPCs might substantially improve the access and quality of clinical pharmacology and other prescribing information.

Criopreservacion de pronucleos: rol en el programa de fertilizacion asistida

Objetivo: Determinar el rol de la criopreservación (CP) de pronúcleos (PN), como una herramienta para disminuir la incidencia de embarazos múltiples y dar otra oportunidad de transferencia embrionaria, sin requerir estimulación ovárica nuevamente, en parejas con infertilidad que requieren como tratamiento algún tipo de procedimiento de Fertilización Asistida (FA). Material y Método: Se analizaron los resultados de 545 procedimientos de FA entre marzo del 2000 y junio del 2003. Resultados: La incorporación de la CP se logra en diciembre del 2001, criopreservando hasta la fecha el 51,3% de las parejas que tiene más de 6 folículos a aspirar. Se han criopreservado 623 PN dando un promedio 6,4 PN por pareja. Se han descongelado 166 PN, sobreviviendo 134 PN, lo que implica un 80,7%. Ciento catorce PN clivaron a embrión de 4 células, equivalente a un 85,1%. Se han transferido 114 PN en 39 ciclos con un promedio de 2,9 embriones por pareja, dando origen a 12 embarazos clínicos (30,7%) con una tasa implantacional del 11,4%. Se observa una reducción del número de embarazos múltiples en dobles del 23% al 15,5%, en triples del 7,6% al 2,2% y la no ocurrencia de cuádruples o más, al comparar el período 2000-diciembre 2001 (sin CP de PN), con diciembre de 2001-junio del 2003.

[Predictive value of endometrial pattern and thickness in the result of in vitro fertilization and embryo transfer]. / Valor predictivo del patrón y del grosor endometrial en el resultado de fecundación in vitro y transferencia embrionaria.

In order to assess the relationship between echographic endometrial thickness and pattern and the probability of clinical pregnancy and delivery we analyzed retrospectively 51 cycles of IFV-ET. Patients were classified in three categories of endometrial thickness: < 9 mm, 9.1-11 mm and > 11 mm and in two types of endometrial pattern: type 1 (non triple line) or type 2 (triple line). The average endometrial thickness of patients who got pregnant and those who did not was 11.8 +/- 1.8 mm and 10.6 +/- 1.7 mm respectively (p = NS). There were no clinical pregnancies in patients with endometrial thickness < 9 mm (p < 0.01). The average endometrial thickness in patients with endometrial pattern type 1 and type 2 was 11.1 +/- 1.2 mm and 10.9 +/- 1.9 mm respectively (p = NS). Patients who presented type 2 endometrial pattern (n = 39) produced eleven clinical pregnancies (28.2%) and those with type 1 (n = 2) only one clinical pregnancy (8.3%), which ended in spontaneous abortion (p < 0.01). When both variables, thickness and pattern, were considered together, patients with endometrial pattern type 2 and thickness > 11 mm had a probability of clinical pregnancy and of delivery of 43.8% and 25%, respectively, who is statistically significant (p < 0.03). We conclude that endometrial thickness and pattern, taken together, offer a valuable prognostic value for the outcome of an IVF-ET cycle.

[The results of a program of in vitro fertilization and tubal embryo transfer (ZIFT)]. / Resultados de un programa de fertilización in vitro y transferencia de embriones a la trompa (ZIFT).

Twenty-one sterile couples, between September 1989, and August 1991, were treated for ovulation stimulation of their cycles, in order to practice in them, a in vitro fertilization and tube embryo transfer (ZIFT). Two protocols of ovulation induction were used, both with leuprolide acetate (Lupron), one in the luteal phase and the other in follicular phase and since the second or the fourth day of the cycle, respectively, gonadotropins were added (Metrodine and Pergonal). Out of all the twenty-nine initiated cycles, twenty-seven were aspirated (93.1%) and twenty-four reached an embryo transfer (82.8%). Seven clinic pregnancies were obtained (29.17% per transfer) and four deliveries (16.67% per transfer). The sterility period average was 69.64 +/- 36.6 months and the patients age average was 34.1 +/- 4.38 years. The global rate of fertilization was 63.53%. With luteal phase Lupron best results were got (pregnancy rate of 38.46% per transfer) and there were not considerable difference in the number of gonadotropins ampulla employed. When embryos were transfer to the tubes and the uteri the pregnant rate was 50% per transfer, in comparison to 18.75% when transfer was made only in the tubes.

[In vitro fertilization program. Preliminary results]. / Programa de fecundación in vitro. Resultados preliminares.

Three infertile couples were submitted to in vitro fertilization and uterine embryo transfer (IVF+ET) and 7 to in vitro fertilization and pronuclear stage tubal transfer (IVF+PROST). In order to programmed menstruation Norethisterone, 10 mg daily, were administered during the cycle preceding the one of controlled ovarian hyperstimulation. In order to inhibit endogenous production of FSH and LH, leuprolide acetate, a Gn-RH agonist, was injected subcutaneously 1 mg daily during 6 days and 0.5 mg fowardly from the luteal phase of the cycle proceeding the one of hyperstimulation until the day of HCG administration. To achieve superovulation pure FSH (Metrodine), HMG (Pergonal) and HCG (Endocorion) were used. Oocyte retrieval was performed through transvaginal puncture under ultrasonographic control. For oocyte and embryo identification and classification, spermatozoa separation and capacitation and gamete insemination and incubation procedures habitual techniques were employed. Pronuclear embryo tubal transfer was performed through a laparoscope 17 hours after insemination and embryo transfer to the uterine cavity after 48 hours. Nine of 10 patients responded to gonadotrophin hyperstimulation and were submitted to ovarian puncture. 69 oocytes (7, per patient) were obtained, 59 (81.15% of which were mature. 74.55% of the inseminated oocytes fertilized. Two patients got pregnant: one, submitted to IVF+PROST, presently has a multiple pregnancy with triplets and the second, submitted to IVF+UT, had a missed abortion at 8 weeks of pregnancy.

Human sperm-cervical mucus interaction and the ability of spermatozoa to fuse with zona-free hamster oocytes.

Samples of semen and cervical mucus were provided by 18 couples. Cervical mucus was obtained for each day possible and stored at 4 degrees C until all the samples were collected. Flat capillary tubes were loaded with the mucous samples and spermatozoa from the husband's semen sample were allowed to migrate through the cervical mucus (3 cm column) into culture medium. The spermatozoa recovered after migration through cervical mucus were assayed in vitro with zona-free hamster oocytes. Control experiments were carried out using spermatozoa from the same semen sample but prepared by the swimming-up technique. Altogether, 557 eggs in the control group and 1236 eggs in the experimental group were analysed, and the results demonstrated that the % of sperm penetration, the mean number of sperm decondensations per penetrated egg and the mean number of spermatozoa adhering per egg all had higher values (P less than 0.05) for the control samples than for the experimental samples. We suggest that cervical mucus modifies human spermatozoa, as measured by their interaction with zona-free hamster oocytes.

Sperm migration through human cervical mucus in women with copper IUD's.

Human cervical mucus from women using Lippes Loop and T-Cu-200 IUDs was used to study sperm migration in vitro using flat capillary tubes. Cervical mucus from women bearing no IUD was used as the control. 100% of the control samples, 83% of the Lippes Loop users, and 88% of the T-Cu-200 users had more than 100 spermatozoa/field of 100x. In 17% and in 11% there were between 40 and 100 spermatozoa/field of 100x in the Lippes Loop and T-Cu-200 users. The presence of copper IUDs does not interfere with sperm migration in vitro through human cervical mucus.

Selection of morphologically abnormal sperm by human cervical mucus.

The important role of cervical mucus from a reproduction standpoint is the transport and selection of spermatozoa. The study of the fertilizing ability of human spermatozoa by the use of zona-free hamster oocytes has shown that morphologically abnormal sperm can fuse with the zona-free hamster oocyte. The high proportion of morphologically abnormal spermatozoa present in human semen is significantly reduced after sperm migration through cervical mucus. The mucus, while a favorable environment for sperm survival, does not seem to contribute to the occurrence of sperm capacitation and acrosome reaction.