Insights into ligand binding by a viral tumor necrosis factor (TNF) decoy receptor yield a selective soluble human type 2 TNF receptor.

Etanercept is a soluble form of the tumor necrosis factor receptor 2 (TNFR2) that inhibits pathological tumor necrosis factor (TNF) responses in rheumatoid arthritis and other inflammatory diseases. However, besides TNF, etanercept also blocks lymphotoxin-α (LTα), which has no clear therapeutic value and might aggravate some of the adverse effects associated with etanercept. Poxviruses encode soluble TNFR2 homologs, termed viral TNF decoy receptors (vTNFRs), that display unique specificity properties. For instance, cytokine response modifier D (CrmD) inhibits mouse and human TNF and mouse LTα, but it is inactive against human LTα. Here, we analyzed the molecular basis of these immunomodulatory activities in the ectromelia virus-encoded CrmD. We found that the overall molecular mechanism to bind TNF and LTα from mouse and human origin is fairly conserved in CrmD and dominated by a groove under its 50s loop. However, other ligand-specific binding determinants optimize CrmD for the inhibition of mouse ligands, especially mouse TNF. Moreover, we show that the inability of CrmD to inhibit human LTα is caused by a Glu-Phe-Glu motif in its 90s loop. Importantly, transfer of this motif to etanercept diminished its anti-LTα activity in >60-fold while weakening its TNF-inhibitory capacity in 3-fold. This new etanercept variant could potentially be used in the clinic as a safer alternative to conventional etanercept. This work is the most detailed study of the vTNFR-ligand interactions to date and illustrates that a better knowledge of vTNFRs can provide valuable information to improve current anti-TNF therapies.

¿Mejora el estudio genético pre-implantacional la probabilidad de embarazo clínico en parejas sometidas a IVF/ICSI?: Revisión sistemática y meta análisis / Does the pre-implantation genetic study improve the probability of clinical pregnancy in couples undergoing IVF / ICSI?

Una de las principales causas de la falla de los ciclos de fecundación in vitro es la aneuploídia embrionaria. OBJETVO: determinar si las pruebas de tamizaje genético pre-implantacional favorece la posibilidad de embarazos MÉTODOS: Se realizó un revisión sistemática y meta-análisis. Buscamos en las bases PUBMED y EMBAS, estudios publicados entre 2006-2016, que compararan el número de embarazos en fecundación in vitro con y sin tamizeje genético preimplantaicon RESULTADOS: De los 115 artículos analizados, 4 cumplieron los criterios de selección. Evaluamos un total de 221 ciclos con tamizje y 592 sin. No encontramos diferencias en la posibilidad de embarazo (RR 0.88; IC95% 0.71-1.10; p=0.28). Al hacer análisis por subgrupo de técnica de tamizaje, encontramos que el uso de hibridación fluosrescente in situ se asoció a una disminución en la posibilidad de embarazo (3 estudios, RR 0.53; IC95% 0.36-0.77; p=0.0009); mientras que el uso de hibidración genómica comparativa se asoció a un aumeto (1 estudio, RR 1.58; IC 95% 1.24-2.00; p<0.001). CONCLUSION: La eficacia de las pruebas de tamizaje genñeticos son dependientes de la técnica, por lo que se deberia favorecer el uso de hibidración genómica comparativa.

Probably, the main cause in IVF failure is the transfer of aneuploid embryos. OBJECT: To determine if the use of preimplantational genetic screening improves the pregnancy rate in IVF cycles, compared to regular IVF. METHODS: We performed a systematic review and meta-analysis, searching in PUBMED and EMBASE databases studies published between 2006-2016, comparing the pregnancy rates in women undergoing IVF with PGS with that of women undergoing IVF only. RESULTS: Of the 115 articles found, 4 met the selection criteria, with a total of 734 women between 33 and 41 years: 221 with PGS and 592 controls. We found no association between the use of PGS and pregnancy (RR 0.88, 95% CI 0.71-1.10, p = 0.28). However, we performed a subgroup analysis by technique of PGS, and found that fluorescent in situ hybridization was associated with a diminished risk of pregnancy (3 studies;(RR 0.53; 95% CI 0.36-0.77; p = 0.0009), whereas comparative genomic hybridization was associated with an increase (1 study, RR 1.58, CI95% 1,24-2.00, p<0.001). CONCLUSION: The effectivity of PGS is determined by the technique for PGS; therefore, only comparative genomic hybridization should be offered.

Maduración in vitro de ovocitos humanos: una opción para preservar la fertilidad de las mujeres: reporte del primer caso realizado en Chile / Oocyte in vitro maturation: alternative approach for fertility preservation: report the first case in Chile

La maduración in vitro (MIV) de ovocitos humanos es parte de las técnicas de fecundación in vitro, que consiste en la aspiración de ovocitos inmaduros. Es ofrecida principalmente a pacientes con alto riesgo de desarrollar un síndrome de hiperestimulación ovárica, especialmente pacientes con síndrome de ovario poliquístico. Adicionalmente, es un método ofrecido a las pacientes oncológicas para preservar su fertilidad. Presentamos el primer caso de MIV realizado en Chile, en la Unidad de Medicina Reproductiva de Clínica Monteblanco, en una paciente con sospecha de resistencia ovárica a la FSH y quien, con el consentimiento de sus padres, realizó este procedimiento para preservar su fertilidad a futuro.

Oocyte in vitro maturation (IVM) is an assisted reproductive technology in which immature oocytes are retrieved from antral follicles. It has been applied mainly in patients with an increased risk of ovarian hyperstimulation syndrome, particularly in patients with polycystic ovarian syndrome. Moreover, it has been proposed as an alternative approach for fertility preservation for oncological patients. We report the first IVM case in Chile, preformed at the Centre for Reproductive Medicine at Clínica Monteblanco, in a patient with suspected ovarian resistance to FSH, who with the consent of her parents, performed IVM to preserve her fertility.

Decreased anti-Müllerian hormone concentration in follicular fluid of female smokers undergoing artificial reproductive techniques.

BACKGROUND: Several reports indicate that women who smoke have an increased risk of failure to conceive compared with their non-smoker counterparts. Here, we assessed the effect of smoking during the Assisted Reproduction Therapy (ART) on a potential marker of ovarian reserve, anti-müllerian hormone (AMH) in the follicular fluid (FF). MATERIALS AND METHODS: This was a cohort prospective study to assess the association between cigarette smoking and AMH concentrations in FF in fifty-six women undergoing their first ART cycle. Self-reported smoking status over time was also collected through personal interview. The main outcome measured was the association between current smoking and AMH concentrations in FF. Smoking status was assessed by FF cotinine concentrations. Analysis of covariance was performed to test statistical interaction between the main outcome and confounders. RESULTS: The mean concentration of AMH in follicular fluid was significantly decreased among smokers (1.02±0.14 vs. 1.74±0.15, P<0.05). No statistical interaction was found between this difference in AMH concentrations and confounders like age and BMI. Thus, our data support the idea that AMH is decreased in active smokers across the fertile age. CONCLUSIONS: The hypothesis of decreased AMH concentration in follicular fluid in female smokers was confirmed. The mechanisms through which cigarette smoking induces this fall in AMH are unknown and additional research is needed to improve our comprehension of the negative impact of smoking on ART outcomes.

[Live birth after the transfer of embryos obtained by fertilization of vitrified oocytes: report of one case]. / Parto tras la transferencia de embriones generados por fecundación de ovocitos vitrificados: Comunicación de un caso.

We report the first successful live birth after the transfer of embryos obtained by fertilization of vitrified oocytes. A couple with primary infertility due to teratozoospermy and chronic an ovulation decided to undergo assisted reproductive technology after 4 failed cycles of super ovulation and intrauterine insemination. The woman underwent a standard luteal phase agonist protocol, with controlled ovarian hyper stimulation with daily 150 IU recombinant gonadotropin and 75 IU urinary gonadotropin for 12 days. Due to the high risk of ovarian hyper stimulation syndrome the couple was advised to delay embryo transfer. Eighteen mature oocytes were recovered, eight were vitrified and 10 fertilized and cryopreserved as pro-nuclei. Two months later, four vitrified oocytes were thawed, and three morphologically-normal embryos were transferred to an estrogen-progesterone-primed uterus, obtaining triple clinical pregnancy. The pregnancy was uneventful until 32 weeks of amenorrhea, when pre-term delivery started. After inducing lung maturity, a cesarean section was performed and three healthy fetuses were delivered. Nowadays, the babies are two and a half years old, and have had a normal psycho-motor development.

Parto tras la transferencia de embriones generados por fecundación de ovocitos vitrificados: Comunicación de un caso / Live birth after the transfer of embryos obtained by fertilization of vitrified oocytes: Report of one case

We report the first successful live birth after the transfer of embryos obtained by fertilization of vitrified oocytes. A couple with primary infertility due to teratozoospermy and chronic an ovulation decided to undergo assisted reproductive technology after 4 failed cycles of super ovulation and intrauterine insemination. The woman underwent a standard luteal phase agonist protocol, with controlled ovarian hyper stimulation with daily 150IU recombinant gonadotropin and 75IU urinary gonadotropin for 12 days. Due to the high risk of ovarian hyper stimulation syndrome the couple was advised to delay embryo transfer. Eighteen mature oocytes were recovered, eight were vitrified and 10 fertilized and cryopreserved as pro-nuclei. Two months later, four vitrified oocytes were thawed, and three morphologically-normal embryos were transferred to an estrogen-progesterone-primed uterus, obtaining triple clinical pregnancy. The pregnancy was uneventful until 32 weeks of amenorrhea, when pre-term delivery started. After inducing lung maturity, a cesarean section was performed and three healthy fetuses were delivered. Nowadays, the babies are two and a half years old, and have had a normal psycho-motor development.

Recent cigarette smoking and assisted reproductive technologies outcome.

OBJECTIVE: To assess the association between recent cigarette smoking (CS) in female and male partners and assisted reproduction technology (ART) outcomes. DESIGN: Cohort prospective study. SETTING: University ART program in Chile. PATIENT(S): One hundred sixty-six couples seeking pregnancy through ART. INTERVENTION(S): Follicular fluid (FF) and serum cotinine concentrations were measured in female partners. Self-reported CS data were collected through personal interviews. MAIN OUTCOME MEASURE(S): The association between female recent smoking, assessed by FF and serum cotinine concentrations, and ART outcomes, such as number of ova retrieved and implantation rates, and the association between self-reported male recent smoking and live birth rates. RESULT(S): A significant age-adjusted association between increased FF cotinine level and decreased number of ova retrieved was found. The male partner's smoking habit significantly decreased the live birth rate from 21.1% to 7.8%. Serum cotinine concentrations paralleled those of FF. CONCLUSION(S): The hypothesis of a detrimental effect of recent female smoking over implantation rates is rejected. However, recent male smoking is associated with significantly decreased live birth rates even after adjusting for confounders. Female recent smoking was significantly associated with decreased number of retrieved ova.

Criopreservación de embriones al tercer día de desarrollo / Third day in vitro-developed embryo cryopreservation

Introducción: Los procedimientos de congelación se hacen indispensables cuando se realiza una hiperestimulación y sobran embriones viables; los costos disminuyen y la tasa de embarazo por aspiración aumenta con la congelación-descongelación de embriones. Objetivos: Presentar nuestra experiencia con congelación-descongelación de embriones. Lugar: Servicio Médico y Laboratorio de Reproducción Asistida, Clínica Ricardo Palma. Diseño: Estudio clínico retrospectivo. Material biológico: Embriones obtenidos por fertilización asistida. Intervenciones: Hiperestimulación ovárica controlada en la fase lútea corta, captura ovular a las 36 horas postadministración de hCG, fertilización in vitro clásica o ICSI transporte como método de fecundación, procesos clásicos de criopreservación y descongelación de embriones. Principales medidas de resultados: Promedio de supervivencia embrionaria en el proceso congelación-descongelación. Resultados: Iniciamos el estudio en octubre de 2003. El número total de ciclos en que se congeló embriones en este periodo fue 154; de estos, solo se descongeló 58. La tasa de embarazo por transferencia fue 30,2 por ciento, obteniéndose 16 embarazos, de ellos 12 embarazos a término y 4 abortos. Conclusiones: Los resultados con criopreservación de embriones en nuestro servicio de reproducción asistida son comparables con los de otros centros de fertilidad.

Introduction: Freezing-unfreezing procedures are essential when hyperestimulation is followed by embryo overproduction; they lower costs and increase pregnancy rates per aspiration. Objectives: To present our experience with embryo freezing-unfreezing. Setting: Assisted Reproduction Medical Service and Laboratory, Clinica Ricardo Palma. Design: Clinical retrospective study. Biologic material: Embryos obtained by assisted fertilization. Interventions: Controlled ovarian hyperestimulation with short lutealphase, ova capture at 36 hours post hCG administration, classical in vitro fertilization or ICSI-transport, classical processes of embryo cryopreservation and unfreezing. Main outcome measures: Embryo survival in freezing-unfreezing process. Results: Westarted our study in October 2003. Number of cycles with frozen embryos during this period was 154; from these we unfroze only 58. Pregnancy rate per transference was 30,2 per cent, obtaining 16 pregnancies, including 12 term pregnancies and 4 abortions. Conclusions: Results with embryo cryopreservation at our assisted reproduction service are consistent with those of other fertility centers.

Resultados de un programa de fertilización in vitro y transferencia de embriones a la trompa; ZIFT / Results of in vitro fertilization and embryo transfer to the tube programme

Entre septiembre de 1989 y agosto de 1991 se trataron 21 parejas estériles, iniciándose 29 ciclos de estimulación de ovulación con el objeto de practicar una fertilización in vitro y transferencia de embriones a la trompa(ZIFT). Se usaron dos protocolos de inducción, ambos con acetato de leuprolide (Lupron), uno en fase lútea y el otro en fase folicular, agregando gonadotrofinas (Metrodine y Pergonal) desde el 2- ó 4- día del ciclo, respectivamente. De los ciclos iniciados, llegaron a la aspiración 27(93,1%) y a la transferencia 24(82,8%). Se obtuvieron 7 embarazos clínicos (29,17% por transferencia) y 4 partos (16,67% por tansferencia). El período promedio de esterilidad fue 69,64ñ36,6 meses y la edad promedio de las pacientes fue de 34,1ñ4,38 años. La tasa global de fertilización fue de 63,53%. Se obtuvieron mejores resultados con el protocolo de Lupron en fase lútea (tasa de embarazo de 38,46% por tansferencia) y no hubo diferencias importantes en el número de ampollas de gonadotrofinas utilizadas. Cuando se transfirieron embriones a las trompas y al útero la tasa de embarazo fue de 50% por transferencia, comparado con el 18,75% cuando se transfirieron sólo a las trompas

Programa de fecundación en vitro: resultados preliminares / In vitro fertilization program: preliminary results

Tres parejas con infertilidad conyuugal fueron sometidas a fertilización in vitro y transferencia uterina (FIV+TU) y 7 a fertilización in vitro y transferencia a la trompa de embriones en estado de pronúcleo (FIV+PROST). Para programar la menstruación, se administraron 10 mg diarios de noretisterona (NET) durante el ciclo anterior al de hiperestimulación ovárica. Con el objeto de inhibir la producción endógena de FSH y LH se indicó acetato de leuprolide, un agonista Gn Rh, 1 mg subcutáneos diarios durante 6 días y posteriormente 0,5 mg diarios desde la mitad del ciclo anterior al de hiperestimulación hasta el día de la administración de HCG. Para provocar la superovulación se empleó FSH pura (Metrodine), HMG (Pergonal) y HCG (Endocorion). La recuperación del ovicitos se efectuó por vía transvaginal bajo control ecográfico. Los procedimientos de identificación de ovocitos y embriones, separación y capacitación de espermatozoides e inseminación e incubación de gametos se practicarón con técnicas habituales. La transferencia a las trompas de los embriones en estado de pronúcleo se efectuó por vía translaparoscópica 17 horas después de la inseminación y la transferencia de embriones al útero por vía transcervical 48 horas después. Nueve de 10 pacientes respondieron a la estimulación de gonadatrofina y fueron sometidos a punción ovárica. Se recuperaron 69 ovocitos (7,6 por paciente) de los cuales 59 (81,15%) fueron maduros. El 74,55% de los ovocitos inseminados fertilizaron. Dos pacientes se embarazaron: una de FIV+PROST cursa un embarazo gemelar triple del primer trimestre y la segunda de FIV+TU presentó un aborto retenido a las 8 semanas de embarazo