Estudio de la microbiota vaginal en los resultados de la terapia de reproducción asistida / Study of the vaginal microbiota in results of assisted reproduction therapies

El microbioma del tracto genital femenino es determinante para mantener un entorno saludable. La microbiota vaginal normal se caracteriza por la abundancia de Lactobacillus, que confieren protección a la vagina huésped contra microorganismos potencialmente patógenos que pueden provocar infecciones del aparato urinario y enfermedades de transmisión sexual. Las alteraciones en la microbiota vaginal por factores intrínsecos, como la edad o el ciclo menstrual, o externos, como la actividad sexual o el embarazo, pueden conducir a un estado de disbiosis microbiana y al desarrollo de enfermedades con efecto perjudicial en la fertilidad. También se ha señalado que la microbiota vaginal puede desempeñar un papel clave en el éxito de las terapias de reproducción asistida. El objetivo de esta revisión es identificar y evaluar los estudios sobre el papel de la microbiota vaginal en la salud de la mujer y la reproducción humana.(AU)

The microbiome of the female genital tract is essential to maintenance a healthy environment. The normal vaginal microbiota is defined by the abundance of Lactobacillus. These microbes confer the host vagina protection from potentially pathogenic microorganisms that may cause urinary tract infections and sexually transmitted diseases. Changes in the vaginal microbiota due to inherent factors, such as age or menstrual period, or external factors like sexual activity or pregnancy, can lead to microbial dysbiosis and the development of pathologies in relation of reduced rates of conception. It has also been suggested that vaginal microbiota may play a key role in the success of assisted reproductive therapies. The objective of this review is to identify and evaluate trials of the vaginal microbiota role in women's health and human reproduction.(AU)

Endometriosis e infertilidad: una puesta al día / Endometriosis and infertility: an update

La endometriosis es una enfermedad sistémica, inflamatoria y crónica, dependiente de estrógenos que causa infertilidad y dolor pélvico crónico. Se asocia a infertilidad, alteraciones inmunológicas y compli- caciones gestacionales. Su diagnóstico no resulta fácil por la ambigüedad de sus manifestaciones clínicas y por la complejidad de ciertas pruebas complementarias. Desconocemos con exactitud su etiopatogenia, aunque cada vez más vamos profundizando en mecanismos fisiopatológicos que la perfilan con mayor precisión. Uno de los inconvenientes para su correcto abordaje en la medicina reproductiva ha sido la manera de valorar su implicación en la fertilidad, más allá de las diferentes clasificaciones respecto de su extensión, pero también han influido las diferentes pautas médico-qui- rúrgicas, sobre todo en su enfoque inicial. Aunque las distintas Sociedades Científicas han aportado uniformidad en su abordaje actual con técnicas de producción asistida, aún quedan retos importantes a resolver relacionados con la calidad ovocitaria o embrionaria. Este trabajo pretende una puesta al día del conocimiento sobre esta patología. (AU)

Endometriosis is a chronic, inflammatory, systemic, estrogen-dependent disease that causes infertility and chronic pelvic pain. It is related to infertility, immunological alterations and gestational complica-tions. Diagnosis of endometriosis is difficult due to the broad variety of clinical manifestations as well as the complexity of certain complementary tests. Even though we do not know exactly its etiopatho-genesis, we are deepening and elaborating on its pathophysiological mechanisms.How we assess its fertility implications has been a great challenge in reproductive medicine. Further-more, its different classifications regarding its extension, and the diversity of medical-surgical guideli-nes have also had an influence, especially in its initial focus. Even though Scientific Societies have provided an uniform approach in assisted reproductive techniques, there are still important challenges in order to relate oocyte or embryo quality. This work aims to update knowledge about this pathology. (AU)

Algunos dilemas éticos presentes y futuros ante los avances en fecundación in vitro / Some present and future ethical dilemmas surrounding advancements in in vitro fertilization

RESUMEN El creciente campo de la reproducción humana asistida ha alcanzado hitos inimaginables. Su continuo desarrollo y las innovaciones que genera, en ocasiones, plantean dilemas tanto éticos como jurídicos. El presente ensayo trata de exponer los cambios progresivos que se están viviendo en el ámbito del origen de la vida debido al desarrollo de nuevas opciones y estrategias en reproducción humana asistida. En primer lugar, se realiza una reflexión interdisciplinar desde la ciencia, la ética y el derecho, sobre la naturaleza humana y los cambios a los que la sociedad se enfrenta, en particular, desde la perspectiva española. En segundo lugar, recoge una breve aproximación en torno a las técnicas biomédicas presentes o futuras en el campo de la reproducción humana. Concluye sobre la necesidad de reflexionar ante el vertiginoso avance de la ciencia en materia de reproducción humana asistida.

ABSTRACT The growing field of assisted human reproduction has achieved unimaginable milestones. Its continuous development and the innovations it generates at times pose both ethical and legal dilemmas. This essay aims to elucidate the progressive changes occurring in the realm of the origin of life due to the development of new options and strategies in assisted human reproduction. First, it constructs an interdisciplinary reflection on human nature and the changes society faces from the perspectives of science, ethics, and law, particularly from the perspective of Spain. Second, it provides a brief overview of current or future biomedical techniques in the field of human reproduction. It concludes with a discussion of the need to reflect on the rapid advancement of science in assisted human reproduction.

Análisis bioético (subjetivismo moral) desde la percepción de los clínicos sobre la situación de los embriones sometidos a fecundación in vitro. Quito-Ecuador / Bioethical analysis (moral subjectivism) from the perception of clinicians on the situation of embryos subjected to in vitro fertilization. Quito-Ecuador / Análise bioética (subjetivismo moral) a partir da percepção dos médicos sobre a situação dos embriões submetidos à fertilização in vitro. Quito-Equador

Resumen: Objetivo. Analizar las percepciones y prácticas de los clínicos en relación con el manejo del embrión sometido a técnicas de fecundación in vitro. Metodología. Cualitativa (subjetivista y fenomenológico). Se realizaron 15 las entrevistas semiestructuradas aplicando un muestreo por saturación dirigidas a personal clínico que haya participado en procedimientos de fecundación in vitro. Los datos se analizaron con el programa Atlas Ti 8.0®. Resultado. Los clínicos consideran al embrión como un ser humano o futuro ser humano y, además, merecedor de respeto y consideración, proponiendo incluso mejoras en los procesos de manipulación y almacenaje. Conclusión. Los embriones no son considerados como entes susceptibles de recibir daño, desde argumentos no solo técnicos sino éticos. Desde la corriente principialista, se describe la necesidad de promover actitudes de responsabilidad y prudencia para evitar el dogmatismo (objetivismo moral) proponiendo una postura deliberativa.

Abstract: The objective of this paper is to analyze the perceptions and practices of clinicians in relation to the management of embryos subjected to in vitro fertilization techniques. Methodology is Qualitative (subjectivist and phenomenological). A total of 15 semi-structured interviews were conducted using saturation sampling for clinical personnel who have participated in vitro fertilization procedures. The data is analyzed with the Atlas Ti 8.0® program. Results: Clinicians consider the embryo as a Human being or future human being, in addition, deserving of respect and consideration even proposing improvements in the processes of handling and storage. Conclusion. Embryos are not considered as entities susceptible of damage from not only technical but ethical arguments. From the principialist current, the need to promote attitudes of responsibility and prudence to avoid dogmatism (moral objectivism) is described, proposing a deliberative position.

Resumo: Objetivo. Analisar as percepções e práticas dos médicos em relação ao manejo do embrião submetido a técnicas de fertilização in vitro. Metodologia. Qualitativo (subjetivo e fenomenológico). Foram realizadas 15 entrevistas semiestruturadas por amostragem de saturação para pessoal clínico que participou de procedimentos de fertilização in vitro. Os dados são analisados com o programa Atlas Ti 8.0®. Resultado. Os médicos consideram o embrião como um ser humano ou futuro, além de merecer respeito e consideração, propondo até melhorias nos processos de manuseio e armazenamento. Conclusão. Os embriões não são considerados como entidades suscetíveis a receber danos não apenas de argumentos técnicos, mas éticos. A partir da corrente principialista, descreve-se a necessidade de promover atitudes de responsabilidade e prudência para evitar o dogmatismo (objetivismo moral), propondo uma posição deliberativa.

Sperm origin impact on early human embryo kinetics / El origen del gameto paterno influye en la cinética embrionaria temprana

Introduction: Time-lapse imaging in embryology is a recent and developing technology, which not only allows constant embryo monitoring but is also a promising non-invasive tool for embryo selection, as it permits the annotation of the embryo's kinetics throughout early development. Several external factors together with patient characteristics are reported as affecting embryo kinetics. Controversy still exists regarding whether sperm origin affects the timing of the embryo's developmental events evaluated by time-lapse monitoring. The aim of this study is to examine the effect of sperm origin on embryonic kinetics in IVF cycles. Material and methods: A retrospective analysis of 161 IVF cycles between 2014 and 2020 were included. The morphokinetic parameters of 220 embryos obtained from couples with severe male factor infertility who underwent testicular sperm extraction (TESE), and 613 embryos from couples with fresh ejaculated spermatozoa were evaluated. Results: Statistically significant morphokinetic differences were observed between embryos from the TESE group compared to the normozoospermic embryos. In fact, 7 kinetic variables were eventually found to be relevant (p<.05). Conclusions: This study showed that embryos derived from testicular-retrieved spermatozoa presented delayed cell divisions, compared to ejaculated spermatozoa embryos.(AU)

Introducción: La tecnología time-lapse en embriología es una metodología de aplicación reciente en los laboratorios de fecundación in vitro (FIV), que además de la monitorización continua de los embriones, permite realizar anotaciones sobre la morfología y la cinética del desarrollo embrionario que pueden emplearse en la selección de embriones. Se ha descrito que la cinética de los embriones en cultivo varía en función de múltiples factores, como la estimulación ovárica, los medios de cultivo empleados, las condiciones de cultivo, etc. Se desconoce cuál es el efecto paterno en la cinética embrionaria y si este efecto depende del origen de los espermatozoides. El objetivo de este estudio es evaluar el efecto del origen de los espermatozoides sobre la cinética embrionaria en los ciclos FIV. Material y métodos: Para ello, se analizaron retrospectivamente 161 ciclos de FIV entre los años 2014 y 2020. Se incluyeron 220 embriones de parejas con infertilidad por factor masculino severo que se sometieron a una biopsia para la recuperación de esperma testicular (TESE) y 613 embriones derivados del eyaculado fresco de varones normozoospérmicos. Resultados: Se observaron diferencias estadísticamente significativas entre los embriones que se originaron en el grupo TESE, en comparación con los normozoospérmicos. De hecho, se encontraron siete variables cinéticas relevantes (p<0,05). Conclusiones: Este estudio muestra que los embriones derivados de espermatozoides recuperados por biopsia testicular presentan un patrón de división tardío, en comparación con los embriones provenientes de espermatozoides del eyaculado.(AU)

Estudio del efecto intercromosómico en portadores de anomalías cromosómicas estructurales equilibradas mediante PGT-SR / Study of the interchromosomal effect in carriers of balanced structuralchromosomal rearrangements by PGT-SR

Los portadores de anomalías estructurales cromosómicas equilibradas, a pesar de ser fe-notípicamente normales, tienen una competencia reproductiva disminuida de manera significativa conrespecto a la población general. Esto se debe a que, durante la gametogénesis, dependiendo de cómo sesegregue la alteración cromosómica en la meiosis I, se generarán gametos normales, equilibrados o des-equilibrados en mayor proporción que en portadores de cariotipos normales. Esta es la causa principalEstudio del efecto intercromosómico en portadores de anomalías cromosómicasestructurales equilibradas mediante PGT-SRStudy of the interchromosomal effect in carriers of balanced structuralchromosomal rearrangements by PGT-SR de la mayor tasa de abortos y descendencia con alteraciones que presentan los individuos portadores de inversiones ytranslocaciones recíprocas o robertsonianas. Otra posible fuente de gametos y/o embriones aneuploides, es el denominadoefecto intercromosómico (EIC), que consiste en una interferencia producida por una alteración cromosómica estructuralsobre la adecuada disyunción y segregación de otros cromosomas no involucrados en dicha alteración.Material y Métodos:Un total de 40 parejas fueron incluidas en el estudio, de las cuales 31 pertenecieron al grupo de es-tudio: catorce translocaciones robertsonianas, trece translocaciones recíprocas y cuatro de inversiones pericéntricas. Endiecinueve casos la mujer era portadora y en los doce restantes era el hombre el afecto. Nueve parejas con cariotipo normal,portadoras de una mutación responsable de enfermedad monogénica fueron incluidas en el grupo control. (AU)

Introduction: Carriers of balanced structural rearrangements, despite being phenotypically normal, they have a signifi-cantly decreased reproductive competence compared to the general population. The reason is because, during gametoge-nesis, depending on how the chromosomal alteration is segregated in meiosis I, normal, balanced, or unbalanced gameteswill be generated in greater proportion than in carriers of normal karyotypes. This is the main cause of the higher rate ofabortions and offspring with alterations that carriers of inversions, reciprocal translocations or Robertsonian translocationspresent. Another possible source of aneuploid gametes and/or embryos is the so-called interchromosomal effect (ICE),which consists of an interference produced by a structural chromosomal alteration on the proper disjunction and segregationof other chromosomes not involved in the rearrangement.Material and methods:A total of 40 couples were included in the study, of which 31 belonged to the study group: fourteenRobertsonian translocations, thirteen reciprocal translocations and four pericentric inversions. As for the affected parent,in nineteen of the cases the woman was the carrier of the chromosomal alteration and in the remaining twelve it was theman who was affected. Nine couples with a normal karyotype, carriers of a mutation responsible for monogenic disease,were included in the control group. (AU)

Inducción de la lactancia en parejas femeninas de mujeres embarazadas cuya gestación se ha obtenido mediante el método ROPA (Recepción de Ovocitos de la Pareja). Aproximación a través de un caso clínico / Lactation induction in female partners of pregnant women undergoing ROPAmethod. A clinical case

La aceptación en la sociedad de parejas homosexuales como nueva estructura familiar ha favorecidoun importante desarrollo en las terapias de reproducción asistida, como el método de Recepción de Ovo-citos de la Pareja (ROPA). La necesidad de mantener el vínculo, no sólo a nivel gestacional sino tambiénen el proceso de la lactancia materna ha favorecido el interés por la inducción de la lactancia en madresno gestantes. Sin embargo, no existe evidencia publicada con respecto la inducción de la lactancia enpacientes como las que se presentan en el caso, sometidas a esta técnica reproductiva. La inducción dela lactancia puede llevarse a cabo mediante métodos farmacológicos, métodos mecánicos, o la combi-nación de ambos. (AU)

The approval and normalization of homosexual couples as a new family structure in our society has benefited an importantdevelopment in assisted reproduction therapies, such as the ROPA method (reception of oocytes from the couple). Theneed to maintain the link in the process of breastfeeding has favored interest in inducing breastfeeding in non-pregnantwomen.However, there is no published evidence regarding the induction of breastfeeding in patients presented in our clinic case,subjected to reproductive techniques.Breastfeeding induction can be carried out by pharmacological methods or mechanical methods, based on breast stimu-lation techniques. (AU)

Selección de embriones en los tratamientos de fecundación in vitro / Selection of embryos in in vitro fertilization treatments

La prevalencia de la esterilidad entre la población en edad reproductiva continúa aumentando año tras año en las sociedades occidentales y el recurso terapéutico en la mayoría de los casos, serán las técnicas de reproducción asistida, principalmente la fecundación in vitro. Aunque los avances conseguidos en fecundación in vitro, han repercutido de forma incontestable en las probabilidades de conseguir una gestación, la eficiencia de la técnica, en términos globales, continúa siendo baja. Uno de los factores de mayor impacto en los resultados de fecundación in vitro es la selección de embriones. Es por ello que entre los principales retos de futuro que se plantean en el campo de la reproducción humana asistida, se encuentra el de conseguir métodos de selección embrionaria fiables que permitan la transferencia del embrión con mayor competencia para implantar. En este artículo se revisan los diferentes métodos de selección embrionaria empleados en fecundación in vitro.

The prevalence of infertility among the population of reproductive age continues to increase year after year in Western societies and the therapeutic resource in most cases will be assisted reproductive techniques, mainly in vitro fertilization. Although the advances made in vitro fertilization have had an undeniable impact on the chances of achieving pregnancy, the efficiency of the technique, in global terms, remains low. One of the factors with the greatest impact on in vitro fertilization results is embryo selection. That is why among the main future challenges that arise in the field of assisted human reproduction, is that of obtaining reliable embryo selection methods that allow the transfer of the embryo with greater competence to implant. In this article, the different embryo selection methods used in in vitro fertilization are reviewed.

Risk of mayor and minor birth defects in children conceived by assisted reproductive technology (IVF/ICSI): A prospective controlled cohort study.

INTRODUCTION: About 0.2-6.1% of newborns in the developed world have been conceived by assisted reproductive techniques (ART). Higher rate of major and minor malformations have been described in this population, but the multiple possible confounders associated make it difficult to establish a direct causal relationship and the specific factors involved. MATERIAL AND METHODS: To determine the risk of these malformations in our population, a collaborative prospective controlled cohort study was designed. We collected the specific ART-data related to the clinical gestation of women treated in a period of 2 years in the Reproduction Unit from a Spanish public tertiary-level hospital. 231 out of 267 newborns of these gestation (88%) participated in the study and were assessed by a pediatrician with expertise in Clinical Genetics and Dysmorphology at 12-20 and 26-40 months of age. At the same time a controlled group of children naturally conceived (NC) was selected according to the following criteria: the next NC newborn belonging to the same group of maternal and gestational age, and type of gestation (single or multiple). 230 controls were chosen and 208 participated in the study (90%). RESULTS: Major malformations were presented in 7.8% of the ART-children and 7.2% of the controls, without founding statistically differences between groups. However, differences were found in the risk of some minor malformations such as capillary malformations and pigmentary lesions, higher in the ART-group. A recurrent pattern of craneofacial anomalies was also unexpectedly detected. CONCLUSIONS: In spite of the high rate of major congenital malformations detected, there were no differences between groups. Thus, our results suggest that ART may affect the normal embryonic development but in a milder way than other confounding factors do. The facial phenotype identified has not previously been described, either the higher risk of capillary malformations and pigmentary lesions. More studies are needed to confirm this association.

Riesgo de malformaciones mayores y menores en niños concebidos por técnicas de reproducción asistida (FIV/ICSI): estudio prospectivo de cohorte controlado / Risk of mayor and minor birth defects in children conceived by assisted reproductive technology (IVF/ICSI): A prospective controlled cohort study

Introducción: En torno al 0,2-6,1% de los recién nacidos en los países desarrollados han sido concebidos por técnicas de reproducción asistida (TRA). Se han descrito tasas más altas de malformaciones congénitas (MC) mayores y menores en esta población, pero los múltiples posibles factores de confusión asociados hacen difícil establecer una relación de causalidad directa con estos procedimientos y conocer los factores específicos implicados. Material y método: Se realizó un estudio prospectivo de cohorte controlado con el objetivo de determinar el riesgo de MC en niños-TRA. Se recogieron los datos específicos de la TRA de una cohorte de gestaciones clínicas de mujeres tratadas en la Unidad de Reproducción de un hospital público de tercer nivel durante dos años; 231 de 267 (87%) niños nacidos de dichas gestaciones-TRA participaron en el estudio y fueron valorados por un pediatra con formación en Genética Clínica y Dismorfología a los 12-20 y a los 26-40 meses de edad. De forma simultánea se seleccionó una cohorte de niños concebidos de forma natural (CN), de acuerdo con los criterios: siguiente recién nacido al caso del mismo grupo de edad materna, edad gestacional y tipo de gestación (única o múltiple); 230 niños CN fueron seleccionados y 208 (90%) participaron en el estudio. Resultados: Se detectaron MC mayores en el 7,8% de casos y en el 7,2% de controles, sin existir diferencias estadísticamente significativas entre ellos. Sí se identificaron diferencias en algunas malformaciones menores como las malformaciones capilares y lesiones pigmentarias, más frecuentes en el grupo TRA. Además, se identificó de forma inesperada un patrón craneofacial recurrente en el grupo TRA. (AU)

Introduction: About 0.2–6.1% of newborns in the developed world have been conceived by assisted reproductive techniques (ART). Higher rate of major and minor malformations have been described in this population, but the multiple possible confounders associated, make it difficult to establish a direct causal relationship, and the specific factors involved. Material and methods: To determine the risk of these malformations in our population, a collaborative prospective controlled cohort study was designed. We collected the specific ART-data related to the clinical gestation of women treated in a period of 2 years in the Reproduction Unit from a Spanish public tertiary-level hospital. 231 out of 267 newborns of these gestation (88%) were exhausted assessed by a Clinical Geneticist expertise in Dysmorphology at 12–20 and 26–40 months of age. At the same time a controlled group of children naturally conceived (NC) was selected according to the following criteria: the next NC newborn belonging to the same group of maternal and gestational age, and type of gestation (single or multiple). 230 controls were chosen and 208 participated in the study (90%). Results: Major malformations were presented in 7.8% of the ART-children and 7.2% of the controls, without founding statistically differences between groups. However, differences were found in the risk of some minor malformations such as capillary malformations and pigmentary lesions, higher in the ART-group. A recurrent pattern of craneofacial anomalies was also unexpectedly detected. (AU)

El estudio de receptividad endometrial ER®map mejora los resultados reproductivos tras fallos previos de implantación en ciclos de fecundación in vitro / ER®map endometrial receptivity study improves reproductive outcomes after previous implantation failure in in vitro fertilisation cycles

Introducción: Los fallos repetidos en fecundación in vitro constituyen un reto en los tratamientos de fertilidad, sobre todo en ciclos con embriones de buena calidad, donde el endometrio parece ser la causa del fracaso reproductivo. Las pruebas diagnósticas dirigidas para la evaluación del endometrio óptimo, antes de una nueva transferencia, siguen siendo un reto para los tratamientos de reproducción asistida. El test de receptividad endometrial Endometrial Receptivity Map (ER®map) (Pronacera Therapeutics SL, Sevilla, España) nos aporta nueva información endometrial para personalizar la transferencia embrionaria siguiente, pudiendo mejorar así los resultados reproductivos de las pacientes con fallos previos de implantación. Objetivo: El objetivo principal es conocer si existen diferencias en la tasa de embarazo evolutivo (OPR) y tasa de embarazo clínico (PR) tras transferencias embrionarias fallidas previas con embriones de buena calidad, entre el grupo de estudio (E) con biopsia endometrial para estudio de receptividad endometrial previa a una nueva transferencia, y el grupo de control (C) con nueva transferencia estándar sin estudio anterior de receptividad endometrial. Material y métodos: Estudio observacional, analítico, longitudinal, retrospectivo de casos y controles históricos, realizado en la Unidad de Reproducción Asistida (URA) del Hospital Quirónsalud Barcelona, incluyendo a 104 pacientes con una o más transferencias embrionarias previas fallidas de embriones de buena calidad entre los años 2017 a 2019. A las pacientes con dos o más transferencias fallidas previas se les realizó una histeroscopia diagnóstica, junto a una analítica con la determinación de anticoagulante lúpico, anticuerpos antiB2 glicoproteina IgG/IgM, anticuerpos anticardiolipina IgG/IgM, y trombofilia hereditaria como parte del estudio de fallos de implantación del centro...(AU)

Introduction: Repeated failures in in vitro fertilization are a challenge in fertility treatments, especially in cycles with good quality embryos, where the endometrium appears to be the cause of reproductive failure. Targeted diagnostic tests for evaluation of the optimal endometrium before a new transfer remains a challenge for assisted reproduction treatments. The Endometrial Receptivity Map (ER®map Pronacera Therapeutics SL, Seville, Spain) test provides new endometrial information to customize the next embryo transfer to improve reproductive outcomes for patients with previous implantation failure. Objective: The main objective is to determine whether there are differences in the ongoing pregnancy rate by embryo transfer (OPR), after previous failed embryo transfers with good quality embryos, between the study group (E) with endometrial biopsy for endometrial receptivity study prior to a new transfer, and the control group (C) with new standard transfer without previous endometrial receptivity study. Material and methods: Observational, analytical, longitudinal, retrospective study of cases and historical controls, conducted in the Assisted Reproduction Unit (ARU) of the Hospital Quirónsalud Barcelona, including 104 patients with one or more previous failed embryo transfers with good quality embryos between the periods 2017-2019. Patients with more than one previous failed transfer underwent a diagnostic hysteroscopy, and an analysis was requested with the determination of: lupus anticoagulant, anti-B2-glycoprotein IgG/IgM antibodies, anti-cardiolipin IgG/IgM antibodies, and hereditary thrombophilia as part of the study of implantation failures in the centre.(AU)

[Risk of mayor and minor birth defects in children conceived by assisted reproductive technology (IVF/ICSI): A prospective controlled cohort study]. / Riesgo de malformaciones mayores y menores en niños concebidos por técnicas de reproducción asistida (FIV/ICSI): estudio prospectivo de cohorte controlado.

INTRODUCTION: About 0.2-6.1% of newborns in the developed world have been conceived by assisted reproductive techniques (ART). Higher rate of major and minor malformations have been described in this population, but the multiple possible confounders associated, make it difficult to establish a direct causal relationship, and the specific factors involved. MATERIAL AND METHODS: To determine the risk of these malformations in our population, a collaborative prospective controlled cohort study was designed. We collected the specific ART-data related to the clinical gestation of women treated in a period of 2 years in the Reproduction Unit from a Spanish public tertiary-level hospital. 231 out of 267 newborns of these gestation (88%) were exhausted assessed by a Clinical Geneticist expertise in Dysmorphology at 12-20 and 26-40 months of age. At the same time a controlled group of children naturally conceived (NC) was selected according to the following criteria: the next NC newborn belonging to the same group of maternal and gestational age, and type of gestation (single or multiple). 230 controls were chosen and 208 participated in the study (90%). RESULTS: Major malformations were presented in 7.8% of the ART-children and 7.2% of the controls, without founding statistically differences between groups. However, differences were found in the risk of some minor malformations such as capillary malformations and pigmentary lesions, higher in the ART-group. A recurrent pattern of craneofacial anomalies was also unexpectedly detected. CONCLUSIONS: In spite of the high rate of major congenital malformations detected, there were no differences between groups. Thus, our results suggest that ART may affect the normal embryonic development but in a milder way than other confounding factors do. The facial phenotype identified has not previously, either the higher risk of capillary malformations and pigmentary lesions. More studies are needed to confirm this association.

Gestación heterotópica abdominal tras fecundación in vitro y transferencia embrionaria. Reporte de un caso y discusión sobre el diagnóstico y manejo / Abdominal heterotopic pregnancy after IVF and embryo transfer. A case report and a review of the diagnosis and management

La coexistencia de una gestación intrauterina y una extrauterina se denomina gestación heterotópica. Es una condición poco frecuente, que ocurre en un 0,001-0,006% de las gestaciones espontáneas y hasta en un 1% de las gestaciones conseguidas mediante técnicas de reproducción asistida.Presentamos un caso de gestación heterotópica con implantación pélvica, una circunstancia extremadamente rara, y discutimos sobre su diagnóstico y su manejo clínico insistiendo en la necesidad de pensar en esta entidad aunque se objetive una gestación intrauterina tras una técnica de reproducción asistida y aunque no existan otros factores de riesgo. Un diagnóstico y tratamiento precoces serán claves para evitar las graves complicaciones asociadas a este tipo de gestación.(AU)

The coexistence of an intrauterine pregnancy and an extra-uterine one is called a heterotopic pregnancy. It is a rare condition that occurs in 0.001-0.006% of spontaneous pregnancies, and in up to 1% of pregnancies achieved through assisted reproduction treatments.The case is presented of a heterotopic pregnancy with pelvic implantation, an extremely uncommon event, followed by a discussion on its diagnosis and clinical management. There must be awareness of this disorder, even if an intra-uterine pregnancy is observed after an assisted reproduction treatment, and although there are no other risk factors.Early diagnosis and treatment is essential to avoid the serious complications associated with this type of pregnancy.(AU)

Manejo expectante de gestación ectópica abdominal tras fecundación in vitro en paciente con salpinguectomía bilateral: reporte de un caso / Expectant management of abdominal ectopic pregnancy following in vitro fertilization in a patient with previous bilateral salpinguectomy: a case report

ANTECEDENTES El embarazo ectópico abdominal es el menos habitual de los embarazos ectópicos, con una prevalencia situada entre el 0.9 - 1.4%. La mortalidad materna es elevada, alcanzando un 20% y la viabilidad fetal mínima. El manejo médico en estas situaciones es complicado ya que no está bien establecido debido a su baja frecuencia. CASO CLÍNICO Mujer de 35 años, con antecedente de esterilidad por endometriosis y salpinguectomía bilateral. Tras 5 fecundaciones in vitro (FIV) consigue una primera gestación, con finalización mediante cesárea por no progresión de parto. Acude a urgencias en su segundo embarazo, logrado tras 3 (FIV), con edad gestacional de 7 semanas. Presenta sangrado vaginal escaso y la ecografía demuestra a nivel de Douglas y hacia fosa iliaca izquierda un saco gestacional de 3 cm con embrión sin latido cardiaco de 5 mm. El nivel de β-hcg es de 1477 mUI/ml. Se diagnostica de gestación ectópica abdominal y se opta por actitud expectante dada la estabilidad clínica de la paciente. En un control a las 48h la β-Hcg es de 464 mUI/ml y la paciente se mantiene estable. En controles posteriores se observan niveles descendentes de β-Hcg y tras un mes la resolución es completa. CONCLUSIÓN El embarazo ectópico abdominal es una entidad poco frecuente pero con una alta tasa de mortalidad. Aunque lo más común es optar por un abordaje quirúrgico es necesario individualizar cada caso y basarse en la clínica y las diferentes pruebas diagnósticas para seleccionar aquellos casos que se pueden beneficiar de un manejo conservador.

BACKGROUND Abdominal ectopic pregnancy accounts for only 0.9-1.4% of all ectopic pregnancies. The maternal mortality rate is high (up to 20%) and fetal viability mínimum. The managment, specially the conservatory management of these cases is difficult because of our limited experiencie due to its low frecuency. CASE PRESENTATION 35-year-old woman, with history of sterility due to endometriosis that required bilateral laparoscopic salpinguectomy. Her first pregnancy (after 5 in vitro fertilization cicles (IVF)) finalized with a caesarean section because of to the lack of labour progresion. She was admitted to our emergency department during her second pregnancy (after 3 IVF cicles), with 7 weeks of gestational age. She had a little vaginal bleeding. Ultrasound scan showed a 5mm gestational sac with a 3mm embryo without cardiac activity in the pouch of Douglas. The β-Hcg level was 1477mUI/ml. The final diagnosis was ectopic abdominal pregnancy and it was decided to undertake an expectant management because she was clinically stable. The β-Hcg level after 48 hours was 464 mUI/ml. In subsequent examinations β-Hcg showed descending levels and after one month the resolution was completed. CONCLUSION Abdominal ectopic pregnancy is very infrequent but it has a high mortality rate. The most common approach is surgical but it is necessary to study all signs and diagnostic tests to select patients that could get profit from a conservatory management.

"Human Life is Inviolable": Costa Rica's Human Rights Crucible.

The Costa Rican Constitutional Court banned in vitro fertilization in 2000, citing the inviolability of life. Conservatives hoped the ban would initiate a hemispheric movement to protect the unborn. But in 2012 the Inter-American Court of Human Rights ruled that reproductive rights are human rights and that women's rights take precedence over embryo rights. The episode precipitated a national identity crisis: how could a country that supports universal health care be labeled a human rights violator as a result of its efforts to protect nascent human life? Expanding the health and human rights framework helps us appreciate how IVF became Costa Rica's human rights crucible.

[Multiple birth trends in the region of Castilla y León (Spain) in a 13 year period]. / Evolución temporal de los partos múltiples en Castilla y León durante 13 años.

INTRODUCTION: Multiple pregnancy has increased in prevalence in the last few years, which could lead to more foetal and maternal morbidity issues. The aim of this study is to describe the trend of multiple pregnancy deliveries in Castilla y León during the last 13years and the subsequent impact on foetal and maternal health. MATERIAL AND METHODS: Data was collected from the hospital discharge reports registered in the Regional Health-care database (SACYL: Health care in Castilla y León) between 2001 and 2013. A cross sectional descriptive study was conducted, including trend analysis with log-linear joint point model, a rhythm metric study, as well as a risk assessment with multivariate analysis. RESULTS: A pronounced upward trend was observed in the proportion of multiple deliveries in this time period, compared to single ones, with an annual percentage change of 3.4% (95% CI: 2.5-4.4). Multiple pregnancy was significantly correlated with advanced maternal age, abnormal glucose tolerance, dystocia and caesarean section delivery, premature birth, foetal malposition, foetal macrosomia, stillbirth, in vitro fertilisation, and hypertensive episodes of pregnancy. In vitro fertilization showed a 9.3 fold increased risk in multiple pregnancy (95% CI: 7.4-11.5), with maternal age increasing the risk up to 5% per year of age (OR: 1.05: 95%CI: 1.04-1.05). No seasonal rhythm was observed in multiple deliveries compared with single ones. CONCLUSION: Multiple pregnancy has experienced a continuous increase, with no seasonal trend, and is associated with the increase in assisted reproductive technology and advanced maternal age. This involves more problems regarding foetal and maternal morbidity and mortality.

Analysis of the truth in advertising on the efficacy provided by assisted reproduction clinics / Análisis sobre la autenticidad de la publicidad sobre la eficacia de clínicas de reproducción asistida / Análise da verdade na publicidade sobre a eficácia fornecida pelas clínicas de reprodução assistida

Abstract: This paper analyses the efficacy data from assisted reproduction clinics, obtained from both scientific society reports and from studies published in specialised journals, in order to compare them with information published by Spanish assisted reproduction clinics on their websites. It aims to verify whether this information matches the reality of the findings in the media analysed or, in contrast, differs from the aforementioned scientific evidence. Our study shows marked discrepancies between the evidence of existing statistical data, and figures published by most of the clinics on their websites, which could constitute false advertising.

Resumen: Este estudio analiza los datos de eficacia de clínicas de reproducción asistida, obtenidos tanto de informes de sociedades científicas como de estudios publicados en revistas especializadas, para compararlos con la información publicada por las clínicas de reproducción asistida de España en sus sitios web. El objetivo es verificar si esta información es conforme a los hallados en informes y revistas o, por el contrario, difiere de la evidencia científica mencionada. Nuestro estudio demuestra marcadas discrepancias entre la evidencia de datos estadísticos existentes y las cifras publicadas por la mayoría de los sitios web de las clínicas, lo cual constituye falsa publicidad.

Resumo: Este artigo analisa os dados de eficácia de clínicas de reprodução assistida, obtidas de relatórios da sociedade científica e de estudos publicados em revistas especializadas, a fim de compará-los com informações publicadas por clínicas de reprodução assistida espanholas em seus websites. O artigo visa verificar se esta informação coincide com a realidade dos resultados encontrados nos meios de comunicação analisados ou, por outro lado, difere da evidência científica acima mencionada. Nosso estudo mostra discrepâncias entre a evidência dos dados estatísticos existentes e indicadores publicados pela maioria das clínicas em seus sites, que podem constituir falsa publicidade.

Multiple sclerosis and pregnancy: a single-centre prospective comparative study. / Esclerosis múltiple y embarazo: estudio unicéntrico prospectivo y comparativo.

INTRODUCTION: Multiple sclerosis (MS) is a autoimmune disorder which preferentially affects young women of childbearing age. During pregnancy, the annualized relapse rate (AAR) is modified, but pregnancy has no harm effect on the long-term course of the disease. We aimed to study the clinical course of our MS patients during pregnancy, and compare their obstetrics outcomes with a control group of non-MS patients. METHODS: A single centre prospective observational study was conducted. We assessed the reproductive history, MS history, pregnancy course and new-born outcome of a cohort of MS patients who had had a pregnancy between january 2007 and july 2012. We compared the global outcomes with a control cohort of 58 age-matched healthy pregnancies. RESULTS: Complete data from 35 consecutive women were analyzed, 40 deliveries. Control groups: 58 patients, 60 deliveries. EDSS at pregnancy 0,7. ARR before pregnancy 0,5. During pregnancy 0,3, after pregnancy 0,4. Twelve patients were on disease-modifying drugs (DMD) before pregnancy, 4 prenatal exposure occurs. The comparison between relapse rate and EDSS before, during and after delivery showed no statistically significant difference. In addition, compared to control group, there were also no differences in the obstetric outcomes. In MS cohort, we found a higher incidence of assisted reproductive treatments and lower breastfeeding rate, both statistically significant. CONCLUSIONS: Our series confirms that pregnancy has no negative long term impact on the progression of MS and also suggest that there is no additional morbidity in the pregnancy, comparing to the rest of the population.

Maduración in vitro de ovocitos con cultivo extendido hasta estadio de blastocisto: Primer nacimiento reportado en el Perú / In vitro oocyte maturation combined with extended blastocyst embryo culture: Report of the first baby born in Peru

La maduración in vitro de ovocitos (MIV) es una técnica de reproducción asistida muy poco difundida entre los centros de reproducción asistida, debido al bajo éxito en obtener embarazos. Sin embargo, en los últimos años, diferentes estrategias empleadas han demostrado tasas de embarazo similares a las técnicas convencionales de fecundación in vitro (FIV). En el presente reporte, describimos el caso clínico del primer nacido vivo usando MIV en combinación del cultivo extendido hasta estadio de blastocisto.

In vitro oocyte maturation is not yet considered a well-established technique in in vitro fertilization (IVF) laboratories. This is due to a lower pregnancy rates. However in the last few years, reports have shown similar pregnancy rates compared to the conventional IVF techniques. The current report describes the first baby born after an IVM treatment in combination with extended blastocyst culture in Peru.

Modulación del estado de óxido-reducción por peróxido de hidrógeno en la etapa de maduración ovocitaria: efecto sobre el desarrollo embrionario en bovinos / Modulation of redox state by hydrogen peroxide in the stage of oocyte maturation: effect on embryonic development in cattle

El estrés oxidativo es definido como un desbalance entre la producción de oxidantes y antioxidantes. La inducción de tolerancia a estrés en los ovocitos conllevaría a un mejor desarrollo embrionario. En bovinos, la incubación de ovocitos maduros con diferentes estresores (térmicos, alta presión hidrostática, oxidativos) incrementaría la tasa de generación de blastocitos. Este estudio evalúa el efecto de la modulación del estado redox incrementando el estrés oxidativo con H2O2 en ovocitos maduros bajo condiciones de cultivo in vitro y su efecto sobre el potencial de desarrollo embrionario. Para ello, ovocitos procedentes de ovarios de matadero fueron madurados en medio TCM-199 suplementado durante 22­23 h, a 38,5 °C, 5 % CO2 y humedad a saturación. Al final de las 22­23 h se incubaron los ovocitos maduros con 0, 50, 100 y 200 µM H2O2. La fecundación in vitro se realizó co-incubando los ovocitos durante 18 h con una concentración final de 1x106 espermatozoides/mL. Los presuntos cigotos fueron denudados y cultivados en medio KSOM-0,4 % BSA a 38,5 °C en atmósfera de baja tensión de O2 (5 % O2, 5 % CO2 y 90 % N2) y humedad a saturación. El estrés oxidativo inducido con H2O2 a una concentración de 50 y 100 µM produce una tasa de división de los embriones similar al control (88,7 %, 83,2 % y 86,4 % respectivamente, p>0,05), disminuyendo significativamente al utilizar una concentración de 200 µM (58,8 %, p<0,05). Asimismo, H2O2 causó un efecto similar en la tasa de blastocitos con 50 µM (20,4 % vs. 25,8 % control, p>0.05) pero disminuyó significativamente con 100 y 200 µM (10,7 % y 3,3 % respectivamente, p<0,05). Es posible, que estos embriones resistentes al estrés oxidativo puedan tener una mayor sobrevida durante los procesos de criopreservación que generan altos niveles de especies reactivas de oxígeno en los embriones.

Oxidative stress is defined as an imbalance between the production of oxidants and antioxidants. The induction of stress tolerance in oocytes leads to a better embryonic development. In cattle incubating mature oocytes with different stressors (thermal, high hydrostatic pressure, oxidative) increase the generation rate of blastocysts. The purpose of this study was to evaluate the effect of modulating the redox state increasing the oxidative stress through H2O2 in mature oocyte under in vitro culture conditions and its effect on the potential of embryonic development. To do this, oocytes from slaughterhouse ovaries were matured in TCM-199 medium supplemented for 22­23 h at 38.5 °C, 5 % CO2 and humidified atmosphere. At the end of 22­23 h, the treatments with 0, 50, 100 and 200 µM H2O2 were applied for 1 h. IVF was performed co-incubating the eggs for 18 h with a final concentration of 1x106 sperm/mL. The presumptive zygotes were denuded and cultured in medium KSOM-0.4 % BSA to 38.5 °C in an atmosphere of low concentration of O2 (5 % O2, 5 % CO2 and 90 % N2) and humidified atmosphere. The results show that the induction of oxidative stress by H2O2 produces a similar effect using a concentration of 50 and 100 mM in the cleavage rate of embryos compared to control (88.7 %, 83.2 % and 86,4 % respectively, p>0.05) and decreasing significantly by using a concentration of 200 mM (58.8 %, p<0.05). Also, H2O2 caused a similar effect on the rate of blastocysts with 50 µM (20.4 % vs. 25.8 control, p>0.05) but decreased significantly with 100 and 200 µM (10.7 % and 3.3 % respectively, p<0.05). It is possible that these embryos resistant to oxidative stress may have a higher survival in the cryopreservation processes that generating high levels of reactive oxygen species.