Genetic Landscape of Nonobstructive Azoospermia and New Perspectives for the Clinic

We thank Alejandro Fernández Sevilla for his valuable help in the development of Figure 2 of this review. The authors were funded by the Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation (ref. SAF2016-78722-R) and the “Ramón y Cajal” program (ref. RYC-2014-16458).Nonobstructive azoospermia (NOA) represents the most severe expression of male infertility, involving around 1% of the male population and 10% of infertile men. This condition is characterised by the inability of the testis to produce sperm cells, and it is considered to have an important genetic component. During the last two decades, di erent genetic anomalies, including microdeletions of the Y chromosome, karyotype defects, and missense mutations in genes involved in the reproductive function, have been described as the primary cause of NOA in many infertile men. However, these alterations only explain around 25% of azoospermic cases, with the remaining patients showing an idiopathic origin. Recent studies clearly suggest that the so-called idiopathic NOA has a complex aetiology with a polygenic inheritance, which may alter the spermatogenic process. Although we are far from a complete understanding of the molecular mechanisms underlying NOA, the use of the new technologies for genetic analysis has enabled a considerable increase in knowledge during the last years. In this review, we will provide a comprehensive and updated overview of the genetic basis of NOA, with a special focus on the possible application of the recent insights in clinical practice.Funded by the Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation (ref. SAF2016-78722-R) and the “Ramón y Cajal” program (ref. RYC-2014-16458)

Reduction of Current Harmonic Distortion in Three-Phase Grid-Connected Photovoltaic Inverters via Resonant Current Control

The resonant current control has been extensively employed to reduce the current harmonic distortion in a wide range of grid-connected distributed generation applications, including photovoltaic (PV) inverters, wind and water turbines, and fuel-cell inverters. However, the performance of these systems is deteriorated when the utility grid voltage experiences abnormal conditions such as voltage harmonics and imbalances. Several advanced control solutions have been recently introduced to cope with this problem but at the cost of a significant increase in the control computational load. This paper first analyzes the limitations of the standard resonant current control operating under abnormal grid conditions and then introduces a control scheme that improves the current harmonic distortion in such adverse conditions without increasing the computational load of the standard current control. This theoretical contribution is validated by means of selected experimental results from a three-phase PV inverterPostprint (published version

Effect of Monotherapy with Darunavir/Ritonavir on Viral Load in Seminal Fluid, and Quality Parameters of Semen in HIV-1-Positive Patients

Patients with human immunodeficiency virus type 1 (HIV-1) who receive antiretroviral therapy (ART) often achieve increased survival and improved quality of life. In this respect, monotherapy with darunavir/ritonavir (mDRV/r) can be a useful treatment strategy. This prospective study analyses the effect of mDRV/r on sperm quality and viral load in a group of 28 patients who had previously been given conventional ART and who had recorded a viral load 20 copies/ml), and that at V1, after mDRV/r treatment, this figure had fallen to 3%. The quality of seminal fluid was close to normal in 57% of patients at V0 and in 62% at V1. We conclude that, similar to ART, mDRV/r maintains HIV-1 viral load in most patients, and that there is no worsening in seminal fluid quality

Aproximación a la síntesis enantioselectiva de achillifolina

En este artículo se presenta una aproximación biomimética a la síntesis enantioselectiva de achillifolina, una lactona sesquiterpénica natural aislada de Achillea millefolium subsp. Millenium. La ciclación carbocatiónica de epoxi-costunolida es la etapa clave de la secuencia sintética. Esta ciclación transanular permite la formación del esqueleto de 1,4-epoxi-ciclodecano presente en (+)-achillifolina.In this paper, an approximation biomimetic synthesis of achillifoline, a natural sesquiterpene lactone isolated from Achillea millefolium subsp. Millenium, is presented. Carbocationic cyclization of epoxycostunolide is the key step of the synthetic sequence. This transannular cyclization, allows the formation of the skeleton of 1,4-epoxy-cyclodecane presents in achillifoline.Agradecemos al Ministerio de Economía y Competitividad de España (Proyecto CTQ2011- 24443) y a la “Junta de Andalucía” (Proyecto P10. FQM.6050) por su generosa financiación

Common Variation in the PIN1 Locus Increases the Genetic Risk to Suffer from Sertoli Cell-Only Syndrome

We aimed to analyze the role of the common genetic variants located in the PIN1 locus, a relevant prolyl isomerase required to control the proliferation of spermatogonial stem cells and the integrity of the blood–testis barrier, in the genetic risk of developing male infertility due to a severe spermatogenic failure (SPGF). Genotyping was performed using TaqMan genotyping assays for three PIN1 taggers (rs2287839, rs2233678 and rs62105751). The study cohort included 715 males diagnosed with SPGF and classified as suffering from non-obstructive azoospermia (NOA, n = 505) or severe oligospermia (SO, n = 210), and 1058 controls from the Iberian Peninsula. The allelic frequency differences between cases and controls were analyzed by the means of logistic regression models. A subtype specific genetic association with the subset of NOA patients classified as suffering from the Sertoli cell-only (SCO) syndrome was observed with the minor alleles showing strong risk effects for this subset (ORaddrs2287839 = 1.85 (1.17–2.93), ORaddrs2233678 = 1.62 (1.11–2.36), ORaddrs62105751 = 1.43 (1.06–1.93)). The causal variants were predicted to affect the binding of key transcription factors and to produce an altered PIN1 gene expression and isoform balance. In conclusion, common non-coding single-nucleotide polymorphisms located in PIN1 increase the genetic risk to develop SCO.Plan Andaluz de Investigacion, Desarrollo e Innovacion (PAIDI 2020) PY20_00212 P20_00583Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation SAF2016-78722-R PID2020-120157RB-I00Proyectos I + D + i del Programa Operativo FEDER 2020 B-CTS-584-UGR20 B-CTS-260-UGR20Spanish Government RYC-2014-16458Spanish Ministry of Economy and Competitiveness through the "Juan de la Cierva Incorporacion" program (MCIN/AEI) IJC2018038026-IEuropean CommissionMCIN/AEIFSE "El FSE invierte en tu futuro" FPU20/02926 BES-2017-081222Portuguese Foundation for Science and Technology (FCT) - European Social Funds (COMPETE-FEDER) Portuguese Foundation for Science and Technology IF/01262/2014FCT from the Portuguese State Budget of the Ministry for Science, Technology and High Education SFRH/BPD/120777/2016European Social Fund through the Programa Operacional do Capital HumanoPortuguese Foundation for Science and Technology European Commission UID/BIM/00009/2013 UIDB/UIDP/00009/2020Instituto de Salud Carlos III (FEDER funds/European Regional Development Fund (ERDF)-a way to build Europe) DTS18/00101Generalitat de Catalunya 2017SGR191SNS-Dpt. Salut Generalitat de Catalunya CES09/020 MCIN/AEI BES-2017-081222 PEstC/SAU/LA0003/2013 POCI-01-0145-FEDER-00727

Oocyte and ovarian tissue cryopreservation in European countries : statutory background, practice, storage and use

STUDY QUESTION: What is known in Europe about the practice of oocyte cryopreservation (OoC), in terms of current statutory background, funding conditions, indications (medical and ‘non-medical’) and specific number of cycles? SUMMARY ANSWER: Laws and conditions for OoC vary in Europe, with just over half the responding countries providing this for medical reasons with state funding, and none providing funding for ‘non-medical’ OoC. WHAT IS ALREADY KNOWN: The practice of OoC is a well-established and increasing practice in some European countries, but data gathering on storage is not homogeneous, and still sparse for use. Ovarian tissue cryopreservation (OtC) is only practiced and registered in a few countries. STUDY DESIGN, SIZE, AND DURATION: A transversal collaborative survey on OoC and OtC, was designed, based on a country questionnaire containing information on statutory or professional background and practice, as well as available data on ovarian cell and tissue collection, storage and use. It was performed between January and September 2015. PARTICIPANTS/MATERIALS, SETTING AND METHODS: All ESHRE European IVF Monitoring (EIM) consortium national coordinators were contacted, as well as members of the ESHRE committee of national representatives, and sent a questionnaire. The form included national policy and practice details, whether through current existing law or code of practice, criteria for freezing (age, health status), availability of funding and the presence of a specific register. The questionnaire also included data on both the number of OoC cycles and cryopreserved oocytes per year between 2010 and 2014, specifically for egg donation, fertility preservation for medical disease, ‘other medical’ reasons as part of an ART cycle, as well as for ‘non-medical reasons’ or age-related fertility decline. Another question concerning data on freezing and use of ovarian tissue over 5 years was added and sent after receiving the initial questionnaire. MAIN RESULTS AND THE ROLE OF CHANCE: Out of 34 EIM members, we received answers regarding OoC regulations and funding conditions from 27, whilst 17 countries had recorded data for OoC, and 12 for OtC. The specific statutory framework for OoC and OtC varies from absent to a strict frame. A total of 34 705 OoC cycles were reported during the 5-year-period, with a continuous increase. However, the accurate description of numbers was concentrated on the year 2013 because it was the most complete. In 2013, a total of 9126 aspirations involving OoC were reported from 16 countries. Among the 8885 oocyte aspirations with fully available data, the majority or 5323 cycles (59.9%) was performed for egg donation, resulting in the highest yield per cycle, with an average of 10.4 oocytes frozen per cycle. OoC indication was ‘serious disease’ such as cancer in 10.9% of cycles, other medical indications as ‘part of an ART cycle’ in 16.1%, and a non-medical reason in 13.1%. With regard to the use of OoC, the number of specifically recorded frozen oocyte replacement (FOR) cycles performed in 2013 for all medical reasons was 14 times higher than the FOR for non-medical reasons, using, respectively, 8.0 and 8.4 oocytes per cycle. Finally, 12 countries recorded storage following OtC and only 7 recorded the number of grafted frozen/thawed tissues. LIMITATIONS, REASONS FOR CAUTION: Not all countries have data regarding OoC collection, and some data came from voluntary collaborating centres, rather than a national authority or register. Furthermore, the data related to use of OoC were not included for two major players in the field, Italy and Spain, where numbers were conflated for medical and non-medical reasons. Finally, the number of cycles started with no retrieval is not available. Data are even sparser for OtC. WIDER IMPLICATIONS OF THE FINDINGS: There is a need for ART authorities and professional bodies to record precise data for practice and use of OoC (and OtC), according to indications and usage, in order to reliably inform all stakeholders including women about the efficiency of both methods. Furthermore, professional societies should establish professional standards for access to and use of OoC and OtC, and give appropriate guidance to all involved. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by ESHRE. There are no conflicts of interest.peer-reviewe

Estudio de la inmunidad durante el embarazo y puerperio

Reducción altaUniv. de Granad

Coste de las técnicas de reproducción asistida en un hospital público Cost of assisted reproduction technology in a public hospital

Objetivos: La mayoría de trabajos sobre costes de las técnicas de reproducción asistida (TRA) identifican el coste directo del procedimiento, sin considerar elementos como los costes estructurales o intermedios, de gran importancia. El objetivo de este trabajo es calcular el coste por proceso de las TRA realizadas en un hospital público en 2003 y compararlo con los resultados de 1998 en el mismo centro. Métodos: El estudio se realiza en la Unidad de Reproducción Humana (URH) del Hospital Universitario Virgen de las Nieves de Granada en 1998 y 2003. Partiendo de los costes totales de dicha unidad, y mediante una metodología de distribución de costes basada en la estructura de costes, calculamos el coste por proceso de las TRA realizadas en este centro, considerando los costes completos. Resultados: Entre 1998 y 2003, la actividad y los costes de la URH analizada evolucionan de forma distinta. El análisis de la actividad muestra la consolidación de técnicas, como la microinyección espermática (ICSI) y la desaparición de otras (ciclo sin reproducción asistida e inseminación artificial conyugal intracervical). En todos los procesos, los costes unitarios por ciclo y por embarazo disminuyen en el período analizado. Conclusiones: Se han producido importantes cambios en la estructura de costes de las TRA de la URH-HUVN entre 1998-2003. Mientras algunos procesos desaparecen, otros se consolidan con una elevada actividad. Los avances técnicos y las innovaciones organizativas, junto con un «efecto aprendizaje», han alterado la estructura de costes de las TRA.<br>Objectives: Most studies on the costs of assisted reproductive technologies (ART) identify the total cost of the procedure with the direct cost, without considering important items such as overhead or intermediate costs. The objective of this study was to determine the cost per ART procedure in a public hospital in 2003 and to compare the results with those in the same hospital in 1998. Methods: Data from the Human Reproduction Unit of the Virgen de las Nieves University Hospital in Granada (Spain) from 1998 and 2003 were analyzed. Since the total costs of the unit were known, the cost of the distinct ART procedures performed in the hospital was calculated by means of a methodology for cost distribution. Results: Between 1998 and 2003, the activity and costs of the Human Reproduction Unit analyzed evolved differently. Analysis of activity showed that some techniques, such as intracytoplasmic sperm injection, were consolidated while others, such as stimulation without assisted reproduction or intracervical insemination were abandoned. In all procedures, unit costs per cycle and per delivery decreased in the period analyzed. Conclusions: Important changes took place in the structure of costs of ART in the Human Reproduction Unit of the Virgen de las Nieves University Hospital between 1998 and 2003. Some techniques were discontinued, while others gained importance. Technological advances and structural innovations, together with a «learning effect», modified the structure of ART-related costs

Aproximación a la síntesis enantioselectiva de achillifolina.

In this paper, an approximation biomimetic synthesis of achillifoline, a natural sesquiterpene lactone isolated from Achillea millefolium subsp. Millenium, is presented. Carbocationic cyclization of epoxy-costunolide is the key step of the synthetic sequence. This transannular cyclization, allows the formation of the skeleton of 1,4-epoxy-cyclodecane presents in achillifolineEn este artículo se presenta una aproximación biomimética a la síntesis enantioselectiva de achillifolina, una lactona sesquiterpénica natural aislada de Achillea millefolium subsp. Millenium. La ciclación carbocatiónica de epoxi-costunolida es la etapa clave de la secuencia sintética. Esta ciclación transanular permite la formación del esqueleto de 1,4-epoxi-ciclodecano presente en (+)-achillifolin