Patient-tailored reproductive health care

Patient-tailored reproductive health care represents an important challenge for the current practice of infertility prevention, diagnosis and treatment. This approach is based on the concept of precision medicine, taking into account genetic, epigenetic, metabolic and lifestyle characteristics of each individual patient. Even though this goal is still far from being wholly achieved, some aspects can already be put into practice nowadays. Personalization can be based on a comprehensive analysis and synthesis of the patients' personal and familial history, taking into account outcomes of previous assisted reproduction technique (ART) attempts, if available, and confronting these data with the past and the latest clinical and laboratory examination outcomes. As to the male fertility status, there is an urgent need for the inclusion of an accurate diagnostic workup of infertile men leading to the choice of the most adequate follow-up for each particular pathological condition. The follow-up of women who have become pregnant as a result of the ART attempt has also to be personalized. This should be done taking into account both the basic data extracted from the patient's file and those derived from the experience gathered during the latest attempt. Last but not least, the individual condition of each couple has to be taken into account when counseling the patients as to the urgency of the actions to be taken to resolve their fertility problem

Assessing the testicular sperm microbiome: a low-biomass site with abundant contamination

We thank all men who generously donated testicular material for the purpose of this study. We also acknowledge the research support by Copan Italia S.p.A Inc., and Clearblue, SPD Swiss Precision Diagnostics GmbH. This study is part of a PhD Thesis conducted at the Official Doctoral Program in Biomedicine of the University of Granada, Spain. This work was supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and European Regional Development Fund (FEDER): grant numbers RYC-2016-21199 and ENDORE (SAF2017-87526-R); by FEDER/Junta de Andalucia-Consejeria de Economia y Conocimiento: MENDO (B-CTS-500-UGR18); by Junta de Andalucia: (PAIDI P20_00158) by the University of Granada, Plan Propio de Investigacion 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES), and the Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades and European Regional Development Fund: (SOMM17/6107/UGR); by Spanish Ministry of Science, Innovation, and Universities: (PRE2018085440 and FPU19/01638); and by Spanish Ministry of Education, Culture, and Sport: (FPU15/01193). Funding for open access charge: Universidad de Granada/CBUA Sequence data of all testicular spermatozoa and negative control samples have been deposited in the National Centre for Biotechnology Information (NCBI) Sequence Read Archive (SRA) database (http://www.ncbi.nlm.nih.gov/sra) under the BioProject ID PRJNA643898. The preliminary results of this study were presented as a poster communication at the 35th Annual ESHRE Meeting (Vienna, 2019).Research question: The semen harbours a diverse range of microorganisms. The origin of the seminal microbes, however, has not yet been established. Do testicular spermatozoa harbour microbes and could they potentially contribute to the seminal microbiome composition? Design: The study included 24 samples, comprising a total of 307 testicular maturing spermatozoa. A high-throughput sequencing method targeting V3 and V4 regions of 16S rRNA gene was applied. A series of negative controls together with stringent in-silico decontamination methods were analysed. Results: Between 50 and 70% of all the detected bacterial reads accounted for contamination in the testicular sperm samples. After stringent decontamination, Blautia (P = 0.04), Cellulosibacter (P = 0.02), Clostridium XIVa (P = 0.01), Clostridium XIVb (P = 0.04), Clostridium XVIII (P = 0.02), Collinsella (P = 0.005), Prevotella (P = 0.04), Prolixibacter (P = 0.02), Robinsoniella (P = 0.04), and Wandonia (P = 0.04) genera demonstrated statistically significant abundance among immature spermatozoa. Conclusions: Our results indicate that the human testicle harbours potential bacterial signature, though in a low-biomass, and could contribute to the seminal microbiome composition. Further, applying stringent decontamination methods is crucial for analysing microbiome in low-biomass site.Copan Italia S.p.A Inc.ClearblueSPD Swiss Precision Diagnostics GmbHSpanish GovernmentEuropean Commission RYC-2016-21199 SAF2017-87526-RFEDER/Junta de Andalucia-Consejeria de Economia y Conocimiento: MENDO B-CTS-500-UGR18 Junta de Andalucia PAIDI P20_00158University of Granada, Plan Propio de Investigacion 2016, Excellence actions: Units of ExcellenceUnit of Excellence on Exercise and Health (UCEES)Junta de Andalucia Consejeria de Conocimiento, Investigacion y UniversidadesEuropean Commission SOMM17/6107/UGRSpanish Government PRE2018085440 FPU19/01638 FPU15/01193Universidad de Granada/CBUA Sequence BioProject PRJNA64389

Molecular Clues to Understanding Causes of Human-Assisted Reproduction Treatment Failures and Possible Treatment Options

More than forty years after the first birth following in vitro fertilization (IVF), the success rates of IVF and of IVF-derived assisted reproduction techniques (ART) still remain relatively low. Interindividual differences between infertile couples and the nature of the problems underlying their infertility appear to be underestimated nowadays. Consequently, the molecular basis of each couple’s reproductive function and of its disturbances is needed to offer an individualized diagnostic and therapeutic approaches to each couple, instead of applying a standard or minimally adapted protocols to everybody. Interindividual differences include sperm and oocyte function and health status, early (preimplantation) embryonic development, the optimal window of uterine receptivity for the implanting embryo, the function of the corpus luteum as the main source of progesterone production during the first days of pregnancy, the timing of the subsequent luteoplacental shift in progesterone production, and aberrant reactions of the uterine immune cells to the implanting and recently implanted embryos. In this article, the molecular basis that underlies each of these abnormalities is reviewed and discussed, with the aim to design specific treatment options to be used for each of them

Cyclic Adenosine Monophosphate: A Central Player in Gamete Development and Fertilization, and Possible Target for Infertility Therapies

Human infertility, of both male and female origin, is often caused by the deficient response of the testis and the ovary to hormonal stimuli that govern sperm and oocyte development and fertilization. The effects of hormones and other extracellular ligands involved in these events are often mediated by G-protein-coupled receptors that employ cyclic adenosine monophosphate (cAMP) as the principal second messenger transducing the receptor-generated signal to downstream elements. This opinion article summarizes the actions of cAMP in sperm and oocyte development and fertilization, leading to therapeutic actions targeting cAMP metabolism to alleviate human male and female infertility

Nuevos avances en la reproducción asistida, mejora de la calidad ovocitaria y de la receptividad uterina

Respecto al uso de la GH en la mejora de la calidad ovocitaria y embrionaria hemos encontrado que no hay diferencias significativas en el número de ovocitos recuperados (sin GH 6.5±3.2 vs con GH 6.9±2.9), pero si en el aumento de los ovocitos de la calidad A (sin GH 2.9±2.7 vs con GH 4.1±2.9), y la disminución de los ovocitos calidad D (sin GH 1.0±1.3 vs con GH 0.3±0.6). En los cigotos encontramos que el patrón normal de fecundación tiene una aumento significativo con el uso de la GH (sin GH 0.6±0.8 vs con GH 1.4±1.2). En los embriones hay diferencias significativas en el aumento del porcentaje de embriones tipo A (sin GH 1.4±1.2 vs con GH 3.2±2.1) y la disminución del porcentaje de embriones tipo C (sin GH 1.0±0.8 vs con GH 0.6±0.8) y D (sin GH 0.6±0.8 vs con GH 0.3±1.6). En la transferencia embrionaria es significativo el porcentaje de aumento de los embriones de tipo A (sin GH 1.0±1.1 vs con GH 1.8±0.8), y la disminución de los de tipo B (sin GH 0.9±0.7 vs con GH 0.3±0.6) y C (sin GH 0.5±0.7 vs con GH 0.1±0.1). La tasa de embarazos clínicos aumenta significativamente con el uso de la GH (sin GH 10.9% vs con GH 42.3%), igualmente ocurre con la implantación clínica (sin GH 4.5% vs con GH 21.2%), los partos (sin GH 6.5% vs con GH 34.6%), y las tasas de nacimientos (sin GH 2.7% vs 17.3%). Respecto al uso de la GH en la mejora de la receptividad uterina encontramos un aumento de la media del espesor endometrial significativo con su uso (sin GH 8.6 vs con GH 9.3). El aumento es significativo también en los supuestos de tasa de embarazos (sin GH 17.1 vs con GH 54.3), tasa implantación (sin GH 10.3 vs con GH 33.3), tasa embriones con latido cardiaco positivo (sin GH 17.1 vs con GH 51.4), tasa de partos (sin GH 17.1 vs con GH 51.4) y tasa de nacidos vivos (sin GH 9 vs con GH 29.3). Respecto al uso del agonista de la GnRH para la mejora de la receptividad uterina encontramos un aumento sustancial de los niveles de progesterona a las 14 días (sin GnRH 13.3 ± 1.9 vs con GnRH 38.2 ± 14.6) de la transferencia embrionaria lo que se traduce en un aumento significativo de la tasa de embarazos clínicos (sin GnRH 12 vs con GnRH 60) y de embarazos evolutivos (sin GH 0 vs con GH 48).Tesis Univ. Granada

Ovarian Aging: Molecular Mechanisms and Medical Management

This is a short review of the basic molecular mechanisms of ovarian aging, written with a particular focus on the use of this data to improve the diagnostic and therapeutic protocols both for women affected by physiological (age-related) ovarian decay and for those suffering premature ovarian insufficiency. Ovarian aging has a genetic basis that conditions the ovarian activity via a plethora of cell-signaling pathways that control the functions of different types of cells in the ovary. There are various factors that can influence these pathways so as to reduce their efficiency. Oxidative stress, often related to mitochondrial dysfunction, leading to the apoptosis of ovarian cells, can be at the origin of vicious circles in which the primary cause feeds back other abnormalities, resulting in an overall decline in the ovarian activity and in the quantity and quality of oocytes. The correct diagnosis of the molecular mechanisms involved in ovarian aging can serve to design treatment strategies that can slow down ovarian decay and increase the quantity and quality of oocytes that can be obtained for an in vitro fertilization attempt. The available treatment options include the use of antioxidants, melatonin, growth hormones, and mitochondrial therapies. All of these treatments have to be considered in the context of each couple’s history and current clinical condition, and a customized (patient-tailored) treatment protocol is to be elaborated

Use of pentoxifylline during ovarian stimulation to improve oocyte and embryo quality: A retrospective study

Objective: This study aims to investigate if the administration of pentoxifylline during ovarian stimulation have an impact on the quantity and quality of oocytes recovered for in vitro fertilization (IVF), the quality of zygotes and embryos resulting from IVF, the serum estradiol and progesterone concentrations, the endometrial thickness and pregnancy outcomes after embryo transfer. Methods: Retrospective crossover study including 18 women with recurrent implantation failur, defined as having a history of at least two consecutive cycles of implantation failure and 25-45 years of age at the time of embryo transfer. Pentoxifylline was added during their following IVF attempt aiming to improve endometrial function. Oocyte, zygote and embryo quality, serum estradiol and progesterone concentrations, endometrial thickness and IVF outcomes were compared between the two sequential attempts. Results: Compared to the first attempt, the outcomes of the second attempt, with the addition of pentoxifylline administration, resulted in higher numbers of total and mature oocytes, better oocyte, zygote and embryo quality, higher serum estradiol concentrations, thicker endometrium and better clinical IVF outcomes. Conclusions: The administration of pentoxifylline during ovarian stimulation seems to improve IVF outcomes, not only by the generating a thicker endometrial lining, but also by producing a higher number of oocytes, with better oocyte, zygote and embryo quality, and higher serum estradiol concentrations. (C) 2022 Elsevier Masson SAS. All rights reserved