Regulación metabólica de la fertilidad. Integración neuroendocrina / Fertility metabolic regulation. Neuroendocrine integration

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Regulación de la actividad GnRH. Los sistemas Kisspeptina/GPR54 y GnIH/GPR147 / GnRH activity regulation. Kisspeptin/GPR54 and GnIH/GPR147 systems

OBJETIVO: Revisar y actualizar la fisiología de la regulación de fertilidad y reproducción, poniendo especial énfasis en los factores neuroendocrinos que controlan la secreción pulsátil de GnRH. MATERIAL Y MÉTODOS: Revisión bibliográfica, utilizando como palabras clave «GnRH», «Kisspeptin», «GnIH», «RF-amide» y RPRF-3, entre otras. RESULTADOS: Siendo la secreción pulsátil de GnRH el elemento clave para el control de la secreción de gonadotrofinas, se describen los mecanismos neuroendocrinos (Kisspeptina, GnIH) que regulan la actividad de las neuronas GnRH

OBJECTIVE: To Review and update the physiology regulating fertility and reproduction, with particular emphasis on neuroendocrine factors controlling the pulsatile secretion of GnRH. MATERIAL AND METHODS: Review of the literature, using as key words «GnRH», «Kisspeptin», «GnIH», «RF-amide» and RPRF-3, among others. RESULTS: Being the pulsatile secretion of GnRH the key element for the control of gonadotrophin secretion, the neuroendocrine mechanisms (Kisspeptine, GnIH) that regulate the activity of GnRH neurons are described

La neurohormona GnRH en la mujer / Neurohormone GnRH in the woman

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Orientación sexual y deseo reproductivo / Sexual orientation and reproductive desires

OBJETIVOS: El objetivo principal del presente estudio es obtener datos sobre la orientación sexual y los deseos reproductivos de una población española no seleccionada. Objetivos secundarios han sido recabar información sobre las actitudes sexuales de esa misma muestra poblacional, la visión de gays y lesbianas de sus posibilidades reproductivas y su relación con los centros públicos y privados de medicina reproductiva. MATERIAL Y MÉTODOS: Una encuesta diseñada a tal efecto fue implementada en el portal del Colectivo Lambda de la Comunidad Valenciana, en internet. El Colectivo Lambda ofreció su colaboración desinteresada y animó a sus miembros a cumplimentarla. Los centros de reproducción integrados en el Grupo EIRE solicitaron a sus pacientes la cumplimentación de la encuesta. Las respuestas a las distintas preguntas correspondientes a las 404 encuestas cumplimentadas fueron transportadas a una hoja Excel y, posteriormente, al programa SPSS, para su tratamiento estadístico. RESULTADOS: A partir de las respuestas obtenidas puede afirmarse que homosexualidad y bisexualidad no son situaciones excluyentes sino que entre homo y heterosexualidad existe una gradación. También ha sido confirmado que la gran mayoría de los individuos desea reproducirse, independientemente de su orientación sexual y que la aceptación de las técnicas de reproducción asistida para resolver los problemas reproductivos de lesbianas y gays, incluida la maternidad subrogada es amplia. En torno al 90% de los encuestados consideran que las personas o parejas LGTB tienen los mismos derechos a ser atendidos en los centros de sanidad pública que las parejas heterosexuales que padecen esterilidad. Considerando el determinismo de la orientación sexual de los seres humanos, es posible aceptar que gays, lesbianas y otros LGTB presentan esterilidad constitucional y que, como tal, deben ser ayudados a tener descendencia biológica sin menoscabo de su dignidad humana

OBJECTIVES: The main objective of this study was to obtain data on sexual orientation and reproductive desires of an un selected Spanish population formed by gays, lesbians, transsexuals and bisexuals (LGTB), without excluding heterosexual persons. Secondary objectives have been obtaining information about the sexual attitudes of this same population sample, as well as the view of gays and lesbians of their reproductive potential and their relationship with public and private reproductive medicine centers. MATERIAL AND METHODS: A survey designed to that effect was implemented on the portal of the Colectivo Lambda of Valencia, on the internet. The collective Lambda offered their generous collaboration and encouraged its members to fill it out. The centers of reproductive medicine integrated in the EIRE group asked their patients filling out the survey. The responses to the different questions corresponding to the 404 completed surveys were transported to an Excel worksheet and, later, to the program SPSS for statistical processing. RESULTS: From the answers it can be argued that homosexuality and bisexuality are not mutually exclusive situations but that between homo and heterosexuality there is a gradation. It has also been confirmed that the vast majority of individuals wish to reproduce, regardless of their sexual orientation and that assisted reproduction techniques are widely accepted to solve reproductive problems of lesbians and gays, including surrogate motherhood. Around 90% of respondents considered that persons or LGBT couples have the same rights to be cared for in reproductive centers of public health than heterosexual couples presenting infertility. Whereas the determinism of the sexual orientation of human beings, it is possible to accept that gays, lesbians and other LGBT present constitutional infertility and that, as such, they must be helped to have biological offspring without detriment to their human dignity

Síndrome de varón 46, XX (SRY +) asociado a Enfermedad de Crohn. A propósito de un caso / 46, XX (SRY +) male syndrome associated with Crohn disease. A case report

OBJETIVO: Presentar el caso de un paciente de fenotipo masculino con testículos y pene de tamaño ligeramente disminuido diagnosticado de azoospermia no obstructiva. Revisión de la literatura. MATERIAL Y MÉTODOS: Exploración física, perfil hormonal, espermiograma, ultrasonografía genital, cariotipo y análisis citogenético mediante microarrays KaryoNIM. RESULTADOS: La exploración clínica mostró un fenotipo masculino con testes y pene disminuidos de tamaño y obesidad. Las determinaciones hormonales evidenciaron un hipogonadismo hipergonadotropo. El estudio seminal mostró una azoospermia y la ecografía genital un aparato genital masculino normal. El cariotipo fue 46,XX, normal de mujer, y el estudio citogenético mostró la traslocación de material genético del cromosoma Y al cromosoma X, incluyendo el gen SRY. La biopsia testicular evidenció la presencia de hialinización tubular con células de Sertoli maduras, sin línea germinal y acusada hiperplasia de células de Leydig. Comentarios y conclusión: El síndrome de varón con cariotipo 46,XX es una etiología inusual de azoospermia. Su asociación a patologías autoinmunes no está actualmente bien aclarada. Aunque la única opción disponible para tratar el problema reproductivo es el uso de semen de donante, el abordaje de estos pacientes debe ser multidisciplinar

OBJECTIVES: To present the case of a patient showing male phenotype with testes and penis size slightly decreased, which was diagnosed with non-obstructive azoospermia. Review of the literature. MATERIAL AND METHODS: Physical examination, hormonal profile, semen analysis, genital ultrasound scan, karyotype and cytogenetic microarray analysis (KaryoNIM). RESULTS: Clinical examination showed a male phenotype with decreased size of testes and penis and obesity. Hormonal determinations evidenced hypergonadotropic hypogonadism. The seminal study showed azoospermia and genital ultrasound a normal male genital tract. Karyotype 46,XX, normal woman, and the cytogenetic study showed the translocation of genetic material from chromosome Y to chromosome X, including the SRY gene. Testicular biopsy showed the presence of tubular hyalinization with mature Sertoli cells, absent germ line and pronounced hyperplasia of Leydig cells. Comments and conclusion: 46,XX male is a rare genetic condition of non-obstructive azoospermia. The association to autoimmune diseases needs to be clarified. Although sperm donation remains the only fertility treatment currently available multidisciplinary approach should be adopted in the management of 46,XX individuals

Mindfulness training as an intervention for substance user incarcerated adolescents: a pilot grounded theory study.

Mindfulness-based treatment for adolescents is a clinical and research field still in its infancy. Literature is needed to address specific subcultural populations to expand this growing field. Further, minimal literature addresses the process of teaching mindfulness to adolescents. The current study investigated how to effectively teach mindfulness to 10 incarcerated adolescent substance users (N = 10) in an urban California detention setting. A grounded theory approach was used to collect and analyze interview data over a 1-year period during 2011 and 2012 in order to develop an initial theory for teaching mindfulness to incarcerated adolescent substance users. Implications, limitations, and future research are discussed.

Manejo del hidrosalpinx en reproducción asistida / Hydrosalpinx management in Assisted Reproduction

La presencia de hidrosalpinx en pacientes sometidas a tratamientos de reproducción asistida empeora los resultados de los mismos. Existe entre los profesionales de la reproducción una amplia gama de diferentes manejos del hidrosalpinx, alguno de los cuales son cuestionables por su falta de base en la medicina de la evidencia. Parece claro que la presencia de hidrosalpinx no interfiere ni en la estimulación ovárica ni en la fecundación de los ovocitos obtenidos pero si en la implantación de los embriones transferidos. Se discutió si el límite para la acción adversa del hidrosalpinx es la detección ultrasonográfica del mismo. El líquido del hidrosalpinx altera el medio y el peristaltismo uterinos. También parece asociarse a abortos y gestaciones ectópicas. El líquido contenido en el hidrosalpinx es embriotóxico . También el endometrio que recibe dicho líquido muestra un desfase y una menor concentración de integrinas así como una menor expresión de HOXA 10. Todos estos efectos sobre el endometrio se corrigen con la salpinguectomía u otras formas de bloqueo del paso del contenido del hidrosalpinx a la cavidad endometrial. El abordaje terapeútico engloba un tratamiento médico con antibióticos y un tratamiento quirúrgico. Se propone un protocolo de abordaje del hidrosalpinx, tanto diagnosticado antes del inicio del tratamiento de reproducción asistida como del diagnosticado en el curso de la misma (AU)

The presence of hydrosalpinges in patients undergoing assisted reproduction treatments impairs their results. There are many different ways of hydrosalpinx management, some of them questionable because of their lack of back up in evidence based medicine. It seems clear that hydrosalpinges do not interfere neither with ovarian stimulation nor with oocyte fertilisation but they do interfere with embryo implantation. In the past, the possibility that only those visible in echography resulted detrimental on the IVF results was discussed. The fluid that replenish the hydrosalpinx harms both, uterine media and peristaltism. Hydrosalpinx is also related with miscarriage and ectopic pregnancies. It was demonstrated that the fluid inside the hydrosalpinx is embryotoxic. The endometriums influenced by this fluid shows differences in development, lower concentration of integrines and lower expression of HOXA 10. All these effects are suppressed by the salpinguectomy or any other form of tubarian blockade. Therapeutic management includes antibiotic and surgical treatments. A management protocol is proposed for two different clinical situations: the diagnostic before starting the assisted reproduction treatment and the diagnostic during the ovarian stimulation (AU)

Vascular endothelial growth factor polymorphisms (-460C/T, +405G/C, and 936C/T) and endometriosis: their influence on vascular endothelial growth factor expression.

OBJECTIVE: To analyze three functional vascular endothelial growth factor (VEGF) polymorphisms (-460C/T, +405G/C, and 936C/T) in women with and without endometriosis and their correlation with VEGF expression in endometrial tissue and peritoneal fluid (PF). DESIGN: Case-control study. SETTING: University-based hospital. PATIENT(S): One hundred eighty-six women with endometriosis and 180 controls without the disease. INTERVENTION(S): Endometrial biopsies were performed by aspiration and PF samples were obtained at laparoscopy. MAIN OUTCOME MEASURE(S): VEGF polymorphisms (-460C/T, +405G/C, and 936C/T) were determined using a polymerase chain reaction (PCR)-restriction fragment length polymorphism assay. Quantitative real-time reverse transcriptase (RT)-PCR assay was used to quantify VEGF-A messenger RNA (mRNA) and VEGF-A antigen levels were quantified by ELISA. RESULT(S): Patients with endometriosis showed a higher VEGF 936T allele frequency than controls. However, the distribution of genotypes and allele frequencies in the other two VEGF (-460C/T, +405G/C) polymorphisms was similar in the endometriosis and control groups. Endometrium and PF from women with endometriosis showed an increase in VEGF levels, but no association was found between the VEGF polymorphisms studied and VEGF expression in endometrial tissue and PF. CONCLUSION(S): These findings suggest that the VEGF 936C/T polymorphism may be associated with the risk of endometriosis in a Caucasian population, but the increased VEGF levels observed in endometriosis do not appear to be associated with this polymorphism.

Plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism and endometriosis. Influence of PAI-1 polymorphism on PAI-1 antigen and mRNA expression.

INTRODUCTION: Endometriosis is a benign gynecologic disease with a high prevalence. It is a multifactorial and polygenic entity in which the fibrinolytic system may be implicated. The objective of this study was to evaluate the plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism in a group of women with and without endometriosis and to analyze the influence of this polymorphism in PAI-1 expression in endometrial tissue and peritoneal fluid. MATERIAL AND METHODS: In 389 women (170 patients with endometriosis and 219 controls) PAI-1 4G/5G polymorphism was determined by PCR amplification using allele-specific primers. Quantitative real-time RT-PCR assay was used to quantify PAI-1 mRNA and PAI-1 antigen (ag) levels were quantified by ELISA. RESULTS: The genotype and allele frequencies of PAI-1 4G/5G polymorphism did not differ significantly between patients and controls. Control women with the 4G/4G genotype had higher endometrial PAI-1ag (P=0.026) and mRNA (P=0.014) levels than those with the 5G/5G genotype. Control carrying the 4G/4G genotype tended to have higher peritoneal fluid PAI-1ag levels than those carrying the 5G/5G genotype. Moreover, PAI-1ag levels in peritoneal fluid were higher in patients than in controls (P=0.003). CONCLUSIONS: The PAI-1 genotype distribution was similar in patients and controls. PAI-1 levels in endometrial tissue and peritoneal fluid seem to be associated with PAI-1 4G/5G polymorphism in controls. The increased PAI-1ag levels observed in peritoneal fluid from patients could contribute to increase the peritoneal adhesions observed in endometriosis.

[Evolution of the bone mass of hypertense menopausal women in treatment with fosinopril]. / Evolución de la densidad ósea de mujeres menopáusicas hipertensas en tratamiento con fosinopril.

BACKGROUND AND OBJECTIVE: The renin-angiotensin system (SRA) acts on the bone metabolism and decreases the mineralization. Menopausal women frequently are hypertense and have risk of developing osteoporosis. The inhibition of SRA could favour the mineralization and protect the bone mass of hypertense women in treatment with antihypertensive drugs that are angiotensin converting enzyme inhibitors. PATIENTS AND METHOD: Cohorts prospective study. 50 menopausal women were recruited and divided in one cohort of non hypertense patients and one cohort of hypertense women who initiated antihypertensive treatment with oral fosinopril. Baseline and after 1 year bone mineral density of lumbar spine and femoral neck was made. RESULTS: There were no significant differences between the bone mass of both groups. Significant changes between the baseline and after the treatment were not demonstrated in the cohort exposed. In the group of non exposed women were demonstrated differences in lumbar spine (baseline, 0.874 g/cm(2); final, 0.854 g/cm(2); p = 0.002) and femoral neck (baseline, 0.743 g/cm(2); final, 0.725 g/cm(2); p = 0.016). CONCLUSIONS: The menopausal and hypertense women who followed treatment with fosinopril did not present the physiological loss of bone mass that affected to menopausal women without treatment.

Evolución de la densidad ósea de mujeres menopáusicas hipertensas en tratamiento con fosinopril / Evolution of the bone mass of hypertense menopausal women in treatment with fosinopril

Fundamento y objetivo: El sistema renina-angiotensina-aldosterona (SRAA) actúa en el metabolismo óseo disminuyendo la mineralización. Las mujeres menopáusicas frecuentemente son hipertensas y tienen riesgo de desarrollar osteoporosis. La inhibición del SRAA podría favorecer la mineralización y proteger la masa ósea de mujeres hipertensas en tratamiento con fármacos antihipertensivos inhibidores de la enzima de conversión de la angiotensina. Pacientes y método: Estudio observacional y prospectivo de cohortes. Se incluyó a 50 mujeres menopáusicas, divididas en una cohorte de pacientes normotensas y una cohorte de mujeres hipertensas, que iniciaron tratamiento antihipertensivo con fosinopril por vía oral. Se realizó una densitometría ósea de columna lumbar y cadera, basal y al cabo de 1 año. Resultados: No se observaron diferencias significativas de la masa ósea entre ambos grupos. En la cohorte expuesta no se evidenciaron cambios significativos antes y después del tratamiento. El grupo de mujeres no expuestas mostró diferencias en columna lumbar (densidad ósea basal, 0,874 g/cm2; final, 0,854 g/cm2; p = 0,002) y en cuello de fémur (densidad ósea basal, 0,743 g/cm2; final, 0,725 g/cm2; p = 0,016). Conclusiones: Las mujeres menopáusicas e hipertensas que siguieron tratamiento con fosinopril no presentaron la pérdida fisiológica de masa ósea que sí afectó a mujeres menopáusicas normotensas sin tratamiento

Background and objective: The renin-angiotensin system (SRA) acts on the bone metabolism and decreases the mineralization. Menopausal women frequently are hypertense and have risk of developing osteoporosis. The inhibition of SRA could favour the mineralization and protect the bone mass of hypertense women in treatment with antihypertensive drugs that are angiotensin converting enzyme inhibitors. Patients and method: Cohorts prospective study. 50 menopausal women were recruited and divided in one cohort of non hypertense patients and one cohort of hypertense women who initiated antihypertensive treatment with oral fosinopril. Baseline and after 1 year bone mineral density of lumbar spine and femoral neck was made. Results: There were no significant differences between the bone mass of both groups. Significant changes between the baseline and after the treatment were not demonstrated in the cohort exposed. In the group of non exposed women were demonstrated differences in lumbar spine (baseline, 0.874 g/cm2; final, 0.854 g/cm2; p = 0.002) and femoral neck (baseline, 0.743 g/cm2; final, 0.725 g/cm2; p = 0.016). Conclusions: The menopausal and hypertense women who followed treatment with fosinopril did not present the physiological loss of bone mass that affected to menopausal women without treatment

Insulin growth factors may be implicated in human sperm capacitation.

This study was designed to determine whether or not insulin-like growth factor (IGF)-1 and its receptor are present in the human male genital tract. The IGF-1 receptor was found in seminal plasma from fertile and infertile men, but no IGF-1 receptor was observed in sperm from patients with a history of more failed fertilization. The presence of the IGF-1 receptor in the plasma membrane of human sperm is proposed as a future tool for male sterility assessment.

Plasminogen activators and plasminogen activator inhibitors in endometriosis.

Endometriosis is one of the most frequent benign gynecological diseases that affect women. Little is known about the pathogenesis and etiology of endometriosis, despite the numerous studies performed in this field. Although endometriosis is a benign disease, the endometrial tissue, after attachment to the peritoneum, has the ability to grow and invade the surrounding tissues. Similar to neoplastic growth, local extracellular proteolysis might take place, and therefore, the fibrinolytic system may be involved. An altered expression of several components of the fibrinolytic system in the endometrium and peritoneal fluid of women with the disease has been suggested as a key factor in the establishment of the endometriotic lesions. There is evidence of increased fibrinolytic activity in the eutopic endometrium of these women, resulting in endometrial fragments with a high potential to degrade the extracellular matrix and facilitate implantation. The peritoneum possesses an inherent fibrinolytic activity that is responsible for the degradation of the fibrin deposits originated after an injury. This physiological function allows a correct repair of the mesothelium, and therefore, prevents the formation of adhesions. Peritoneal fluid of women with endometriosis and pelvic adhesions has shown to have an increased fibrinolytic activity that may be implicated in reducing the formation of new adhesions. Endometriotic tissue has abnormal proteolytic capacity, which is determined by modifications of the fibrinolytic parameters in this tissue. Proteolytic status is determined by the imbalance between plasminogen activators and plasminogen activator inhibitors, which are expressed differently depending on the type of lesion considered and the stage of the disease. The aim of the present study is to review the role of the plasminogen activator system in endometriosis, consider the clinical implications and focus on possible further research efforts and therapeutic applications in this disease.

Carbohydrate analysis of the zona pellucida and cortical granules of human oocytes by means of ultrastructural cytochemistry.

BACKGROUND: The zona pellucida (ZP), the mammalian oocyte coat, consists of a restricted number of highly glycosylated proteins. In vitro sperm binding studies suggest a higher binding affinity for the outer region of the ZP compared to its inner region in different species. However, the reason for this difference in binding distribution remains unresolved. Many studies suggest that the carbohydrate sequences linked to ZP glycoproteins act as ligands for sperm binding to this matrix. METHODS: Lectins and antibodies that recognize different carbohydrates were employed to perform an ultrastructural analysis of human ZP and cortical granule glycosylation. RESULTS: This study reveals variable glycosylation of the human ZP throughout its thickness, with pronounced differences between the most external and internal regions of this matrix. The binding studies also indicate that ZP glycoproteins express some carbohydrate sequences not previously detected in other species. Finally, cytochemical analysis of human cortical granules suggests similarities in glycosylation to ZP glycoproteins but not to cortical granules from other mammalian species. CONCLUSION: A heterogeneous carbohydrate composition was observed in the thickness of the human ZP that could be responsible for the different sperm binding affinity detected between the outer and inner regions of the ZP.

Cost-effectiveness of recombinant versus urinary follicle-stimulating hormone in assisted reproduction techniques in the Spanish public health care system.

PURPOSE: To evaluate the relative cost-effectiveness of recombinant and urinary follicle-stimulating hormone (FSH) in assisted reproduction techniques in the Spanish National Health Service. METHODS: Markov modelling was used to compare costs and outcomes of three complete treatment cycles using recombinant or urinary FSH for controlled ovarian stimulation. Cost and effectiveness estimates were obtained from the literature and from Spanish clinicians. A Monte Carlo technique was used to randomise the distribution of outcomes at each stage. The analysis was performed by passing a virtual population of 100,000 patients through the computer simulation in each of 5000 Monte Carlo simulations. RESULTS: The cost per pregnancy was Euro12,791+/-1202 ($11,346+/-1066) with recombinant and Euro13,007+/-1319 ($11,537+/-1170) with urinary FSH (p < 0.0001). The mean number of cycles per pregnancy was 4.69 and 5.21, respectively. CONCLUSIONS: Recombinant FSH is more cost-effective than urinary FSH in the Spanish public health care system.