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González Martín, Roberto
Domínguez Hernández, Francisco (dir.) Departament de Bioquímica i Biologia Molecular |
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Aquest document és un/a tesi, creat/da en: 2022 | |
Decreased fertility rates have been observed in recent decades, mainly in industrialized regions, which has increased the need for assisted reproductive techniques. Contributing factors responsible for this decline in human fertility have included socioeconomic factors as well as environmental and lifestyle factors, such as environmental and dietary exposures. Although their influence has been extensively studied in men, their impact on female fertility is much less well evaluated. Therefore, the aim of the present thesis was to evaluate the concentrations of phytoestrogens (daidzein and genistein), parabens (M-Paraben, P-Paraben), phthalates (MEHP) and a panel of nineteen trace elements, both essential and non-essential, in follicular fluid, plasma and urine obtained on the day of vaginal oocyte retrieval from 60 women undergoing IVF treatment with single euploid blastocyst transfer. O...
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Decreased fertility rates have been observed in recent decades, mainly in industrialized regions, which has increased the need for assisted reproductive techniques. Contributing factors responsible for this decline in human fertility have included socioeconomic factors as well as environmental and lifestyle factors, such as environmental and dietary exposures. Although their influence has been extensively studied in men, their impact on female fertility is much less well evaluated. Therefore, the aim of the present thesis was to evaluate the concentrations of phytoestrogens (daidzein and genistein), parabens (M-Paraben, P-Paraben), phthalates (MEHP) and a panel of nineteen trace elements, both essential and non-essential, in follicular fluid, plasma and urine obtained on the day of vaginal oocyte retrieval from 60 women undergoing IVF treatment with single euploid blastocyst transfer. Organic compound concentration was evaluated by UPLC-MS/MS, while trace elements were evaluated by ICP-MS. Generalized linear models were applied to explore the association between the compounds and variables of ovarian reserve, response to ovarian stimulation, fertilization and embryo development, ploidy and clinical outcome of IVF treatment, adjusted for different covariates of interest. In fully adjusted models we observed that higher phytoestrogen concentrations in follicular fluid and urine were significantly associated with greater ovarian response to hormonal stimulation, higher embryo fertilization and better clinical outcomes after IVF treatment. Likewise, higher concentrations of essential trace elements, such as copper and copper/zinc ratio in follicular fluid and plasma, and manganese in plasma, were significantly associated with a greater ovarian response to hormonal stimulation and better embryological outcomes after IVF treatment. Conversely, higher concentrations of trace elements, such as lithium, strontium, barium and arsenic, in follicular fluid and/or plasma are associated with lower ovarian reserve, lower response to ovarian stimulation and worse embryological outcomes in IVF treatment. In addition, higher concentrations of molybdenum, barium and the phthalate metabolite MEHP in urine are significantly associated with worse clinical outcomes after IVF treatment. Finally, we did not observe associations between paraben concentrations in follicular fluid or urine with the different IVF treatment variables evaluated. These results suggest a direct impact of environmental and dietary compound exposure on IVF variables.En las últimas décadas se han observado menores tasas de fertilidad, fundamentalmente en regiones industrializadas, lo que ha incrementado la necesidad de recurrir a técnicas de reproducción asistida. Entre los factores responsables de este descenso de la fertilidad humana se han incluido tanto factores socioeconómicos como factores ambientales y de estilo de vida, entre los que se incluye la exposición a factores ambientales y procedentes de la dieta. Aunque su influencia ha sido bastante estudiada en hombres, su impacto sobre la fertilidad femenina se encuentra mucho menos evaluada. Por lo tanto, el objetivo de la presente tesis ha sido evaluar las concentraciones de fitoestrógenos (daidzeína y genisteína), parabenos (M-Parabeno, P-Parabeno), ftalatos (MEHP) y un panel de diecinueve elementos traza, tanto esenciales como no esenciales, en líquido folicular, plasma y orina obtenidos el día de la punción ovárica procedente de 60 mujeres que se sometieron a un tratamiento de FIV con transferencia de un único blastocisto euploide. La concentración de los compuestos orgánicos fue evaluada mediante UPLC-MS/MS, mientras que los elementos traza se evaluaron mediante ICP-MS. Se aplicaron modelos lineales generalizados para explorar la asociación entre los compuestos y variables de reserva ovárica, respuesta a la estimulación ovárica, fecundación y desarrollo embrionario, ploidia y resultados clínicos del tratamiento de IVF, ajustados por distintas covariables de interés. En los modelos completamente ajustados observamos que mayores concentraciones de fitoestrógenos en líquido folicular y orina se asociaron significativamente con una mayor respuesta ovárica a la estimulación hormonal, mayor fecundación embrionaria y mejores resultados clínicos tras el tratamiento de fecundación in vitro. En esta misma línea, mayores concentraciones de elementos traza esenciales, como el cobre y la ratio cobre/zinc en líquido folicular y plasma, y el manganeso en plasma, se asociaron significativamente con una mayor respuesta ovárica a la estimulación hormonal y mejores resultados embriológicos en el tratamiento de fecundación in vitro. Por el contrario, mayores concentraciones de elementos traza, como el litio, el estroncio, el bario y el arsénico, en líquido folicular y/o plasma se asocian con menor reserva ovárica, menor respuesta a la estimulación ovárica y peores resultados embriológicos en el tratamiento de fecundación in vitro. Además, mayores concentraciones de molibdeno, bario y el metabolito de ftalato MEHP en orina se asocian significativamente con peores resultados clínicos tras el tratamiento de fecundación in vitro. Por último, no hemos observado asociaciones entre las concentraciones de parabenos en líquido folicular u orina con las distintas variables del tratamiento de fecundación in vitro evaluadas. Estos resultados sugieren un impacto directo de la exposición a compuestos ambientales y procedentes de la dieta sobre las variables de FIV.
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