Gestación subrogada: el debate indocumentado continúa / Surrogacy: the undocumented debate continues

En los últimos días se ha reactivado el debate social que supone la gestación subrogada o gestación por sustitución (y no, como se utiliza inexactamente con frecuencia: “vientres de alquiler”). Y, como casi siempre ocurre en este tipo de controversias, la discusión se ha centra- do más en el plano legal de la cuestión que en analizar en profundidad los interrogantes éticos o médicos del debate. (AU)

Reproducción asistida y riesgo de cáncer infantil / Assisted reproduction and childhood cancer risk

Recientemente se ha publicado un trabajo (Weng SS, Huang YT, Huang YT, Li YP, Chien LY. Assisted Reproductive Tech- nology and Risk of Childhood Cancers. JAMA Netw Open. 2022 Aug 1;5(8) ( https://jamanetwork.com/journals/jamane- tworkopen/fullarticle/2795793) en el cual se evaluó el riesgo de cáncer infantil en los niños nacidos después de un trata- miento de fertilidad, según los datos del registro nacional de Taiwán.Este estudio de cohortes basado en la población a nivel nacional incluyó datos de registro de 2.308.016 niños divididos en tres grupos, desde el 1 de enero de2004 hasta el 31 de diciembre de 2017. Se identificó un total de 1880 niños con cáncer infantil incidente. (AU)

Relationships between lipids levels in blood plasma, follicular fluid and seminal plasma with ovarian response and sperm concentration regardless of age and body mass index / Relación entre los niveles de lípidos en plasma, líquido folicular y plasma seminal con la respuesta ovárica y concentración espermática independientemente de la edad y el índice de masa corporal

Purpose: There is a considerable literature supporting the role of lipids in fertility. However, little is known about their impact on male and female gametes. Our study aimed to investigate the relationships between lipids levels in serum, follicular fluid and seminal plasma with ovarian response and sperm concentration regardless of age and body mass index (BMI).Methods: 51 follicular fluid and serum samples of IVF-ICSI cycles and 52 seminal plasma and serum samples of males in the infertility study were analyzed for cholesterol, triglycerides, and non-esterified fatty acids. The parameters used to assess gonadal response were number of mature oocytes in metaphase II and total motile sperm. Differences between groups were studied by means Principal Component Analysis, Kolmogorov–Smirnov test, Pearson correlation, Student's T, and multivariate linear regression.Results: Using a multivariate linear regression model to exclude the effect of the age and BMI, we found that the lipid profile in follicular fluid and plasma influence inversely and significantly on ovarian response and the number of matured oocytes recovered. Moreover, we found that seminal lipid levels are predictors of seminal quality independent of plasma lipid values.Conclusion: Our current analysis demonstrates the association of low ovarian response and low number of motile sperms with abnormal lipids levels. (AU)

Objetivo: Existen muchas publicaciones que apoyan el papel de los lípidos en la fertilidad. Sin embargo, se sabe poco sobre su impacto en los gametos masculinos y femeninos. Nuestro estudio tuvo como objetivo investigar las relaciones entre los niveles de lípidos en plasma sanguíneo, líquido folicular y plasma seminal con la respuesta ovárica y concentración espermática, independientemente de la edad y el índice de masa corporal (IMC).Métodos: Se analizaron 51 muestras de plasma sanguíneo y líquido folicular de ciclos de FIV-ICSI y 52 muestras de plasma sanguíneo y plasma seminal de varones en estudio de infertilidad para analizar el nivel de colesterol, triglicéridos y ácidos grasos no esterificados. Los parámetros utilizados para evaluar la respuesta gonadal fueron el número de ovocitos maduros y el número total de espermatozoides móviles. Las diferencias entre los grupos se estudiaron mediante la prueba de análisis de componentes principales, la prueba de Kolmogorov-Smirnov, la correlación de Pearson, la T de Student y regresión lineal multivariante.Resultados: Utilizando un modelo de regresión lineal multivariante para excluir el efecto de la edad y el IMC, se encontró que el perfil de lípidos en el líquido folicular y el plasma influyen inversa y significativamente en la respuesta ovárica y el número de ovocitos maduros recuperados. Además, los niveles de lípidos seminales son predictores de calidad seminal independientemente de los valores de lípidos en plasma.Conclusión: Los resultados de este estudio demuestran la asociación de la baja respuesta ovárica y bajo número de espermatozoides móviles con niveles anormales de lípidos. (AU)

Relationships between lipids levels in blood plasma, follicular fluid and seminal plasma with ovarian response and sperm concentration regardless of age and body mass index.

PURPOSE: There is a considerable literature supporting the role of lipids in fertility. However, little is known about their impact on male and female gametes. Our study aimed to investigate the relationships between lipids levels in serum, follicular fluid and seminal plasma with ovarian response and sperm concentration regardless of age and body mass index (BMI). METHODS: 51 follicular fluid and serum samples of IVF-ICSI cycles and 52 seminal plasma and serum samples of males in the infertility study were analyzed for cholesterol, triglycerides, and non-esterified fatty acids. The parameters used to assess gonadal response were number of mature oocytes in metaphase II and total motile sperm. Differences between groups were studied by means Principal Component Analysis, Kolmogorov-Smirnov test, Pearson correlation, Student's T, and multivariate linear regression. RESULTS: Using a multivariate linear regression model to exclude the effect of the age and BMI, we found that the lipid profile in follicular fluid and plasma influence inversely and significantly on ovarian response and the number of matured oocytes recovered. Moreover, we found that seminal lipid levels are predictors of seminal quality independent of plasma lipid values. CONCLUSION: Our current analysis demonstrates the association of low ovarian response and low number of motile sperms with abnormal lipids levels.

¿Cuál es el conocimiento que poseen las donantes de ovocitos sobre su salud reproductiva? / What is the knowledge of oocyte donors about their reproductive health?

Los donantes de gametos constituyen un grupo especialmente involucrado en los tratamientos de re- producción asistida, así como en la salud reproductiva, pues ayudan a muchos pacientes a solucionar sus problemas reproductivos. No obstante, existen pocos estudios en España que aborden el conoci- miento que las donantes de gametos tienen acerca de su salud reproductiva. Por ello, el objetivo de este estudio ha sido conocer el grado de conocimiento que las donantes de gametos tienen sobre salud re- productiva y fertilidad. Se ha realizado un estudio prospectivo, transversal y multicéntrico que incluyó donantes de ovocitos de 10 clínicas de reproducción asistida en España. Durante 2 meses se han reclu- tado donantes entre 19 y 35 años, de las cuales, 63 han sido incluidas en el estudio, en el que se ha re- alizado un cuestionario de 41 preguntas divididas en tres partes: características sociodemográficas (11 preguntas), conocimientos sobre fertilidad (22 preguntas) y un cuestionario en escala de Likert para de- terminar la información que tenían sobre salud reproductiva, así como los riesgos acerca de su fertilidad (8 preguntas). Además de la estadística descriptiva, se ha realizado el análisis estadístico con Chi-cua- drado y p<0,05 se consideró significativo.Los resultados mostraron que las participantes evalúan el aumento de la edad de las mujeres como un factor de riesgo decisivo para la fertilidad, pero sin un conocimiento exacto, pues el 39,7 % afirmó que la disminución de la fertilidad sucedía entre los 35 y 40 años, y un 30 % afirmó que sucedía entro los 40 y los 45 años. Sólo el 47 % de las encuestadas entiende qué es la reserva ovárica. El 47,6 % de las donantes cree que las mujeres crean nuevos óvulos cada mes.Los resultados obtenidos en este estudio nos muestran que las donantes son conscientes de que existen alteraciones de la fertilidad, pero sus conocimientos sobre salud reproductiva pueden ser insuficientes. (AU)

Seminal Plasma and Serum Afamin Levels Are Associated with Infertility in Men with Oligoasthenoteratozoospermia.

The plasma glycoprotein afamin has been previously identified as an alternative carrier protein for vitamin E in extravascular fluids such as plasma and cerebrospinal, ovarian follicular, and seminal fluids. However, to date, no study has established a relationship between afamin levels and infertility in women or men. The purposes of our study were (i) to assess the level of afamin in serum and seminal fluids in infertile men compared to healthy controls and (ii) to study the association between polymorphisms in afamin genes and male infertility. This observational, prospective study evaluated the afamin levels in serum and seminal fluids from infertile men (n = 39) and compared them to those in healthy controls (n = 30). We studied the association between single-nucleotide polymorphisms (SNPs) in the 5`-untranslated region (5`-UTR) of the afamin gene and infertility and analyzed a total of 1000 base pairs from the untranslated region of the afamin gene. Subjects with low sperm motility and low sperm concentration had higher median seminal afamin (18.9 ± 2.9 ng/mg of proteins) and serum afamin concentrations (24.1 ± 4.0 ng/mg of proteins) than subjects with normal sperm parameters (10.6 ± 1.4 ng/mg of proteins) (p < 0.02) (15.6 ± 1.4 ng/mg of proteins) (p < 0.002). A total of five different polymorphisms were found, including one deletion and four single-nucleotide polymorphisms (SNPs). A new transversion (A/T) (position 4:73481093) was identified in an oligoasthenoteratozoospermic patient and was associated with high levels of afamin in plasma and seminal fluids. The prevalence of this variant in our study in the case homozygous for TT is 0.985 (98.5%), and in the case heterozygous for TA is 0.015 (1.5%). Our results suggest that genetic variations in afamin might be associated with male infertility. These findings could significantly enhance our understanding of the molecular genetic causes of infertility.

COVID-19 y reproducción asistida / No disponible

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The use of fluorescence in situ hybridization analysis on sperm: indications to perform and assisted reproduction technology outcomes.

PURPOSE: To determine the consequences of an altered sperm fluorescence in situ hybridization (FISH) result for ART outcomes and the indications for a sperm FISH analysis. METHODS: Data from 439 infertile men were collected. Bivariate analyses were performed to determine the association of men's age, seminal alterations, and sperm FISH indication, with the incidence of X, Y, 13, 18, and 21 sperm chromosomal abnormalities. A multivariate logistic regression analysis was performed to establish the most predictive variables for altered sperm FISH. Results from the IVF/ICSI cycles were collected for 248 out of 439 patients. Two distinct groups were established: 151 couples that used their own oocytes and 97 couples involved in egg donation programs. In both groups, ART outcomes were compared between normal and altered sperm FISH. RESULTS: Teratozoospermia and oligozoospermia were associated with sperm chromosome anomalies (p < 0.05). Indications for sperm FISH analysis with the highest predictability were teratozoospermia, male age, oligozoospermia, and implantation failure (AUC = 0.702). Embryo quality (p = 0.096), pregnancy rate (p = 0.054), and implantation rate (p = 0.089) were higher in own-oocytes couples with normal sperm FISH than in altered sperm FISH couples, although differences were not statistically significant. In donor-oocytes couples, in which high-quality embryos were transferred later than in own-oocytes couples (3.8 vs. 3.0 days), we did not identify differences in the ART outcome between normal and altered sperm FISH couples. In both groups, the possible interference of woman age was negligible. CONCLUSIONS: Sperm FISH is indicated in middle-aged oligoteratozoospermic patients with implantation failures in previous IVF/ICSI cycles. Sperm chromosome anomalies have a moderate detrimental impact on embryo quality, implantation, and pregnancy rates.

Efecto de la edad del varon en los resultados seminales y reproductivos / Effect of the male age on the seminal and reproductive results

La influencia de la edad paterna avanzada en los resultados reproductivos tras la realización de ciclos de FIV/ICSI es un tema controvertido. Existen trabajos que demuestran la influencia negativa de la edad paterna avanzada en la tasa de gestación y un aumento de la tasa de abortos, mientras que otros estudios no encuentran diferencias significativas. En base a estos resultados contradictorios, el objetivo de este estudio fue analizar la influencia de la edad paterna en la calidad de semen y en la tasa de gestación y aborto en ciclos de FIV/ICSI con ovocitos propios y en ciclos con ovocitos de donante. La influencia directa de la edad se analizó con un modelo regresión logística univariante con constante y el análisis multivariante para descartar efecto de confusión de cualquiera de las covariables sobre el efecto de la edad paterna en la tasa de gestación y tasa de abortos. En los ciclos con ovocitos propios, los resultados obtenidos demuestran que no existe correlación significativa entre la edad y parámetros morfológicos del semen (n:526) como la concentración (Pearson: -0,049, p:0,263), la movilidad (Pearson:-0,018, p:0,675) o el REM (Pearson:-0,047, p:0,284). Tampoco encontramos diferencias en la media de edad entre el grupo de ciclos en los que se consiguió embarazo (38,77 años, DE:4,52) y los que no se consiguió (38,12 años, DE:5,06) p:0,1553, n:530. En el seguimiento de los embarazos conseguidos (n:128) tampoco encontramos diferencia en la edad del varón entre los embarazos que acabaron en un aborto (38,75 años, DE:4,74) y los que continuaron hasta el nacimiento a término (37,49 años, DE:5,38), p:0,168. En los ciclos con donación de ovocitos tampoco encontramos correlación significativa entre la edad y parámetros morfológicos del semen (n:300) como la concentración (Pearson: -0,069, p:0,231), la movilidad (Pearson:-0,061, p:0,291) o el REM (Pearson:-0,088, p:0,129) o el índice de fragmentación de la muestra seminal (n:223, Pearson:-0,077, p:0,254). No se hallaron tampoco diferencias en la media de edad entre el grupo de ciclos en los que se consiguió embarazo (41,89 años, DE:5,49) y los que no se consiguió (41,96 años, DE:6,07) p:0,923, n:307 como tampoco encontramos diferencia en la edad del varón entre los embarazos que acabaron en un aborto (43,19 años, DE:6,51) y los que continuaron hasta el nacimiento a término (41,97 años, DE:6,83), p:0,371. Como conclusión, en nuestro estudio, la edad paterna no parece influir negativamente en la calidad de semen del varón ni sobre los resultados reproductivos, tanto en ciclos de FIV/ICSI con ovocitos propios como en ciclos con ovocitos procedentes de donante

The influence of advanced paternal age on reproductive outcomes after IVF / ICSI cycles is controversial. There are studies that show the negative influence of advanced paternal age on the gestation rate and an increase in the abortion rate, while other studies do not find significant differences. Based on these contradictory results, the objective of this study was to analyze the influence of paternal age on semen quality and on the gestation and abortion rate in IVF / ICSI cycles with own oocytes and in cycles with donor oocytes. The direct influence of age was analyzed with a univariate logistic regression model with constant and multivariate analysis to rule out the confounding effect of any of the covariates on the effect of paternal age on the gestation rate and abortion rate. In the cycles with own oocytes, the results obtained show that there is no significant correlation between age and semen morphological parameters (n: 526) as the concentration (Pearson: -0.049, p: 0.263), mobility (Pearson: -0.018) , p: 0.675) or REM (Pearson: -0.047, p: 0.284). We also found no differences in the mean age between the group of cycles in which pregnancy was achieved (38.77 years, SD: 4.52) and those that were not achieved (38.12 years, SD: 5.06). : 0.1553, n: 530. In the follow-up of pregnancies achieved (n: 128), we also found no difference in the age of the male between pregnancies that ended in an abortion (38.75 years, SD: 4.74) and those that continued until the birth at term ( 37.49 years, DE: 5.38), p: 0.168. In the cycles with oocyte donation, we did not find significant correlation between age and semen morphological parameters (n: 300) such as concentration (Pearson: -0.069, p: 0.231), mobility (Pearson: -0.061, p: 0.291) or the REM (Pearson: -0.088, p: 0.129) or the fragmentation index of the seminal sample (n: 223, Pearson: -0.077, p: 0.254). There were also no differences in the mean age between the group of cycles in which pregnancy was achieved (41.89 years, SD: 5.49) and those that were not achieved (41.96 years, SD: 6.07). ) p: 0.923, n: 307 as we did not find any difference in the age of the male between the pregnancies that ended in an abortion (43.19 years, SD: 6.51) and those that continued until the birth at term (41.97 years, DE: 6.83), p: 0.371. In conclusion, in our study, paternal age does not seem to have a negative effect on male semen quality or on reproductive outcomes, either in cycles of IVF / ICSI with own oocytes or in cycles with donor oocytes

Oxidative stress in follicular fluid of young women with low response compared with fertile oocyte donors.

The aim of this study was to determine the concentrations of oxidative stress markers, antioxidant enzymes and cytokines in the follicular fluid of young women with low response in ovarian stimulation cycles compared with high responders and fertile oocyte donors of the same age, to assess the impact of oxidative stress on ovarian reserve. The activity of follicular fluid antioxidant enzymes glutathione transferase, glutathione reductase and glutathione peroxidase was significantly lower in young women with reduced ovarian reserve compared with that in high responders and oocyte donors. Follicular fluid concentrations of oxidative stress marker malondialdehyde combined with 4-hydroxyalkenals and nitric oxide were higher in low responders than in high responders and oocyte donors. Significant differences between low responders and donors in concentrations of IL-2, IL-6, IL-8 and vascular endothelial growth factor were observed, with higher concentrations in low responders. However, IL-10 concentration was lower in low responders than in high responders and donors. No significant differences were found in follicular fluid concentrations of tumour necrosis factor alpha between the three groups. These results demonstrate that different concentrations of oxidative stress markers, oxidant enzymes and cytokines in low responders compared with high responders and oocyte donors may negatively impact ovarian response.

Situación actual de la técnica time lapse en el laboratorio / Current status of time-lapse systems in the laboratory

El uso de los sistemas time lapse está cada vez más extendido en los laboratorios, se ha demostrado su utilidad a la hora de seleccionar mejor los embriones en combinación con la morfología, que hasta hoy era el método utilizado para realizar esta selección. Aunque existen autores que no están muy de acuerdo con esta afirmación, hay una gran mayoría que coincide en que la monitorización continua de los embriones ofrece una información relevante a la hora de elegir los mejores embriones de un cultivo. Durante los últimos años han surgido estudios avalando el uso de esta técnica, así se ha descrito que se puede conseguir elevar las tasas de embarazo y apostar con más fuerza por la transferencia de embrión único. Todo lo descrito en la literatura habla de resultados con patrones de división y los distintos estudios que validan esos modelos, pero ninguno nombra en profundidad las especificaciones propias de cada sistema, por tanto, el objetivo de este estudio ha sido el intentar resaltar las diferencias existentes entre las plataformas que se pueden encontrar en el mercado e indicar el futuro de cada una de ellas

The use of time-lapse systems is increasingly widespread in laboratories, it has proved useful in the selection of the best embryos when combined with their morphology, the traditional method used until now. Although there are some authors that disagree with this statement, a large majority agrees that the continuous monitorization of the embryos offers relevant information at the time of choosing the best embryos within a culture. In recent years there have been studies that support the use of this technique, and have proven that higher pregnancy rates can be achieved with its use, placing more emphasis on single embryo transfer. Everything published in the literature describes the results of with division patterns and the various studies that validate those models, but none provide an in-depth description of their specifications, thus the aim of this study was to highlight the differences between each of the platforms found on the market and indicate the predicted future of each of them

¿Debemos de congelar todos los embriones para transferir en diferido? / Should we transfer frozen instead of fresh embryos?

Existen evidencias crecientes en la literatura que demuestran que la estimulación ovárica, la cual produce niveles suprafisiológicos de hormonas, puede disminuir la tasa de gestación frente a los ciclos de criotransferencias. Además, el desarrollo endometrial puede controlarse de forma más precisa en los ciclos con embriones congelados y descongelados. Ya que la criopreservación es un procedimiento de rutina en el laboratorio de FIV, y dado el incremento de resultados, la política de congelación de todos los embriones para transferir en diferido, es una alternativa emergente para mejorar los resultados en FIV. Con la política de congelar todos los embriones, se criopreservan todos los embriones obtenidos en un ciclo de FIV y la transferencia se realiza más tarde, o bien en un ciclo natural o sustituido. La ventaja de este método es que proporciona un mejor ambiente y más fisiológico a los embriones, y pueden obtenerse mejores tasas de gestación y menos morbilidad materna y perinatal. Sin embargo, existen controversias en la literatura sobre el uso generalizado de esta estrategia. Por eso, el objetivo de esta revisión es examinar la literatura al respecto, identificando resultados de estudios randomizados en los que se criopreservan todos los embriones y se comparan con los resultados de embriones en fresco. También se estudian los posibles inconvenientes de esta técnica

Growing evidence in the literature shows that controlled ovarian stimulation, with supraphysiologic hormonal levels, may decrease pregnancy rate against frozen-thawed cycles. Moreover, endometrial development can be controlled more precisely during its priming for frozen-thawed embryo transfer vs. for controlled ovarian stimulation. Therefore, as the embryo cryopreservation has become a routine procedure in IVF labs , the ''freeze-all'' policy has emerged as an alternative to fresh ET to improve IVF outcomes. With the freeze-all policy, the entire cohort of embryos is cryopreserved, and the ET is performed later in a natural cycle, or in a cycle with hormonal replacement for endometrial priming. The potential advantage of this method is that it provides a more physiologic environment in which ET can occur; this advantage could lead to better pregnancy rates and decrease maternal and perinatal morbidity. However, controversies remain regarding patient selection and the threshold at which a cycle becomes supraphysiologic. The purpose of the present systematic review was to examine the literature and identify results of randomized clinical trials to assess if the cryopreservation of all embryos of good quality, and subsequent transference, is associated with improvements in the ART outcomes compared with fresh embryo transfer

Diagnostic accuracy of sperm DNA degradation index (DDSi) as a potential noninvasive biomarker to identify men with varicocele-associated infertility.

PURPOSE: Varicocele is a frequent cause of impaired testicular function that has been associated with increased levels of sperm DNA fragmentation (SDF). Sperm with degraded DNA (DDS), as observed using the sperm chromatin dispersion (SCD) test, represent a subpopulation of spermatozoa with extensive DNA and nuclear protein damage. The aim of this work was to determine the usefulness of sperm DNA degradation index (DDSi) as a novel noninvasive biomarker to identify infertile men with varicocele. METHODS: A total of 593 semen samples obtained from men attending infertility clinics were analyzed for SDF and DDS with the SCD test. These samples were classified as: (1) fertile donors; (2) infertile patients with least two failed assisted reproduction cycles; (3) leukocytospermia; (4) Chlamydia trachomatis infection; (5) testicular cancer, and (6) infertile men with varicocele. The DDSi was obtained by determining the proportion of DDS in the whole sperm population presenting with fragmented DNA. The diagnostic accuracy of DDSi was evaluated by correlation coefficient and receiver operating characteristics analyses. RESULTS: A positive correlation (r ≥ 0.52) was observed between the SDF and the frequency of degraded sperm in all patient groups. The sperm DNA degradation index (DDSi) was at least twice as higher in infertile men with varicocele (mean: 0.54) compared with other clinical conditions and fertile donors (means ranging from 0.02 to 0.21; P < 0.0001). A DDSi ≥ 0.33 identified patients with varicocele with 94 % accuracy. CONCLUSION: Although DDS is not pathognomonic of varicocele, the DDSi is a useful noninvasive biomaker to identify infertile individuals with varicocele when examining sperm DNA damage during a routine semen analysis. This finding may alert practitioners and laboratories performing semen analysis that in the presence of an abnormal DDSi it is likely that a given patient has varicocele. It is therefore strongly recommended that such patients be referred to urologists in order to undergo a full andrological examination and be properly counseled.

Can DNA fragmentation of neat or swim-up spermatozoa be used to predict pregnancy following ICSI of fertile oocyte donors?

This study compared the potential of assessing sperm DNA fragmentation (SDF) from neat semen and the subsequent swim-up (SU) procedure to predict pregnancy when conducting ICSI of fertile donor oocytes. Infertile females (n=81) were transferred embryos resulting from intracytoplasmic sperm injection (ICSI) of their partner's spermatozoa and proven donor oocytes. This model normalized the impact of female factor in putative sperm DNA repair. Semen was blindly assessed for SDF using Halosperm immediately following ejaculation (NS) and after swim-up at the time of ICSI fertilisation. There was a decrease in SDF values of the ejaculated semen sample following the swim-up protocol (P=0.000). Interestingly, pregnancy could be equally predicted from SDF values derived from either neat or swim-up semen samples. Receiver operator curves and the derived Youden's indices determined SDF cutoff values for NS and SU of 24.8% and 17.5%, respectively. Prediction of pregnancy from NS SDF had a sensitivity of 75% and a specificity of 69%, whereas for SU SDF was 78% and 73%, respectively. While increased levels of SDF negatively impact reproductive outcome, we have shown that a reduction in SDF following sperm selection using ICSI with proven donor oocytes is not mandatory for achieving pregnancy. This suggests that a certain level of DNA damage that is not detectable using current technologies could be impacting on the relative success of assisted reproductive technology (ART) procedures. Consequently, we propose a modification of the so called 'iceberg model' as a possible rationale for understanding the role of SDF in reproductive outcome.

Análisis de la dinámica de la fragmentación de ADN en espermatozoides para la optimización de la Inseminación Artificial Intrauterina / Dynamic analysis of sperm DNA fragmentation for optimizing intrauterine artificial insemination

Introducción y Objetivos: De forma normal existe un porcentaje de espermatozoides con ADN fragmentado en el eyaculado. Sin embargo, la manipulación de las muestras de semen para R.A. puede aumentar el grado basal de fragmentación. Aunque los mecanismos de procesamiento del semen que pueden afectar a la fragmentación no son todavía conocidos, el objetivo es analizar la influencia del swim-up en la dinámica de fragmentación del ADN espermático a lo largo del tiempo en las mismas condiciones en las que se procesa el semen para IAC, y evaluar si la fragmentación del ADN espermático tras swim-up, así como su evolución en el tiempo puede predecir la posibilidad de gestación en IAC. Material y métodos: Las muestras de semen utilizadas se han obtenido de 25 parejas en tratamiento de IAC el mismo día de la Inseminación. La fragmentación del ADN se midió con el Kit Halosperm (SCD). Se empleó la T de Student para la comparación estática de medias entre ambos grupos y tests de regresión lineal, exponencial y logarítmica para el estudio dinámico. Resultados: En todo momento, dentro del intervalo estudiado, el índice de fragmentación del semen capacitado se mantiene significativamente inferior al del semen fresco. Conclusiones: Los resultados apoyan la idea de que la centrifugación que conlleva el swim-up no induce daño adicional en el ADN espermático y que es recomendable utilizar las muestras de semen post swimup para inseminación en un intervalo de una hora (AU)

Introduction: A certain level of damaged DNA is present in mature sperm cells after a natural ejaculation. Additionally, sperm management for artificial reproduction techniques (ART) may increase the basal rate of DNA damage. Unfortunately, the mechanisms and processes involved in Sperm DNA Fragmentation (SDF) are not fully illuminated. The main aim of this investigation was to analyse the influence of swim-up on the evolution of sperm DNA fragmentation values over time, emulating the experiment within the same set-up of sperm handling as used for insemination and to evaluate whether the degree of sperm DNA fragmentation as well the evolution over time can predict IUI outcome. Material and methods: Semen samples were obtained from couples undergoing IUI (only one cycle per couple was included) for infertility treatment at the Clinica Tambre in Madrid, Spain. A total of 25 males provided 25 samples that were analysed. SDF fragmentation was assessed using the sperm chromatin dispersion (SCD) test using the Halosperm kit (Halotech DNA, Madrid). Statistical analysis was performed using T-Student and regression analysis . Results: Mean values of DNA fragmentation in the spermatozoa prepared by swim-up are lower than before selection in all times studied. Conclusion: The results of this study support the notion that the swim-up technique, as practised in our laboratory, does no induce DNA damage to human spermatozoa, as assessed by SCD assay. We therefore propose that sperm samples be used before an hour after processing in intrauterine insemination (AU)

An improved experimental model for understanding the impact of sperm DNA fragmentation on human pregnancy following ICSI.

Using donor oocytes of proven fertility, the effect of sperm DNA fragmentation (SDF) and motility on reproductive success was examined in 70 couples undergoing ICSI. Both SDF and sperm motility were assessed at the time of sperm injection and using the same sperm sample that was processed for ICSI. While there was no difference in the fertilization rate, cleavage rate, embryo quality, or sperm motility between pregnant and nonpregnant couples, the SDF of nonpregnant couples (SDF = 23.9%) was higher than that of pregnant couples (SDF = 17.0%; U Mann-Whitney 347; P = .002). Using a combination of the sensitivity and specificity measures from the production of ROC (receiver-operating characteristic) curves and the Youden index, we determined a threshold SDF value for our data set of 17% for predicting pregnancy (77.8% sensitivity and 71.1% specificity). Our results suggest that proven donor oocytes in combination with SDF assessment at the time of sperm injection represent a useful experimental model for reducing the confounding influences of sperm DNA repair by the oocyte and iatrogenic sperm damage.

Endometrial expression of selected genes in patients achieving pregnancy spontaneously or after ICSI and patients failing at least two ICSI cycles.

The objective of this study was to identify the endometrial gene expression profile in receptive phase, which could represent a useful prognostic tool for selecting IVF patients. Endometrial expression of 47 selected genes biopsied during the window of implantation in natural cycles was compared between patients who achieved a successful pregnancy spontaneously or after subsequent intracytoplasmic sperm injection (ICSI) cycles and patients who did not achieve a pregnancy after at least two failed ICSI cycles. The comparative analysis showed significantly different levels of expression in 19 genes, five implicated in apoptosis (CASP8, FADD, CASP10, APAF1, ANXA4), three in immunity (LIF, SPP1, C4BPA), five in transcriptional activity (MSX1, HOXA10, MSX2, HOXA11, GATA2), two in lipid metabolism (LEPR, APOD) and four in oxidative metabolism (AOX1, ALDH1A3, GPX3, NNMT). The evidence for these genes being differently expressed could represent the starting point of identifying the ideal receptive endometrial gene expression profile, which could be used in the future as a prognostic tool for IVF patients. Gene expression analysis technology has opened new important perspectives on the study of the physiological processes of different tissues and organs. Specifically for the endometrium, it would be really interesting to find out an endometrial gene expression profile of receptive phase, which could be used in future as a useful prognostic tool for selecting IVF patients. To achieve this aim, the objective of the present paper was the comparison of endometrial expression in natural cycles of 47 selected genes between the biopsies of patients who achieved a successful pregnancy, either spontaneously or after subsequent ICSI cycles, and those of patients who did not achieve a pregnancy after at least two failed ICSI cycles. The comparative analysis showed a significant different expression in 19 genes: five implicated in programmed cell death, known as apoptosis (CASP8, FADD, CASP10, APAF1, ANXA4), three in immunity (LIF, SPP1, C4BPA), five in transcriptional activity (MSX1, HOXA10, MSX2, HOXA11, GATA2), two in lipid metabolism (LEPR, APOD) and four in oxidative metabolism (AOX1, ALDH1A3, GPX3, NNMT). The evidence of these genes being differently expressed could represent the starting point of identifying the ideal receptive endometrial gene expression profile which could be used in the future as a prognostic tool for IVF patients.