Rates of hypogonadism forms in Klinefelter patients undergoing testicular sperm extraction: A multicenter cross-sectional study.

INTRODUCTION AND OBJECTIVES: Adult patients with Klinefelter syndrome (KS) may present with testicular volume loss and a decrease in circulating testosterone (T) levels. However, the actual rate of hypogonadism in adult KS men is unknown. We aimed to (a) assess the prevalence of different forms of hypogonadism in a cohort of KS patients with non-obstructive azoospermia (NOA); and (b) investigate potential preoperative predictor of positive sperm retrieval (SR) at surgery in the same cohort of men. METHODS: Complete data from 103 KS men with NOA who underwent testicular sperm extraction (TESE) between 2008 and 2019 at five centers were analyzed. Comorbidities were scored with the Charlson Comorbidity Index (CCI). Patients were categorized into four groups of hypogonadism as follows: eugonadism [normal total T (tT) (≥3.03 ng/mL) and normal luteinizing hormone (LH) (≤9.4 mUI/mL)], secondary hypogonadism [low tT (≤3.03 ng/mL) and low/normal LH (≤9.4 mUI/mL)], primary hypogonadism [low tT (≤3.03 ng/mL) and elevated LH (≥9.4 mUI/mL)], and compensated hypogonadism [normal tT (≥3.03 ng/mL) and elevated LH (≥9.4 mUI/mL)]. Descriptive statistics tested the association between clinical characteristics and laboratory values among the four groups. RESULTS: Median (IQR) patients age was 32 (24, 37) years. Baseline follicle-stimulating hormone and tT levels were 29.5 (19.9, 40.9) mUI/mL and 3.8 (2.5, 11.0) ng/mL, respectively. Eugonadism, primary hypogonadism, and compensated hypogonadism were found in 16 (15.6%), 34 (33.0%), and 53 (51.4%) men, respectively. No patients had secondary hypogonadism. Positive SR rate at TESE was 21.4% (22 patients); of 22, 15 (68.2%) patients underwent assisted reproductive technology and five (22.7%) ended in live birth children. Patients' age, BMI, CCI, FSH levels, and positive SR rates were comparable among hypogonadism groups. No preoperative parameters were associated with positive SR at logistic regressions analysis. CONCLUSIONS: Findings from this cross-sectional study showed that 15.6% of adult KS men have normal tT values at presentation in the real-life setting. Most KS patients presented with either compensated or primary hypogonadism. Sperm retrieval rates were not associated with different forms of hypogonadism.

Sperm retrieval rates in non-mosaic Klinefelter patients undergoing testicular sperm extraction: What expectations do we have in the real-life setting?

BACKGROUND: A recent meta-analysis (Human Reproduction Update 23, 2017 and 265) reported positive sperm retrieval rates (SRR) in 50% of patients with Klinefelter syndrome (KS) undergoing testicular sperm extraction (TESE). However, these results do not reflect the rates of SR that we observe in clinical practice. We assessed the rate and potential predictors of SR in Klinefelter patients in the real-life setting. MATERIALS AND METHODS: We reviewed clinical data of 103 KS men who underwent TESE between 08/2008 and 03/2019 at five tertiary referral Andrology centers. Patients underwent testis ultrasound, hormonal evaluation, and genetic testing. All patients were azoospermic based on the 2010 WHO reference criteria. Conventional TESE (cTESE) or microsurgical TESE (mTESE) was performed based on the surgeon's preference. We used descriptive statistics and logistic regression models to describe the whole cohort. RESULTS: Median (IQR) patient's age was 32 (24-37) years. Baseline serum FSH and total testosterone levels were 29.5 (19.9-40.9) mUI/mL and 3.8 (2.5-11.0) ng/mL, respectively. Conventional TESE and mTESE were performed in 38 (36.5%) and 65 (63.5%) men, respectively. The sperm retrieval rate was 21.4% (22/103 men). Fifteen patients used spermatozoa for ICSI and five ended in live birth children. Patients with positive SR were similar to those with a negative TESE in terms of clinical, hormonal, and procedural parameters (all P > .05). Logistic regression analyses confirmed the lack of association between clinical, hormonal, and procedural parameters with SR outcome. DISCUSSION: Given the conflicting results in the literature regarding SRR in KS, patients should be carefully counseled regarding TESE outcomes based on data from published literature and local results. CONCLUSIONS: In the real-life setting, we observed a lower SRR (21.4%) than that reported in meta-analyses in our cohort of KS patients. No associations between clinical, hormonal, and procedural variables with TESE success were found.

[Exploration of testicular function]. / Exploración de la función testicular.

The main endocrine function of the testis after puberty is testosterone production. In most cases, hypogonadism in adult men can be diagnosed by determining total testosterone concentration. Due to the circadian rhythm of testosterone secretion, blood samples should be extracted early in the morning. The results of commercially available methods for analysis show considerable variability. Furthermore, the threshold for the symptoms of hypogonadism may differ in each individual. For these reasons, moderately low testosterone levels should be interpreted with caution before a diagnosis of hypogonadism can be established. In these cases, determination of either free or bioavailable testosterone can be useful. Direct methods can be used or the respective concentrations can be calculated on the basis of total testosterone and sex hormone-binding globulin (SHBG). This latter method is easy to perform but the results are less reliable. Endocrinological evaluation of the testes should also include analysis of the gonadotropins (follitropin [FSH] and lutropin [LH]), which are described in another article in this series. Inhibin B is a biological marker of the amount and the physiological status of Sertoli cells in the postpubertal testis. Inhibin B may improve the information given by FSH for the determination of spermatogenic reserve in non-obstructive azoospermia, but determination of this glycoprotein is not currently used for routine assessment. The most important laboratory test to study reproductive function in men is semen analysis. However, the predictive power of this test is limited by the analytical imprecision of current methods, all of which are manual, and by the biological variability of most of their components. Special attention should be paid to pre-analytical procedures, because they require the understanding and participation of the patient. Some organizations and societies have proposed standardized methods to help improve the quality of semen analysis and reliable exchange of the results of seminogram. Biochemical markers of the prostate, seminal vesicles and epididymis in seminal plasma can indicate the level of damage in hypospermia or azoospermia. The fertility potential of sperm cells can be investigated with a variety of tests and assays, but none of them can yet be recommended for routine practice. Congenital hypogonadism is frequently caused by chromosome abnormalities, particularly sex chromosomal aneuploidies. Other causes of infertility include structural aberrations of autosomes. The main cytogenetic technique performed to determine chromosome constitution is karyotyping. To detect submicroscopic defects, this test can be performed in conjunction with fluorescent in situ hybridization (FISH).

Infección por SARS-CoV-2: implicaciones para la salud sexual y reproductiva. Una declaración de posición de la Asociación Española de Andrología, Medicina Sexual y Reproductiva (ASESA) / SARS-CoV-2 infection: implications for sexual and reproductive health. A position statement of the Asociación Española de Andrología, Medicina Sexual y Reproductiva (ASESA)

OBJETIVO: El objetivo de esta revisión es resumir la evidencia disponible sobre los posibles efectos adversos del SARS-CoV-2 en el sistema reproductor masculino y proporcionar una declaración de posición oficial de la Asociación Española de Andrología, Medicina Sexual y Reproductiva (ASESA). MÉTODOS: Se realizó una búsqueda exhaustiva en las bibliotecas Pubmed, Web of Science, Embase, Medline, Cochrane y MedRxiv. RESULTADOS: No se ha confirmado la orquitis como una posible complicación de la infección por SARS-CoV-2. Un estudio informó que el 19% de los hombres con COVID-19 presentaban molestias escrotales sugestivas de orquitis viral, que no se pudo confirmar. Es posible que el virus no infecte los testículos directamente, si no que desencadene una respuesta autoinmune secundaria y que cause una orquitis autoinmune. COVID-19 se ha asociado con anormalidades en la coagulación por lo que la orquitis podría ser el resultado de una vasculitis segmentaria. Los datos disponibles sobre la presencia del virus en semen son contradictorios. Sólo un estudio informó de la presencia de ARN en el 15,8% de enfermos de COVID-19. La presencia de ácido nucleico o antígeno en el semen no implica la existencia de virus con capacidad de replicación o infección. En hombres con COVID-19 se ha observado un incremento significativo de LH en suero y una drástica disminución de la ratio T/LH y FSH/LH, congruente con un hipogonadismo subclínico. CONCLUSIONES: Los datos disponibles y los hallazgos de los estudios recientes se basan en tamaños de muestra pequeños y proporcionan informaciones contradictorias. Existe la posibilidad teórica de que pueda producirse daño testicular y posterior infertilidad después de la infección por COVID-19, por lo que especialmente para aquellos hombres en edad reproductiva, se debe sugerir consulta y evaluación de la función gonadal y análisis de semen. En cuanto a la posibilidad de transmisión sexual, no hay evidencia suficiente para respaldar la necesidad de que las parejas asintomáticas eviten las relaciones sexuales para protegerse contra la transmisión del virus. Se necesita más investigación para comprender los impactos a largo plazo del SARS-CoV-2 en la función reproductiva masculina, incluidos sus posibles efectos sobre la fertilidad y la función endocrina testicular

OBJECTIVE: The main objective of this revision is to summarize the current existing evidence of the potential adverse effects of SARS-CoV-2 on the male reproductive system and provide the recommendations of the Asociación Española de Andrología, Medicina Sexual y Reproductiva (ASESA) concerning the implications of COVID-19 infection in the management of male infertilty patients and testicular endocrine dysfunction. METHODS: A comprehensive systematic literature search of the databases of PubMed, Web of Science, Embase, Medline, Cochrane and MedRxiv, was carried out. RESULTS: The presence of orchitis as a potential complication of the infection by SARS-CoV-2 has not yet been confirmed. One study reported that 19% of males with COVID-19 infection had scrotal symptoms suggestive of viral orchitis which could not be confirmed. It is possible that the virus, rather than infecting the testes directly, may induce a secondary autoimmune response leading to autoimmune orchitis. COVID-19 has been associated with coagulation disorders and thus the orchitis could be the result of segmental vasculitis. Existing data concerning the presence of the virus in semen are contradictory. Only one study reported the presence of RNA in 15.8% of patients with COVID-19. However, the presence of nucleic acid or antigen in semen is not synonyms of viral replication capacity and infectivity. It has been reported an increase in serum levels of LH in males with COVID-19 and a significant reduction in the T/LH and FSH/LH ratios, consistent with subclinical hypogonadism. CONCLUSIONS: The findings of recent reports related to the potential effects of COVID-19 infection on the male reproductive system are based on poorly designed, small sample size studies that provide inconclusive, contradictory results. Since there still exists a theoretical possibility of testicular damage and male infertilty as a result of the infection by COVID-19, males of reproductive age should be evaluated for gonadal function and semen analysis. With regard to the sexual transmission of the virus, there is not sufficient evidence to recommend asymptomatic couples to abstein from having sex in order to protect themselves from being infected by the virus. Additional studies are needed to understand the long-term effects of SARS-CoV-2 on male reproductive function, including male fertility potential and endocrine testicular function

Exploración de la función testicular / Exploration of testicular function

La principal función endocrina del testículo a partir de la pubertad es la síntesis de testosterona, y determinar su concentración total en el adulto es suficiente, en la mayoría de los casos, para diagnosticar elhipogonadismo. Debido a las variaciones circadianas de la concentración de testosterona, la extracción debe realizarse a primera hora de la mañana. Existe una considerable variabilidad en los resultados de los diversos métodos comerciales de análisis. Además, el umbral que determina la aparición de los síntomas de hipogonadismo puede ser distinto en cada individuo. Por ello, valores moderadamente bajos deben considerarse con cautela antes de confirmar el diagnóstico. En estos casos, la determinación de la testosterona libre o la biodisponible puede ser de ayuda. Se pueden utilizar métodos de análisis directo o calcular las respectivas concentraciones a partir de la testosterona total y de la globulina transportadora de hormonas sexuales (SHBG), método más sencillo aunque menos preciso. La evaluación endocrinológica del testículo también debe incluir el análisis de las gonadotropinas (folitropina [FSH] ylutropina [LH]), que se describen en otro artículo de esta serie. La inhibinaB es un indicador biológico de la cantidad de células de Sertoli y de suestado funcional en el testículo maduro (..) (AU)

The main endocrine function of the testis after puberty is testosterone production. In most cases, hypogonadism in adult men can be diagnosed by determining total testosterone concentration. Due to the circadian rhythm of testosterone secretion, blood samples should be extracted early in the morning. The results of commercially available methods for analysis show considerable variability. Furthermore, the threshold for the symptoms of hypogonadism may differ in each individual. For these reasons, moderately low testosterone levels should be interpreted with caution before a diagnosis of hypogonadism can be established. In these cases, determination of either free or bioavailable testosterone can be useful. Direct methods can be used or the respective concentrations can be calculated on the basis of total testosterone and sex hormone-binding globulin (SHBG). This latter method is easy to perform but the results are less reliable. Endocrinological evaluation of the testes should also include analysis of the gonadotropins (follitropin [FSH] and lutropin [LH]), which are described in another article in this series. Inhibin B is a biological marker of the amount and the physiological status of Sertoli cells in the postpubertal testis. Inhibin B may improve the information given by FSH for the determination of spermatogenic reserve in non-obstructive azoospermia, but determination of this glycoprotein is not currently used for routine assessment. The most important laboratory test to study reproductive function in men is semen analysis. However, the predictive power of this test is limited by the analytical imprecision of current methods, all of which are manual, and by the biological variability of most of their components (..) (AU)

Tumor de células de Leydig del testículo / Leydig cell tumor of testis

OBJETIVO: Presentamos una revisión de los pacientes con tumor testicular de células de Leydig (TTCL) en nuestro centro, realizando asimismo una comparación con la literatura referente al tema. MÉTODO: Estudio retrospectivo de las historias clínicas de los pacientes diagnosticados de TTCL en nuestro centro, tomando en consideración edad, motivo de consulta, antecedentes de patología testicular, tamaño y situación del tumor, patrón ecográfico, patrón histológico, estudio hormonal, seminograma, tratamiento y evolución clínica. RESULTADOS: Siete pacientes afectos de TTCL representan 2,1 por ciento de todos los tumores testiculares en nuestro centro. La edad media al diagnóstico es de 40 años, cuya manifestación clínica inicial fue de aumento de volumen testicular, ginecomastia, disfunción sexual o hallazgo casual en ecografía testicular por seguimiento de criptorquidia. Ecográficamente se identifican mayoritariamente como tumores de aspecto hipoecoico e hipervasculares. El estudio hormonal, con alteración en 4 pacientes, demuestra disminución de testosterona con aumento de estradiol séricos. El seminograma inicial se manifiesta con presencia de azoospermia, oligozoospermia severa o criptozoospermia en cuatro pacientes. Seis de los pacientes han sido tratados quirúrgicamente mediante orquiectomía simple vía inguinal, y uno con sólo tumorectomía. El seguimiento ha demostrado benignidad en todos los casos, con una media de 41 meses. CONCLUSIONES: El TTCL se presenta habitualmente como masa testicular, acompañándose o precedido por manifestaciones hormonales en 20 por ciento de los casos, con feminización en el adulto y masculinización en el niño. Son siempre benignos en edad pediátrica y en el 90 por ciento de adultos. Ecográficamente suelen ser hipoecoicos. Los criterios de malignidad histológica no se corresponden siempre con la clínica, siendo el criterio definitivo de malignidad la presencia de metástasis en el momento del diagnóstico o durante el seguimiento. No existe tratamiento eficaz para la enfermedad metastásica. Trás la extirpación de la glándula, regresan las manifestaciones clínicas hormonales en 90 por ciento de casos (AU)