Diagnostic value of urinary luteinizing hormone levels in the monitoring of precocious puberty treatment

ABSTRACT Objective To determine whether first-voided urinary LH (FV-ULH) - level measurement can adequately assess pubertal suppression as much as standard tests can. Subjects and methods The study group included patients with central precocious puberty and rapidly progressing early puberty who received up to 3 - 4 doses of GnRHa therapy monthly and did not have adequate hormonal suppression after GnRH stimulation (90-minute LH level > 4 IU/L). Design: All of the participants underwent an LHRH test just after admission to the study. According to the stimulated peak LH levels, the patients were divided into 2 groups and followed until the end of the first year of treatment. The concordance between FV-ULH and stimulated LH levels was assessed. Results The FV-ULH levels in patients with inadequate hormonal suppression were significantly high compared to patients with adequate hormonal suppression. FV-ULH levels were very strongly correlated with stimulated LH levels (r = 0.91). Its correlation with basal LH levels was significant (r = 0.65). However, this positive correlation was modestly weakened after the first year of treatment. The cutoff value for FV-ULH of 1.01 mIU/mL had the highest sensitivity (92.3%) and specificity (100%). Conclusion FV-ULH levels, using more reliable and sensitive assay methods, can be used to monitor the adequacy of GnRHa therapy.

Seminal characteristics of piabanha before and after induction with different hormones / Características seminais de piabanha antes e após a indução com diferentes hormônios

The migratory species piabanha does not reproduce in lentic environments since it requires environmental stimuli for the maturation and extrusion of gametes, and therefore hormonal induction is mandatory. Current study compares the seminal characteristics of Brycon insignis without any hormonal induction (Control - Ctrl) and with two types of hormonal inductors, or rather, carp pituitary extract (T1 - 2.5 mg kg-1 body weight) and GnRH analogues, the latter applied in two different concentrations (T2 - 0.7 mg kg-1 body weight and T3 - 1.4 mg kg-1 body weight). Post-induction analyses showed that the hormones increased the motility rate - Ctrl (95%), T1 (100%), T2 (100%) and T3 (98%), although sperm concentration - Ctrl (11.52 x 109); T1 (4.37 x 109); T2 (4.34 x 109); T3 (4.01 x 109) decreased. Assessments for sperm vigor, motility time and spermatic morphology did not vary with hormonal induction. Hormonal inducer does not alter negatively the seminal characteristics of the piabanha, and the choice for the proper hormone depends on the preference of the dispenser.

A espécie migradora piabanha não possui a capacidade de reproduzir em ambientes lênticos devido à necessidade de estímulos ambientais para a maturação e extrusão dos gametas, por isso a necessidade da indução hormonal. No presente estudo, as características seminais do Brycon insignis foram comparadas sem indução hormonal (Ctrl) e utilizando dois tipos de indutores hormonais - Extrato de Hipófise de Carpa (T1 - 2,5 mg kg-1 de peso vivo) e Análogos de GnRH, sendo este último aplicado em duas concentrações distintas (T2 - 0,7 mg kg -1 de peso vivo e T3 - 1,4 mg kg-1 de peso vivo). As análises realizadas após a indução mostraram que os hormônios utilizados produziram um aumento da taxa de motilidade - Ctrl (95%), T1 (100%), T2 (100%) e T3 (98%), porém houve uma diminuição na concentração espermática - Ctrl (11,52 x 109), T1 (4,37 x 109), T2 (4,34 x 109) e T3 (4,01 x 109). Os restantes das avaliações, vigor espermático, tempo de motilidade e morfologia espermática não apresentaram variações com a indução hormonal. Portanto, a utilização do indutor hormonal não altera negativamente as características seminais de piabanha, e a escolha do mesmo se deve à preferência do manipulador.

Factores clínico-terapéuticos que influyen en el logro de embarazo en pacientes tratadas por fertilización in vitro / Clinical and therapeutic factors influencing the achievement ofpregnancy among patients undergoing in vitro fertilization

Introducción: La fertilización in vitro es la técnica de reproducción asistida de alta tecnología que con más frecuencia se emplea como tratamiento en pacientes infértiles. Objetivo: determinar los factores clínico-terapéuticos que influyen en el logro de embarazo clínico mediante la técnica de fertilización in vitro. Métodos: se realizó un estudio de cohorte longitudinal retrospectivo, en 654 parejas infértiles para precisar la influencia de algunos factores, como la edad materna, años de infertilidad, causa y tipo de infertilidad, número de folículos aspirados, grosor endometrial, estradiol sérico antes de la administración de gonadotropina coriónica humana, calidad del semen, valor basal de hormona folículo estimulante, esquema de tratamiento con análogos de hormona liberadora de gonadotropinas y las modificaciones a este, en el logro de embarazo por fertilización in vitro. Resultados: se obtuvo que el 25,10 por ciento de las pacientes incluidas quedaron embarazadas. Entre las pacientes que se embarazaron y las que no, hubo diferencia estadísticamente significativa en cuanto a la edad (p= 0,001), concentración de estradiol (p= 0,003), grosor endometrial (p= 0,001) y folículos aspirados (p= 0,045). La infertilidad secundaria incrementó la probabilidad de embarazarse en 15 por ciento, el semen óptimo en 47 por ciento y el esquema terapéutico con acetato de leuprorelina en 28 por ciento. En el análisis multivariado, las variables más relacionadas con el logro de embarazo fueron, el esquema terapéutico con acetato de leuprorelina (p= 0,001), el semen óptimo (p= 0,028) y el grosor endometrial (p= 0,036).Conclusiones: el esquema de tratamiento, la calidad del semen y el grosor endometrial, son factores independientes que influyen en que una paciente sometida a la técnica de fertilización in vitro se embarace(AU)

Introduction: In vitro fertilization is the high technology assisted reproduction method most commonly used in the treatment of infertile patients. Objective: determine the clinical and therapeutic factors influencing the achievement of pregnancy by in vitro fertilization.Methods: a retrospective longitudinal cohort study was conducted with 654 infertile couples to determine the influence of a number of factors upon the achievement of pregnancy by in vitro fertilization. The factors considered were maternal age, years of infertility, type of infertility and cause, number of aspirated follicles, endometrial thickness, serum estradiol before the administration of human chorionic gonadotropin, semen quality, basal follicle-stimulating hormone, and treatment with gonadotropin-releasing hormone analogues and its modifications. Results: 25.10 percent of the patients included became pregnant. A statistically significant difference was found between patients becoming and not becoming pregnant as to age (p= 0.001), estradiol concentration (p= 0.003), endometrial thickness (p= 0.001) and aspirated follicles (p= 0.045). Secondary infertility increased the probability of becoming pregnant by 15 percent, optimal semen by 47 percent and treatment with leuprorelin acetate by 28 percent. The multivariate analysis variables most closely related to the achievement of pregnancy were treatment with leuprorelin acetate (p= 0.001), optimal semen (p= 0.028) and endometrial thickness (p= 0.036). Conclusions: treatment scheme, semen quality and endometrial thickness are independent factors influencing the achievement of pregnancy in patients undergoing in vitro fertilization(AU)

Avanços na etiologia, no diagnóstico e no tratamento da puberdade precoce central / Advances in the etiology, diagnosis and treatment of central precocious puberty

O início da puberdade caracteriza-se pelo aumento de amplitude e frequência dos pulsos do hormônio secretor de gonadotrofinas (GnRH) após um período de relativa supressão hormonal durante a infância. A reemergência da secreção pulsátil do GnRH resulta em aumento na secreção de gonadotrofinas, hormônio luteinizante (LH) e folículo estimulante (FSH), pela hipófise anterior e consequente ativação gonadal. A ativação prematura do eixo hipotálamo-hipófise-gonadal resulta em puberdade precoce dependente de gonadotrofinas, também conhecida como puberdade precoce central (PPC), e se caracteriza pelo desenvolvimento dos caracteres sexuais secundários antes dos 8 anos nas meninas e 9 anos nos meninos. O início do desenvolvimento puberal provém da interação complexa de fatores genéticos, nutricionais, ambientais e socioeconômicos. O diagnóstico clínico da PPC baseia-se em reconhecimento de desenvolvimento puberal progressivo, concentrações púberes de LH em condição basal e/ou após estímulo com GnRH e avanço de idade óssea. A ressonância magnética de encéfalo é útil no estabelecimento de diagnóstico diferencial entre as formas orgânica ou idiopática. Os análogos de GnRH de ação prolongada representam o tratamento de escolha da PPC. O componente genético da PPC foi recentemente fortalecido pela evidência de mutações no gene MKRN3, localizado no braço longo do cromossomo 15, em crianças com PPC familial. Nessa revisão, dados clínicos e terapêuticos da PPC serão amplamente discutidos, visando à atualização e à conduta criteriosa dessa condição clínica de grande relevância na endocrinologia pediátrica.

The onset of puberty is first detected as an increase in the amplitude and frequency of pulses of gonadotropin-releasing hormone (GnRH) after a quiescent period during childhood. The reemergence of pulsatile GnRH secretion leads to increases in the secretion of the gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) by the pituitary gland, and the consequent activation of gonadal function. Early activation of the hypothalamic–pituitary–gonadal axis results in gonadotropin-dependent precocious puberty, also known as central precocious puberty (CPP), which is clinically defined by the development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. Pubertal timing is influenced by complex interactions among genetic, nutritional, environmental, and socioeconomic factors. CPP is diagnosed on the basis of clinical signs of progressive pubertal development before the age of 8 years in girls and 9 years in boys, pubertal basal and/or GnRH-stimulated LH levels, and advanced bone age. Magnetic resonance imaging of the central nervous system is essential for establishing the CPP form as organic or idiopathic. Depot GnRH-analogues represent the first-line of therapy in CPP. Very recently, the genetic component of CPP was demonstrated by the evidence that the deficiency of the MKRN3 gene, located on long arm of chromosome 15, causes familial CPP in humans. In this current review, clinical and therapeutic aspects of the CPP will be discussed, contributing to adequate diagnosis and criterious approach of this relevant condition of pediatric endocrinology.

Manejo de la pubertad precoz: Guías Clínicas del Servicio de Endocrinología del Instituto Autónomo Hospital Universitario De Los Andes

La pubertad precoz (PP) se caracteriza por la aparición de caracteres sexuales secundarios antes de los 8 años en niñas y 9 años en niños, generalmente se acompaña de aceleración de la velocidad de crecimiento y de la maduración esquelética. Se clasifica en Pubertad Precoz Central (PPC) en cuyo caso existe activación completa del eje hipotálamo hipófiso gonadal (EHHG), Pubertad Precoz Periférica (PPP), aquella resultado de la exposición a esteroides sexuales, independiente de gonadotropinas, y la denominada Pubertad Precoz Combinada o Mixta, cuando la maduración del eje hipotálamo hipofisario se produce tras el estímulo de una PP de causa periférica, produciendo secundariamente una PPC. La más frecuente es la PPC, y en las niñas la etiología es idiopática en el 90% de los casos, a diferencia de los niños en quienes la causa es principalmente orgánica. En este artículo se hacen consideraciones sobre las diferentes estrategias de diagnóstico y tratamiento de la PP y se presenta el protocolo del Servicio de Endocrinología del IAHULA, Mérida, Venezuela.

Precocious puberty (PP) is characterized by the appearance of secondary sexual characteristics before 8 years old in girls and 9 in boys, usually accompanied by acceleration of growth velocity and skeletal maturation. The PP is classified in Central Precocious Puberty (CPP) in which case there is full activation of the hypothalamic pituitary gonadal axis (HHGA), Peripheral Precocious Puberty (PPP), that result from exposure to sex steroids, gonadotropin-independent, and Combined or Mixed Precocious Puberty, when the maturation of the hypothalamic pituitary axis occurs after a peripheral cause of PP, that secondarily produce a CPP. The most common is the CPP; the etiology in girls is idiopathic in 90% of cases, unlike boys in whom the cause is mainly organic. In this paper, considerations about the different strategies for diagnosis and treatment of PP are made, and the protocol of the Endocrinology Unit, IAHULA, Mérida, Venezuela is presented.

Protocolo largo con análogos de GnRH versus protocolo corto con antagonistas: ¿existen diferencias en cuanto a los resultados de los ciclos de FIV-ICSI? / Protocol with GnRH analogues vs antagonists of GnRH: exist differences in the results of the IVF-ICSI cycles?

Objetivo: Valorar si existen diferencias en los resultados de los ciclos de FIV-ICSI en función del protocolo de estimulación empleado. Método: Estudio retrospectivo descriptivo de pacientes infértiles que fueron sometidas a ciclos de FIV-ICSI en el Hospital Universitario La Paz, entre los meses de enero y septiembre de 2010, comparando un protocolo largo de estimulación con análogos de GnRH vs un protocolo corto con antagonistas de GnRH. Las variables analizadas fueron: tasa de gestación, necesidad de cancelación del ciclo, dosis total de gonadotropinas requerida durante la estimulación, niveles de estradiol sérico el día de la administración de la hCG, número de folículos puncionados, complejos obtenidos, número de ovocitos maduros y de embriones conseguidos. Resultados: No hubo diferencias estadísticamente significativas en los resultados de los ciclos en función del protocolo de estimulación empleado, en ninguna de las variables analizadas. Conclusiones: Este estudio no encontró diferencias en los resultados de los ciclos de FIV-ICSI con relación al uso de análogos o antagonistas de GnRH. Es necesarios más estudios con mayores tamaños muestrales para definir qué tipo de pacientes serían subsidiarias de recibir cada tratamiento para conseguir resultados óptimos.

Aims: To assess if there exist any differences in the results of the IVF-ICSI cycles depending on the stimulation protocol employed. Methods: Retrospective descriptive study of infertile patients who underwent IVF-ICSI cycles at La Paz University Hospital, between January and September 2010, comparing sitmulation protocol with GnRH agonists vs antagonists of GnRH. The variables analyzed were pregnancy rate, cancellation rate, total dose of gonadotropin required for stimulation, serum estradiol levels on the day of hCG administration, number of follicles punctured, complexes obtained, number of mature oocytes and of embryos obtained. Results: No statistically significant differences where found in the results of cycles depending on the protocol of stimulation used in any of the variables analyzed. Conclusions: This study didn't find any difference in the outcome of IVF-ICSI cycles in relation to the use of GnRH agonists or antagonists. We need more studies with larger sample sizes to determine which is the best treatment to each patient in order to achieve optimal results.