RESUMO
OBJECTIVE: To compare fixed daily doses of the recombinant FSH (rFSH) Gonal-F (150 IU vs. 225 IU) for ovarian stimulation in IVF-ET. DESIGN: Single-center prospective, randomized study. Assisted conception unit of a university hospital. One hundred twenty-four women aged 23-41 years participated in the study. Exclusion criteria were as follows: FSH of >10 IU/L, polycystic ovarian syndrome, one ovary or previous ovarian surgery, previous poor response to ovarian stimulation, or ovarian hyperstimulation syndrome (OHSS). INTERVENTION(S): Randomized to commence 150 IU or 225 IU of Gonal-F per day without dose alterations during treatment. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved and total rFSH dose. RESULT(S): More oocytes were retrieved in women aged
Assuntos
Fertilização in vitro/métodos , Hormônio Foliculoestimulante/uso terapêutico , Oócitos/fisiologia , Indução da Ovulação , Resultado da Gravidez , Proteínas Recombinantes/uso terapêutico , Adulto , Relação Dose-Resposta a Droga , Feminino , Hormônio Foliculoestimulante Humano , Folistatina/uso terapêutico , Humanos , Infertilidade Feminina/classificação , Infertilidade Feminina/fisiopatologia , Ciclo Menstrual/fisiologia , Oócitos/citologia , Seleção de Pacientes , Gravidez , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Analyses of the follicular reserve and activity of the ovary are central to our understanding of the regulation of follicular development. We have carried out a prospective analysis of endocrine and biophysical assessments under three differing basal conditions: the early follicular and mid-luteal phases, and following GnRH analogue down-regulation. METHODS: Hormonal analyses were carried out before and after a single dose of FSH on spontaneously ovulating women (n = 58). Ovarian volume and antral follicle count (AFC) were also determined. RESULTS: Inhibin B and estradiol concentrations were increased by FSH under all three conditions, and inhibin A in the follicular phase and after down-regulation. Basal hormone concentrations, except inhibin A and B after down-regulation, did not generally correlate with AFC. A close relationship between inhibin B and AFC was evident at all stages after FSH administration (r = 0.70-0.77). AFC and inhibin B after FSH stimulation were well correlated with the number of oocytes recovered after superovulation. Multivariate analysis demonstrated that inhibin B after FSH administration in the down-regulated state showed the closest correlation with oocyte number. In the more clinically useful early follicular and luteal phases, basal FSH was the most significant contributor to the number of oocytes, with a significant contribution from luteal phase AFC. CONCLUSIONS: These data extend our understanding of the relationships between follicular number, follicular functional activity, and the recruitable follicular population. Down-regulation and subsequent FSH stimulation was required to clearly demonstrate the close relationship between inhibin B and the ovarian reserve. Without such complex manipulation, early follicular phase FSH (supplemented by AFC in the relatively hypogonadotrophic luteal phase) remains of greater value in predicting the ovarian reserve than the currently known direct products of the ovary.
Assuntos
Hormônio Foliculoestimulante/sangue , Hormônio Foliculoestimulante/farmacologia , Inibinas/sangue , Ciclo Menstrual/fisiologia , Folículo Ovariano/fisiologia , Hipófise/metabolismo , Adulto , Envelhecimento/metabolismo , Regulação para Baixo , Feminino , Fertilização in vitro , Fase Folicular , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônios/sangue , Humanos , Fase Luteal , Oócitos , Concentração Osmolar , Indução da Ovulação , Estudos Prospectivos , Proteínas Recombinantes/farmacologia , Valores de Referência , Análise de Regressão , Coleta de Tecidos e Órgãos , Resultado do TratamentoRESUMO
BACKGROUND: Local modulation of 11beta-hydroxysteroid dehydrogenase (11betaHSD) activity, to promote increased availability of anti-inflammatory glucocorticoids, is proposed as a compensatory response to inflammatory stimuli. Human 11betaHSD type 1 (11betaHSD1) is principally an 11-oxoreductase that reversibly reduces cortisone to cortisol. METHODS: Since ovulation is an acute inflammatory process, we examined the influence of pro-inflammatory cytokines on expression of 11betaHSD1 mRNA and metabolism of cortisone to cortisol by human ovarian surface epithelium (HOSE) in vitro. RESULTS: Northern analysis showed an approximately 1.5 kb-sized 11betaHSD1 mRNA transcript in total RNA that was up-regulated approximately 3-fold by interleukin (IL)-1alpha (0.5 ng/ml) at 24 h. By real-time RT-PCR, induction of 11betaHSD1 mRNA by IL-1alpha was measurable at 6 h and maximal at 12 h. Primary HOSE cell cultures also showed low-level 11-oxoreductase activity that was stimulated time- and dose-dependently by IL-1alpha and IL-1beta. The 11betaHSD1 mRNA and 11-oxoreductase responses to 0.5 ng/ILalpha were both suppressed by IL-1 receptor antagonist (25 ng/ml). CONCLUSIONS: Cultured HOSE cells express IL-1-responsive 11betaHSD1 and 11-oxoreductase activity mRNA in vitro. An 11betaHSD1-catalysed increase in anti-inflammatory glucocorticoid activity caused by pro-inflammatory cytokines could contribute to the local resolution of inflammation during ovulation.