RESUMEN
BACKGROUND: Endometriosis is the major cause of progressive pelvic pain and subfertility. Up to 50% of reproductive-age women suffer from pelvic pain. Endometriosis is a classic indication for IVF. Compared with women whose inability to procreate is caused by simple tubal infertility, women with endometriosis often have lower pregnancy rates following in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). The administration of gonadotrophin-releasing hormone (GnRH) agonists prior to IVF/ICSI can improve the successful pregnancy rate. Whether a briefer treatment interval would be efficacious has not been studied. METHODS/DESIGN: Eligible and consenting women will be randomly assigned to one of two treatments (one cycle of a GnRH agonist or two cycles of a GnRH agonist) prior to IVF/ICSI using a table of random numbers. The primary outcome of this trial is clinical pregnancy rate. Other outcomes include gonadotrophin (Gn) duration, the total dose of follicle-stimulating hormone (FSH) used, number of oocytes retrieved, number of embryos available for transfer, implantation rate, the abortion rate, live birth rate, and incidence of moderate-to-severe ovarian hyperstimulation. The sample size of this trial is estimated to be 421 participants for each of the two arms. Appropriate interim analyses will be conducted by a data monitoring and ethics committee (DMEC), and the final test will be an intention-to-treat analysis. TRIAL REGISTRATION: This trial has been assigned the following registry number: NCT03006406 .
Asunto(s)
Endometriosis/fisiopatología , Infertilidad/tratamiento farmacológico , Luteolíticos/uso terapéutico , Inyecciones de Esperma Intracitoplasmáticas/métodos , Pamoato de Triptorelina/uso terapéutico , Adulto , Tasa de Natalidad , Femenino , Humanos , Infertilidad/etiología , Luteolíticos/sangre , Embarazo , Índice de Embarazo , Estudios Prospectivos , Método Simple Ciego , Pamoato de Triptorelina/sangreRESUMEN
BACKGROUND: Few data are available on quarterly 11.25 mg GnRH analog treatment in central precocious puberty (CPP). AIM: To assess the efficacy of triptorelin 11.25 mg in children with CPP. PATIENTS: 17 patients (16 females) with CPP (7.9 ± 0.9 years) were treated with triptorelin 11.25 mg/90 days. METHODS: Gonadotropins, basal-, and GnRH-stimulated peak, gonadal steroids, and pubertal signs were assessed at preinclusion and at inclusion visit, 3 months, 6 months, and 12 months of treatment. Results. At 3, 6, and 12 months, all patients had suppressed LH peak (<3 IU/L after GnRH stimulation), as well as prepubertal oestradiol levels. Mean LH peak values after GnRH test significantly decreased from 25.7 ± 16.5 IU/L at baseline to 0.9 ± 0.5 IU/L at M3 (P < 0.0001); they did not significantly changed at M6 and M12. CONCLUSIONS: Triptorelin 11.25 mg/90 days efficiently suppressed the pituitary-gonadal axis in children with CPP from first administration.
Asunto(s)
Pubertad Precoz/tratamiento farmacológico , Pamoato de Triptorelina/uso terapéutico , Niño , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/metabolismo , Hormona Liberadora de Gonadotropina/sangre , Gónadas/metabolismo , Humanos , Hormona Luteinizante/metabolismo , Luteolíticos/sangre , Luteolíticos/uso terapéutico , Masculino , Hipófisis/metabolismo , Factores de Tiempo , Resultado del Tratamiento , Pamoato de Triptorelina/sangreRESUMEN
Horses are about five times more sensitive to the luteolytic effect of prostaglandin F2alpha (PGF) than cattle, as indicated by a recommended clinical dose of 5 mg in horses and 25 mg in cattle. Novel evaluations of the PGF plasma disappearance curves were made in mares and in heifers, and the two species were compared. Mares and heifers (n = 5) of similar body weight were injected (Min 0) intravenously with PGF (5 mg per animal). Blood was sampled every 10 sec until Min 3, every 30 sec until Min 5, every 10 min until Min 60, and every 30 min until Min 240. The mean PGF concentration was greater (P < 0.05) in mares than in heifers at Min 1 through Min 60 and at Mins 180 and 240. The mean time to maximum PGF concentration was not different between mares (42.0 ± 8.6 sec) and heifers (35.0 ± 2.9 sec). The apparent plasma clearance, distribution half-life, elimination half-life, and maximum plasma PGF concentration were 3.3 ± 0.5 L h(-1) kg(-1), 94.2 ± 15.9 sec, 25.9 ± 5.0 min, and 249.1 ± 36.8 ng/ml, respectively, in mares and 15.4 ± 2.3 L h(-1) kg(-1), 29.2 ± 3.9 sec, 9.0 ± 0.9 min, and 51.4 ± 22.6 ng/ml, respectively, in heifers. Plasma clearance was about five times less (P < 0.0005), maximum plasma PGF concentration was five times greater (P < 0.002), and the distribution half-life and elimination half-life were about three times longer (P < 0.005) in mares than in heifers. The fivefold greater plasma clearance of PGF in heifers than in mares corresponds to the recommended fivefold greater clinical dose of PGF in cattle and supported the hypothesis that the metabolic clearance of PGF is slower in mares than heifers.
Asunto(s)
Bovinos/sangre , Dinoprost/sangre , Caballos/sangre , Animales , Dinoprost/administración & dosificación , Dinoprost/farmacocinética , Femenino , Semivida , Luteolíticos/administración & dosificación , Luteolíticos/sangre , Luteolíticos/farmacocinética , Tasa de Depuración Metabólica , Especificidad de la EspecieRESUMEN
Prostaglandin F2α (PGF) is considered to be the main luteolysin in cattle. We have previously demonstrated that cortisol (Cr) suppresses PGF production in non-pregnant bovine endometrium. This study was carried out to test whether exogenous PGF increases ovarian and/or uterine PGF production and to determine the temporal relationship between PGF and Cr in ovarian and uterine circulations during PGF-induced luteolysis in cows. Catheters were inserted into the ovarian vein (OV), uterine vein (UV) and jugular vein (JV) of 10 cows on Day 9 of the oestrous cycle (Ovulation = Day 0) for frequent blood collection. On Day 10, the cows were divided randomly into two groups and treated with a luteolytic dose of a PGF analogue (cloprostenol) or saline solution. Blood samples were collected at -0.25, 0, 0.25, 0.5, 1 and 2 h and then at 2-h intervals until 12 h after treatment (0 h). The basal concentrations of PGF and Cr in OV and UV plasma were not significantly different. Injection of a PGF analogue induced more than twofold increases in the levels of PGF between 0.25 and 1 h in UV plasma, but not in OV plasma. PGF increased (p < 0.05) the concentrations of Cr in OV, UV and JV plasma between 0.5 and 1 h. The Cr levels in OV, UV and JV plasma were similar. The PGF levels in UV plasma decreased after Cr reached its highest levels. The overall results suggest that the uterus rather than the ovary increases PGF production in response to PGF injection. Based on the temporal changes of PGF and Cr in the ovarian and uterine circulations, Cr may act to reduce uterine PGF production in non-pregnant cows in vivo.
Asunto(s)
Bovinos , Dinoprost/sangre , Dinoprost/farmacología , Hidrocortisona/sangre , Luteólisis/efectos de los fármacos , Útero/irrigación sanguínea , Animales , Dinoprost/metabolismo , Femenino , Hidrocortisona/metabolismo , Luteolíticos/sangre , Luteolíticos/metabolismo , Luteolíticos/farmacología , Ovario/irrigación sanguíneaRESUMEN
The present study was conducted to assess effects of the gonadotropin-releasing hormone agonist (GnRHa) triptorelin in dairy heifers. The peptide was released from a commercial 4-week depot formulation (Decapeptyl Depot) administered at animals' estrus (day 0). First experiment (EXP I, n=5), which was aimed to explore the availability of peptide, detected a maximum of triptorelin concentration between day 2 and 5 after depot injection, and the peptide remained detectable by RIA in peripheral blood for about 3 weeks. In further experiments, the peptide release was terminated on day 9 (EXP II, n=16) or day 21 (EXP III, n=47). Treatment effects were studied on follicular development, the characteristics of cumulus-oocyte complexes (COCs) (EXP II; EXP IIIa) and secretions of LH and progesterone (EXP IIIb). Results showed that the occurrence of the pre-ovulatory LH surge was more uniform in treated heifers than that in controls. The duration of ovulation periods was similar amongst the heifers of EXP II, but more compact amongst those of EXP III each compared with the respective controls. Post-ovulatory, the number of LH pulses was significantly reduced by treatment, whereas both basal LH and progesterone concentrations were elevated on a few days. Follicular growth was reduced only by the prolonged influence of the GnRHa. There were increased proportions of both degenerated COCs and immature oocytes from small follicles (<3mm in diameter), and meiotic configuration and quality of oocytes isolated from follicles 3-5mm were changed after the prolonged, 21-day treatment. These results indicate that a continuous influence of a GnRHa over more than 1 week may increasingly impair the development of bovine follicles and oocytes. This may have some significance for the development of novel GnRH-based techniques in regulating the reproductive function in cattle.
Asunto(s)
Bovinos/fisiología , Hormona Liberadora de Gonadotropina/agonistas , Luteolíticos/administración & dosificación , Folículo Ovárico/efectos de los fármacos , Pamoato de Triptorelina/administración & dosificación , Animales , Cromatina/fisiología , Preparaciones de Acción Retardada , Femenino , Análisis de los Mínimos Cuadrados , Hormona Luteinizante/sangre , Luteolíticos/sangre , Luteolíticos/farmacocinética , Oocitos/fisiología , Folículo Ovárico/citología , Folículo Ovárico/diagnóstico por imagen , Folículo Ovárico/fisiología , Progesterona/sangre , Distribución Aleatoria , Pamoato de Triptorelina/sangre , Pamoato de Triptorelina/farmacocinética , UltrasonografíaRESUMEN
Anovulatory patients with clomiphene-resistant polycystic ovarian syndrome were treated by two different stimulation protocols. Follicular maturation was induced in 14 women with hMG; 12 of them received pure FSH in a later series after previous pituitary desensitization with the LHRH agonist D-Trp-6-LHRH (Decapeptyl). Both basal and stimulated serum androstenedione, testosterone, and free testosterone were elevated in the hMG-treated group compared with controls. However, only androstenedione exhibited a significant increase between early and late follicular levels. Marked suppression of these androgens has been observed after two weeks of LHRH agonist pretreatment, but nearly the same concentrations were obtained with pure FSH on the day of hCG administration. Again, only the increase of androstenedione levels proved to be significant. Polycystic follicular maturation, hyperstimulation, and peak estradiol levels were comparable with the two protocols. Nevertheless, more pregnancies were achieved using the LHRH agonist+FSH combination (4 vs. 1). It is suggested that 2 weeks' suppression of ovarian androgens with LHRH agonist is not sufficient to neutralize the unfavourable intraovarian mechanisms interfering with normal folliculogenesis. More data are required to confirm the superiority of LHRH agonist pretreatment in the management of polycystic ovarian syndrome.
Asunto(s)
Andrógenos/sangre , Hormona Folículo Estimulante/uso terapéutico , Hormona Liberadora de Gonadotropina/análogos & derivados , Menotropinas/uso terapéutico , Inducción de la Ovulación/métodos , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Androstenodiona/sangre , Anovulación/etiología , Deshidroepiandrosterona/sangre , Estradiol/sangre , Femenino , Hormona Liberadora de Gonadotropina/uso terapéutico , Humanos , Hormona Luteinizante/sangre , Luteolíticos/sangre , Hipófisis/efectos de los fármacos , Hipófisis/metabolismo , Síndrome del Ovario Poliquístico/complicaciones , Globulina de Unión a Hormona Sexual/análisis , Testosterona/sangre , Pamoato de TriptorelinaRESUMEN
1. Following single intramuscular doses of [14C]fluprostenol (0.5--2.4 micrograms/kg) to three female horses and to three gelded male horses, radioactivity was present in the plasma within 5 min; peak concn. (0.32--1.30 ng/ml fluprostenol equiv.) occurred 5 to 90 min after injection. Radioactivity was still present in the plasma of the females after three days. About 88% of fluprostenol is bound to plasma proteins. 2. Radioactivity was present in the parotid saliva of the gelded male horses within 10 min. Peak concn. (45--91 pg/ml fluprostenol equiv.) occurred from 5 min to 1 h after injection. Saliva : plasma concn. ratios varied inversely with saliva flow rate and limiting ratios were 0.33 and 0.41 for the combined results of two experiments on each of two male horses; the calculated value is 0.46 Chromatography indicated that the majority of plasma and saliva radioactivity was [14C]fluprostenol. 3. Excretion of radioactivity in the urine was rapid and virtually complete 12 h after dosing. The total radioactivity excreted in urine by the female horses was 45% of the dose (96 h) and by the gelded male horses 53% (30 h). About 30% of the radioactivity present in the urines was unchanged fluprostenol. 4. Faecal excretion, which was substantially complete after 2 days, accounted for 32% of the radioactivity administered to the female horses. 5. Tissue conc. of radioactivity in the female horses at four days were below the limits of detection (90 pg/g), but 0.2--0.9% of the dose was detected at the site of injection.