Efficacy of low-dose human chorionic gonadotropin (hCG) in a GnRH antagonist protocol.
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PURPOSE: To examine the efficacy of low-dose hCG using a GnRH antagonist protocol. METHODS: Prospective randomized study was performed at the Kyono Ladies Clinic. One hundred ninety-two women (<40 -years old, <3 previous cycles) were randomly assigned to GnRH agonist (buserelin) long protocol (LP, n = 66), GnRH antagonist (cetrorelix) with no low-dose hCG protocol (NhCGP, n = 63), or GnRH antagonist with low-dose hCG protocol (hCGP, n = 63). RESULTS: The hCGP was associated with reduced total amounts of FSH, increased oocyte maturation rate, high-quality day 3 embryos rate, and number of frozen embryos. Ovarian hyperstimulation syndrome (OHSS) tended to be lower in the GnRH antagonist protocol. Pregnancy and implantation rates did not differ significantly between study groups. CONCLUSIONS: Daily low-dose hCG supplementation in the late follicular phase could improve the outcome in FSH based-GnRH antagonist protocol. This protocol, however, does require further modifications, including determination of the optimal doses for hCG and gonadotropin pretreatment. (+info)
Outcome of frozen-thawed blastocysts derived from gonadotropin releasing hormone agonist or antagonist cycles.
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PURPOSE: The aim of this retrospective study was to compare the outcome of frozen-thawed blastocysts derived from the cycles using controlled ovarian stimulation with GnRH agonists vs. GnRH antagonists. METHODS: Survival, pregnancy and cumulative live birth rates in 231 freeze-thaw cycles derived from the GnRH agonist cycles (GnRH agonist group), and in 175 freeze-thaw cycles derived from the GnRH antagonist cycles (GnRH antagonist group) were compared. RESULTS: In the GnRH agonist group significantly higher proportion of blastocysts survived the thawing procedure than in the GnRH antagonist group (86.1% versus 78.5%; p < 0.01). The differences in cumulative live birth rates did not differ significantly between the groups: in the GnRH agonist group the cumulative live birth rate was 16.5%, and in the GnRH antagonist group it was 14.2%. CONCLUSIONS: Frozen-thawed blastocysts derived from the GnRH agonist cycles have better survival rates and similar cumulative live birth rates than those derived from the GnRH antagonist cycles. (+info)
Specializations of a G-protein-coupled receptor that appear to aid with detection of frequency-modulated signals from its ligand.
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The primate GnRH receptor (GnRHR) is a GPCR (G-protein-coupled receptor) that transduces both amplitude- and frequency-modulated signals; each modality conveys information that regulates primate reproduction. Slower GnRH pulses favor release (and higher circulating levels) of pituitary FSH, while faster pulses favor LH release. We used radioligand binding and inositol phosphate production (a measure of G-protein coupling) in association with mutational analysis to identify the impact of evolved sequence specializations that regulate receptor concentration at the plasma membrane and Kd in primate GnRHRs. Our results show that mutations appear to provide a mechanism that allows independent adjustment of response sensitivity and squelching (suppression) of low-level signals (noise), both desirable features for recognition of frequency-modulated signals. We identify specific amino acid residues that appear to be involved in these processes. This investigation occurred in light of recent observations that restriction of GnRHR plasma membrane expression developed under strong convergent pressure and concurrently with the complex pattern of cyclicity associated with primate reproduction. The findings present an evolved means for increased effectiveness of detection of a frequency-modulated signal and provide a strategy to identify similar mechanisms in other receptors. (+info)
Adrenalectomy attenuates the effect of chemical castration on energy balance in rats.
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The individual and combined influences of castration and adrenalectomy on energy balance in rats were investigated in a 2 x 2 factorial design. Castration was chemically achieved by treating rats with Buserelin, a gonadotropin-releasing hormone (GnRH) agonist. During the treatment, the rats were weighed every 2 or 3 d, and the total amount of food consumed was determined. At the end of the 14-d treatment period, rats were killed and their carcasses were analyzed for protein, fat and energy content. In the sham-operated groups, body weight gain was greater in Buserelin-treated rats than in saline-infused animals. However, in the adrenalectomized rats, there was no difference in body weight gain between the Buserelin- and saline-infused animals. In sham-operated groups, body protein and body fat gains were significantly larger in Buserelinthan in saline-infused animals. In saline-infused groups, protein gain was greater in adrenalectomized than in sham-operated animals. On the other hand, in the Buserelin-infused rats, there was no difference in the protein gain between the adrenalectomized and sham-operated rats. The adrenalectomized groups of rats ate less and deposited less fat and energy than their respective sham-operated counterparts. In the sham-operated groups, both the intake and the gain of energy were larger in the Buserelin-treated than in saline-infused rats. The present study indicates that adrenalectomy can significantly attenuate the influence of castration on energy gain, providing evidence that adrenals and ovaries can interact in the regulation of energy balance. (+info)
Induction of ovulation with GnRH and PGF(2 alpha) at two different stages during the early postpartum period in dairy cows: ovarian response and changes in hormone concentrations.
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The aims of this study were 1) to determine whether dairy cows can be induced to ovulate by the treatment with gonadotropin releasing hormone (GnRH) followed by prostaglandin F(2 alpha) (PGF(2 alpha)) during the early postpartum period and 2) to describe their ovarian and hormonal responses according to ovarian status. Cows were divided in two groups and received 10 microg of buserelin followed by 500 microg of cloprostenol 7 days apart starting from 21 (GnRH21, n=7) or around 37 days postpartum (GnRH37, n=7). The groups were further classified according to presence (-CL) or absence (-NCL) of functional corpora lutea (CL) on the day of GnRH treatment (d 0): GnRH21-NCL (n=4), GnRH21-CL (n=3) and GnRH37-CL (n=7). Ovarian morphology was monitored and the concentrations of P(4), E(2), FSH and insulin-like growth factor 1 (IGF-1) were measured. All cows ovulated after administration of GnRH. The P(4) levels of the GnRH21-NCL group from d 0 to d 5 were lower than those of the GnRH21-CL (P<0.05) and GnRH37-CL groups (P<0.01). In contrast, the E(2) levels of the GnRH21-NCL group within d 2 to d 6 were higher (P<0.05) than those of the other groups. Compared with the GnRH37-CL group, the GnRH21-NCL group had more small follicles on d 2 (P<0.05), d 3 (P<0.01) and d 4 (P<0.01) and more large follicles on d 5 (P<0.05). The induced CL and new ovulatory follicles were larger in the GnRH21-NCL group compared with the GnRH21-CL (P<0.001 and P<0.01) and GnRH37-CL groups (P<0.001 and P<0.05). IGF-1 did not differ among the groups. The GnRH21-NCL group had higher FSH levels than the GnRH21-CL (P<0.01) and GnRH37-CL groups (P<0.001) on d 0. Low P(4) and high FSH levels may suggest higher gonadotropin support on the enhanced ovarian morphology of the GnRH21-NCL group. PGF(2 alpha) treatment induced CL regression and subsequent ovulation in 3/4 (75%), 3/3 (100%) and 7/7 (100%) cows in the GnRH21-NCL, GnRH21-CL and GnRH37-CL groups, respectively. In conclusion, a 7-day GnRH-PGF(2 alpha) synchronization protocol can effectively induce dairy cows to ovulate as early as 21 days postpartum, regardless of ovarian status. (+info)
Clinical outcome with half-dose depot triptorelin is the same as reduced-dose daily buserelin in a long protocol of controlled ovarian stimulation for ICSI/embryo transfer: a randomized double-blind clinical trial (NCT00461916).
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BACKGROUND: Traditional doses of depot GnRH agonist may be excessive for ovarian stimulation. We compared half-dose depot triptorelin (Group I) with reduced-dose daily buserelin (Group II) in a long protocol ICSI/embryo transfer through a double-blind randomized clinical trial. METHODS: Controlled ovarian stimulation (COS) was started by a pretreatment with oral contraceptives for 21 days. Then, 182 patients were randomized into two groups of 91. Group I received 1.87 mg triptorelin depot i.m. followed by daily s.c. injections of saline. Group II (reduced-dose protocol) received a bolus injection of i.m. saline followed by daily s.c. injections of 0.5 mg buserelin, which was then reduced to 0.25 mg at the start of human menopausal gonadotrophin stimulation. When transvaginal ultrasound showed at least two follicles of 16-20 mm diameter, HCG was given and ICSI was performed 40-42 h later. RESULTS: No significant differences were seen in the mean (SD) number of follicles at HCG administration, as our primary outcome [10.3 (4.4) in Group I versus 11.1 (4.2) in Group II, P = 0.180, mean difference = 0.86, 95% confidence interval 0.39-2.11]. The other early results of COS, clinical and ongoing pregnancy rates, or early pregnancy loss were also not significantly different between the groups. Group I endured longer stimulation period [11.2 (1.8) days versus 10.6 (1.9), P = 0.030]. CONCLUSIONS: Clinical outcomes were not significantly different between Group I and Group II. (+info)
Effects of an agonist of gonadotropin-releasing hormone on ovarian follicles in cattle.
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Three experiments were conducted to examine effects of Buserelin, a potent agonist of gonadotropin-releasing hormone, on characteristics of ovarian follicles in cycling cows and heifers. In experiment 1, heifers were injected once with 10 micrograms Buserelin on Day 11, 12, or 13 of the estrous cycle (estrus = Day 0), or once with 20 micrograms of Buserelin on Day 12. Additionally, two groups were injected with a luteolytic dose of prostaglandin F2 alpha (PGF2 alpha) on Day 13 preceded with or without a Buserelin injection (10 micrograms) on Day 12. A control group did not receive a Buserelin injection. Ovaries were recovered and weighed after animals were slaughtered on Day 15. Follicle diameters were measured with calipers. Follicles for all experiments were classified as small (class 1: 3-5 mm diameter), medium (class 2: 6-9 mm), or large (class 3: greater than 9 mm). Heifers receiving only Buserelin had an increased number of medium-sized follicles compared to controls. Buserelin injection administered 24 h before PGF2 alpha reduced the decline in the average weight of the ovaries containing the corpus luteum (7.8 g for Buserelin before PGF2 alpha vs. 6.7 g for no Buserelin before PGF2 alpha). Buserelin pretreatment appeared to delay or prevent complete luteolysis by the injected PGF2 alpha. In experiment 2, 0, or 10 micrograms Buserelin was injected on Day 12 and follicle development was monitored by ultrasonography in situ from Day 12 to estrus. Follicles also were classified as clear or cloudy; cloudy was associated with flocculent material in the follicular fluid or with an indistinct follicular wall.(ABSTRACT TRUNCATED AT 250 WORDS) (+info)
Randomised trial of chemotherapy versus endocrine therapy in patients presenting with locally advanced breast cancer (a pilot study).
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Sixty patients with locally advanced breast cancer, but with no evidence of distant metastases were randomised to receive primary endocrine therapy or chemotherapy after assessment and 'Trucut' biopsy of the primary tumour. After 12 weeks all patients were assessed. Eight out of 30 (27%) of the patients who received chemotherapy showed complete clinical regression of the primary cancer, eight patients' tumours had regressed by more than 50%, and ten showed a 25-50% reduction in bi-dimensional diameter. Only four (13%) patients' tumours failed to reduce in size. Seven patients were judged to require mastectomy at the end of the 12 week period of treatment with chemotherapy. In contrast, only three out of 30 (10%) patients receiving endocrine therapy showed a greater than 50% reduction in tumour size, and four patients had a 25-50% reduction at 12 weeks. The remaining patients' tumours either stabilised (12 patients) or enlarged (11 patients). We conclude that primary chemotherapy in patients with primary breast cancer is more effective in rapidly reducing the size of the primary breast cancer than endocrine therapy (P = 0.001) and alters significantly the future management of these patients. However, at 65 weeks on completion of the follow-up, there is no significant difference in the number of patients' disease-free, locally or distant recurrent, or dead. (+info)