scholarly journals 224FOLLICULAR GROWTH IN SHEEP SUPEROVULATED WITH FSH AFTER PRE-TREATMENT WITH GNRH ANTAGONISTS

2004 ◽  
Vol 16 (2) ◽  
pp. 233 ◽  
Author(s):  
C. Lopez-Alonso ◽  
T. Encinas ◽  
A. Veiga-Lopez ◽  
R.M. Garcia-Garcia ◽  
J.M. Ros ◽  
...  
Keyword(s):  
Single Dose ◽  
Gnrh Antagonist ◽  
Statistical Significance ◽  
Ovarian Response ◽  
Significant Rise ◽  
Current Data ◽  
High Dose ◽  
Gnrh Antagonists ◽  
Short Period ◽  
Pre Treatment

In sheep, the injection of a single dose of 1.5mg of the GnRH antagonist Teverelix (Antarelix™, Zentaris, Frankfort, Germany) eliminates large dominant follicles and increases the number of smaller follicles (2–3mm in size) in a short period of time (Lopez-Alonso et al., 2003. Reprod. Abstr. Ser., 30:71). This treatment would be beneficial for increasing the efficiency of ovarian stimulatory protocols, since embryo output is enhanced in the presence of a high number of small follicles, coincidentally with the absence of large follicles, at starting the FSH treatment. However, possible effects of this single high dose of GnRH antagonist on the capacity of follicles to develop in response to FSH treatments has not been determined. In this study, we have characterized patterns of follicular development during a superovulatory treatment with purified ovine FSH (Ovagen™, ICPbio, Auckland, NZ) in sheep treated i.m. with 1.5mg of Antarelix (n=6) or saline (n=4) on Day 9 after the insertion of a progestagen sponge (Chronogest®, Intervet Int, Boxmeer, The Netherlands). Ewes were superovulated with eight decreasing doses (1.5×3, 1.25×2 and 1×3mL) of Ovagen™ injected twice daily from Day 12 of sponge insertion. Number and size of all >2-mm follicles was determined by transrectal ultrasonography just prior to every FSH injection from the first dose to the withdrawal of progestagen sponges. At the start of the gonadotrophin treatment on Day 12, ewes treated with GnRH antagonist showed a higher number of 2–3mm follicles than control ewes (16.2±3.8 v. 5.3±0.3, P<0.05), and a lower number of >4mm follicles (2.2±0.5 v. 5.0±0.6, P<0.01). Thereafter, administration of Ovagen™ induced a significant rise in the number of >4mm follicles at sponge removal in both groups (P<0.0005 for treated ewes and P<0.01 for controls). This number was higher in females treated with GnRH antagonist than in control sheep, although differences did not reach statistical significance (19.3±3.8 v. 12.7±5.4). Current data confirm that administration of a single dose of GnRH antagonist decreases presence of large follicles and increases the number of smaller follicles at the first day of FSH injection. This pre-treatment does not affect competence of follicles to grow in response to superovulatory FSH treatments. Moreover, the number of preovulatory follicles at sponge removal was higher than in untreated ewes. We conclude that the pre-treatment with a single dose of 1.5mg of Antarelix™ on Day 9 of sponge insertion, three days before starting the FSH treatment in a superovulatory protocol, might increase the ovarian response and, thereafter, the yields of follicles.

scholarly journals 101 OVARIAN RESPONSE AND DEVELOPMENTAL COMPETENCE OF OOCYTES COLLECTED BY OPU IN SHEEP TREATED WITH GnRH ANTAGONIST

2005 ◽  
Vol 17 (2) ◽  
pp. 201
Author(s):  
F. Berlinguer ◽  
A. Gonzalez-Bulnes ◽  
S. Succu ◽  
G. Leoni ◽  
I. Rosati ◽  
...  
Keyword(s):  
Single Dose ◽  
Gnrh Antagonist ◽  
Ovarian Response ◽  
Blastocyst Stage ◽  
Developmental Competence ◽  
Control Group ◽  
Gnrh Antagonists ◽  
Group A ◽  
Group B

The use of a single dose of GnRH antagonists during the progestagen treatment prior to superovulatory treatment protocols in sheep increases the number of smaller follicles able to grow and ovulate in response to the exogenous FSH treatment (Lopez-Alonso C et al. 2004 Reprod. Fertil. Dev. 16, 233). The aim of our study was to test if such treatment affects the in vitro developmental competence of oocytes collected by ovum pick up (OPU) from GnRH-antagonist treated sheep during an ovarian by perstimulation protocol. Adult Sarda sheep (n = 18) were synchronized by the insertion of intravaginal sponges (Day 0) which were left in situ for 12 days; on Day 7, group A (n = 10) received a single dose of 3 mg of Antarelix (Teverelix, Europeptides, France) s.c., while group B (n = 8) served as control. All animals received 96 IU of FSH (Ovagen, ICP, New Zealand) administered in 4 equal doses given i.m. every 12 h starting on Day 10. Twelve hours after the last FSH administration oocytes were collected by OPU technique. Follicular growth was monitored by transrectal ultrasonography from Day 7 to Day 11. Collected oocytes were matured, fertilized, and cultured in vitro up to blastocyst stage under standard conditions used in our laboratory (Berlinguer F et al. 2004 Theriogenology 61, 1477–1486). After IVF, uncleaved oocytes were stained with acetolacmoid to evaluate chromatin configuration, while the cleaved ones were cultured in SOF + 0.4% BSA up to the blastocyst stage. Data were analyzed by ANOVA statistical analysis after arcsine transformation of the value percentages. Ultrasonographic monitoring showed a significant increase in the number of follicles (mean ± SEM) present in the ovaries from Day 8 to Day 11 of treatment in group A compared to group B (Day 8: 19 ± 5.1 vs. 13 ± 3.4, P > 0.05; Day 9: 20.1 ± 4.6 vs. 14.1 ± 2.4, P > 0.001; Day 10: 22.5 ± 6.1 vs. 14.7 ± 2.7, P > 0.001; Day 11: 25.3 ± 5.1 vs. 20.5 ± 4.1, P > 0.05), thus confirming that GnRH antagonist administration enhances ovarian response to exogenous FSH stimulation. On the other hand, oocytes collected from untreated sheep lead to a higher blastocyst output (P = 0.014), as illustrated in the table. These results indicated that although GnRH antagonist administration caused a significant increase in the ovarian response to the hormonal treatment, the final blastocyst output was significantly lower compared to that of the control group. This finding seems to suggest an impairment in the developmental competence of treated sheep oocytes. Table 1. In vitro maturation, fertilization, and developmental capacity of oocytes collected from follicles of GnRH antagonist-treated (group A) and untreated (group B) sheep This work was supported by funds from the Spanish MEC (projects SC 00-051-C3.1 and HI2002-0004) and the Italian MIUR (cofin).

scholarly journals 220ENDOCRINE AND OVARIAN FUNCTION AFTER GNRH ANTAGONIST TREATMENTS IN GOATS

2004 ◽  
Vol 16 (2) ◽  
pp. 231 ◽  
Author(s):  
A. Gonzalez-Bulnes ◽  
J. Santiago Moreno ◽  
R.M. Garcia-Garcia ◽  
C.J.H. Souza ◽  
A. Lopez-Sebastian ◽  
...  
Keyword(s):  
Gnrh Antagonist ◽  
Ovarian Function ◽  
Ovarian Response ◽  
Developmental Competence ◽  
Gnrh Antagonists ◽  
Inhibin A ◽  
Beneficial Effects ◽  
Gonadotrophin Secretion ◽  
Pituitary Secretion ◽  
Ovulatory Period

In goats, as in other mammals, the use of treatment with GnRH antagonists (GnRHa) inhibits gonadotrophin secretion, causing a suppression of the growth of large ovarian follicles. Thus, GnRHa treatment could be useful to decrease the effects of dominant follicles prior to ovarian stimulation, increasing the number of gonadotrophin-responsive follicles at the start of FSH treatments and improving the ovarian response in terms of transferable embryos. However, in goats, the beneficial effects of this treatment is annulled by a high number of unfertilised ova and degenerated embryos (2003, Cognie et al., Theriogenology 59, 171–188), which suggests deficiencies in oocyte developmental competence per se or induced by endocrine or follicular alterations during the peri-ovulatory period. We have tested whether these failures can be related to a prolongation of gonadotrophin down-regulation and/or alterations in follicular function after cessation of the antagonist, during the period of administration of the superovulatory treatment, around 4 days after the end of GnRHa treatment. A total of 15 does received 45-mg FGA intravaginal sponges (Chronogest®, Intervet Int, H), the first group of 10 females were treated with daily injections of 0.5mg of the GnRHa Teverelix (Antarelix™, Zentaris, G) for 6 days from Day 5 of sponge insertion, while five does acted as controls receiving saline. Endocrine and ovarian function were monitored daily from Day −5 to Day 4 (Day 0=day of last GnRHa injection). Pituitary activity was determined by measuring plasma FSH and LH, and follicular activity by ultrasonographic monitoring of all >2mm follicles and by assessing plasma inhibin A levels. During GnRH antagonist treatment, the mean plasma LH concentration was lower in treated than control goats (0.5±0.2 v. 0.7±0.5ng/mL, P<0.0005); however, the FSH levels remained unaffected (0.8±0.4 v. 0.8±0.5ng/mL). In this period, treated does also showed an increase in the number of small follicles 2–3mm in size (10.7±0.7 v. 8.4±0.6, P<0.05), and a decrease in both the number of follicles >4mm in size (5.0±0.3 v. 6.8±0.5, P<0.005) and the secretion of inhibin A (120.9±10.7 v. 151.6±12.6pg/mL, P<0.05). After GnRHa treatment, LH levels increased in treated goats from the day after the last Teverelix injection (Day 1), so that LH levels were the same as controls on Day 3 (0.6±0.1 v. 0.6±0.2ng/mL). However, there were even greater numbers of small follicles than during the period of GnRHa treatment (15.4±0.6 in treated v. 8.9±0.7 in control, P<0.0005). Moreover, the number of follicles >4mm in size and the secretion of inhibin A remained lower in treated goats (3.9±0.3 follicles and 84.4±7.0pg/mL v. 5.4±0.5 follicles, P<0.05 and 128.9±14.2pg/mL, P<0.05). These results indicate that pituitary secretion of gonadotrophins is restored shortly after the end of GnRHa treatment, but the number of follicles and the secretion of inhibin A are affected. This may be relevant to the failures in ovulation and/or fertilization reported for superovulatory protocols with GnRHa pre-treatments in goats.

scholarly journals Evaluation of GnRH antagonist pre-treatment before ovarian stimulation in a delayed-start antagonist protocol in normal ovulatory women undergoing IVF/ICSI: a randomized controlled trial (RCT)

2021 ◽  
Author(s):  
Yisheng Zhang ◽  
Liling Liu ◽  
Jie Qin ◽  
Hongyi Huang ◽  
Lintao Xue ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Live Birth ◽  
Pregnancy Outcomes ◽  
Gnrh Antagonist ◽  
Controlled Trial ◽  
Statistical Significance ◽  
Control Group ◽  
Gnrh Antagonist Protocol ◽  
Pre Treatment ◽  
Antagonist Protocol

Abstract Background: Synchronization of follicles is key to improving ovulation stimulation with the GnRH antagonist protocol. GnRH antagonist administration in the early follicular phase can quickly decrease gonadotrophin (Gn) levels and achieve downregulation before stimulation, which improves synchronization. A small RCT showed that pre-treatment with a GnRH antagonist for three days before stimulation might increase oocyte retrieval but cannot increase the pregnancy rate. This study investigated whether the "delayed-start" protocol in ovulatory women can increase the synchronization of follicles and pregnancy outcomes compared with the conventional GnRH antagonist protocol.Methods: This RCT included 136 normal ovulatory women undergoing IVF/ICSI. Both groups were treated with recombinant FSH (r-FSH) and a flexible GnRH antagonist protocol. The women were randomized into two equal groups with or without GnRH antagonist from day 2 of the menstrual cycle. Our primary outcome was the number of oocytes retrieved. Secondary outcomes included the pregnancy and live birth rates.Results: Both groups had similar baseline characteristics. The number of oocytes retrieved in the study group was comparable to that in the control group (9.5(8.0-13.0) vs. 11.0(7.0-14.8),P=0.469). There was no statistical significance among the follicular size differences. The fertilization rate, number of good-quality embryos, implantation rate, pregnancy rate, ongoing pregnancy rate, live birth rate per ET cycle, and miscarriage rate were all similar between the two groups.Conclusion: This large RCT analysed the "delayed-start" GnRH antagonist protocol applied to normal ovulatory women performing IVF/ICSI. The number of oocytes retrieved and pregnancy outcomes did not vary significantly. Future trials need to confirm these findings.Trial registration: Chinese Clinical Trial Registry, ChiCTR1800019730. Registered 26 November 2018,http://www.chictr.org.cn/showproj.aspx?proj=29969.

Mobilisation of Autologous Stem Cells Using a Single Fixed Dose Injection of Pegfilgrastim; Feasibility in Extensively Pre-Treated Lymphoma and Myeloma Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5220-5220 ◽  
Author(s):  
Paula F. Ypma ◽  
Arif A. Muradin ◽  
P.W. Wijermans
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Single Dose ◽  
Optimal Dose ◽  
Fixed Dose ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Pre Treatment

Abstract In patients with multiple myeloma and refractory or relapsed lymphoma consolidation high-dose chemotherapy combined with stem cell rescue is an established therapy in chemosensitive disease. A commonly used approach to mobilise CD34+ haematopoietic stem cells is the administration of granulocyte colony-stimulating factor following a course of chemotherapy. Pegylation of filgrastim decreases renal clearance of the molecule. Pegfilgrastim is subject to a distinct method of clearance compared to filgrastim. The clearance therefore depends almost solely on a neutrophil receptor mediated process. This means clearance is self-regulated and increases when the number of neutrophils with G-CSF receptors augments in the blood. In earlier series of patients, pegfilgrastim showed to be effective in mobilising blood progenitor cells in single fixed doses of 6 mg. as well as 12 mg. The optimal dose and scheduling of the injection and apheresis is not completely established in various patients groups with diverse extents of chemotherapeutic pre-treatment. In this study we compared the mobilisation kinetics of patients with different haematological malignancies using either filgrastim or one injection of pegfilgrastim in two different doses. 58 patients with various indications for autologous stem cell transplantation were studied. The transplantation indications were multiple myeloma, NHL and Hodgkin’s lymphoma. Patients received a single dose of either 6 mgs or 12 mgs of pegfilgrastim; a third group of patients was treated with filgrastim daily. Filgrastim administration was stopped as soon as sufficient numbers of stem cells were harvested. Harvesting in both groups started as soon as an absolute CD 34+ count of >1 × 107 per litre was reached. The required number of stem cells was 3 × 106/kg bodyweight (6 × 106/kg in multiple myeloma patients). Mobilisation kinetics and apheresis results were compared in the three groups. The one-way analysis of variance (ANOVA) was used to compare the data. 26 Patients received a single dose of 6 mgs pegfilgrastim and 10 patients received a dose of 12 mgs of pegfilgrastim. 22 Patients, matched for disease type and pre-treatment regimens, age and gender received filgrastim daily. The filgrastim was administered in an average total dose of 4,2 mgs. (7,7 m gr./kg/day). Table 1 shows results of the apheresis. Of 26 patients who received pegfilgrastim 6 mgs, 5 patients showed a failure mobilising stemcells (21%). In 2 of those 5 patients harvesting succeeded eventually after additional stimulation with filgrastim and another 2 patients were mobilised in a later stage after additional chemopriming and filgrastim in high dosage. One of the patients receiving 12 mgs. of pegfilgrastim also needed additional filgrastim administration. None of the filgrastim mobilisation procedures failed. The results indicate that a single dose pegfilgrastim of 6 mgs is not capable of mobilising sufficient peripheral blood stem cells in all patients. In this study, both doses of pegfilgrastim showed a reduced CD34 cells harvest and less efficient apheresis procedures. Table 1: Results Apheresis pegfilgrastim pegfilgrastim filgrastim 6 mg (n=26) 12 mg (n=10) (n=22) * p<0,05 day 1st apheresis, mean (SD) * 12.2 (1.4) 12.1 (0.9) 13.5 (2.4) max. blood CD34+ count (×107/L), mean (SD) 8.6 (7,7) 7.9 (6,6) 11.6 (10) number CD34+ cells (×106/kg), mean (SD) 8.2 (4.6) 8 (2,5) 11 (6,2) number CD34+ cells (×106/kg)per litre proc. volume, mean (SD) * 440 (290) 461 (350) 797 (650) failure apheresis 5 1 0

scholarly journals Fixed Versus Flexible Antagonist Protocol in Women with Predicted High Ovarian Response except PCOS : A Randomized Controlled Trial

2020 ◽  
Author(s):  
Xiu Luo ◽  
Li Pei ◽  
Fujie Li ◽  
Chunli Li ◽  
Guoning Huang ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Treatment Duration ◽  
Gnrh Antagonist ◽  
Controlled Trial ◽  
Ovarian Response ◽  
Gnrh Antagonists ◽  
Vitro Fertilization ◽  
Randomized Controlled ◽  
Significant Difference

Abstract Background: No previous study directly compares the fixed day-5 initiation versus the flexible initiation of GnRH antagonist administration in IVF/ICSI for those patients who are predicted as high ovarian responders without PCOS. To evaluate whether the number of oocytes retrieved is different by using the two GnRH antagonist protocols in Chinese women with predicted high ovarian response except PCOS.Methods: A randomized controlled trial of 201 infertile women with predicted high ovarian response except PCOS undergoing in vitro fertilization. Ovary stimulation was performed using recombinant FSH and GnRH antagonists. GnRH antagonist ganirelix (0.25 mg/d) was started either on day 5 of stimulation (fixed group) or when LH was >10 IU/L, and/or a follicle with mean diameter >12 mm was present, and/or serum E2 was >300pg/ml. Patient monitoring was initiated on day 3 of stimulation in flexible group.Result(s): No significant difference was observed between the fixed and flexible groups regarding the number of oocyte retrieved(16.72±7.25 vs. 17.47±5.88, P=0.421), the Gonadotropin treatment duration(9.53±1.07 vs. 9.67±1.03, P=0.346)and total Gonadotropin dose(1427.75±210.6 vs. 1455.94±243.44, P=0.381). GnRH antagonist treatment duration in fixed protocol was statistically longer than the flexible protocol (6.57±1.17 vs 6.04±1.03, P=0.001). There was no premature LH surge in either protocol. Conclusion(s): Fixed GnRH antagonist administration on day 5 of stimulation appear to achieve a comparable oocyte retrieved compared with flexible antagonist administration.Trial registration: NCT02635607 posted on December 16, 2015 in clinicaltrials.gov.

Effects of administration of testosterone and gonadotrophin-releasing hormone (GnRH) antagonist on basal and GnRH-stimulated gonadotrophin secretion in orchidectomized monkeys

1991 ◽  
Vol 129 (3) ◽  
pp. 363-370 ◽  
Author(s):  
S. Khurshid ◽  
G. F. Weinbauer ◽  
E. Nieschlag
Keyword(s):  
Gnrh Antagonist ◽  
Combined Treatment ◽  
High Dose ◽  
Similar Response ◽  
Primate Model ◽  
Gnrh Antagonists ◽  
Releasing Hormone ◽  
Gonadotrophin Secretion ◽  
Gonadotrophin Releasing Hormone ◽  
Range Study

ABSTRACT The aim of the present investigation was to investigate the effects of testosterone on basal and gonadotrophin-releasing hormone (GnRH)-stimulated gonadotrophin secretion in the presence and absence of a GnRH antagonist in a non-human primate model (Macaca fascicularis). Orchidectomized animals were used in order to avoid interference by testicular products other than testosterone involved in gonadotrophin feedback. Concomitant and delayed administration of testosterone at doses that provided serum levels either within the intact range (study 1) or markedly above that range (study 2) did not influence the suppression of basal gonadotrophin release induced by the GnRH antagonist during a 15-day period. To assess the possible effects of testosterone treatment at the pituitary level (study 3) GnRH stimulation tests (500 μg) were performed before and on days 8 and 15 of treatment with high-dose testosterone and GnRH antagonist alone or in combination. Testosterone alone abolished the gonadotrophin responses to exogenous GnRH observed under pretreatment conditions. With GnRH antagonist alone, an increased responsiveness (P <0·05) to GnRH was seen on day 8 and a similar response compared with pretreatment on day 15. Following combined treatment with GnRH antagonist and testosterone, GnRH-induced gonadotrophin secretion was consistently lower compared with that after GnRH antagonist alone (P <0·05), but was increased compared with that after testosterone alone (P<0·05). Thus, in the presence of a GnRH antagonist the feedback action of testosterone on LH and FSH was diminished. The present work in GnRH antagonist-treated orchidectomized monkeys demonstrates that (I) unlike in rats, testosterone fails to stimulate FSH secretion selectively, (II) the negative feedback action of testosterone on GnRH-stimulated LH and FSH secretion is altered in the presence of a GnRH antagonist and (III) GnRH antagonists induce a transient period of increased responsiveness of gonadotrophic hormone release to exogenous GnRH. The observation that a GnRH antagonist reduced the feedback effects of testosterone suggests that testosterone action on pituitary gonadotrophin release, at least in part, is mediated via hypothalamic GnRH. Journal of Endocrinology (1991) 129, 363–370

Can testosterone alone maintain the gonadotrophin-releasing hormone antagonist-induced suppression of spermatogenesis in the non-human primate?

1994 ◽  
Vol 142 (3) ◽  
pp. 485-495 ◽  
Author(s):  
G F Weinbauer ◽  
A Limberger ◽  
H M Behre ◽  
E Nieschlag
Keyword(s):  
Gnrh Antagonist ◽  
High Dose ◽  
Partial Recovery ◽  
Primate Model ◽  
Gnrh Antagonists ◽  
Releasing Hormone ◽  
Testosterone Substitution ◽  
Gonadotrophin Releasing Hormone ◽  
Group 2 ◽  
Human Primate

Abstract The combination of gonadotrophin-releasing hormone (GnRH) antagonist and delayed testosterone substitution provides a promising approach towards male contraception. However, the GnRH antagonists used clinically so far cause side-effects and have to be administered continuously. We therefore used the non-human primate model to see whether the GnRH antagonist cetrorelix (which exhibits a favourable benefit-to-risk ratio in terms of anti-gonadotrophic action in normal men) induces complete and reversible suppression of spermatogenesis and whether GnRH antagonist-induced suppression of spermatogenesis can be maintained by testosterone alone. Four groups of adult cynomolgus monkeys (Macaca fascicularis; five per group) were injected daily with 450 μg cetrorelix/kg ([N-acetyl-d-2-naphthyl-Ala1, d-4-chloro-Phe2, d-pyridyl-Ala3, d-Cit6, d-Ala10]-GnRH). Group 1 received the GnRH antagonist for 7 weeks followed by vehicle administration for another 11 weeks; group 2 was treated with GnRH antagonist for the entire 18 weeks with each animal receiving a single testosterone implant during weeks 11–18 to restore the ejaculatory response to electrostimulation; group 3 received the GnRH antagonist for 18 weeks and testosterone buciclate (TB) was injected during week 6 of GnRH antagonist treatment; group 4 was subjected to GnRH antagonist administration for 7 weeks and received TB (200 mg/animal) during week 6. Under GnRH antagonist treatment alone serum concentrations of testosterone were suppressed. TB maintained testosterone levels two- to fourfold above baseline levels in groups 3 and 4 and prevented the recovery of LH secretion for about 20 weeks after GnRH antagonist withdrawal, whereas inhibin levels increased significantly from week 8 onwards. Group 2 animals were azoospermic during weeks 12–18 of GnRH antagonist administration. The TB-replaced groups developed azoospermia or became severely oligozoospermic. Quantitation of cell numbers by flow cytometry during weeks 6 and 18 revealed that TB (groups 3 and 4) had prevented a further decline of germ cell production compared with group 2 but had maintained the spermatogenic status present at week 6 (onset of TB substitution). All inhibitory effects of cetrorelix and/or TB were reversible after cessation of treatment. These findings demonstrate that cetrorelix reversibly inhibits spermatogenesis in a non-human primate model. Although TB maintained the GnRH antagonist-induced suppression of spermatogenesis, azoospermia was not achieved. This latter effect may reflect either a direct spermatogenesis-supporting effect of the high dose of TB or the partial recovery of inhibin secretion (indirectly reflecting FSH secretion) or a combination of both. Thus, maintenance of GnRH antagonist-induced spermatogenic inhibition by testosterone alone appears theoretically possible. Whether this regimen will, however, permit the induction of sustained azoospermia remains to be seen, preferably in human studies. Journal of Endocrinology (1994) 142, 485–495

Seven-day administration of the gonadotropin-releasing hormone antagonist Cetrorelix in normal cycling women

1994 ◽  
Vol 131 (3) ◽  
pp. 280-285 ◽  
Author(s):  
Lieselotte Sommer ◽  
Kerstin Zanger ◽  
Thomas Dyong ◽  
Christoph Dorn ◽  
Johannes Luckhaus ◽  
...  
Keyword(s):  
Side Effects ◽  
Sigmund Freud ◽  
Gnrh Antagonist ◽  
Treatment Cycle ◽  
Day Treatment ◽  
Gonadotropin Releasing Hormone ◽  
High Dose ◽  
Gnrh Antagonists ◽  
Blood Samples ◽  
Releasing Hormone

Sommer L, Zanger K, Dyong T, Dorn C, Luckhaus J, Diedrich K, Klingmüller D. Seven-day administration of the gonadotropin-releasing hormone antagonist Cetrorelix in normal cycling women. Eur J Endocrinol 1994;131:280–5. ISSN 0804–4643 In contrast to gonadotropin-releasing hormone (GnRH) agonists, GnRH antagonists do not show any stimulatory effect on the pituitary but their clinical usage was precluded by severe side effects and high dose requirements. We report here on a 7-day treatment using the potent GnRH antagonist Cetrorelix ([Ac-d-Nal(2)1, d-Phe(4Cl)2, d-Pal(3)3, d-Cit6, d-Ala10]GnRH) on five women 23–33 years old. All women were ovulatory and were studied during three consecutive cycles: a control cycle, a treatment cycle and a post-treatment control cycle. Throughout the control cycles blood samples were obtained daily during cycle days 8–18 and on days 21 and 23 during the remainder of the control cycles. On the eighth day of the treatment cycle women were hospitalized at 07.00 h for 26 h. Repeated blood samples were drawn at 15-min intervals during the entire period. Subjects received 3 mg of Cetrorelix sc for the first time at 09.00 h on the eighth day of the cycle and daily at 08.00 h for the following 6 days. Blood samples were obtained daily over a period of 25 days and every third day throughout the remainder of the treatment cycle. Twenty-four hours after the first application of Cetrorelix, luteinizing hormone (LH) and estradiol were in the subnormal range and remained subnormal until the end of medication. The suppressive effect of Cetrorelix compared to pretreatment values lasted at least 6 days for LH and FSH and 11 days after the last Cetrorelix injection for estradiol. An LH surge followed by postovulatory progesterone values was found 22.6 ± 1.4 days after the last injection. During application of the GnRH antagonist, LH was reduced to 16.1 ± 0.7%, FSH to 58.7 ± 1.3% and estradiol to 17.9 ± 0.4% compared to the individual pretreatment values. The consecutive cycle after completion of treatment was comparable to the length of the pretreatment cycle. No serious side effects were observed. In summary, the results of this study give evidence of the effectiveness and safety of this new GnRH antagonist used in low dosages for possible therapeutic application in sex-hormone-dependent diseases in women. Dietrich Klingmüller, Institut für Klinische Biochemie der Universität Bonn, Sigmund Freud Str. 25, D53105 Bonn, Germany

scholarly journals Efficacy and safety of high dose hydroxyurea in transfusion dependent thalassemic children: a quasi experimental study

2017 ◽  
Vol 4 (4) ◽  
pp. 1514
Author(s):  
Kiran Suthar ◽  
Pramod Sharma ◽  
Manish Verma ◽  
Vishnu Kr. Goyal
Keyword(s):  
Statistical Significance ◽  
Significant Rise ◽  
P Value ◽  
High Dose ◽  
Comparison Study ◽  
Post Intervention ◽  
Before And After ◽  
Quasi Experimental ◽  
Haemoglobin Synthesis ◽  
Day Care Centre

Background: This study was conducted to find out whether high dose hydroxyurea is an effective and safe modality, in inducing haemoglobin synthesis to decrease blood transfusion requirement in transfusion dependent thalassemics.Methods: This quasi experimental un-control before and after comparison study was conducted in Thalassemia Day Care Centre, Department of Pediatrics over a period of six months after obtaining an approval from the Institute’s ethical committee. Fifty transfusions dependent thalassemic children belonging from 2 to 18 yrs were given hydroxyurea in dose of 20mg/kg after getting consent. Pre and post intervention haemoglobin and HbF levels were obtained using Hb electrophoresis by HPLC. Paired t test was applied to find out statistical significance and p value <0.05 was taken as significant.Results: Significant rise in haemoglobin pre and post intervention (p<0.001) but the rise in HbF was not significant (p=0.110). One patient had bone marrow depression which was reversible with drug withdrawal and one patient had rise in s. creatinine.Conclusions: High dose hydroxyurea is an effective and safe drug in inducing Hemoglobin synthesis in transfusion dependent thalassemics.  

Sign in / Sign up

Export Citation Format

Share Document