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 ◽  
...  

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.

2005 ◽  
Vol 17 (2) ◽  
pp. 201
Author(s):  
F. Berlinguer ◽  
A. Gonzalez-Bulnes ◽  
S. Succu ◽  
G. Leoni ◽  
I. Rosati ◽  
...  

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).


1986 ◽  
Vol 110 (1) ◽  
pp. 145-150 ◽  
Author(s):  
G. R. Marshall ◽  
F. Bint Akhtar ◽  
G. F. Weinbauer ◽  
E. Nieschlag

ABSTRACT If the suppressive effects of gonadotrophin-releasing hormone (GnRH) antagonists on gonadotrophin secretion are mediated through GnRH-receptor occupancy alone, it should be possible to restore serum gonadotrophin levels by displacing the antagonist with exogenous GnRH. To test this hypothesis, eight adult crab-eating macaques (Macaca fascicularis), weight 4·7–7·6 kg, were subjected to the following treatment regimens. A GnRH-stimulation test was performed before and 4, 12 and 24 h after a single s.c. injection of the GnRH antagonist (N-Ac-d-p-Cl-Phe1,2,d-Trp3,d-Arg6,d-Ala10)-GnRH (ORG 30276). The stimulation tests were performed with 0·5, 5·0 or 50 μg GnRH given as a single i.v. bolus. Blood was taken before and 15, 30 and 60 min after each bolus for analysis of bioactive LH and testosterone. The GnRH-challenging doses were given as follows: 0·5 μg GnRH was injected at 0 and 4 h, followed by 5·0 μg after 12 h and 50 μg after 24 h. One week later, 5·0 μg GnRH were given at 0 and 4 h, followed by 50 μg after 12 h and 0·5 μg after 24 h. Finally, after another week, the GnRH challenges began with 50 μg at 0 and 4 h, followed by 0·5 μg at 12 h and 5·0 μg at 24 h. This design permitted comparison of the LH and testosterone responses with respect to the dose of GnRH and the time after administration of GnRH antagonist. The areas under the response curves were measured and statistical evaluation was carried out by means of non-parametric two-way analysis of variance followed by the multiple comparisons of Wilcoxon and Wilcox. Four hours after the antagonist was injected, the LH and testosterone responses to all three doses of GnRH were suppressed. At the lowest dose of GnRH (0·5 μg) the responses remained reduced even after 24 h, whereas the higher doses of GnRH elicited an LH and testosterone response at 12 and 24 h which was not significantly different from that at 0 h. These data demonstrate that the suppression of LH secretion by a GnRH antagonist in vivo can be overcome by exogenously administered GnRH in a dose- and time-dependent manner, thus strongly supporting the contention that GnRH antagonists prevent gonadotrophin secretion by GnRH-receptor occupancy. J. Endocr. (1986) 110, 145–150


2004 ◽  
Vol 61 (5) ◽  
pp. 977-985 ◽  
Author(s):  
A. Gonzalez-Bulnes ◽  
J. Santiago-Moreno ◽  
R.M. Garcia-Garcia ◽  
C.J.H. Souza ◽  
A. Lopez-Sebastian ◽  
...  

1989 ◽  
Vol 122 (2) ◽  
pp. 519-526 ◽  
Author(s):  
K.-L. Kolho ◽  
I. Huhtaniemi

ABSTRACT Suppression of neonatal rat pituitary-testis function by gonadotrophin-releasing hormone (GnRH) antagonists results in delayed sexual maturation and infertility. Since the mechanism is not understood, the acute effects of a GnRH antagonist on gonadotrophin secretion in neonatal male rats has been studied in more detail. Treatment with a GnRH antagonist analogue, N-Ac-d-Nal(2)1,d-p-Cl-Phe2,d-Trp3,d-hArg(ET2)6,d-Ala10-GnRH (2 mg/kg per day) on days 1–10 of life had prolonged effects on gonadotrophin secretion; serum LH and FSH recovered in 1 week, but the pituitary content took 2 weeks to recover. Likewise, LH and FSH responses to acute in-vivo stimulation with a GnRH agonist were still suppressed 1 week after the treatment. Interestingly, a rebound (86% increase) in basal serum FSH was found 16 days after treatment with the antagonist. Whether testis factors influence gonadotrophin secretion during treatment with the GnRH antagonist and/or in the subsequent recovery period was also assessed. Neonatal rats were castrated on days 1, 5 or 10 of the 10-day period of antagonist treatment. Orchidectomy on days 1 and 5 only marginally affected gonadotrophin secretion. When orchidectomy was performed at the beginning of the recovery period, no effects on pituitary recovery were seen within 1 week of castration. After 16 days, serum LH and FSH in the antagonist-treated and control castrated rats were equally increased but the pituitary contents of the antagonist-treated rats were still suppressed. Finally, the effect of testosterone treatment on the recovery of gonadotrophin secretion after antagonist suppression was studied in intact and orchidectomized animals. The rats were implanted with testosterone capsules for 7 days after treatment with the GnRH antagonist in the neonatal period. Testosterone suppressed pituitary LH contents similarly in all groups of animals, but had no effects on serum LH. Paradoxically, serum FSH was suppressed 50% by testosterone in intact and castrated antagonist-treated rats and in castrated controls but not in intact controls. These findings suggest that suppression of FSH by testosterone is only seen in neonatal animals with low endogenous levels of this androgen, whether due to GnRH antagonist treatment or castration. It is concluded that neonatal treatment with a GnRH antagonist results in prolonged suppression of LH and FSH secretion, that testis factors play only a minor role in pituitary modulation during the antagonist suppression and that more disturbances are observed in the post-treatment recovery of FSH secretion than in that of LH. Journal of Endocrinology (1989) 122, 519–526


2020 ◽  
Author(s):  
Xiu Luo ◽  
Li Pei ◽  
Fujie Li ◽  
Chunli Li ◽  
Guoning Huang ◽  
...  

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.


1991 ◽  
Vol 129 (3) ◽  
pp. 363-370 ◽  
Author(s):  
S. Khurshid ◽  
G. F. Weinbauer ◽  
E. Nieschlag

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


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiu Luo ◽  
Li Pei ◽  
Fujie Li ◽  
Chunli Li ◽  
Guoning Huang ◽  
...  

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 > 600 pg/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 oocytes 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.


2004 ◽  
Vol 16 (2) ◽  
pp. 233 ◽  
Author(s):  
C. Lopez-Alonso ◽  
T. Encinas ◽  
A. Veiga-Lopez ◽  
R.M. Garcia-Garcia ◽  
J.M. Ros ◽  
...  

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 &gt;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&lt;0.05), and a lower number of &gt;4mm follicles (2.2±0.5 v. 5.0±0.6, P&lt;0.01). Thereafter, administration of Ovagen™ induced a significant rise in the number of &gt;4mm follicles at sponge removal in both groups (P&lt;0.0005 for treated ewes and P&lt;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.


Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 860
Author(s):  
Wu-Sheng Sun ◽  
Hoon Jang ◽  
Mi-Ryung Park ◽  
Keon Bong Oh ◽  
Haesun Lee ◽  
...  

Oxidative stress has been suggested to negatively affect oocyte and embryo quality and developmental competence, resulting in failure to reach full term. In this study, we investigated the effect of N-acetyl-L-cysteine (NAC), a cell-permeating antioxidant, on developmental competence and the quality of oocytes and embryos upon supplementation (0.1–10 mM) in maturation and culture medium in vitro using slaughterhouse-derived oocytes and embryos. The results show that treating oocytes with 1.0 mM NAC for 8 h during in vitro maturation attenuated the intracellular reactive oxygen species (ROS) (p < 0.05) and upregulated intracellular glutathione levels (p < 0.01) in oocytes. Interestingly, we found that NAC affects early embryonic development, not only in a dose-dependent, but also in a stage-specific, manner. Significantly (p < 0.05) decreased cleavage rates (90.25% vs. 81.46%) were observed during the early stage (days 0–2), while significantly (p < 0.05) increased developmental rates (38.20% vs. 44.46%) were observed during the later stage (from day 3) of embryonic development. In particular, NAC supplementation decreased the proportion of apoptotic blastomeres significantly (p < 0.05), resulting in enhanced hatching capability and developmental rates during the in vitro culture of embryos. Taken together, our results suggest that NAC supplementation has beneficial effects on bovine oocytes and embryos through the prevention of apoptosis and the elimination of oxygen free radicals during maturation and culture in vitro.


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