• Fisheries and Aquatic Sciences
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• 제3권1호
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• pp.37-43
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• 2000

We used a mammalian GnRH antagonist, $[Ac-3,4-dehydro-Pro^1,\;D-p-F-Phe^2,\;D-Trp^{3.6}]$-GnRH, to examine the details of the salmon type gonadotropin-releasing hormone (sGnRH) and GnRH agonist analog $(Des-Gly^{10}$[d-Ala^6]-ethylamide GnRH; GnRHa) functions in the control of maturational gonadotropin (GTH II) secretion, in precocious male rainbow trout, in both in vivo and in vitro experiments. In the in vivo study, plasma GTH II levels increased by sGnRH or GnRHa treatment, but the response was more rapid and stronger in the GnRHa treatment group. The increase in GTH II was significantly suppressed by the GnRH antagonist, while the antagonist had no effect on basal GTH II levels in both groups. The GnRH antagonist showed stronger suppression of GTH II levels in the sGnRH treatment fish than in the GnRHa treatment fish. In addition, plasma androgenic steroid hormones (testosterone and 11-ketotestosterone) increased by the sGnRH or GnRHa treatment. The GnRH antagonist significantly inhibited the increases in plasma androgenic steroid hormone levels stimulated by the sGnRH or GnRHa, while the antagonist had no effect on basal androgenic steroid hormone levels in both groups. In the in vitro study, treatment with sGnRH or GnRHa increased GTH II release from the cultured dispersed pituitary cells, but the response was stronger in the GnRHa treatment group. The increase in GTH II release by GnRH was suppressed by adding the GnRH antagonist, dose­dependently. On the other hand, basal release of GTH II did not decrease by the GnRH antagonist treatment in both groups. These results suggest that the GnRH antagonist, $[Ac-3,4-dehydro-Pro^1,\;D-p-F-Phe^2,\;D-Trp^{3.6}]-GnRH$, used in this study is effective in blocking the action of GnRH-induced GTH II release from the pituitary gland both in vivo and in vitro.

• Clinical and Experimental Reproductive Medicine
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• 제29권4호
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• pp.251-258
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• 2002

Objective : The aim of this study was to evaluate the outcomes of the GnRH antagonist (Cetrotide) minimal stimulation protocol comparing with GnRH agonist combined long step down stimulation protocol in PCOS patients. Materials and Method: From Apr 2001 to May 2002, 22 patients (22 cycles) were performed in controlled ovarian hyperstimulation using by GnRH antagonist and GnRH agonist for PCOS patients. GnRH antagonist (Cetrotide) combined minimal stimulation protocol was administered in 10 patients (10 cycles, Study Group) and GnRH agonist long step down stimulation protocol was administered in 12 patients (12 cycles, Control Group). We compared the pregnancy rate/cycle, total FSH (A)/cycle, Retrieved oocyte/cycle, the incidence of ovarian hyperstimulation syndrome, multiple pregnancy rate between the two groups. Student-t test were used to determine statistical significance. Statistical significance was defined as p<0.05. Results: Group of GnRH antagonist (Cetrorelix) minimal stimulation protocol produced fewer oocytes (6.4 versus 16.3 oocytes/cycle) using a lower dose of FSH (22.2 versus 36.1 Ample/cycle) and none developed OHSS and multiple pregnancy. Although the trends were in favour of the GnRH antagonist (Cetrorelix) protocol, the differences did not reach statistical significance. This was probably due to small sample size. Conclusion: The use of GnRH antagonist reduce the risk of ovarian hyperstimulation and multiple pregnancy. We suggest that GnRH antagonist might be alternative controlled ovarian hyperstimulation method, especially in PCOS patients who will be ovarian high response.

• Clinical and Experimental Reproductive Medicine
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• 제37권3호
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• pp.239-244
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• 2010

목 적: 본 후향적 연구는 성선자극호르몬분비호르몬 작용제 (gonadotropin-releasing hormone [GnRH] agonist)와 길항제 (GnRH antagonist) 치료를 받은 불량반응군의 결과를 비교, 분석하고자 하였다. 연구방법: 총 172회의 체외수정시술 주기에서 GnRH agonist 또는 antagonist protocol로 과배란유도를 시행받고 채취된 난자의 수가 5개 이하인 불량반응군을 대상군으로 하였다. 난포 및 채취된 난자의 수, 수정률 등의 결과를 두 군 간에 비교하였다. 결 과: GnRH agonist long protocol과 antagonist protocol 두 군 간에 난포 및 난자의 수와 수정률은 차이를 보이지 아니하였다. 반면, 과배란유도 제7/8일의 혈중 $E_2$ 농도는 GnRH antagonist군에서 더 높았던 반면, 사용한 평균 성선자극호르몬의 용량은 유의하게 적고 과배란유도 기간은 짧은 것을 확인할 수 있었다 (각각 p<0.01). 결 론: 불량 반응군에서 GnRH agonist long protocol에 비하여 GnRH antagonist protocol의 경우 노력이 상대적으로 적게 필요한 반면 비슷한 임상적 결과를 고려할 때, GnRH antagonist protocol이 상대적으로 우수한 것으로 생각된다.

• Clinical and Experimental Reproductive Medicine
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• 제29권4호
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• pp.259-267
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• 2002

Objective: This study was performed to compare the clinical outcomes of GnRH antagonist (Cetrorelix) single dose and multiple dose protocols for controlled ovarian hyperstimulation with GnRH agonist long protocol. Materials and Method: From September 2001 to March 2002, 48 patients (55 cycles) were performed controlled ovarian hyperstimulation for ART using by either GnRH antagonist and GnRH agonist. Single dose of 3 mg GnRH antagonist was administered in 15 patients (17 cycles, single dose group) at MCD #8 and multiple dose of 0.25 mg of GnRH antagonist was administered in 15 patients (18 cycles, multiple dose group) from MCD #7 to hCG injection day. GnRH agonist was administered in 18 patients (20 cycles, control group) by conventional GnRH agonist long protocol. We compared the implantation rate, number of embryos, and clinical pregnancy rate among three groups. Student-t test and Chi-square were used to determine statistical significance. Statistical significance was defined as p<0.05. Results: There were no significant differences in ampules of used gonadotropins, number of mature oocytes, obtained embryos between single and multiple dose group, but compared with control group, ampules of used gonadotropins, number of mature oocytes, obtained embryos were decreased significantly in both groups. Clinical pregnancy rate and implantation rate were not different in three groups. There were no premature LH surge and ovarian hyperstimulation syndrome in three groups. Multiple pregnancy were occurred 1 case in multiple dose group and 2 case in control group. Conclusions: GnRH antagonist is a safe, effective, and alternative method in the controlled ovarian hyperstimulation compared with GnRH agonist. Clinical outcomes and efficacy of both single and multiple dose protocol are similar between two groups.

• Clinical and Experimental Reproductive Medicine
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• 제30권1호
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• pp.95-103
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• 2003

Objective : To assess and compare the clinical outcomes between GnRH agonist long protocol and GnRH antagonist short protocol in oocyte donation program. Materials and Methods: Of total 18 oocyte donation cycles, controlled ovarian hyperstimulation (COH) were performed with GnRH agonist long protocol and GnRH antagonist short protocol in initial 9 cycles and later 9 cycles, respectively. Oral estradiol valerate and progesterone in oil we re administrated to all recipients for endometrial preparation. Oral estradiol administration was started from donor cycle day 1 after full shut down of gonadal axis with GnRH agonist in patients with ovarian function. Progesterone was injected from oocyte retrieval day of donor initially, then continuously till pregnancy 12 weeks if pregnancy was ongoing. We compared the parameters of clinical outcomes, such as number of the retrieved oocytes, fertilization rate, high grade embryo production rate, clinical pregnancy rate, implantation rate, ongoing pregnancy rate, COH duration, total gonadotropin dose for COH between GnRH agonist long protocol group and GnRH antagonist group. Statistical analysis was performed using Mann-Whitney test, p<0.05 was considered as statistically significant. Results: The number of retrieved oocytes, fertilization rate, high grade embryo production rate, clinical pregnancy rate, implantation rate, ongoing pregnancy rate were $14.89{\pm}7.83$, 81%, 64%, 78%, 31%, 78%, respectively in GnRHa long protocol group and $11.22{\pm}8.50$, 79%, 64%, 67%, 34%, 56%, respectively in GnRH antagonist group. There was no significant differences in parameters of clinical outcomes between 2 groups (all p value >0.05). Duration and total gonadotropin dose for COH were $10.94{\pm}1.70$ days and $43.78{\pm}6.8$ vials in 18 cycles, $12.00{\pm}1.73$ days and $48.00{\pm}6.93$ vials in agonist group, $9.88{\pm}0.78$ days and $39.55{\pm}3.13$ vials in antagonist group, respectively. In GnRH agonist long protocol group, significantly longer duration and higher gonadotropin dose for COH were needed (p=0.012). Conclusion: In oocyte donation program, clinical outcomes from controlled ovarian hyperstimulation with GnRH antagonist were comparable to those from GnRH agonist long protocol group, so controlled ovarian hyperstimulation with GnRH antagonist may be effective as GnRH agonist long protocol. At least there may not be harmful effects of GnRH antagonist on oocyte development and quality.

• Clinical and Experimental Reproductive Medicine
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• 제34권2호
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• pp.125-131
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• 2007

목 적: 난소 반응이 저하된 환자에서 GnRH agonist flare up protocol과 GnRH antagonist protocol의 효용성을 비교하고자 하였다. 연구방법: 2003년 1월부터 2005년 8월까지 체외수정시술을 받은 환자들 가운데 이전의 체외수정시술 주기에서 5개 이하의 난자가 채취되고 기저 FSH 농도가 12 mIU/ml 이상인 총 144명 가운데 73명은 GnRH agonist flare up요법을 사용하였고 71명은 GnRH antagonist 요법을 사용하였다. 양군간에 주기의 취소율, 채취된 난자수, 양질의 수정란의 수, 착상율, 임신율, 출산율을 비교하였다. 결 과: 각 군간에 나이는 평균 37.4세와 38.1세로 antagonist group에서 높았으나 통계학적 유의성은 없었다. 그 외에 기저 FSH 농도와 이전 주기의 취소율도 통계학적 유의성은 없었다. GnRH agonist flare up 주기와 GnRH antagonist 주기에서 취소율은 각각 30.1%, 53.5%로 GnRH antagonist protocol에서 유의 있게 높게 나타났다. 채취된 난자수도 각각 4.18개와 2.16개로 차이를 보였으며 난소 과자극 기간은 각각 10.5일과 9.2일로 antagonist protocol에서 약간 낮은 모습을 보였다. 최고 혈중 E$_2$의 농도와 good embryo 개수도 GnRH agonist flare up요법에서 유의 있게 높게 나타났다. 각 군에서의 착상율, 이식 주기당 임신율, 이식 주기당 출생율은 GnRH agonist flare up요법에서 약간 높은 경향을 보이기는 하였으나 통계학적인 유의성은 없었다. 결 론: 두 군간의 비교에서 GnRH agonist flare up 요법이 시작 주기당 임신율, 출산율에서 높은 경향을 보였으나 통계학적 의의는 없었다. 하지만 난소기능이 저하된 환자에서 난자의 채취 개수는 GnRH agonist flare up 요법이 GnRH antagonist를 사용한 주기보다 의의있게 높게 나타났다. 이러한 연구 결과로 볼 때 저 반응군에 있어서 GnRH antagonist flare up요법이 저 반응군에 있어 향상된 난소 반응을 기대할 가능성이 높을 것으로 생각된다.

• Animal cells and systems
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• 제13권4호
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• pp.429-437
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• 2009

The control mechanism of gonadotropin-releasing hormone (GnRH) on gonadotropin (GTH) release was studied using cultured pituitary cell or cultured whole pituitary obtained from Testosterone (T) treated and control immature rainbow trout. The release of FSH was not changed by salmon type GnRH (sGnRH), chiken-II type (cGnRH-II), GnRH analogue ([des-$Gly^{10}D-Ala^6$] GnRH ethylamide) and GnRH antagonist ([Ac-3, 4-dehydro-$Pro^1$, D-p-F-$Phe^2$, D-$Trp^{3,6}$] GnRH) in cultured pituitary cells of T-treated and control fish. Indeed, FSH release was not also altered by sGnRH in cultured whole pituitary. All tested drugs had no effect on the release of LH in both culture systems of control fish. The levels of LH, in contrast, such as the pituitary content, basal release and responsiveness to GnRH were increased by T administration in both culture systems. In addition, the release of LH in response to sGnRH or cGnRH-II induced in a dose-dependent manner from cultured pituitary cells of T-treated fish, but which is not significantly different between in both GnRH at the concentration examined. Indeed, LH release was also increased by sGnRH in cultured whole pituitary of T-treated fish. GnRH antagonist suppressed the release of LH by sGnRH ($10^{-8}\;M$) and GnRH analogue ($10^{-8}\;M$) stimulation in a dose-dependent manner from cultured pituitary cells of T-treated fish, and which were totally inhibited by $10^{-7}\;M$ GnRH antagonist. These results indicate that the sensitivity of pituitary cells to GnRH is elevated probably through the T treatment, and that GnRH is involved in the regulation of LH release. GnRH-stimulated LH release is inhibited by GnRH antagonist in a dose-dependent manner. The effects of gonadal steroids on FSH levels are less clear.

• Clinical and Experimental Reproductive Medicine
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• 제28권4호
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• pp.265-270
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• 2001

Objective : The aim of this study was to evaluate the outcome the GnRH antagonist (Cetrotide) short protocol in controlled ovarian hyperstimulation comparing with GnRH agonist long protocol. Materials and Method: From July 2000 to November 2001, 26 patients, 28 cycles were performed in controlled ovarian hyperstimulation by GnRH antagonist and GnRH agonist. GnRH antagonist (Cetrotide) was administered in 12 patients (14 cycles, Group 1) and GnRH agonist (Lucrin, Sub Q, Group 2) in 14 patients (14 cycles). Ovulation induction was performed by hMG (Pergonal) in group 1, and by Combo (Metrodine HP + Pergonal) in group 2. We compared the fertilization rate, good quality embryo, and clinical pregnancy rate between the two groups. Student-t test and Chi-square were used to determine statistical significance. Statistical significance was defined as p<0.05. Results: Ovarian hyperstimulation syndrome did not occurred in which estradiol (E2) level was $3874{\pm}809\;pg/ml$ and the number of retrieved oocytes was $18.4{\pm}2.4$. The number of used gonadotropin ampules was significantly decreased in Group 1 (26.0 vs. 33.1, p<0.04). There were no significant difference in the number of preovulatory oocyte ($10.6{\pm}6.9$ vs. $10.0{\pm}6.1$), fertilization rate ($74.8{\pm}23.4$ vs. $72.2{\pm}21.8$), good quality embryo ($58.7{\pm}23.6$ vs. $38.7{\pm}36.6$), and embryo transfer ($4.3{\pm}1.6$ vs. $4.4{\pm}1.6$). Although the age of the group 1 was older than the group 2 (34.4 vs. 30.8), there was no significant difference in clinical pregnancy rate (50.0% vs. 57.1%). Conclusions: We suggest that GnRH antagonist was a safe, effective, and alternative method in the controlled ovarian hyperstimulation, especially in PCOD patients who will be develop the ovarian hyperstimulation syndrome.

• Clinical and Experimental Reproductive Medicine
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• 제31권3호
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• pp.191-200
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• 2004

Objective: To compare the clinical efficacy of double intrauterine insemination with single intrauterine insemination in GnRH antagonist combined ovarian hyperstimulation (Mild ovarian hyperstimulation) Materials and Methods: From Jan. 2001 to Jul. 2004, a retrospective clinical analysis was done of a total of 295 cycles in 170 patients who underwent ovarian hyperstimulation for ART (assisted reproductive technique). Subjects were divided into three groups; only clomiphene citrate ovarian hyperstimulation (n=55, 95cycles), GnRH antagonist combined ovarian hyperstimulation (soft ovarian hyperstimulation) (n=66 99cycles), and GnRH agonist combined ovarian hyperstimulation (short protocol) (n=49, 101cycles) Each group were randomly devided into two subgroups. One group underwent single IUI and the other group underwent double IUI. Results: GnRH antagonist group and GnRH agonist group had similar pregnancy rate. In GnRH antagonist Group, pregnancy rate was 36.1% in single IUI subgroup and was 36.6% in double IUI subgroup. These finding were not statistically significant. And Pregnancy rate was 20.8% in single IUI subgroup and was 19.3% in double IUI subgroup in single clomiphene citrate group, and 36.3% in single IUI subgroup and was 33.3% in double IUI subgroup in GnRH agonist group. These finding were not statistically significant, too. Conclusion: Pregnancy rate of GnRH antagonist was high and complication rate such as OHSS and multiple pregnancy was lower. In GnRH antagonist group, to compare with single IUI and double IUI, the result do not statistically differ. So GnRH antagonist single injection with single IUI was relatively comparable ART in infertiliry patient.

• Clinical and Experimental Reproductive Medicine
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• 제41권4호
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• pp.158-164
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• 2014

Objective: To assess whether an early GnRH antagonist start leads to better follicular synchronization and an improved clinical pregnancy rate (CPR). Methods: A retrospective cohort study. A total of 218 infertile women who underwent IVF between January 2011 and February 2013. The initial cohort (Cohort I) that underwent IVF between January 2011 and March 2012 included a total of 68 attempted IVF cycles. Thirty-four cycles were treated with the conventional GnRH antagonist protocol, and 34 cycles with an early GnRH antagonist start protocol. The second cohort (Cohort II) that underwent IVF between June 2012 and February 2013 included a total of 150 embryo-transfer (ET) cycles. Forty-three cycles were treated with the conventional GnRH antagonist protocol, 34 cycles with the modified early GnRH antagonist start protocol using highly purified human menopause gonadotropin and an addition of GnRH agonist to the luteal phase support, and 73 cycles with the GnRH agonist long protocol. Results: The analysis of Cohort I showed that the number of mature oocytes retrieved was significantly higher in the early GnRH antagonist start cycles than in the conventional antagonist cycles (11.9 vs. 8.2, p=0.04). The analysis of Cohort II revealed higher but non-significant CPR/ET in the modified early GnRH antagonist start cycles (41.2%) than in the conventional antagonist cycles (30.2%), which was comparable to that of the GnRH agonist long protocol cycles (39.7%). Conclusion: The modified early antagonist start protocol may improve the mature oocyte yield, possibly via enhanced follicular synchronization, while resulting in superior CPR as compared to the conventional antagonist protocol, which needs to be studied further in prospective randomized controlled trials.