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Early gonadotropin-releasing hormone antagonist start improves follicular synchronization and pregnancy outcome as compared to the conventional antagonist protocol

  • Park, Chan Woo;Hwang, Yu Im;Koo, Hwa Seon;Kang, Inn Soo;Yang, Kwang Moon;Song, In Ok
    • 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.

GnRH-agonist에 의한 인간 과립-황체화 세포의 세포사멸과 PBR 단백질의 발현 (Apoptosis and Peripheral Benzodiazepin Receptor (PBR) Expression in Human Granulosa-Luteal Cells by GnRH-agonist)

  • 김세광;염윤희;윤정미;배상욱;양현원;조동제;윤용달;송찬호
    • Clinical and Experimental Reproductive Medicine
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    • 제31권2호
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    • pp.83-94
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    • 2004
  • Objective: To investigate whether GnRH-agonist (GnRH-Ag) using in IVF-ET affects apoptosis of human granulosa-luteal cells and expression of peripheral benzodiazepine receptor (PBR) protein involved in the apoptosis of the cells. Methods: Granulosa-luteal cells obtained during oocyte retrieval were cultured and treated with $10^{-5}M$ GnRH-Ag. Apoptosis of the cells by the treatment was confirmed using DNA fragmentation analysis 24 h after culture. The presence of PBR protein within the cells was examined by immunofluorescence staining and the expression of the protein was analyzed by Western blotting. In addition, it was measured for progesterone and nitric oxide (NO) produced by granulosa-luteal cells after GnRH-Ag treatment. To evaluate the relationship between NO production and PBR expression, sodium nitroprusside (SNP) as a NO donor was added in media and investigated the expression of PBR protein by Western blotting. Results: Apoptosis increased in the granulosa-luteal cells 24 h after GnRH-Ag treatment, whereas the expression of PBR protein significantly decreased. Furthermore, the production of progesterone and nitric oxide (NO) by the cells significantly fell from 12 h after the treatment. In the results of Western blotting after SNP treatment, the expression of PBR protein increased in the treatment with SNP alone to the granulosa-luteal cells, but was suppressed in the treatment with GnRH-Ag and SNP. Additionally, the staining result of PBR protein in the cells showed the even distribution of it through the cell. Conclusion: These results demonstrate that GnRH-Ag treatment induces apoptosis, decreasing expression of PBR protein and NO production in human granulosa-luteal cells. The present study suggests that one of the apoptosis mechanism of human granulosa-luteal cells by GnRH-Ag might be a signal transduction pathway via NO and PBR.

인공수정시술주기에서 내인성 LH, GnRH Agonist 및 hCG를 이용한 배란유발후 임신율의 비교연구 (Comparison of Pregnancy Rates by Intrauterine Insemination after Ovulation Trigger with Endogenous LH Surge, GnRH Agonist or hCG in Stimulated Cycles)

  • 이종인;허영문;전은숙;윤정임;정구성;홍기언;유승환;이현숙;홍정의;이지삼
    • Clinical and Experimental Reproductive Medicine
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    • 제26권3호
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    • pp.389-398
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    • 1999
  • Objective: This study was designed to evaluate the effects of endogenous LH surge, GnRH agonist (GnRH-a) or human chorionic gonadotropin (hCG) as ovulation trigger on pregnancy rate by intrauterine insemination (IUI). Method: Patients received daily 100 mg of clomiphene citrate (CC) for 5 days starting on the third day of the menstrual cycle followed by human menopausal gonadotropin (hMG) for ovulation induction. Follicles larger than >16 mm in diameter were present in the ovary, frequent LH tests in urine were introduced to detect an endogenous LH surge. Final follicular maturation and ovulation were induced by GnRH-a 0.1 mg (s.c.) or hCG $5,000{\sim}10,000$ IU (i.m.) administration except natural ovulation. Pregnancy was classified as clinical if a gestational sac or fetal cardiac activity was seen on ultrasound. Results: There were no differences in age, duration of infertility and follicle size, but more ampules of hMG were used in GnRH-a group compared to hCG 10,000 IU treated group (p<0.05). Lower level of estradiol ($E_2$) on the day of hCG or GnRH-a injection was observed in hCG 10,000 IU group than other treatment groups (p<0.01). The overall clinical pregnancy rate was 19.8% per cycle (32/162) and 22.2% per patient (32/144). Pregnancy rate was higher in natural-endogenous LH surge group (37.5%, 9/24) than GnRH-a (18.8%) or hCG treated group (20.9% & 13.9%), but this difference was not statistically significant. No patient developed ovarian hyperstimulation. Abortion rate was 22.2% (2/9) in hCG 5,000 IU group. Delivery or ongoing pregnancy rate was 37.5% (9/24), 18.8% (3/16), 16.3% (7/43) and 13.9% (11/79) in endogenous LH surge, GnRH-a, hCG 5,000 IU and hCG 10,000 IU treatment groups, respectively. Conclusion: These results support the concept that use of natural-endogenous LH surge in stimulated cycles may be more effective to obtain pregnancies by IUI than GnRH-a or hCG administration.

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The influence of gonadotropin-releasing hormone agonists on anthropometric change in girls with central precocious puberty

  • Yoon, Jong Wan;Park, Hyun A;Lee, Jieun;Kim, Jae Hyun
    • Clinical and Experimental Pediatrics
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    • 제60권12호
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    • pp.395-402
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    • 2017
  • Purpose: The potential effect of gonadotropin-releasing hormone agonist (GnRHa) treatment on the weight of girls with central precocious puberty (CPP) remains a controversy. We investigated anthropometric changes during and after GnRHa treatment among girls with CPP. Methods: This retrospective study evaluated data from 127 girls with CPP who received GnRHa treatment for ${\geq}2years$. Height, weight, and body mass index (BMI) values were compared at the baseline (visit 1), after 1 year of GnRHa treatment (visit 2), the end of GnRHa treatment (visit 3), and 6-12 months after GnRHa discontinuation (visit 4). Results: The height z score for chronological age (CA) increased continuously between visit 1 and visit 4. No significant differences were observed in BMI z score for CA between visits 1 and 4. However, an increasing trend in the BMI z score for bone age (BA) was observed between visits 1 and 4. The numbers of participants who were of normal weight, overweight, and obese were 97, 22, and 8, respectively, at visit 1, compared to 100, 16, and 11, respectively, at visit 4 (P=0.48). Conclusion: Among girls with CPP, the overall BMI z score for CA did not change significantly during or after GnRHa treatment discontinuation, regardless of their BMI status at visit 1. However, the BMI z score for BA showed an increasing trend during GnRHa treatment and a decreasing trend after discontinuation. Therefore, long-term follow-up of BMI changes among girls with CPP is required until they attain adult height.

Changes of Sexual Behaviors in Rapamycin-injected Cichlid Fish Astatotilapia burtoni Males

  • Kim, Tae Ha;Sohn, Young Chang
    • 한국발생생물학회지:발생과생식
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    • 제20권3호
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    • pp.267-274
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    • 2016
  • Cichlid fish species exhibit characteristic sexual behaviors according to not only reproductive stages but also social status. In a reproductive season, Astatotilapia burtoni males compete for females and a small number of dominant winners finally obtain the chance of spermiation. In addition to the characteristic behaviors, the dominant males have relatively bigger gonadotropin-releasing hormone 1 (GnRH1) neurons in the preoptic area (POA) of brain compared to those of subordinate males. Although the stimulatory effect of GnRH1 in vertebrate reproduction is well established, little is known about the triggering signal pathway to control GnRH1 neurons and GnRH1-mediated sexual behavior. In the present study, we evaluated the potential effect of TOR inhibitor rapamycin in relation to the cichlid male behaviors and GnRH1 neuron. After 14 h and 26 h of intraventricular injection of rapamycin, behavior patterns of chasing and courtship display did not show significant changes between rapamycin- and DMSO-injected males. Behaviors of spawning site entry increased in rapamycin-injected fish at 26 h post-injection than at 14 h post-injection significantly (P<0.05). Meanwhile, there was a tendency that GnRH1 neurons' soma size in the POA shrank by rapamycin injection, whereas the testes did not show notable changes. Taken together, these results suggest the possible role of TOR signal on GnRH1-mediated sexual behavior in cichlid dominant males, although further biological characterization of the TOR signaling pathway will be required to clarify this matter.

자궁근종 환자에서 Gonadotropin Releasing Hormone(GnRH) 유사체 투여 후 자궁근종 세포 증식에 관한 연구 (The Activity of Proliferating Cell Nuclear Antigen(PCNA) of Uterine Myoma after Treatment with Gonadotropin Releasing Hormone(GnRH) Analogue)

  • 이병석;이보연;박기현;조동제;이국;송찬호;김호근
    • Clinical and Experimental Reproductive Medicine
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    • 제19권2호
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    • pp.175-179
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    • 1992
  • The factors involved in the initial neoplastic transformation and subsquent growth of uterine fibroid are poorly understood. The reduction in uterine fibroid volume associated with the chronic administration of the mechanisms mediating the decrease in fibroid volume in GnRH-a treated patients are poorly defined. The purpose of this study was to determine the proliferating cell nuclear antigen(PCNA) in fibroid from-women pretreated with GnRH analogue(GnRH-a) compared with controls. Tissue was obtained from 16 premenopausal women with uterine fibroid who received GnRH-a(D-Trp6-GnRH) intramusculary every 28 days for four injections. The mean proliferating index(PI) in patients with uterine fibroids was $2.25{\pm}0.9$, and in controls was $8.82{\pm}1.8$(P<0.001). The proliferating index was not corrleated with the reduction of fibroid volume. In this clinical study, although hypoestrogenism may be the main factor that reduce the volume of fibroid, other factors are also considered to be involved in that process. And the regrowth of uterine fibroid may be affected by increased production of PCNA after stopping GnRH-a.

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Excess of leptin inhibits hypothalamic KiSS-1 expression in pubertal mice

  • Ahn, Sung-Yeon;Yang, Sei-Won;Lee, Hee-Jae;Byun, Jong-Seon;Om, Ji-Yeon;Shin, Choong-Ho
    • Clinical and Experimental Pediatrics
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    • 제55권9호
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    • pp.337-343
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    • 2012
  • Purpose: Leptin has been considered a link between metabolic state and reproductive activity. Defective reproductive function can occur in leptin-deficient and leptin-excessive conditions. The aim of this study was to examine the effects of centrally injected leptin on the hypothalamic KiSS-1 system in relation to gonadotropin-releasing hormone (GnRH) action in the initial stage of puberty. Methods: Leptin (1 ${\mu}g$) was injected directly into the ventricle of pubertal female mice. The resultant gene expressions of hypothalamic GnRH and KiSS-1 and pituitary LH, 2 and 4 hours after injection, were compared with those of saline-injected control mice. The changes in the gene expressions after blocking the GnRH action were also analyzed. Results: The basal expression levels of KiSS-1, GnRH, and LH were significantly higher in the pubertal mice than in the prepubertal mice. The 1-${\mu}g$ leptin dose significantly decreased the mRNA expression levels of KiSS-1, GnRH, and LH in the pubertal mice. A GnRH antagonist significantly increased the KiSS-1 and GnRH mRNA expression levels, and the additional leptin injection decreased the gene expression levels compared with those in the control group. Conclusion: The excess leptin might have suppressed the central reproductive axis in the pubertal mice by inhibiting the KiSS-1 expression, and this mechanism is independent of the GnRH-LH-estradiol feedback loop.

Hyperbranched Polymer를 이용한 나뭇가지꼴 카보실란 거대분자의 합성 (Synthesis of Dendritic Carbosilanes by the Use of Hyperbranched Polymers)

  • 김정균;강성경;박은미
    • 대한화학회지
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    • 제43권4호
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    • pp.393-400
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    • 1999
  • Hyperbranched polymer를 이용한 나뭇가지꼴 카보실란 거대분자를 합성하였다 Hyperbranched polymer의 영세대 화합물의 합성은 $HSiMe_{3-n}$$(CH_2CH=CH_2)_n$(n=2; $AB_2$,3;$AB_3$형)의 수소화규소첨가반응 방법을 이용하여 합성하였다. Hyperbranched polymer $AB_2$$AB_3$형 고분자 화합물은 수소화규소첨가반응과 알켄첨가반응에 의해 Gn+1형 나뭇가지꼴 거대분자로 성장하였다. Gn+2P세대 화합물은 $HSiMeCl_2$와의 수소화규소첨가반응 방법에 의해 모든 가지가 동일형 화합물을 형성하지 못했다. Gn과 Gn+1형 고분자 화합물은 9-BBN과의 반응과 반응생성물의 산화반응에 의해서 polysilol을 형성하였다. 반응의 정도는 NMR에 의해서 확인할 수 있었다.

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