• Clinical and Experimental Pediatrics
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• 제50권2호
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• pp.198-204
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• 2007

목 적: 성조숙증에서 관찰된 최근의 연구 결과를 보면 사춘기 발육이 빠른 당시에는 신장이 커보일 수 있으나 결국 최종성인신장은 감소하게 된다. 이에 사춘기를 중단시킴으로써 최종 성인신장을 증가시킬 수 있을 것이라는 기대로 성선자극호르몬 방출호르몬 효능약제를 사용하여 골성숙의 기간을 연장하고자 하였다. 또한 조기 사춘기로 인하여 최종성인신장의 예후가 불량한 소아에서 성선자극호르몬 방출호르몬 효능약제 및 성장호르몬의 병합요법 효과를 성선자극호르몬 방출호르몬 효능약제 단독 사용 시의 효과와 비교하여 각각의 성장 촉진 효과를 알아보고자 하였다. 방 법: 역연령에 비하여 골연령이 증가되어 있으며 조기 사춘기를 보이는 여아를 대상으로 GnRHa 및 성장호르몬을 단기간 투여하였다. 제 1군은 triptorelin을 단독으로 4주에 한 번씩 근육주사하였고, 제 2군은 성장호르몬을 병합하여 치료하였다. 치료 기간은 약 1년이었으며 치료 시작시와 치료 후의 두 군간의 역연령, 골연령, 역연령과 골연령의 차이, 예측성인신장, 표적키, 표적키와 예측성인신장과의 차이, 혈청 IGF-1 및 IGFBP-3치를 비교하였다. 결 과: 치료 시작시 두 군 간의 골연령, 표적키, 예측성인신장, 예측성인신장과 표적키의 차이는 없었으나 골연령과 역연령의 차이 및 역연령은 유의한 차이를 보였다. 혈청 IGF-1 및 IGFBP-3값의 차이는 없었고 평균 치료기간은 $1.06{\pm}0.93$년이었다. 치료 후의 골연령과 역연령의 차이는 전체적으로 감소하였으며 두 군간에도 유의한 차이를 보였다. 치료 후의 예측성인신장은 치료전과 비교했을 때 모두 증가하여 단기간의 치료에도 효과가 있었으며 두 군 모두 의미 있는 값을 가지나 특히 성장호르몬을 같이 사용한 2군에서 더욱 큰 차이를 보여 병합요법의 성장촉진효과를 알 수 있었다. 표적키와 예측성인신장의 차이는 전체적으로 치료전보다 의미 있는 감소를 보였으며 두 군을 비교했을때 역시 2군에서 더욱 의미 있게 감소하였다. 혈청 IGF-1과 IGFBP-3는 GnRHa 사용 후에 성장호르몬-IGF 축이 억제되어 1군에서 모두 감소하였으나 성장호르몬을 병합한 2군에서는 모두 증가하였고 이때 통계적인 의미는 없었다. 결 론: 조기 사춘기로 인하여 역연령에 비해 골연령이 증가함으로써 성인신장에 나쁜 영향을 끼치는 경우에는 단기간의 GnRHa의 사용으로 사춘기의 빠른 진행을 억제하고 골성숙의 기간을 연장시킴으로써 예측성인신장을 증가시킬 수 있다. 또한 성장호르몬 병합요법으로 예측성인신장이 표적키에 도달하는데 있어 GnRHa 만으로 성장호르몬-IGF 축이 억제된 경우보다 성장촉진 효과를 나타낸다. 그러나 이는 단기간 사용 시의 치료효과이므로 최종성인신장의 비교를 위해서는 향후 장기적인 추적관찰이 필요하다.

• Clinical and Experimental Reproductive Medicine
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• 제17권1호
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• pp.29-44
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• 1990

In 105 patients with the past history of poor response to the previous controlled ovarian hyperstimulation(COH) due to poor follicular growth or premature LH surge, the effectiveness of pituitary suppression with gonadotropin-releasing hormone agonist(GnRH agonist) in IVF/GIFT program was evaluated in 112 cycles of COH using a combination regimen of Leuprolide acetate (Lupron TAP Pharmaceuticals, USA) and FSH/hMG or pure FSH from May to December, 1989 at SNUH. Starting on day 21 of the menstrual cycle(MCD #21, Day 1), Lupron (1.0mg/day, subcutaneous) was administered once a day till next MCD #3(suppression phase). After the confirmation of pituitary suppression, ovarian follicular growth was stimulated with FSH/hMG or pure FSH from MCD #3(Day + 1), and Lupron was continued with hMG or FSH until hCG administration (D 0) (stimulation phase). After suppression phase, serum E2 level decreased from 183.7${\pm}$95.1(Day 1) to 17.4${\pm}$12.3pg/ml (Day +1), and serum progesterone level from 19.17${\pm}$8.67 to 0.12${\pm}$0.05ng/ml. But there was no decresas in serum LH and FSH levels; LH from 12.74${\pm}$6.21 to 15.49${\pm}$4.93mIU/ml,FSH from 7.60${\pm}$3.84 to 8.58${\pm}$3.15 rnlU/ml. There was no occurrence of premature LH surge during COH. Eleven cycles(9.8%) were cancelled due to poor follicular growth during stimulation phase, and 3 cycles (3.0%) failed in the transvaginal oocytes fretrieval. Serum E2 level was 1366.8${\pm}$642.4 on D 0 and 1492.3${\pm}$906.9pg/ml on D+1. 7.00${\pm}$3.32 follicles(FD${\geq}$12mm) were observed on D 0, and 6.11${\pm}$4.15 oocytes were retrieved, with the oocyte retrieval rate per follicle of 95.0%. 3.59${\pm}$2.57 oocytes were fertilized and cleaved with the oocyte cleavage rate of 55.7%. In 83 IVF patients, 4.08${\pm}$2.39 embryos were transferred, and 16 pregnancies were obtained with the pregnancy rate per ET 2.39 mebryos were transferred, and 16 pregnancies were obtained with the pregnancy rate per ET of 19.3%. In 6 GIFT patients, 7.83${\pm}$3.31 oocytes were retrieved and transferred with maximum number of 6, but no pregnancy was obtained. When compared with the previous 108 cycles of COH using FSH/hMG or pure FSH regimen, the cancellation rate during COH was significantly decreased, and all the parameters of the outcome of COH including the pregnancy rate were increased. These data suggest that GnRH agonist therapy for pituitary suppression is an effective adjunct to the current gonadotropin regimens for COH in IVF/GIFT and can increase the probability of oocytes retrieval and pregnancy, especially in the previous poor responders.

• 한국발생생물학회지:발생과생식
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• 제6권2호
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• pp.131-139
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• 2002

최근 난포에서 GnRH와 그 수용체의 발현이 확인되면서 GnRH가 국소적으로 난소의 기능을 조절하고,특 히 과립세포의 세포자연사(apoptosis)를 유도하는 것으로 보고되고 있다. 그러나 황체에서 GnRH와 그 수용체의 발현과 기능에 대해서는 잘 알려져 있지 않다. 따라서 본 연구는 임신한 흰쥐의 황체세포에서 GnRH와 그 수용체가 발현되는지를 확인하고, 또한 GnRH가 황체세포의 세포자연사를 직접적으로 유발시킬 수 있는지를 알아보고자 시행하였다. 임신된 흰쥐로부터 황체세포를 획득하여 배양한 후 면역조직화학적 염색과 Western blot 방법으로 GnRH와 그 수용체의 발현을 확인한 결과 배양된 황체세포에서 GnRH와 그 수용체가 강하게 발현되는 것을 관찰할 수 있었다. GnRH가 배양된 황체세포의 세포자연사에 미치는 영향을 조사하기 위하여, $10^{-6}$ GnRH-agonist(GnRH-Ag)를 처리한 후 3, 8, 12시간에 TUNEL 방법과 DNA 분절화 검증 방법으로 세포자연사를 조사하였다. TUNEL 결과 세포자연사를 보이는 황체세포는 처리 후 12 시간에 GnRH-Ag 처리군에서 유의하게 증가하였다(p<0.05). 또한 DNA 분절화를 조사한 결과에서도 TUNEL 결과와 유사하게 GnRH-Ag처리 후 12 시간에 DNA 분절화가 유의하게 증가하였다(p<0.05). 이러한 세포자연사의 증가가 cytochrome c 방출과 연관이 있는지를 알아보고자 미토콘드리아로부터 방출된 cytochrome c를 Western blot 방법으로 정량한 결과, GnRH-Ag 처리 후 12 시간에 cytochrome c가 미토콘드리아로부터 세포질쪽으로 방출된 것을 확인할 수 있었다. 결론적으로 임신된 흰쥐의 황체세포에서 GnRH와 그 수용체 단백질이 발현되며 GnRH-Ag가 GnRH 수용체에 결합함으로써 cytochrome c가 미토콘드리아로부터 방출되고, 이로 인해 황체세포가 세포자연사하는 것을 알 수 있었다. 이러한 결과들은 국소적으로 분비되는 GnRH가 미토콘드리아로부터 cytochrome c의 방출을 유발시켜 황체세포의 세포자연사를 유도할 수 있다는 것을 제시하고 있다.

• 대한한방소아과학회지
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• 제30권4호
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• pp.60-65
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• 2016

Objectives The purpose of this study is to emphasize the importance of preventing precocious puberty. This study assessed current number of the patients with early puberty and their medical expenses from 2010 to 2015. Methods Using the data from Korean Statistical Information Service and Heathcare Bigdata Hub, number of patients diagnosed with precocious puberty by gender, age, and year from 2010 to 2015 were reviewed. Also, annual medical insurance expenses and the incidence of leuprorelin use were reviewed. Results Number of the patients with precocious puberty has increased from 29,251 in 2010 to 75,945 in 2015. Total medical insurance expenses have increased from 25,716,431 won in 2010 to 56,367,981 won in 2015. The use of lueprorelin also has increased annually from 11,097,590,000 won in 2010 to 21,617,585,000 won in 2015. Conclusions As a result, the patients diagnosed with precocious puberty are increasing in number, and their medical costs have been rising as well. It may be necessary to control the environmental causes of precocious puberty to reduce not only the physical and psychosocial health problems, but also the social costs.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제19권2호
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• pp.130-138
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• 2016

Purpose: This study was conducted to analyze the change in the obesity index in girls receiving a gonadotropin-releasing hormone agonist (GnRHa), based on treatment duration, and to aid in nutritional counseling by investigating dietary habits and lifestyle. Methods: Anthropometric examinations were conducted on 62 girls treated with GnRHa from January 2010 through July 2014. Parents were asked to fill out questionnaires on patient dietary habits and lifestyle. Results: The group taking GnRHa for over 1 year had a higher rate of obesity increase than the group taking GnRHa for less than 1 year, but they had common habits related to obesity, which should be corrected. In addition, 69.2% of the normal weight group taking GnRHa for over 1 year gained weight, and needed more intensive programs, which include physical exercise and nutritional education. Although girls with precocious puberty showed a decrease in the intake of high-calorie foods with nutritional intervention regardless of treatment duration, they still had problems that needed improvement, such as shorter meals and lack of exercise. Conclusion: Girls with precocious puberty and their parents should emphasize maintenance of proper body weight, especially when treatment for over 1 year is anticipated. Consistent education in nutrition, ways to increase intensity and duration of physical activity, and the need to slow down mealtimes are important in managing obesity; doctors need to perform regular checkups and provide nutritional counseling.

• Clinical and Experimental Reproductive Medicine
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• 제48권1호
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• pp.1-10
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• 2021

In Korean women, a westernized lifestyle is associated with an increased risk of breast cancer. Fertility preservation has become an increasingly important issue for women with breast cancer, in accordance with substantial improvements in survival rate after cancer treatment. The methods of controlled ovarian hyperstimulation (COH) for fertility preservation in breast cancer patients have been modified to include aromatase inhibitors to reduce the potential harm associated with increased estradiol levels. Random-start COH and dual ovarian stimulation are feasible options to reduce the total duration of fertility preservation treatment and to efficiently collect oocytes or embryos. Using a gonadotropin-releasing hormone agonist as a trigger may improve cycle outcomes in breast cancer patients undergoing COH for fertility preservation. In young breast cancer patients with BRCA mutations, especially BRCA1 mutations, the possibility of diminished ovarian reserve may be considered, although further studies are necessary. Herein, we review the current literature on the practical issues surrounding COH for fertility preservation in women with breast cancer.

• Clinical and Experimental Reproductive Medicine
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• 제21권1호
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• pp.13-20
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• 1994

Status of endometrium is a very important factor which influences the implantation of fertilized embryos. In this study, we evaluated the possibility that the endometrial depth and pattern assessed by vaginal sonography on the day of human chorionic gonadotropin (HCG) injection in in vitro fertilization (IVF) cycles could be used to predict the IVF outcome. A total of 112 cycles using gonadotropin releasing hormone agonist (GnRHa) for ovulation induction were evaluated. We classified all patients into group A(<9mm) or group B(${\geq}$ 9mm) according to endometrial depth, and into group l(hyperechogenic), group 2(isoechogenic) or group 3(hypoechogenic and triple line) according to endometrial pattern. The other classification was made considering both endometrial depth and pattern. There was no significant correlation between serum estradiol level and endometrial sonographic findings(depth and pattern)(p>0.05). The pregnancy rate of group A(31.3%) did not differ significantly from that of group B(43.7%), but no pregnancies were found in any patients with endometrial depth less than 6mm. The pregnancy rate was 40%, 35.7%, and 44.6 % for group 1, gorup 2, and group 3, respectively, but there was no statistically significant difference between these groups(p>0.05). In combined classification, there was a trend of higher pregnancy rate in case of endometrial depth greater than 9mm and hypoechogenic triple line pattern, but there was no statistically significant differences between these groups(p>0.05). The conclusion from the present data is that endometrial ultrasonography on the day of hCG administration had no predictive value for conception in IVF cycles.

• 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.

• Clinical and Experimental Reproductive Medicine
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• 제42권2호
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• pp.67-71
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• 2015

Objective: Elevated serum progesterone (P) levels on triggering day have been known to affect the pregnancy rate of in vitro fertilization (IVF). This study aimed to identify the possible factors influencing serum P levels on triggering day in stimulated IVF cycles. Methods: Three hundred and thirty consecutive fresh IVF cycles were included in the study. All cycles were first attempts and were performed in a single infertility center. The indications for IVF were male factor infertility (n=114), ovulatory infertility (n=84), endometriosis (n=61), tubal infertility (n=59), unexplained infertility (n=41), and uterine factor infertility (n=39). A luteal long protocol of a gonadotropin-releasing hormone (GnRH) agonist (n=184) or a GnRH antagonist protocol (n=146) was used for pituitary suppression. Ovarian sensitivity was defined as the serum estradiol level on triggering day per 500 IU of administered gonadotropins (OS[a]) or the retrieved oocyte number per 500 IU of administered gonadotropins (OS[b]). Results: Univariate analysis revealed that the serum P level on triggering day was associated with the serum estradiol level on triggering day (r=0.379, p<0.001), the number of follicles ${\geq}14mm$ (r=0.247, p<0.001), the number of retrieved oocytes (r=0.384, p<0.001), and ovarian sensitivity (OS[a]: r=0.245, p<0.001; OS[b]: r=0.170, p=0.002). The woman's age, body mass index, antral follicle count, and basal serum follicle stimulating hormone and estradiol levels were not associated with serum P level on triggering day. The serum P level on triggering day did not show significant variation depending on the type or cause of infertility, pituitary suppression protocol, or the type of gonadotropins used. Conclusion: The serum P level on triggering day was closely related to the response to ovarian stimulation.

• Clinical and Experimental Reproductive Medicine
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• 제21권1호
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• pp.43-48
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• 1994

To evaluate the effectiveness of GnRH agonist for the treatment of uterine myoma as a cause of infertility, fourteen women were recruited to the study. The patients were treated with a delayed-release formulation of D-$Trp^6$-LHRH in biodegradable microcapsules(Decapeptyl-CR), administered intramuscularly at four week intervals for a period of six monthes. The first injection was given on day 21 of the cycle. Serum estradiol levels fell significantly to the mean value of 257.7pgjml 4 weeks after the first injection. Eleven patients in fourteen treated patients had a reduction in the size of uterine myoma as assessed by ultrasonography, two patients had no change of size and one patient had a increase of size. After the first or second injection, all patients became amenorrheic, then resumption of menstruation ocurred at 12 to 14 weeks after the last injection. Common side effects were hot flush, sweating and dyspareunia, whitch were acceptale. In Eleven patients who had a reduction in the size of uterine myoma by treatment with a delayed- release formulation of D-$Trp^6$-LHRH(Decapeptyl-CR), after above treatment with GnRH agonist, then four patients were treated with myomectomy, three patients had pregnancy and full term delivered by Cesarean section. These data suggest that administration of a delayed-release formulation of a GnRH agonist can be a worthwhile and convenient approach to the medical treatment of uterine myoma as a cause of infertility.