• Childhood Kidney Diseases
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• 제23권2호
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• pp.124-127
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• 2019

Herlyn-Werner-Wunderlich (HWW) syndrome is a rare congenital anomaly of the genitourinary tract comprising uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Patients with HWW syndrome usually present symptoms such as dysmenorrhea, abdominal pain, pelvic mass, and purulent vaginal discharge. If not treated at an appropriate time, complications such as infertility, endometriosis, pyosalpinx, and subsequent pelvic adhesions may occur. Here, we report a case of HWW syndrome in a 7-year-old-girl who was also diagnosed as having central precocious puberty. She was brought to the pediatric department with chief complaints of lump in her breast and vaginal discharge. When she was around 2 months old, she was confirmed to have a single kidney on ultrasonography. We checked her past medical history and diagnosed her as having HWW syndrome based on the results of imaging studies, including abdominal ultrasonography and pelvic magnetic resonance imaging. She underwent treatment with gonadotropin-releasing hormone analogue for 2 years. During 24 months of follow-up, she showed no serious problems or complications. If renal anomalies are identified immediately after birth or in infancy, further screening tests should be conducted prior to menstruation for determining congenital abnormalities of the reproductive tract and vice versa.

• Clinical and Experimental Reproductive Medicine
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• 제48권2호
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• pp.184-187
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• 2021

Radical trachelectomy is a fertility-preserving alternative to radical hysterectomy in carefully selected young women with early-stage cervical cancer. However, in cases with subsequent severe cervical stenosis, assisted reproductive techniques can be difficult. This is a case report of a 34-year-old patient who underwent robot-assisted radical trachelectomy and cerclage for early-stage (IB2) adenosquamous carcinoma. Three months after surgery, the patient underwent ovarian stimulation using a gonadotropin-releasing hormone antagonist protocol. As it was impossible to perform transcervical embryo transfer due to the almost complete absence of the cervical opening, transmyometrial embryo transfer under ultrasound guidance was performed. This resulted in a successful singleton pregnancy. This is the first case of successful pregnancy conceived by in vitro fertilization with transmyometrial embryo transfer in a patient who had previously undergone robot-assisted radical trachelectomy.

• 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.

• 한국발생생물학회지:발생과생식
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• 제26권3호
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• pp.107-115
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• 2022

Kisspeptins, products of KISS1 gene, are ligands of the G-protein coupled receptor (GPR54), and the kisspeptin-GPR54 signaling has an important role as an upstream regulator of gonadotropin releasing hormone (GnRH) neurons. Interestingly, extrahypothalamic expressions of kisspeptin/GPR-54 in gonads have been found in primates and experimental rodents such as rats and mice. Hamsters, another potent experimental rodent, also have a kisspeptin-GPR54 system in their ovaries. The presence of testicular kisspeptin-GPR54 system, however, remains to be solved. The present study was undertaken to determine whether the kisspeptin is expressed in hamster testis. To do this, reverse transcription-polymerase chain reactions (RT-PCRs) and immunohistochemistry (IHC) were employed. After the nest PCR, two cDNA products (320 and 280 bp, respectively) were detected by 3% agarose gel electrophoresis, and sequencing analysis revealed that the 320 bp product was correctly amplified from hamster kisspeptin cDNA. Modest immunoreactive (IR) kisspeptins were detected in Leydig-interstitial cells, and the weak signals were detected in germ cells, mostly in round spermatids and residual bodies of elongated spermatids. In the present study, we found the kisspeptin expression in the testis of Syrian hamster. Further studies on the local role(s) of testicular kisspeptin are expected for a better understanding the physiology of hamster testis, including photoperiodic gonadal regression specifically occurred in hamster gonads.

• 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.

• 한국발생생물학회지:발생과생식
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• 제13권4호
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• pp.257-264
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• 2009

6-hydroxydopamine(6-OHDA)는 파킨슨 질환 동물 모델의 제조에 널리 사용되는 신경독소로 도파민성 뉴런에 대한 특이적인 독성을 나타낸다. 도파민 신호는 중추신경계의 광범위한 영역에서 생리 기능을 조절하는데, 이에 따라 파킨슨병 환자와 6-OHDA를 처리한 동물들의 신경내분비 활성에 극심한 변화가 있을 것으로 예상할 수 있다. 하지만 6-OHDA 주사 모델에서 시상하부-뇌하수체 신경내분비 회로에 관한 연구들은 전무한 실정이다. 본 연구는 6-OHDA에 의한 뇌 카테콜아민 합성의 차단이 성체 수컷 흰쥐의 시상하부-뇌하수체 호르몬 유전자들의 전사 활성에 일으키는 변화를 조사한 것이다. 생후 3개월의 수컷 흰쥐(SD strain)에 개체 당 $200{\mu}g$의 6-OHDA를 $10{\mu}\ell$의 생리식염수에 녹여 뇌실 내 주사(icv)하였고, 2주 후에 모든 실험동물들을 희생시켰다. 시상하부-뇌하수체 호르몬 유전자들의 mRNA 수준을 조사하기 위해 total RNA를 추출하여 반-정량적 RT-PCR을 시행하였다. 카테콜아민 생합성에서 속도조절효소로 작용하는 tyrosine hydroxylase(TH)의 경우 6-OHDA군에서 대조군에 비해 유의한 발현 감소가 나타났고(대조군:6-OHDA군=1:0.72${\pm}$0.02AU, p<0.001), 이를 통해 6-OHDA 주사의 효력을 확인 하였다. 시상하부에서 gonadotropin-releasing hormone(GnRH)과 corticotropin releasing hormone(CRH)의 mRNA 수준은 6-OHDA군이 대조군에 비해 유의하게 낮았다(GnRH, 대조군:6-OHDA군=1:0.39${\pm}$0.03AU, p<0.001; CRH, 대조군:6-OHDA군=1:0.76${\pm}$0.07AU, p<0.01). 뇌하수체에서 glycoprotein hormone들의 공통적인 alpha subunit(Cg$\alpha$)과 LH beta subunit(LH-$\beta$) 그리고 FSH beta subunit(FSH-$\beta$)의 mRNA 수준의 경우 모두 6-OHDA군에서 대조군에 비해 유의한 감소를 나타냈다(Cg$\alpha$, 대조군:6-OHDA군=1:0.81${\pm}$0.02AU, p<0.001; LH-$\beta$, 대조군:6-OHDA군=1:0.68${\pm}$0.04AU, p<0.001; FSH-$\beta$, 대조군:6-OHDA군=1:0.84${\pm}$0.05AU, p<0.01). 이와 유사하게, 6-OHDA군에서의 뇌하수체 adrenocorticotrophic hormone(ACTH) 전사 수준 역시 대조군에 비해 유의하게 낮았다(대조군:6-OHDA군=1:0.86${\pm}$0.04AU, p<0.01). 본 연구는 중추신경계로의 도파민 신경독소 주입에 의해 두 가지의 시상하부-뇌하수체 신경내분비 회로인 GnRH-성선자극호르몬 회로와 CRH-ACTH 회로의 전사 활성이 하향 조정됨을 증명하였다. 이러한 결과는 시상하부로의 CA 입력은 시상하부-뇌하수체 기능 조절을 통해 생식소와 부신의 활성에 영향을 미침을 시사하는 것으로, 파킨슨병 환자들에게서 빈번하게 발생하는 성 기능 장애와 열악한 스트레스 반응을 설명할 단서를 제공한다.

• Clinical and Experimental Reproductive Medicine
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• 제19권1호
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• pp.41-48
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• 1992

Serum level of ${\beta}$ subunit of human chorionic gonadotropin (${\beta}-hCG$) was studied to evaluate its predictability of pregnancy outcome in 98 in vitro fertilization and embryo transfer(IVF-ET) patients using gonadotropin-releasing hormone(GnRH) agonist. Serial serum ${\beta}-hCG$ levels were established for 42 singleton pregnancies, 20 normal multiple pregnancies, 18 preclinical abortions, 14 clinical abortions and 4 ectopic pregnancies. In comparison to normal singleton pregnancies, multiple pregnancies showed significantly higher ${\beta}-hCG$ levels on the post-ET day 10 to 13 and day 24 to 25. Clinical abortions did not show significantly lower ${\beta}-hCG$ levels in early pregnancy except the post-ET day 16-17, but showed significantly lower ${\beta}-hCG$ levels from the post-ET day 22, compared with singleton pregnancies. Preclinical abortions showed significantly lower ${\beta}-hCG$ levels than those of singleton pregnancies. Ectopic pregnancies showed lower ${\beta}-hCG$ levels than those of singleton pregnancies without statistical significance. In conclusion, determination of serum ${\beta}-hCG$ level in early pregnancy is a useful tool for the prediction of preclinical abortions and multiple pregnancies and serial measurement of serum ${\beta}-hCG$ levels will be helpful in predicting clinical abortion.

• 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.

• 한국수산과학회지
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• 제33권1호
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• pp.55-59
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• 2000

무지개 송어의 뇌하수체 및 배양액에 존재하는 GTH II 농도를 측정하기 위해 Avidin- Biotin complex를 이용한 sandwich EIA 계을 개발했다. Protein A sepharose affinity chromatography을 통해서 얻어진 연어 GTH II의 rabbit IgG에 biotinylation시킨 것 (Biotin-salmon GTH II rabbit IgG)을 제2 항체로 사용하였고, Non-Biotin salmon GTH II rabbit IgG는 단지 protein A sepharose affinity chromatography에서 얻어진 IgG를 제 1 항체로 사용하였다. EIA는 sandwich법에 의해서 이루어졌으며, 효소반응 기질로는 TMB(3,3'5,5-tetramethylbenzidine)를 이용했으며, 반응후 450 nm의 흡광도에서 automatic microplate reader로 측정하였다. 그 결과, $0.12\;{\~}\;125\;ng/ml$의 범위에서 용량반응곡선을 얻었으며, 측정감도 (최소 검출량)는 거의 0.58 ng/ml 정도 였다. 그리고 뇌하수체 추출물 및 배양액 각각의 희석곡선은 GTH II 표존곡선과 일치 하였다. 또한 이러한 GTH II의 표준곡선는 뇌하수체내 다른 peptide hormone와는 교차반응을 거의 나타내지 않았다. Testosterone을 처리한 미성숙 무지개 송어의 뇌하수체 세포배양계를 이용하여 sGnRH에 의한 GTH II 분비량을 본 sandwich EIA계와 RIA계를 비교 조사한 결과, 거의 같은 분비량을 나타냈을 뿐만아니라 같은 분비 pattern을 나타냈다. 이러한 결과로부터 본 sandwich법 EIA계에 의해서 연어과 어류의 뇌하수체 추출물 및 뇌하수체 배양액 중의 GTH II 함량 및 분비량을 측정하는데 있어서 안정된 assay계라고 생각되어진다.

• 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.