Cyclophosphamide와 Paclitaxel 항암치료 시 GnRH agonist 1, 2 및 GnRH antagonist 투여에 의한 생쥐난포 보존효과

양회생 ( Hoe Saeng Yang ) 대한산부인과학회 2009 Obstetrics & Gynecology Science Vol.52 No.8

목적: 생쥐에서 cyclophosphamide와 paclitaxel의 용량에 따른 원시난포의 파괴정도와 일시적으로 난소를 억제시켜 항암제의 세포독성을 회피하는 GnRHa I과 II 그리고 GnRH antagonist를 병행 투여하여 각기 다른 용량에서 원시난포의 보존효과를 알아보기 위하여 실험하였다. 연구 방법: 생쥐에 각각 50 mg/kg, 75 mg/kg의 cyclophosphamide와 12.5 mg/kg, 19 mg/kg의 paclitaxel을 투여하여 대조군과 비교하여 원시난포의 파괴 정도와 세포자멸사 지표를 측정하였다. 또한 GnRHa I, GnRH antagonist 그리고 GnRHa II를 각각 0.1 mg/kg을 병용투여해서 원시난포의 증가정도와 세포자멸사지표의 감소정도를 측정하였다. 결과: 원시난포의 경우 cyclophosphamide와 paclitaxel의 저용량에서 GnRHa I, II, GnRH antagonist 모두 원시난포 보존효과가 있었고 고용량에서는 GnRH antagonist에서만 보존효과가 있었다. 효과가 있었던 GnRH analogues 각 군 간의 차이는 없었다. 세포자멸사 지표에서는 cyclophosphamide, paclitaxel의 저용량, 고용량 모두에서 GnRHa I, II 및 GnRH antagonist 투여 시 감소하였다. 저용량에서 GnRH analogues 각 군 간의 비교에서는 GnRHa I이 가장 효과적 이었다. 결론: GnRH analogue의 병행투여 군에서 통계적인 유의성을 보인 것으로 보아 항암치료를 받는 가임여성에서도 비슷한 효과를 기대할 수 있으며 이를 뒷받침할 임상연구가 필요할 것으로 생각된다. Objective: The degree of destruction of primordial follicles was investigated following the administration of cyclophosphamide or paclitaxel respectively in mouse ovaies. And then the effect of GnRHa I, GnRH antagonist and GnRHa II on the primordial follicles was evaluated following the administration of cyclophosphamide or paclitaxel. Methods: Saline or cyclophosphamide (50 mg/kg or 75 mg/kg) were intraperitoneally injected into seven-week old female ICR mice. GnRHa I (Leuplin(R)), GnRH antagonist (Cetrotide(R)) or GnRHa II (H-6038) was injected into mice, and administered with 50 mg/kg and 75 mg/kg of cyclophosphamide following 9 days treatment with GnRH analogues. After collecting ovaries, H&E staining was performed and the number of primordial follicles was counted. To confirm the induction of apoptosis, TUNEL assay was performed. Another experimental groups of mice were administered with a low concentration (12.5 mg/kg) or a high concentraion (19 mg/kg) of paclitaxel. Results: Cyclophosphamide and paclitaxel cause mild to moderate destruction of primordial follicles in mouse ovaries. The number of primordial follicles in the group of high dose was noted less than in that of low dose treated with cyclophosphamide or paclitaxel. Increased the apoptotic indices were shown in the group of cyclophosphamide or paclitaxel compared to in saline only treated group. Treatment with GnRHa I, GnRH antagonist and GnRHa II significantly increased the number of primordial follicles at a low concentration of cytotoxic agents (P<0.05), whereas the number of primoridal follicle increased only in GnRHa I antagonist treated group at a high concentration of cyclophosphamide or paclitaxel (P<0.05). Conclusion: The present study shows that GnRH analogues alleviate destruction of primordial follicles caused by cyclophosphamide and paclitaxel in mouse ovaries, suggesting that GnRH analogues may be applicable to increase fertility opportunity in malignant cancer patients of reproductive age planning future pregnancies.

난관수종액이 생쥐 체외수정과 배아 발달에 미치는 영향

양회생(Hoe Saeng Yang) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.7

N/A Objective : To ascertain if hydrosalpinges are associated with reduced pregnancy rates and increased pregnancy loss after IVF-ET, a study was conducted. Increased volume and leakage of hydrosalpinx fluid may exert negative effects on follicular development and embryo quality and/or render the uterine environment hostile to embryogenesis. This study was undertaken to examine the effect of hydrosalpinx fluid an mouse embryogenesis in vitro. Methods :The study was designed by comparison of mouse embryo blastulation rate in media containing increasing concentrations of hydrosalpinx fluid. In vitro fertilization rate and the development of one-, two-, four-cell mouse embryos in medium containing 0% (Control), 0.3%, 0.6%, 0.9%, 5%, 10% and 20% of human hydrosalpinx fluid-containing media was observed. Results :In vitro fertilization and culture of mouse embryo at 0% (control), 0.3%, 0.6%, 0.9%, 5%, 10%, 20% hydrosalpinx fluid concentrations demonstrated significantly 1ower blastulation rate at each level compared with the controls (p<0.05). In vivo fertilization and culture of embryo at the same increasing concentration of hydrosalinx fluid showed the same results (p<0.05). And the difference of each embryo development (zygote, 2cell, 4cell) was not significant. Conclusion :Hydrosalpinx fluid is highly embryotoxic. Procedures such as, salpingectomy ar proximal tubal occlusion to circumvent the passage of hydrosalpinx fluid into the uterine cavity may have beneficial effects on the developmental environment for embryos in vivo.

만삭 임산부에서 Misoprostol 및 Dinoprostone 질정이 자궁경부 숙화 및 분만유도에 미치는 영향

김종호(Jong Ho Kim),양회생(Hoe Saeng Yang) 대한산부인과학회 2000 Obstetrics & Gynecology Science Vol.43 No.2

목적: 만삭 초산모에서 misoprostol과 dinoprostone을 자궁 경부의 숙화를 위해 질내 투여 후 옥시토신을 정주 하였을 때 분만에 미치는 효용성과 안전성을 알아보기 위해 시행하였다. 연구 방법: 유도 분만을 위해 내원한 임신 37주 이상의 초산모에게 무작위로 misoprostol 50㎍과 dinoprostone 3㎎을 자궁 경부의 숙화를 위해 질내 투여 12 시간 후에 모든 산모에게 옥시토신을 정맥 투여하여 분만을 유도하였을 때 두 군간의 분만까지의 시간, 제왕절개술의 빈도 그리고 태아 및 산모에 미치는 영향을 비교하였다. 결과: 초산모 113명을 대상으로 misoprostol 50㎍ 질내투여군 39명과 dinoprostone 3㎎ 질내투여군 74명이었으며, Misoprostol 질내 투여 후 옥시토신을 투여한 군에서 dinoprostone을 투여 후 옥시토신을 투여한 군 보다 의미 있게 분만시간이 짧았으며(1274±496 versus 1512±501 minutes)(p<0.001), 분만 방법, 제왕절개술의 빈도, 태아 및 산모에 미치는 영향은 유의한 차이가 없었다. 결론: 자궁경관의 숙화가 이루어지지 않은 산모에 있어 유도 분만시 옥시토신을 사용하기 전에 misoprostol을 투여하여 자궁 경관의 숙화를 유도하는 것이 효과적이고 안전한 방법으로 생각된다. 그리고 앞으로 misoprostol에 대한 적절한 투여 방법과 용량 및 안전성에 대한 더 많은 연구가 이루어져야 할 것으로 사료된다. Objective: To compare the efficacy and safety of intravaginal administerd misoprostol and PGE2 (dinoprostone) with oxytocin for inducing labor in women with an unfavorable cervix. Methods: One hundred thirteen patients with indicated for labor induction and unfavorable cervix were randomly assigned and received either misoprostol 50㎍ intravaginal with oxytocin intravenous injection or prostaglandin E2(dinoprostone) 3㎎ intravaginal with oxytocin intravenous injection. Results: Thirty-nine subjects were assigned to misoprostol with oxytocin group and 74 to the PGE2 with oxytocin group. The median interval from induction to vaginal delivery was significantly shorter in the misoprostol with oxytocin group(1274±496 versus 1512±501 minutes)(p<0.001). No significant difference between two groups were mode of delivery, neonatal and maternal outcomes. Conclusion: Intravaginal misoprostol and PGE2 vaginal insert appear to be safe agents for cervical ripening and labor induction. Misoprostol is more effective than PGE2 vaginal insert with oxytocin injection.

산후우울증의 선별도구 간 일치도 및 관련 요인 연구

김미운 ( Mi Woon Kim ),양회생 ( Hoe Saeng Yang ),김장락 ( Jang Rak Kim ) 대한산부인과학회 2009 Obstetrics & Gynecology Science Vol.52 No.11

목적: 본 연구는 산후우울증의 선별 척도간 일치도와 유병률을 알아보고, 관련 요인을 파악하기 위해 시행되었다. 연구 방법: 연구에 동의한 323명의 환자에게 산후 1주일째에 3 종류의 산후우울증 선별 검사와 개인 정보를 위한 설문을 시행하였으며, 산부인과 정보는 의무기록에서 얻었다. EPDS와 BDI에 공통으로 위험군인 경우를 산후우울증으로 정의하였고, 유병률, 검사간 일치도 및 관련요인을 파악하였다. 결과: 산후우울증 유병률은 19.8%, Kappa지수는 EPDS, BDI, QIDS-SR16에서 각각 0.803, 0.711, 0.395였다. 산후우울증 관련요인은 단순분석시 수유방법, 흡연력, 산전 불안/우울증상, 부모와의 거주, 결혼 만족도, 임신전 시부모와의 관계, 산후조리형태 등이, 로지스틱 회기분석 시 미숙아 분만, 조제분유 수유, 결혼 불만족, 전문직 남편, 산전 불안/우울 증상 등이 유의한 관련요인으로 나타났다 (P<0.05). 결론: 산후 1주일째 2가지 선별 검사를 동시 이용하여 효과적으로 산후우울증 유병률을 파악하였으며, EPDS가 가장 높은 일치도를 나타내었다. 여러 관련 요인들이 파악되었고 향후 더욱 많은 연구가 필요하리라 생각된다. Objective: This study was performed to assess agreements among screening tests, to estimate prevalence, and to identify related factors with postpartum depression. Methods: For 323 women at 7 days postpartum, self-administered questionnaires were given including postpartum depression screening test such as EPDS, QIDS-SR16, BDI and questionnaires for their demographic and psycho-social information. Obstetric information were collected from medical records. Simultaneous positive cases in EPDS and BDI were defined as gold standard and used to estimate the prevalence of postpartum depression and agreements between 3 kind of screening test and gold standard. Related factors of postpartum depression were analysed by using SPSS. Results: The prevalence of postpartum depression was 19.8% and the Kappa indices were 0.711 in BDI, 0.803 in EPDS, and 0.395 in QIDS-SR16. Feeding method, smoking history, antenatal anxiety/depression symptoms, residence status, marital satisfaction, relationship with husband`s parents, and postpartum care method in univariate analysis and premature delivery (odds ratio: 2.9), formulated feeding (odds ratio: 3.8), marital dissatisfaction (odds ratio: 4.3), professional husband`s occupation (odds ratio: 4.4), and antenatal anxiety/depression symptoms (odds ratio: 4.4) in the logistic regression analysis were significantly related to postpartum depression (P<0.05). Conclusion: Simultaneous test of BDI and EPDS was effective to evaluate postpartum depression prevalence at 1-week postpartum and highly agree with EPDS. Significant related factors were defined and further prospective community-based studies are warranted.

자궁부속기 종양 염전의 임상,병리학적 고찰

하준영 ( Ha Jun Yeong ),양회생 ( Yang Hoe Saeng ) 대한산부인과학회 2004 Obstetrics & Gynecology Science Vol.47 No.2

목적 : 자궁부속기 종양 염전의 조기 진단 및 난소기능 보존을 위해, 염전의 발생빈도, 임상 양상, 이학적 소견, 염전의 위치 및 정도, 임신과의 관계, 초음파 소견, 병리조직학적 소견을 분석하고자 한다. 연구 방법 : 1993년 3월부터 2003년 3월까지 동국대학병원 산부인과에서 자궁부속기 종양으로 진단되어 수술한 510예 중 수술소견 및 병리조직학적 소견 상, 염전이 확인된 50예를 대상으로 후향적으로 분석하였다. 결과 : 자궁부속기 종양으로 수술한 경우는 임신이 동반된 42예를 포함하여 510예였고 이중 염전이 발생한 경우는 임신이 동반된 16예 (38%)를 포함하여 50예 (10%)였다. 염전이 발생한 50예에 대한 임상적 양상은 다음과 같다. 연령별 발생빈도는 20-30대군 (20-39세)으로 36예 (72%)였고, 미산부에서 21예 (42%)로 가장 높았다. 기왕 수술병력과의 관계에서 수술병력이 없는 경우가 42예 (84%)였다. 빈도별 증상으로 하복부 동통 48예 (96%), 소화기계 증상 42예 (84%), 비뇨기계 증상 11예 (22%), 질 출혈 4예 (8%)였고, 일반혈액 검사 상 백혈구 증가의 경우는 28예 (56%)였다. 초음파 소견상 종양벽의 비대는 46예 (90%)에서 관찰되었고, 고형질 내부음영 40예 (78%), 격막의 존재가 12예 (24%)였다. 수술적 소견으로 염전체의 크기는 5-9 cm이 30예 (58%)로 가장 많았고, 염전의 정도는 360°와 720° 회전된 염전체가 40예 (78%)였다. 발생 위치는 우측 27예 (55%), 좌측 22예 (45%)였다. 수술방법으로는 개복수술이 41예 (82%), 복강경수술 9예 (18%)였다. 전체 수술 중, 보존적 종양 절제술의 경우는 5예 (12%)였다. 병리조직 소견상 괴사 소견 44예 (86%), 내부출혈 소견 39예 (76%)였다. 조직학적으로는 기능성 낭종 25예 (49%), 양성 신생물은 22예 (43%)였다. 악성 신생물은 1예 (2%)가 있었다. 임신 중 염전체의 종류로는 황체낭종 9예 (56%)로 가장 많았으며, 염전체의 수술 후 임신의 예후는 만삭분만이 9예 (56%), 유산이 2예 (12%), 조산 분만이 1예 (6%)였다. 결론 : 오심, 구토를 동반한 급성 하복부 동통을 보이는 20-30대 가임기 여성에서 백혈구의 증가가 있고, 초음파 상 자궁부속기에 종양벽 두께의 증가를 보이는 5-9 cm 크기의 낭성 종양이 발견되면 염전을 고려하여, 적절하고 신속한 진단 및 치료를 시행해야 한다. Objective : We analyzed the frequency, clinical symptom, physical exam, site and the degree of torsion, ultrasound findings, histological aspects and the relationship between the pregnancy of ovarian torsion in order to help the early detection of the disease and conservation of the ovary. Methods : Out of 510 operative cases of adnexal mass patients in Dongguk university hospital from March 1993 to March 2003, 50 histologically confirmed cases of ovarian torsion were selected and retrospectively analyzed. Results : Operative cases of adnexal mass were 510 including the 42 complicated by pregnancy and out of these, torsion occurred in 50 cases (10%) with 16 pregnancy complication. Clinical features of 50 torsion cases are as follows. The frequencies of uterine adnexal tumor torsion were reported by age, 36 cases (72%) in their twenties and thirties, with 21 (42%) nulliparous women at the highest. 42 (84%) had no previous operative history. On the clinical features and physical exam, in the order of frequency, 48 cases (96%) of lower abdominal pain were the highest, and 42 (84%) of GI symptoms, 11 (22%) of urogenital symptoms, and 4 cases (8%) of vaginal bleeding was noted. Under CBC study, 28 (56%) leukocytosis were reported. And on the ultrasound findings, 46 cases (90%) of tumor with hypertrophic wall were noted, septum existed in 12 cases (24%), and 40 (78%) represented internal shadow of the solid portion. The tumor size between 5 to 9 centimeters were the most with 30 cases (58%), and the sum of torsions with 360 and 720 degrees consisted of 40 (78%), occupying for the most of the cases. 27 (55%) of right side existed compared to the 22 (45%) of left. 42 had no previous transabdominal surgery. In the method of operation, 41 (82%) explorative surgeries and 9 cases (18%) of laparoscopic surgery was done, and 5 of these were conservative (12%). The necrosis was noted in 44 cases, and internal bleeding was present in 39 cases. Histologically, functional cyst consisted highest in numbers with 25 (49%), where benign neoplasm with 22, and one malignant neoplasm. About relationship with pregnancy, 9 cases (56%) of corpus luteal cyst were the most. Outcome of the pregnancy was 9 (56%) full term deliveries, 2 abortions (12%), and 1 (6%) preterm delivery. Conclusion : Ovarian torsion should be considered when women in between their twenties and thirties with abrupt onset of lower abdominal pain along with nausea and vomiting, leukocytosis, and 5 to 9 cm sized cystic mass with the wall hypertrophy present in ultrasound. Immediate and accurate diagnosis and treatment should follow.

산전 태아 체중 평가에 도플러 초음파의 이용

김종호(Jong Ho Kim),최석철(Suck Chul Choi),양회생(Hoe Saeng Yang),심재철(Jae Chul Sim),배철성(Cheol Seong Bae),윤혜원(Hae Won Yoon),강민아(Min A Kang) 대한산부인과학회 1999 Obstetrics & Gynecology Science Vol.42 No.3

N/A Objective: The objective of this study was to determine the relationship between the fetal doppler flow velocimetry and birth weight in low risk pregnancy population. Methods: From December 1995 to May 1996, We prospectively performed doppler study in 254 uncomplicated, term pregnant women, who visited Pohang Hospital, Dongguk University. Using pulsed color doppler, we measured umbilical artery RI, middle cerebral artery RI and middle cerebral-umbilical artery RI ratio within one week before delivery. Results: The result was that low birth weight group (below 2500gm) had very significant lationship with umbilical artery RI(P<0.01), middle cerebral artery RI(P<0.05) and middle cerebral-umbilical artery RI ratio(P<0.05), but there was no significant relationship in these blood flow indices between normal birth weight group (2501gm- 3999gm) and macrosomia group (above 4000gm). Conclusions: We concluded that application of doppler ultrasonopaphy in the assessment of fetal weight is somewhat helpful for identification of low birth weight, not for macrosomia.

Fentanyl과 Midazolam이 생쥐 체외수정과 배아발달에 미치는 영향

정상윤(Sang Yoon Jung),이은주(Eun Joo Lee),양회생(Hoe Saeng Yang),심재철(Jae Chul Sim) 대한산부인과학회 2000 Obstetrics & Gynecology Science Vol.43 No.6

N/A Ojective: To assess the effect of fentanyl and midazolam on in vitro fertilization rate and early embryo development in a mouse IVF model.Methods: Mouse oocytes were exposed in vitro to fentanyl at a concentration of 0(control), 50, 250, 500, 1000, 5000 pg/ml, and midazolam, 0(control), 2.5, 12.5, 25, 50, 250 ng/ml for 30 minutes, washed and inseminated. Thereafter fertilization was assessed. And subsequent in vitro development to the blastocyst stage was monitored daily.Results: Where fertilization occurred, subsequent embryo cleavage and development up to the blastocyst stage was affected significantly by the presence of fentanyl and midazolam solution in the medium(i.e., 14% to 31%, 10% to 35%), in comparison with control group( 60%, 62%).Conclusion: It can be concluded from these experiments that even a brief exposure of cumulus enclosed oocytes to a low concentration of fentanyl, midazolam is deleterious to subsequent cleavage.

완전 고환성 여성화증후군 환자에 생긴 Sertoli 세포선종 1 예

강민아(Min A Kang),김종호(Jong Ho Kim),최석철(Suck Chul Choi),양회생(Hoe Saeng Yang),심재철(Jae Chul Sim),김정란(Jung Ran Kim) 대한산부인과학회 1999 Obstetrics & Gynecology Science Vol.42 No.1

Testicular feminization is an uncommon genetic disorder with considerably familial predisposition and results in total feminization due to end-organ unresponsiveness to androgens. It is characterized by the presence of testes in phenotypically female with adequate breast development, normal extemal genitalia, absence of mullerian structures, and meager or absence of body hair. These patients characteristically have male karyotype(XY) and negative sex chromatin and are at increased risk of undergoing malignant transformation of the undescended gonad. In recent times, the malignant potential of the dysgenetic gonads in the intersex patients with a Y chromosome has been stressed by many authors, but few reports of an association between testicular feminization syndrome and benign tumors such as Sertoli cell adenomas. In the present study, postoperative pathology revealed that the gonads were Sertoli cell adenomas. The main features of clinical presentation and histological studies are briefly discussed with a review of the literature.

자궁강내 인공수정 시 임신율에 영향을 주는 요인

김연경 ( Yeon Kyoung Kim ),신동명 ( Dong Myung Shin ),김도균 ( Do Gyun Kim ),양회생 ( Hoe Saeng Yang ) 대한산부인과학회 2005 Obstetrics & Gynecology Science Vol.48 No.4

Udenafil (Zydena)이 생쥐의 수정과 초기 배아 발달에 미치는 영향

천근수 ( Keun Soo Cheon ),심재철 ( Jae Chul Sim ),양회생 ( Hoe Saeng Yang ) 대한산부인과학회 2011 Obstetrics & Gynecology Science Vol.54 No.9

목적: Udenafil (Zydena)이 생쥐의 수정률, 그리고 배아 발달에 미치는 영향을 알아보기 위하여 실험을 시행하였다. 연구방법: 수컷 생쥐에게 udenafil (사람 경구 용량과 같은 0.06 mg/0.05 mL)을 투여한 후 암컷과 교미 시켜서 교미 후 첫째 날, 둘째 날, 셋째 날 그리고 넷째 날 각각 수정률과 초기 배아 발달 정도를 알아보기 해 대조군과 비교하여 미수정난, 1-cell (zygote), 2-cell, 4-cell, 8-cell, morula 그리고 blastocyst의 개수의 차이를 평가하였다. 결과: 실험결과 첫째 날은 udenafil을 투여한 군에서 대조군에 비해 수정되지 않은 난자수가 더 많았고 1-cell (zygote)의 경우는 대조군에 비하여 더 적었으며 2-cell의 경우도 대조군에 비하여 더 적었다. 둘째 날은 udenafil을 투여한 군에서 대조군에 비해 수정되지 않은 난자수가 더 많았고 1-cell (zygote)의 경우는 대조군에 비하여 더 적었으며 2-cell의 경우도 대조군에 비하여 더 적었으며 4-cell 역시 대조군에 비하여더 적었다. 셋째 날은 udenafil을 투여한 군에서 대조군에 비해 수정되지 않은 난자수가 더 많았고 1-cell (zygote)의 경우는 대조군에 비하여 더 많았으며 8-cell의 경우도 대조군에 비하여 더 많았으나 morula는 대조군에 비하여 더 적었다. 넷째 날은 udenafil을 투여한 군에서 대조군에 비해 수정되지 않은 난자수가 더 많았고 1-cell (zygote)의 경우는 대조군에 비하여 더 많았으며 morula의 경우는 대조군에 비하여 더 적었으며 morula 역시 대조군에 비하여 더 적었다. 결론: 본 연구에서 udenafil이 동물 실험에 있어서 수정률을 낮추고, 배아 발달을 억제한다고 논증하고있다. 이는 불임센터에서 임신을 위해 성교전에 udenafil을 복용하는 이들에게 udenafil이 수정률과 배아 발달에 좋지 않은 영향을 미친다는 것을 암시를 하고 있다. Objective: To determine the effect of udenafil, a cyclic monophosphate-specific type 5 phosphodiesterase inhibitor, on fertilization and early embryo cleavage of mice, Methods: This mammal study included randomly assigned male and female mice, The females were sacrificed after mating to evaluate their oocytes and embryos in four different time intervals following the treatment. Female mice were injected intraperitoneally with 5 IU of gonadotropin and human chorionic gonadotropin to stimulate follicular growth and induce ovulation. They were separately caged with males that had been gavaged with udenafil (0.06 mg/0.05mL) and allowed to mate. After 24, 48, 72, and 96 hours of time intervals, females were killed, their oviducts were dissected out, and retrieved embryos were assessed for blastomere number and quality. Fertilization rates and numbers of embryos were evaluated after treatment. Results: Fertilization rates were reduced in females that were mated with udenafil gavaged males. Over days 2-4, the numbers of embryo that of the treated group were significantly fewer than in the control group. There was also a tendency of impaired cleavage rates with those embryos. Conclusion: The impairments of fertility caused by udenafil have important implications for infertility centers and couples who are using this drug precoitally while attempting to conceive.