A Prospective Comparison of Fertilizability of in vitro Matured Human Oocytes Obtained from Stimulated Cycle: Conventional Versus ICSI

지병철,안소정,문정희,황은주,서창석,김석현,문신용,Jee, Byung-Chul,An, So-Jung,Moon, Jeong-Hee,Hwang, Eun-Ju,Suh, Chang-Suk,Kim, Seok-Hyun,Moon, Shin-Yong The Korean Society for Reproductive Medicine 2009 Clinical and Experimental Reproductive Medicine Vol.36 No.4

목 적: 고식적 체외수정시술과 세포질내정자주입법을 사용하여 체외성숙 난자를 수정시키고 수정률과 배발달율을 비교하고자 하였다. 연구방법: 2007년 1월부터 2008년 8월까지 난소과자극과 체외수정시술을 받은 59명의 여성에서 135개의 배아소포 단계의 미성숙난자만을 얻어 75 mIU/mL rFSH, 0.5 IU/mL rhCG, 10 ng/mL rEGF가 포함된 체외성숙용 배양액에서 최대 48시간까지 배양하였다. 체외성숙된 난자는 고식적 체외수정방법 (n=41) 또는 세포질내정자주입법 (n=94)을 이용하여 수정시켰으며 이후 배발달율을 관찰하였다. 결 과: 고식적 체외수정군과 세포질내정자주입군에서 체외성숙률은 각각 51.2%와 59.6%였고, 수정률은 각각 71.4%와 80.4%로 두 군간에 통계적으로 유의한 차이는 없었다. 배발달율도 두 군에서 비슷하게 관찰되었다. 결 론: 난소과자극을 통해 얻은 미성숙난자는 고식적 체외수정법을 사용하더라도 세포질내정자주입법과 동등한 수정률과 배발달율을 보임을 확인하였다. Objective: The aim of this study was to compare the fertilization and cleavage rates of human in vitro matured oocytes after fertilized by conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Methods: A total of 135 GV stage oocytes were obtained from 59 women who received ovarian stimulation and IVF during Jan 2007 to Oct 2008. Ovarian hyperstimulation was performed using hMG or recombinant FSH with GnRH antagonist and then ovulation triggered by recombinant hCG. The immature oocytes obtained from stimulation cycles were cultured in IVM medium up to 48 hrs; commercial medium supplemented with rFSH 75 mIU/mL, rhCG 0.5 IU/mL and rEGF 10 ng/mL. The in vitro matured oocytes were fertilized by conventional IVF (41 GV oocytes) or ICSI method (94 GV oocytes). Results: Maturation rate were 51.2% and 59.6% in conventional IVF group and ICSI group, respectively. There was no significant difference in fertilization rates between two groups; 71.4% and 80.4%, respectively. The cleavage rate was also similar in two groups. Conclusion: The presented data suggest that conventional IVF has comparable fertilization and cleavage potential compared with ICSI as the insemination method of immature human oocytes obtained from stimulated cycle.

호르몬 대체요법 후 유방 실질의 음영 증가

지병철(Byung Chul Jee),김형석(Hyung Suk Kim) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.5

N/A Purpose : To verify the increase of mammographic density in women with 1-year hormone replacement therapy(HRT). Methods : A total of 53 HRT users who received same HRT regimen during 1 year with a normal baseline mammogram and 1-year follow-up mammogram was recruited. Seventy-three never-users were allocated as control group. Results : The increase of mammographic density was observed in 22.6% of 1-year HRT users, compared with 6.8% in never-users (P=0.023). The odds ratio was 3.98 (95% CI : 1.31~12.1) in 1-year HRT users, and 8.37 (95% CI : 2.36~29.6) in continuous combined regimen group compared to control. Conclusion : The incidence of dense mammogram was significantly higher in women with 1-year HRT users than in control, and the risk was remarkable in continuous combined regimen group.

최우수논문상(생식내분비학)

지병철 ( Byung Chul Jee ),( Jee Hyun Kim ),( Hyun Ju Lee ),( Eun Jeong Yu ),( Chang Suk Suh ),( Seok Hyun Kim ) 대한산부인과학회 2015 대한산부인과학회 학술대회 Vol.101 No.-

Objective: To evaluate the dose eHect of recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) or brain-derived neurotrophic facIo`` (BDNF) in culture medium on the development of in vitro fertilized mouse embryos. Methods: Mature oocytes were retrieved from superovulated female BDF1 mice and inseminated by sperm from male BDF1 mice. On day 1, two-cell stage embryos were divided and cultured until day 5 in the embryo maintenance medium supplemented with 0, 1, 2, 5, or 10 ng/mL of rmGM·CSF or supplemented with 0, 5, 10, or 20 ng/mL of BDNF Blastocyst formation rate and their cell numbers were assessed Results: The blastocyst formation rate and the total ce I count in blastocyst was similar in all the rmGM·CSF treatment groups when compared with the control. However, the blastocyst formation rate and the total cell count was significantly higher in the group supplemented with 10 ng/mL of BDNF compared with the control (63.9%, 45.B±11 .5 vs. 52.3%. 38.0±6.8; P<O.05, respectively), Conclusion: Supplementation of 10 ng/mL of BDNF enhanced the developmental potential 01 mouse preimplantation embryos, but supplementation of rmGM·CSF did not.

Aniline Blue 염색을 이용한 정자 핵성숙 평가의 지표로서 저장액 팽창검사의 의의

지병철(Byung Chul Jee),문신용(Shin Yong Moon) 대한산부인과학회 1999 Obstetrics & Gynecology Science Vol.42 No.8

목적: 정자의 저장액 팽창검사의 결과로서 미부 팽창의 특정 형태가 aniline blue 염색법으로 평가되는 정자의 핵성숙 정도를 어느 정도 예측할 수 있는지를 타진하여 보고자 하는 것이다. 연구방법: 정액검사에서 비정상 정액소견을 보이는 남성 5명과 가임력이 증명되고 정상 정액소견을 보이는 남성 8명을 대상으로 정자처리 과정 전후로 sodium citrate 저장액 처리 및 aniline blue 염색을 동시에 시행하였다. 결과: 비정상정액군 및 가임남성군에서 정자처리 전후로 e 타입을 보이면서 동시에 aniline blue 음성을 보이는 빈도가 가장 높게 나타났으며, aniline blue 음성을 보이는 빈도는 비정상정액군과 가임남성군 사이에 차이는 없었으나, 정자처리를 시행한 이후에는 비정상정액군과 가임남성군 모두에서 이 빈도가 유의하게 증가하였다. 비정상정액군에서 정자처리 군만을 제외하고 비팽창 양상에 비하여 미부팽창 양상에서 aniline blue 음성을 보이는 정자의 빈도가 유의하게 증가하는 것으로 나타났다. 결론: 이상의 결과로 정자의 저장액 팽창 검사로 나타나는 특정 양상은 aniline blue 염색법을 이용한 정자의 핵성숙 정도를 예견하는데 매우 유용하였으며, 정자의 저장액 팽창 검사는 최대한 성숙한 핵을 가지면서 정자막의 기능도 양호한 정자를 선별하는데 있어 개개 정자에 실제 적용할 수 있는 간편하고 유용한 방법으로 사료된다. Objective : Many cases of fertilization failure after ICSI is attributed to decondensation defect of sperm head, therefore, selection of sperm with well-condensed, fully-matured nucleus is critical for successful fertilization. During mammalian spermiogenesis, replacement of the somatic histones by protamines allows normal sperm nuclear condensation. The degree of condensation can be shown with the aid of acidic aniline blue staining, which is able to discriminate between lysine-rich histones and arginine- or cysteine-rich protamines. The objective of this study was to investigate the possible relation between nuclear maturity of human sperm and hypo-osmotic swelling patterns. Hypo-osmotic swelling test is very simple and convenient test to measure functional integrity of human sperm membrane, and each already tested sperms can be used for fertilization. Methods : For assessment of sperm nuclear maturity, aniline blue staining was performed on the slides, already undergone hypo-osmotic swelling test in 5 subfertile patients with abnormal semen parameters and 8 fertile donors. After 3 hours swim-up, these procedures were repeated in each cases. Results : Sperms with negative aniline blue were significantly increased after swim-up in each group. There was a significant increase in the proportion of negative aniline blue in sperms with swelling patterns(e+f+g) compared to sperms with non-swelling patterns(a), except swim-up group in subfertile patients. Conclusion : Choosing the swelling patterns, rather than non-swelling sperms after hypo-osmotic test may be beneficial for the selection of sperms with well-condensed, mature nucleus and intact membrane.

산욕기 체질량지수 및 복부지방률의 동태

지병철 ( Byung Chul Jee ),최영식 ( Young Sik Choi ),구승엽 ( Seung Yup Ku ),서창석 ( Chang Suk Suh ),최영민 ( Young Min Choi ),김정구 ( Jung Gu Kim ),문신용 ( Shin Yong Moon ),김석현 ( Seok Hyun Kim ) 대한산부인과학회 2005 Obstetrics & Gynecology Science Vol.48 No.3

목적: 산욕기 동안 체질량지수로 표현되는 과체중 또는 비만과 복부지방률로 표현되는 남성형 비만의 빈도를 각각 알아보고, 산욕기 각 시기별로 남성형 비만을 예측할 수 있는 체질량지수의 기준치를 제시하고자 하였다. 연구 방법: 만삭에 단태아를 출산한 43명의 건강한 여성을 대상으로 분만 다음날과 분만 1주째, 그리고 분만 6주째에 체질량지수를 구하고 생체 전기 임피던스법을 이용하는 체성분 분석기를 이용하여 복부지방률을 측정하였다. 결과: 체질량지수는 분만 Objective: To investigate the dynamics of body mass index (BMI) and abdominal fatness of women in postpartum period, and to find cut-off values of BMI to predict android obesity. Methods: Forty-three uncomplicated postpartum women were included. BMI and a

내경정맥 혈전증을 동반한 중증 난소과자극증후군

지병철 ( Byung Chul Jee ),김진아 ( Jin Ah Kim ),구승엽 ( Seung Yup Ku ),서창석 ( Chang Suk Suh ),김석현 ( Seok Hyun Kim ),최영민 ( Young Min Choi ),김정구 ( Jung Gu Kim ),문신용 ( Shin Yong Moon ) 대한산부인과학회 2004 Obstetrics & Gynecology Science Vol.47 No.6

Thromboembolic disease associated with superovulation is extremely rare, but severe ovarian hyperstimulation syndrome is considered as one of the most important risk factors. We recently experienced a case of deep vein thrombosis occurring at left internal jugular, subclavian, and innominate vein combined with severe ovarian hyperstimulation syndrome. She experienced a miscarriage, and the thrombi were resolved completely after anticoagulant therapy. Although thromboembolic phenomenon is hard to predict, and occurs in spite of appropriate management of severe ovarian hyperstimulation syndrome, the measurement of factors associated with thrombophilia and prophylactic use of low dose heparin are recommended.

Use of aromatase inhibitor (Letrozole) combined with gonadotropin in intrauterine insemination cycles; non-randomized, comparative, multi-center study

지병철 ( Byung Chul Jee ),( Seung Yup Ku ),( Chang Suk Suh ),( Do Young Hwang ),( Ki Chul Kim ),( Jae Hoon Jung ),( Won Don Lee ),( Seok Hyun Kim ) 대한산부인과학회 2004 대한산부인과학회 학술대회 Vol.90 No.-

Apoptosis of granulosa cells recovered from patients participating in an in vitro fertilization program

지병철 ( Byung Chul Jee ),( Chang Suk Suh ),( Seok Hyun Kim ),( Young Min Choi ),( Jung Gu Kim ),( Shin Yong Moon ),( Jin Yong Lee ) 대한산부인과학회 1999 대한산부인과학회 학술대회 Vol.84 No.-

Seminal Tumor Necrosis Factor-alpha Level and Sperm Nuclear DNA Integrity in Healthy Donors

김현준,지병철,문정희,이정렬,서창석,김석현,Kim, Hyun-Jun,Jee, Byung-Chul,Moon, Jeong-Hee,Lee, Jung-Ryeol,Suh, Chang-Suk,Kim, Seok-Hyun The Korean Society for Reproductive Medicine 2009 Clinical and Experimental Reproductive Medicine Vol.36 No.1

Objectives: Seminal concentration of tumor necrosis factor-alpha (TNF-${\alpha}$) relevant to sperm nuclear DNA integrity has not been studied. The present study aimed to evaluate seminal concentration of TNF-${\alpha}$ in correlation with sperm parameters and nuclear DNA integrity in asymptomatic healthy donors. Methods: Semen samples were obtained by masturbation from forty-five healthy donors. Results: Sperm quality was assessed by computer-assisted semen analysis and nuclear DNA integrity measured by the TUNEL assay in raw semen. TNF-${\alpha}$ concentrations were measured by ELISA in frozen-thawed seminal plasmas. Sperm DNA fragmentation rates were ranged between 1.9% and 53.0% (mean${\pm}$SD, 12.4${\pm}$9.6%). Univariate analysis revealed that DNA fragmentation rate was not associated with sperm concentration or motility but had a correlation with linearity negatively (r=-0.325, p=0.03) and age positively (r=0.484, p=0.001). The mean seminal concentration of TNF-${\alpha}$ was 4.9 pg/mL with a range from 1.1 to 22.6 pg/mL. The TNF-${\alpha}$ concentration had no correlation with clinically relevant parameters of sperm quality or nuclear DNA fragmentation rate. Conclusion: Our results indicate that sperm nuclear DNA fragmentation may be not associated with seminal TNF-${\alpha}$ level or sperm quality in asymptomatic healthy donors. 목 적: 정액 내 tumor necrosis factor-alpha (TNF-${\alpha}$) 농도와 정자 DNA 손상 및 정액 검사 소견과의 관련성을 평가하고자 하였다. 연구방법: 정액 표본은 45명의 건강한 남성에서 자위에 의하여 획득하였다. 정자의 상태는 컴퓨터 정액 분석기를 이용하여 판정하였으며, 두부의 DNA 손상은 TUNEL 분석방법에 의해 측정하였다. TNF-${\alpha}$ 농도는 동결-융해된 정장액에서 ELISA법으로 측정하였다. 결 과: 정자 DNA 손상율은 1.9%에서 53% (mean ${\pm}$ SD, 12.4${\pm}$9.6%)로 매우 광범위하게 나타났다. 단변량분석에 의하면 DNA 손상 정도와 정자의 농도, 운동성과는 관련이 없었으나, 직진운동성 (linearity)과는 음의 상관 관계를 나타내었으며 (r=-0.325, p=0.03) 연구 대상 남성의 연령과는 양의 상관 관계를 나타내었다 (r=0.484, p=0.001). 정액내에 존재하는 TNF-${\alpha}$ (>1 pg/mL)는 연구 대상 남성의 73.3% (33/45)에서 검출되었으며 평균 농도는 4.9 pg/mL, 범위는 1.1에서 22.6 pg/mL이었다. 정액 검사 상의 정자 상태와 정자 DNA 손상과는 유의한 관련성이 나타나지 않았다. 결 론: 본 연구에서는 정자 DNA의 손상이 남성의 연령과 관련성이 있음을 확인하였으나, TNF-${\alpha}$와의 관련성은 확인할 수 없었다.

The Efficacy of Letrozole in Women with a Poor Endometrial Response to Clomiphene Citrate

장은정,지병철,Jang, Eun-Jeong,Jee, Byung-Chul The Korean Society for Reproductive Medicine 2010 Clinical and Experimental Reproductive Medicine Vol.37 No.1

목 적: 클로미펜을 이용한 배란유도 주기에서 불량한 자궁내막 발달을 보이는 불임 여성에서 레트로졸의 효용성을 알아보고자 하였다. 연구방법: 2004년 3월부터 2009년 8월까지 분당서울대학교병원에서 클로미펜을 이용한 배란유도 주기에서 자궁내막 두께가 6.5 mm 이하여서 다음 주기에 레트로졸을 사용하였던 18명의 불임 여성을 선정하였다. 환자들의 평균 연령은 $30.7{\pm}2.8$세, 불임 기간은 $33.1{\pm}26.6$개월이었다. 불임의 인자는 자궁내막증이 1명, 다낭성난소증후군이 5명, 원인불명의 불임증이 12명이었다. 레트로졸은 2.5 mg의 용량으로 월경 3~5일 사이에 시작하여 5일간 투여하였다. 결 과: 이전 클로미펜 사용시와 비교하였을 때 레트로졸 주기에서 우성난포의 개수는 더 적었으나 ($1.1{\pm}0.3$ vs. $2.2{\pm}1.5$, p=0.011) 자궁내막 두께는 유의하게 증가하였으며 ($8.4{\pm}1.7$ mm vs. $5.8{\pm}0.5$ mm, p<0.001) 자궁내막 패턴 중 type C의 빈도는 이전 클로미펜 주기에서 50%이었던 것이 레트로졸 사용시 94.4%로 유의한 증가를 보였다 (p=0.036). 레트로졸을 이용한 배란 유도 주기에서 임신율은 11.1%였다. 결 론: 얇은 자궁내막 발달을 보였던 클로미펜 주기에 비해 레트로졸 사용시 자궁내막이 좀 더 두꺼워지고 패턴이 호전되는 것으로 보아 클로미펜에 불량한 자궁내막을 보이는 여성에서 이차 선택약제로 레트로졸의 사용은 유용한 방법으로 사료된다. Objective: To examine the efficacy of letrozole in infertile women showing a poor endometrial development at previous ovulation induction cycle by using clomiphene citrate. Methods: Eighteen infertile women were selected who showed a poor endometrial development (endometrial thickness$\leq$6.5 mm) after clomiphene treatment (50~100 mg) as ovulation induction for timed coitus. The mean age of the patients was $30.7{\pm}2.8$ years old and the mean duration of infertility was $33.1{\pm}26.6$ months. The infertility factors were identified as corrected endometriosis (n=1), polycystic ovary syndrome (n=5) and unexplained (n=12). Letrozole was given orally in a dose of 2.5 mg for 5 days starting 3~5 of menstrual cycle. Results: The number of follicles was significantly lower in the letrozole cycle when compared with previous clomiphene cycle ($1.1{\pm}0.3$ vs. $2.2{\pm}1.5$, p=0.011). The endometrial thickness (mm) at the time of triggering or LH surge was significantly greater in the letrozole cycle ($8.4{\pm}1.7$ vs. $5.8{\pm}0.5$, p<0.001). The endometrial pattern 'type C' was significantly higher in the letrozole cycle (94.4% vs. 50%, p=0.036). The pregnancy was achieved in 11.1% of the letrozole cycle. Conclusion: Use of letrozole was associated with more thick and improved endometrium than previous clomiphene cycles in which thin endometrium was identified. Use of letrozole appears to be an effective strategy for second-line treatment in women with inadequate endometrial response to clomiphene.