계류유산 환자에서 자궁 경을 통한 유산아 관찰의 진단적 유용성에 관한 연구

양광문 ( Kwang Moon Yang ),차선화 ( Sun Hwa Cha ),김해숙 ( Hae Suk Kim ),김진영 ( Jin Young Kim ),김혜옥 ( Hye Ok Kim ),안현경 ( Hyun Kyong Ahn ),최준식 ( June Seek Choi ),류현미 ( Hyun Mee Ryu ),강인수 ( In Soo Kang ),궁미경 ( Mi 대한산부인과학회 2005 Obstetrics & Gynecology Science Vol.48 No.2

Objective: Approximately 15-20% of all clinically recognized pregnancies result in spontaneous abortion and 60-70% of these are attributable to detectable chromosome abnormalities. Although the incidence of first trimester losses is high, spontaneous abor

조기 난소 부전 환자에서 공여 난자를 이용한 체외수정 및 배아이식술 후 산과적 결과

양광문 ( Kwang Moon Yang ),김해숙 ( Hae Suk Kim ),안현경 ( Hyun Kyung Ahn ),박찬우 ( Chan Woo Park ),허걸 ( Hur Kuol ),강인수 ( Inn Soo Kang ),궁미경 ( Mi Kyoung Koong ) 대한산부인과학회 2005 Obstetrics & Gynecology Science Vol.48 No.1

임신낭내 무태아와 유태아의 유산아 염색체 분석 : 무태아 임신의 발생은 염색체 이상과 관련 있는가 ?

양광문(Kwang Moon Yang),안현경(Hyun Kyong Ahn),유근재(Keun Jai Yoo),송인옥(In Ok Song),김진영(Jin Yeong Kim),송지홍(Ji Hong Song),강인수(Inn Soo Kang),전종영(Jong Young Jun),궁미경(Mi Kyung Koong),최범채(Bum Chae Choi) 대한산부인과학회 2002 Obstetrics & Gynecology Science Vol.45 No.4

Objectives : Approximately 15-20% of all clinically recognized pregnancies result in spontaneous abortion between 8 and 12 weeks. In some early abortus only the extra-embryonic components of the conceptus survive, either as fragments of placenta or as empty gestational sac, and these have been termed ‘anembryonic pregnancies`. Despite their common occurrences, the etiology of anembryonic conceptuses is poorly understood. The purpose of this study was to evaluate whether chromosomal abnormalities relate to a role in anembryonic pregnancy. Materials and Methods : The study, that consisted of 143 pregnancies from chromosomally normal couples that aborted in first trimester period between January 1, 1994 and December 27, 1997, had chromosomal analysis performed on the products of conception and had ultrasonographic examination prior to spontaneous abortion. The tissue was processed and analysed using standard G-banding cytogenetic techniques with long-term cultures. Results : The patient characteristics of the anembryonic pregnancy were not significantly different from those of the embryonic pregnancy. Among products of conception from embryonic pregnancies, 45% (52/115) had normal chromosomal analyses and 55% (63/115) had abnormal chromosomal analyses. Products of conception from anembryonic pregnancies resulted in 54% (15/28) of abnormal chromosome analyses and normal chromosomal analyses resulted in 46% (13/28) (p>0.05, Chi-square test). The frequency of aneuploidy and polyploidy were not different between products of conception from anembryonic pregnancy and embryonic pregnancy. Also, the gender ratio of euploid spontaneous pregnancy losses showed similar in this study. Conclusion : There are no differences in frequency of abnormal karyotypes in products of conception from anembryonic pregnancies compared with miscarriage after the demonstration of fetal pole. If further studies are need for the evaluation of these etiologies, and then immuno-molecular studies in early placental tissues from anembryonic pregnancy might be helpful.

임신 제 1삼분기에 자연유산 된 환자에서 질식초음파로 확인된 태아심장박동 유무에 따른 자연유산 수태물의 핵형 비교

양광문 ( Kwang Moon Yang ),송인옥 ( In Ok Song ),유근재 ( Keun Jae Yoo ),허걸 ( Kuon Hur ),한국선 ( Kuk Sun Han ),전진현 ( Jin Hyun Jun ),박소현 ( So Yeon Park ),김진영 ( Jin Young Kim ),전종영 ( Jong Young Jun ),강인수 ( Inn Soo 대한산부인과학회 2002 Obstetrics & Gynecology Science Vol.45 No.12

Objective : Genetic defects of the zygote, such as chromosome aberration, are the most frequent cause of abnormal embryonic development and spontaneous abortion. Recent advances in ultrasonographic technology have allowed documentation of early embryonic

착상과 임신 초기 면역반응에서 T 림프구의 역할

양광문,Yang, Kwang-Moon 대한생식의학회 2009 Clinical and Experimental Reproductive Medicine Vol.36 No.3

착상, 태반생성 및 임신 유지 등 생식과정에서 semi-allograft인 배아 및 태아가 생존하기 위해서는 모체 면역계의 면역관용이 요구된다. 면역관용은 분자 생물학적으로 염증반응과 항염증반응의 적절한 균형을 유지하는 인식되고 있으며, 생식과정에서 모체 면역계의 T 림프구, 자연살해세포, 수지상 세포, 대식세포 등 여러 면역세포의 유기적인 협조하에 이루어진다. 면역세포들은 특정 항원 및 사이토카인의 자극에 따라 정반대의 성질을 가진 사이토카인을 생산, 분비할 수 있는 특성을 가지고 있어 각각을 염증성 또는 항염증성 면역세포로 명확히 구분할 수 없으며 면역세포의 이러한 특성에 의해 생산 및 분비되는 사이토카인의 종류에 따라 Th0 형 (Th 0 cell, Tc 0 cell, NK 0 cell), Th1형 (Th 1 cell, Tc 1 cell, NK 1 cell), Th2 형 (Th 2 cell, Tc 2 cell, NK 2 cell), Th3 형 세포 (Th 3 cell, Tc 3 cell, NK 3 cell)로 분류하기도 한다. 즉, 착상 시기에 혈관신생 및 영양막의 자궁 내 침투를 위한 적절한 염증성 사이토카인(inflammatory cytokine)의 분비 및 임신의 지속을 위한 항염증성 (anti-inflammatory) 사이토카인의 분비 등 생식과정에서 수반되는 염증성과 항염증성 면역반응의 적절한 균형을 유지하는 기전은 특정 면역세포만의 작용으로 결론 지을 수 없으며 면역 세포간 network의 산물이라 할 수 있다 (Figure 5). 면역세포 중 최근 그 존재가 알려진 면역조절 T림프구 (T reg cell)는 여러 연구자들에 의해 면역관용에 관여함이 일관되게 보고되고 있어 자궁 내모체-태아간 접촉면에서 면역세포들 간의 network에 중추적인 역할을 할 것으로 인식되고 있으나 작용기전으로 제시되고 있는 가설들을 뒷받침 할 만한 객관적인 연구가 필요한 실정이다. 본 고찰에서는 착상과 임신 유지 등 생식과정에 수반되는 면역세포 및 그 세포들의 작용기전중 T 림프구의 역할에 중점을 두고 그 분류 및 기능에 대해 정리해 보았다. 결론적으로 착상과 임신의 유지 등 생식과정에서 T 림프구는 면역관용과 거부에 적극적으로 작용하며 착상부전, 습관성유산 등 면역학적 병인이 유사한 생식장애 (poor reproductive performance)들의 발병에 중요한 역할을 하는 것은 의심할 여지가 없다. 하지만 향후 T 림프구 및 그와 연관된 면역세포들의 작용에 대한 확실한 분자학적 규명이 요구된다.

말초혈액 CD56+Natural Killer (NK) cell의 증가에 기인하여 면역글로불린 치료 후 분만한 습관성 유산 환자에서 향후 계획 임신 전 시행한 말초혈액 NK cell의 변화에 대한 연구

김문영 ( Moon Young Kim ),김해숙 ( Hae Suk Kim ),차선화 ( Sun Hwa Cha ),궁미경 ( Mi Kyung Koong ),송현정 ( Hyun Jung Song ),송인옥 ( In Ok Song ),유근재 ( Keun Jae Yu ),강인수 ( Inn Soo Kang ),양광문 ( Kwang Moon Yang ) 대한산부인과학회 2004 Obstetrics & Gynecology Science Vol.47 No.10

Objective : The aim of this study was to evaluate the change of peripheral blood CD56+NK cell fraction in recurrent pregnancy loss patients who successfully treated with intravenous immunoglobulin (IVIg) in previous pregnancy. Methods : The study subjects

말초혈액자연살해세포가 증가된 반복유산 환자의 탈락막자연살해세포의 발현

연명진,양광문,박찬우,송인옥,강인수,홍성란,조동희,조용균,Yeon, Myeong-Jin,Yang, Kwang-Moon,Park, Chan-Woo,Song, In-Ok,Kang, Inn-Soo,Hong, Sung-Ran,Cho, Dong-Hee,Cho, Yong-Kyoon 대한생식의학회 2008 Clinical and Experimental Reproductive Medicine Vol.35 No.2

목 적: 말초혈액 $CD56^+$ 자연살해세포 (natural killer cell)이 증가되어 있는 반복유산 환자들의 탈락막 $CD56^+/CD16^+$ 자연살해세포의 분포를 확인하고 말초혈액자연살해세포의 발현양상과 상관관계가 있는지 확인해 보고자 한다. 연구방법: 반복유산 환자 중 계류유산이 되어 자궁경부확장배출술과 배아 염색체검사를 시행하였던 환자 가운데 배아 염색체검사가 정상이고 말초혈액에서 자연살해세포 중 $CD56^+$ 자연살해세포가 증가된 환자들 29명을 대상으로 연구하였으며, 대조군으로는 배아 염색체검사가 비정상인 32명을 선택하였다. 이 환자들의 검체에서 착상부위를 포함한 자궁 탈락막세포를 확인하여 면역조직화학염색을 통해 $CD56^+$와 $CD16^+$ 자연살해세포의 분포를 확인하였다. 면역조직화학염색은 score와 백분율을 구하여 평가하였다. 결 과: 연구군과 대조군의 탈락막조직 $CD56^+$ 자연살해세포 score ($43.6{\pm}24.5$ vs. $23.9{\pm}16.3$ P =0.001)와 $CD56^+$ NK cell percentage ($42.1{\pm}11.7$ vs. $33.9{\pm}15.8$ P =0.027)는 유의한 차이가 있었다. 그러나 탈락막조직 $CD16^+$ NK cell score ($18.7{\pm}9.5$ vs. $13.2{\pm}39.4$ P =0.108)와 $CD16^+$ 자연살해세포 percentage ($24.7{\pm}5.9$ vs. $23.4{\pm}11.7$ P =0.599)는 통계학적으로 유의한 차이가 없었다. 말초혈액자연살해세포가 증가되어 있는 환자군에서 탈락막자연살해세포의 score와 말초혈액자연살해 세포의 백분율간에 직접적인 상관관계는 없었다 (peripheral $CD56^+$ NK cell percentage vs. decidual $CD56^+$ NK cell score, r=-0.016, P =0.932, peripheral $CD16^+$ NK cell percentage vs. decidual $CD16^+$ NK cell score, r=0.008, P =0.968). 결 론: 본 연구에서는 말초혈액 CD56^+ 자연살해세포가 증가되어 있는 반복유산 환자의 계류유산된 조직에서 탈락막 $CD56^+$ 자연살해세포가 증가되어 있다는 것을 보여 주었다. 또한 탈락막자연살해세포와 말초혈액자연살해세포의 증가 양상에서는 직접적인 상관관계는 없었다. 이는 탈락막자연살해세포가 반복유산의 면역학적인 기전에서 중요한 역할을 할 것이라는 가능성을 제시하여 준다. Objective: The purpose of this study was to quantify decidual $CD56^+$ and $CD16^+$ NK cell subtype population and to evaluate the correlation between decidual NK cell expression and peripheral $CD56^+$ NK cell expression in women with a history of recurrent abortion and increased peripheral NK cells. Methods: Twenty-nine women with recurrent abortion and elevated peripheral $CD56^+$ NK cell percentage who had chromosomally normal conceptus were included in this study. Thirty-two women with recurrent abortion who had chromosomally abnormal conceptus were used as controls. Distribution of $CD56^+$ and $CD16^+$ NK cells in decidual tissues including implantation sites was examined by immunohistochemical staining. The degree of immunohistochemical staining was interpreted by score and percentage. Results: There was a significant difference in decidual $CD56^+$ NK cell score ($43.6{\pm}24.5$ vs. $23.9{\pm}16.3$ P =0.001) and $CD56^+$ NK cell percentage ($42.1{\pm}11.7$ vs. $33.9{\pm}15.8$ P =0.027) between increased peripheral NK cell group and control group. However, there was no statistically significant difference in decidual $CD16^+$ NK cell score ($18.7{\pm}9.5$ vs. $13.2{\pm}39.4$ P =0.108) and $CD16^+$ NK cell percentage ($24.7{\pm}5.9$ vs. $23.4{\pm}11.7$ P =0.599). There was no significant correlation between decidual NK cell score and peripheral NK cell percentage in increase peripheral NK cell group (peripheral $CD56^+$ NK cell percentage vs. decidual $CD56^+$ NK cell score, r=-0.016, P =0.932, peripheral $CD16^+$ NK cell percentage vs. decidual $CD16^+$ NK cell score, r=0.008, P =0.968). Conclusion: This study shows that $CD56^+$ decidual NK cells are increased in decidua of women exhibiting a history of recurrent abortion with increased $CD56^+$ peripheral NK cell. There was no significant correlation between decidual and peripheral NK cell increment in increase peripheral NK cell group. This study suggests the possibility that decidual NK cells may play an important role in the immune mechanism of recurrent abortion.

반복 유산 및 착상실패를 보이는 환자에서 Th1 면역반응에 대한 연구

한애라,양광문,곽영희,Han, Ae-Ra,Yang, Kwang-Moon,KwakKim, Joanne 대한생식의학회 2010 Clinical and Experimental Reproductive Medicine Vol.37 No.3

목 적: 반복적 유산 또는 반복적 착상실패 환자의 T 림프구의 Th1 면역반응 정도를 알아보고, T 림프구 활성 정도를 분석하고자 하였다. 연구방법: 반복적 유산 및 반복적 착상실패를 경험한 37명의 환자를 연구군으로 설정하고, 유산이나 불임의 병력이 없이 정상분만의 경력이 있는 11명의 가임 여성을 대조군으로 모집하였다. 유세포분석기를 이용하여, 이들의 말초혈액 중 T helper 세포 내 TNF-$\alpha$와 INF-$\gamma$ 및 IL-10의 발현도를 측정하고 Th1/Th2 세포 비율 (TNF-$\alpha$/IL-10 및 INF-$gamma$/IL-10 발현도)을 계산하여 Th1 면역반응의 우세 정도 및 T 림프구의 활성도를 분석하였으며, 활성 표지자인 CD154와 CD69 발현 정도를 비교하였다. 결 과: 연구군의 평균연령은 $35.3{\pm}4.3$세였으며, 이들에서 T helper cell 내 TNF-$\alpha$/IL-10의 발현 비율이 대조군에 비해 유의하게 높았고 ($42.1{\pm}2.3$ vs. $28.7{\pm}2.7$, p=0.002), CD154와 CD69의 발현율 또한 대조군에 비해 전반적으로 높았다. CD154의 경우, T helper cell ($1.7{\pm}0.5$ vs. $0.3{\pm}0.2$, p=0.038)과 T suppressor cell ($0.6{\pm}0.2$ vs. $0.1{\pm}0.0$, p=0.024) 모두에서 유의하게 높은 발현을 보인 반면, CD69의 경우, 전체 T 림프구 ($5.6{\pm}1.9$ vs. $1.3{\pm}5.4$, p=0.046)와 T suppressor cell ($4.8{\pm}1.3$ vs. $1.8{\pm}0.2$, p=0.035)에서 통계적으로 높은 발현을 확인할 수 있었다. 결 론: 반복적 유산 및 반복적 착상실패를 보이는 여성에서 T 림프구의 활성도와 Th1 면역반응이 증가하였으며 이는, 이들 여성에서 활성화된 T 림프구가 Th1 면역반응을 유도하여 초기 임신의 유지와 착상에 좋지 않은 영향을 미치기 때문으로 생각된다. Objective: To evaluate whether T helper 1 (Th1) immune response is predominant in women with reproductive failures (recurrent spontaneous abortion and recurrent implantation failure) and the activation of T cell is related to Th1 propensity. Methods: Women with a history of recurrent implantation failure or recurrent spontaneous abortion comprise the study group (n=37). Controls are normal fertile women without a history of infertility or pregnancy losses (n=11). Th1/Th2 ratios of interferon (INF)-$\gamma$/interleukin (IL)-10 and tumor necrosis factor (TNF)-$\alpha$/IL-10 expression on $CD3^+/4^+$ cells, CD154, and CD69 expression on T cells are measured by flow cytometric analysis. Results: The ratios of TNF-$\alpha$ to IL-10 expressing on $CD3^+/4^+$ cells (Th1/Th2 cell ratios) are significantly higher in study group ($42.1{\pm}2.3$) as compared with that of controls ($28.7{\pm}2.7$) (p=0.002). The overall trend of CD154 and CD69 expression on T cells are elevated in study group than those of controls. The proportion (%) of $CD3^+/4^+/154^+$ cells ($1.7{\pm}0.5$ vs. $0.3{\pm}0.2$, p=0.038) and the % of $CD3^+/8^+/154^+$ cells ($0.6{\pm}0.2$ vs. $0.1{\pm}0.0$, p=0.024) are significantly higher in study group. The % of $CD3^+/69^+$ cells ($5.6{\pm}1.9$ vs. $1.3{\pm}5.4$, p=0.046) and % of $CD3^+/8^+/69^+$ cells ($4.8{\pm}1.3$ vs. $1.8{\pm}0.2$, p=0.035) among $CD3^+/8^+$ cells are significantly increased in study group. Conclusion: Women with reproductive failures have Th1 propensity with increased T cell activation. These finding means that activated T cell has a harmful effect on early pregnancy and implantation by induction of Th1 immunity.

일측 난관절제술을 시행한 환자에서 체외수정 시술 후 발생한 동측 원발성 난소 임신

김문영 ( Moon Young Kim ),송현정 ( Hyun Jung Song ),안현경 ( Hyun Kyung Ahn ),이승헌 ( Seung Heon Lee ),유근재 ( Keun Jae Yu ),전이경 ( Lee Kyung Jun ),궁미경 ( Mi Kyung Koong ),강인수 ( In Soo Kang ),양광문 ( Kwang Moon Yang ) 대한산부인과학회 2004 Obstetrics & Gynecology Science Vol.47 No.6

Marcus and Brinsden have reported the first ovarian pregnancy achieved by IVT-ET in 1993. They reported seven cases of primary ovarian pregnancy from 116 ectopic pregnancies after IVF. With advancement of ART, the incidence of ectopic pregnancy is increasing, but ovarian pregnancy is still a rare complication. We report a case of ipsilateral primary ovarian pregnancy after IVF-ET with a patient with previous unilateral salpingectomy with a brief review of literature.

클로미펜에 부적절한 반응을 보이는 다낭성 난소 증후군 환자에서 Aromatase Inhibitor의 유용성

김혜옥,양광문,허걸,박찬우,차선화,김해숙,김진영,송인옥,궁미경,Kim, Hye Ok,Yang, Kwang Moon,Hur, Kuol,Park, Chan Woo,Cha, Sun Hwa,Kim, Hae Suk,Kim, Jin Yeong,Song, In Ok,Koong, Mi Kyung 대한생식의학회 2005 Clinical and Experimental Reproductive Medicine Vol.32 No.1

Objective: To evaluate the effectiveness of aromatase inhibitor (AI) for ovulation induction in polycystic ovary syndrome (PCOS) patients with thin endometrium, hyper-responsiveness after clomiphene citrate (CC) treatment. Material and Methods: A prospective study was performed in 43 PCOS patients (50 cycles) with ovulatory dysfunction between March 2004 and September 2004. AI group (total 36 cycles) included the patients 1) with thin endometrium below 6 mm on hCG day after CC (n=17), 2) with more than 5 ovulatory follicles after 50mg of CC (n=4), 3) who do not want multiple pregnancy (n=14). Patients were treated with Letrozole 2.5mg for days 3 to 7 of the menstrual cycle. CC group (total 14 cycles) were treated with CC 50~100 mg. Results: In PCOS patients, ovulation was occurred 97.2% after AI use. Between AI group and CC group, there was no significant difference in the mean age, duration of infertility, interval of menstruation, basal FSH, prior treatment cycles, and the day of hCG administration. But, the number of mature follicles (${\geq}15mm$) was lower in the AI group ($1.08{\pm}0.45$ vs. $1.64{\pm}0.75$) (p=0.018), and the thickness of endometrium (mm) was significantly thicker in the AI group ($10.35{\pm}1.74$ vs. $9.23{\pm}1.61$) (p=0.044), and E2 (pg/ml) concentration on hCG day was lower in the AI group ($116.9{\pm}75.8$ vs. $479.5{\pm}300.8$) (p=0.001). Among the AI group, patients with prior thin endometrium (below 6 mm) during CC treatment showed $10.6{\pm}1.6mm$ in the endometrial thickness and $106.6{\pm}66.8pg/ml$ in $E_2$ concentration. Patients with more than 5 ovulatory follicles after CC showed decreased follicle number ($1.25{\pm}0.5$) compared to prior CC cycle. Conclusions: In PCOS patients, AI group showed significantly thicker endometrium, lesser number of mature follicles, and lower E2 concentration on hCG day than CC group. AI might be useful alternative treatment for ovulation induction in PCOS patients with thin endometrium and hyper-responsiveness after CC treatment.