자궁내막증을 갖는 불임환자에서 체외수정시술시 내과적 외과적 치료의 유용성

유근재(Keun Jai Yoo),양광문(Kwang Moon Yang),송지홍(Ji Hong Song),이재훈(Jae Hoon Lee),김계현(Kye Hyun Kim),송인옥(In Ok Song),최범채(Bum Chae Choi),궁미경(Mi Kyoung Koong),최규홍(Kyu Hong Choi),강인수(In Soo Kang) 대한산부인과학회 2000 Obstetrics & Gynecology Science Vol.43 No.3

Objective: The aim of study was to evaluate the efficacy of medical and/or laparoscopic surgical treatment for improvement of reproductive outcome of in vitro fertilization and embryo transfer (IVF-ET) in the patients with endometriosis. Methods: 296 IVF-ET cycles except 18 cycles of cancelled embryo-transfer (unfertilization; 16 cycles, high risk of ovarian hyperstimulation syndrome; 2 cycles) in 191 infertile women with endometriosis from January 1, 1995 to December 31, 1998 were included in this study. All women's ages were ≤ 35 and the factor for infetility was endometriosis only and day 3 follicle stumulating hormone (FSH) level of all the cycles was ≤ 10 mIU/ml in this study. All the baseline study about infertility was done before initiating treatment of infertility. The stage of endometriosis was recorded during diagnostic laparoscopy by WHO critera. Medical treatment (GnRH agonist or danazole) or laparoscopic surgery was done independently or combinedly by the physician's decision according to the disease entity and symptoms. Short or long protocols were used for controlled ovarian hyperstimulation and 3 day embryos were transferred (maximally 4 embryos) by standard procedures in our institute. We classified the cases as 4 groups : group 1 (without pre-treatment, 80 cycles), goup 2 (laparoscopic surgery only, 37 cycles), group 3 (medication only, 140 cycles), group IV (combined pre-treatment, 39 cycles). Results: The mean age (years old, mean ± SEM) was 31.5 ± 0.3 (group 1), 31.6 ± 0.5 (group 2), 31.5 ± 0.2 (group 3), 31.7 ± 0.4 (group 4) respectively. The duration of infertility (months) was 57.7 ± 3.3, 64.5 ± 4.8, 59.1 ± 1.9, 52.0 ± 3.7 respectively among groups. The viable pregnancy rate (over 28 gestational weeks, VPR) was 12.5 % (10/80) in goup 1, 13.5 % (5/37) in goup 2, 14.3 % (20/140) in group 3, 30.8 % (12/39) in group 4 and there was statistically significant difference between group 1 and group 4 (P=0.03, Chi square test). The total used gonadotropins (ampules) for controlled ovarian hyperstimulation were 28.2 ± 0.6

체외 실험상 원인불명 습관성 유산환자에서 얻은 말초혈액 단핵구와 태반항원 반응 후 제일형 보조 T 세포 사이토카인 ( IFN - γ ) 의 분비 양상

유근재(Keun Jai Yoo),송인옥(In Ok Song),최범채(Bum Chae Choi),강인수(Inn Soo Kang),박인서(In Sou Park),변혜경(Hye Kyung Byun),이지애(Ji Ae Lee),김정욱(Jeong Wook Kim),김현주(Hyun Joo Kim) 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.12

Objective: A dichotomous Thl and Th2 cytokine profile has been associated with reproductive failure and success, respectively. The purpose of our study was to determine the levels of Thl cytokine (IFN- y ) secreted by peripheral blood mononuclear cells (PBMCs) form women with unexplained recurrentabortion (URA) and fertile controls in response to trophoblast antigen. Methods: PBMCs were isolated from 30 nonpregnant women with URA and from 10 nonpregnant fertile controls. Following 4 days of culture (1 * 10(6) cells/mL) with and without a protein extract derived from a trophoblast cell line (30 ug/mL, protein). None of the women had allergies, atopy or recent infection. Cytokines were measured in supernatants with enzyme-linked immunosorbent assay (ELISA) kits. IFN- r kit was obtained from BOISOURCE (lower limit of sensitivity, 15.6 pg/mL for IFN- r ). All values below the lowest limit of sensitivity as determined by test kit standards were considered negative. The cytokine stimulation test is considered positive if the IFN- r concentration increases by 200% or more with the trophoblast antigen stimulation. Datas are presented as mean+ SEM. Nonparametric testing (Mann-Whitney U) was used for analysis with P<0.05 considered statistically significant. Results: The Thl-type cytokine (IFN- r ) was detected in 20(67%) of 30 supernatants from women with URA. In contrast, 2 (20%) of trophoblast-activated PBMC culture supernatants from the 10 parus women with normal reproductive histories was detected IFN- r and but were significantly lower than levels in women with URA who had secreted IFN- r upon trophoblast stimulation (99.80+ 18.17 pg/mL versus 166.47 + 36.96 pg/mL, p<0.05). Spontaneous secretion of IFN- r was significantly higher in culture supernatants from women with URA than in supernatants from women with successful reproductive histories (41.36.09+6.99 pg/mL versus 25.89+9.34 pg/mL, p<0.05). Conclusion: These data indicate that there are significant differences between women with URA and women with normal reproductive histories in their regulation of the Thl-cytokine (IFN- r) in response to trophoblast. Thl-type immunity to trophoblast is associated with URA and may play a role in reproductive failure.

고식적 체외수정시술과 난자 세포질내 정자주입술에 의해 태어난 아이의 주산기 결과 및 선천성 기형 발생빈도의 비교 연구

임정은,유근재,이종표,이문섭,현우영,전진현,홍수정,송지홍,송인옥,백은찬,최범채,손일표,궁미경,강인수,전종영,박인서,Lim, Jeong-Eun,Yoo, Keun-Jai,Lee, Jong-Pyo,Lee, Moon-Seob,Hyun, Woo-Young,Jun, Jin-Hyun,Hong, Soo-Jeong,Song, Ji-Hong,Song, In-Ok,Paik, 대한생식의학회 1998 Clinical and Experimental Reproductive Medicine Vol.25 No.3

The safety of ICSI as a novel procedure of assisted fertilization may be assessed by the health of the baby born. In order to evaluate the safety of ICSI, perinatal outcome and congenital anomaly of the babies born after ICSI were compared with those of babies born after IVF (control group). We analysed the clinical data from the obstetric and pediatric records, including the information obtained through telephone. The results are as follows; Mean gestational age $({\pm}SEM)$ and birth weight in singleton pregnancy were $38.8{\pm}1.9$ weeks and $3209.7{\pm}501.9gm$ in IVF group, $39.0{\pm}2.2$ weeks and $3289.9{\pm}479.5gm$ in ICSI group, respectively. Mean gestational age and birth weight in twins were $36.8{\pm}2.1$ weeks and $2512.8{\pm}468.0gm$ in IVF group, $36.5{\pm}2.8$ weeks and $2492.7{\pm}537.1gm$ in ICSI group. In IVF group, perinatal mortality rates were 8.5 in singletons and 56.6 in twins; for the ICSI singletons and ICSI twins, the perinatal mortality rates were 11.6 and 49.0, respectively. The incidence of congenital malformations was 3.6% (8/224) in IVF group and 2.1% (4/188) in ICSI group, there was no statistical difference (p>0.05, Fisher's exact test). The incidence of major congenital anomalies was 0.9% (2/224; pulmonary artery hypoplasia, renal cystic dysplasia) in IVF group and 1.1% (2/188; holoprosencephaly, Cri du chat syndrome) in ICSI groups (p>0.05, Fisher's exact test). Similarly, there was no significant difference in incidence of minor congenital anormalies 2.7% (6/224) in IVF group and 1.1% (2/188) in ICSI group respectively (p>0.05, Fisher's exact test). In conclusion, there was no difference in the perinatal outcome and the incidence of congenital anomalies between the babies born after ICSI and those after conventional IVF.

폐쇄성 무정자증과 비폐쇄성 무정자증에서 체외수정시술 후의 임신 결과 비교

박찬우,궁미경,양광문,김진영,유근재,서주태,송상진,박용석,강인수,전진현,Park, Chan-Woo,Koong, Mi-Kyoung,Yang, Kwang-Moon,Kim, Jin-Young,Yoo, Keun-Jai,Seo, Ju-Tae,Song, Sang-Jin,Park, Yong-Seog,Kang, Inn-Soo,Jun, Jin-Hyun 대한생식의학회 2003 Clinical and Experimental Reproductive Medicine Vol.30 No.3

Objective: To compare the pregnancy outcomes after in vitro fertilization with intracytoplasmic sperm injection (IVF-ICSI) between obstrucvtive and non-obstrucvtive azoospermia. Methods: From January 1994 to December 2002, 524 patients with obstructive azoospermia (886 cycles) and 163 patients with non-obstructive azoospermia (277 cycles) were included in this study. Microsurgical epididymal sperm aspiration (MESA) or testicular sperm extraction (TESE) in obstructive azoospermia and TESE in non-obstructive azoospermia were perfomed to retrieve sperm, which was used for ICSI and then fertilized embryos were transferred. The results of ICSI - fertlization rate (FR), clinical pregnancy rate (CPR), clinical abortion rate (CAR) and delivery rate (DR) - were statistically analysed in obstructive versus non-obstructive azoospermia. Results: There were no differences in the number of retrieved oocytes, injected oocytes for ICSI and oocyte maturation rate. FR was significantly higher in obstructive than non-obstructive azoospermia (71.7% vs. 61.1%, p<0.001). There was no difference in CPR per embryo transfer cycle. After pregnancy was established, however, CAR was significantly higher in non-obstructive than obstructive azoospermia (25.6% vs. 12.5%, p=0.004). DR per clinical pregnancy cycle was significantly higher in obstructive than non-obstructive azoospermia (78.0% vs. 64.4%, p=0.012). In the karyotype ananlysis of abortus, abnormal karyotypes were found in 75.0% (6/8) of obstructive and 55.6% (5/9) of non-obstructive azoospermia. Conclusion: Our data show significantly higher FR in obstructive than non-obstructive azoospermia. Though there was no differrence in CPR, CAR was significantly higher in non-obstructive than obstructive azoospermia. The abortion may be related to the abnormal karyotype of embryo, but further investigations are necessary to elucidate the cause of clinical abortion in azoospermia.

제왕절개 분만 후 발견된 치골관절 이개

문우남(Woo Nam Moon),유근재(Keun Jai Yoo),정환욱(Hwan Wook Chung),오한진(Han Jin Oh) 대한산부인과학회 2000 Obstetrics & Gynecology Science Vol.43 No.10

Objective : The objectives of this study are to observe the clinical characteristics, outcome of treatment and incidence of diastasis of symphysis pubis after cesarean section, and to evaluate the risk factors of the lesion.Methods : 8,089 cesarean section cases of our center from 1997 to 1999 were reviewed. The diagnostic criteria of diastasis were; 1) positive signs and symptoms of pelvic instability, 2) radiological evidence of widening of symphysis pubis more than 6mm and/or vertical mobility more than 3mm, or widening of sacroiliac joint more than 4mm. Several factors that increase the risk of this lesion were reviewed and analyzed by t- test and chi-square test. Results : Twenty-one diastasis of symphysis pubis were diagnosed out of 8,089 cesarean section cases during that period and all were available for over one year follow-up. The widening of the joint ranged from 3mm to 28mm. Eight cases accompanied vertical mobility. The history of pelvic girdle relaxation during pregnancy and over weight gain were proved to increase the risk of the lesion (P<0.005).Conclusion : We should have in mind that diastasis of symphysis pubis after cesarean section delivery could be found and history of pelvic girdle relaxation symptom and overweight during pregnancy might be the risk factors. Further studies with more cases would be needed to disclose the etiology and risk factors.

습관성유산 및 불임환자에서 자궁중격절제술 후 임신의 결과

송지홍(Ji Hong Song),유근재(Keun Jai Yoo),송인옥(In Ok Song),백은찬(Eun Chan Paik),최범채(Bum Chae Choi),손일표(Il Pyo Son),전종영(Jong Young Jun),박인서(In Sou Park),궁미경(Mi Kyoung Koong),강인수(In Soo Kang) 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.12

Uterine anomalies have been reported in 4% of women with infertility and in up to 15% of those with recurrent abortion. One of the major intrauterine disorder associated with infertility and recurrent abortions is intrauterine septum, The reproductive outcome of 41 patients of intrauterine septum (7 complete, 34 incomplete) with repeated abortions or infertility was assessed after the uterine septotomy. 5 of 7 patients with comlete uterine septum undergone uterine septotomy (3; hysteroscopic metroplasty, 2; abdominal metroplasty) had total 6 pregnancies and all of them had live biths. 28 patients with incomplete uterine septum got the hysteroscopic intrauterine septotomy and the viable pregnancy rate was 62% (3 ongoing pregnancies, 13 live biths of total 26 pregnancies). 6 patients with incomplete uterine septum had not the operation and 5 patients had 5 live births after total 6 pregnancies with 1 spontaneus abortion. Even though, the number of cases were small, the live birth rate in the group of septotomy of the patients of complete uterine septum (100%, 6/6) was higher than that in the group of not-done (50%, 1/2). The live birth rate in the group of not-done of the patients with incomplete uterine septum (83%, 5/6) was higher than that in the group of hysteroscopic uterine septotomy (62%, 16/26), but 5 of 6 had short uterine septal length (<1 cm), 1 had 1.5 cm septal length in the group of not-done. All the patients with successful pregnancy outcome had no other co-factors at the diagnostic laparoscopy, but the 5 primary infertility patients with no live birth even after treatment (all were with incomplete septum; 3 undergone hysteroscopic septotomy, 2 not-done with one abortion) had other co-factors such as endometriosis, peritoneal or tubal facor. In conclusion, hysteroscopic uterine septotomy would be useful for the patients with habitutal abortion or infertility and more advanced managemnet protocols should be applied to the patients having other co-factors if there was no pregnancy even after the uterine septotomy.

혈청 항 - 카디오리핀 항체 양성인 반복 유산환자의 임신 부산물에 대한 염색체 분석

이동진(Dong Jin Lee),유근재(Keun Jai Yoo),최범채(Bum Chae Choi),김석훈(Suk Hoon Kim),허걸(Hur Kuol),김계현(Kye Hyun Kim),박지혜(Chi Hye Park),박소연(So Yeon Park),최규홍(Kyu Hong Choi),조동희(Dong Hee Cho),강인수(In Soo Kang) 대한산부인과학회 2000 Obstetrics & Gynecology Science Vol.43 No.5

Objective : It has been suggestes that various mechanism of fetal loss are associated with anticardiolipin(ACA) and humoral immunity in the patients with recurrent spontaneous abortion. Thus we have investigated the relationship between ACA and chromosomal anomaly to know the clinical impact of ACA to early fetal loss as comparing to the chromosomal anomaly in the patients of recurrent spontaneous abortions. Materials and Methods : Patients(n=88) with a history of recurrent spontaneous abortion (2 or more) between January 1, 1994 and June 30, 1999 were included in this study. Quantitative measurement of serum ACA was performed by ELISA and chromosomal analysis of chorionic villi obtained from aborted conceptuses was done by using standard G-banding technique. Results: The incidence rate of ACA positive was 27%(24/88) and that of chromosomal abnormality was 57%(50/88). The incidence rate of abnormal karyotype was 54% (13/24) in ACA positive. Among 24 ACA positive, 10 had IgG-ACA positive, 10 had IgM-ACA positive and 4 had both types of ACA. The incidence rate of chromosomal anomalies was 30% (3/10) in IgG-ACA positive, 90%(9/10) in IgM-ACA positive and there was significant difference between these two groups (p=0.02). The incidence rate of chromosomal trisomy was 59% (23/37) in ACA negative, 62% (8/13) in ACA positive and there was no significance between two groups. Conclusion : The significantly low incidence of chromosomal abnormalities in conceptal products of patients with IgG-ACA comparing that of patients with IgM-ACA suggests that this isotype of antibody have influence on the genesis of spontaneous abortions in genetically normal pregnancy. In further studies, additional trials are mandatory for obtaining a definitive conclusions about relationship between pathologic changes of conceptal products and pathophysiologic effects of IgG-ACA.

습관성 유산 환자에서 저용량 면역글로불린 치료와 말초혈액 내 Natural Killer (NK) 세포의 임계치에 관한 연구

차선화,김해숙,김혜옥,송인옥,유근재,궁미경,강인수,양광문,Cha, Sun Hwa,Kim, Hae Suk,Kim, Hye Ok,Song, In Ok,Yoo, Keun Jai,Koong, Mi Kyung,Kang, Inn Soo,Yang, Kwang Moon 대한생식의학회 2005 Clinical and Experimental Reproductive Medicine Vol.32 No.3

Objectives: We aimed to investigate the clinical effect of low-dose intravenous immunoglobulin treatment in unexplained recurrent spontaneous aborters (RSA) with elevated peripheral CD56+ natural killer (NK) cell levels and to determine the pre-conceptional NK cell percentage predictive of subsequent successful pregnancy outcome. Materials and Methods: Sixty four cases of unexplained recurrent miscarriage with elevated peripheral NK cells (>15%) were received low dose IVIg infusion at the dosage of 400 mg/Kg/month after confirmation of gestational sac and continued until 20 weeks. The patients were divided into two groups according to the pregnancy outcome: Group I was success of treatment defined as live birth at or after 25 gestational weeks and Group II was failure of treatment. The preconceptional levels of the peripheral blood NK cells were compared between two groups. Results: Fifty-three pregnancies resulted in live births after 25 weeks and 11 resulted in abortion (Overall success rate of IVIG treatment was 82.8%). Preconceptional CD56+ NK cell percentage in group II ($27.4{\pm}1.9%$) was higher than those in group I ($22.3{\pm}0.8%$). By using ROC curve, optimal discrimination between success and failure of treatment was achieved with ${\leq}27%$ of preconceptional NK cell percentage. Conclusion: In RSA patients with elevated NK cells, we suggest that preconceptional peripheral blood CD56+ NK cell level could be a useful marker for predicting successful treatment outcome of low-dose IVIg infusion.

유전질환 및 염색체 이상의 예방을 위한 착상전 유전진단의 결과

김진영,임천규,송인옥,유근재,양광문,한국선,허걸,송지홍,전진현,민동미,박소연,전종영,궁미경,강인수,Kim, Jin-Yeong,Lim, Chun-Kyu,Song, In-Ok,Yoo, Keun-Jai,Yang, Kwang-Moon,Han, Kuk-Sun,Hur, Kuol,Song, Ji-Hong,Jun, Jin-Hyun,Min, Dong-Mi,Park, So- 대한생식의학회 2002 Clinical and Experimental Reproductive Medicine Vol.29 No.4

Objective s: Chromosome aneuploidy is associated with recurrent abortion and congenital anomaly and genetic diseases occur repeatedly in the specific families. Preimplantation genetic diagnosis (PGD) can prevent aneuploidy or genetic disease by selecting normal embryos before implantation and is an alternative to prenatal diagnosis. The aim of this study is to assess the outcome of PGD cycles by using FISH or PCR, and to determine the clinical usefulness and values in patients with risk of chromosomal aneuploidy or genetic disease. Materials and Methods: From 1995 to Apr. 2001, a total of 108 PGD cycles in 65 patients with poor reproductive outcome were analyzed. The indications of PGD were translocation (n=49), inversion (n=2), aneuploidy screening (n=7), Duchenne muscular dystrophy (n=5) and spinal muscular atrophy (n=2). PGD was applied due to the history of recurrent abortion, previous birth of affected child or risk of aneuploidy related to sex chromosome aneuploidy or old age. Blastomere biopsy was performed in 6$\sim$10 cell stage embryo after IVF with ICSI. In the single blastomere, chromosome aneuploidy was diagnosed by using FISH and PCR was performed for the diagnosis of exon deletion in DMD or SMA. Results: The FISH or PCR amplification was successful in 94.3% of biopsied blastomeres. The rate of transferable balanced emb ryos was 24.0% in the chromosome translocation and inversion, 57.1% for the DMD and SMA, and 28.8% for the aneuploidy screening. Overall hCG positive rate per transfer was 17.8% (18/101) and clinical pregnancy rate was 13.9% (14/101) (11 term pregnancy, 3 abortion, and 4 biochemical pregnancy). The clinical pregnancy rate of translocation and inversion was 12.9% (11/85) and abortion rate was 27.3% (3/11). In the DMD and SMA, the clinical pregnancy rate was 33.3% (3/9) and all delivered at term. The PGD results were confirmed by amniocentesis and were correct. When the embryos developed to compaction or morula, the pregnancy rate was higher (32%) than that of the cases without compaction (7.2%, p<0.01). Conclusions: PGD by using FISH or PCR is useful to get n ormal pregnancy by reducing spontaneous abortion associated with chromosome aneuploidy in the patients with structural chromosome aberration or risk of aneuploidy and can prevent genetic disease prior to implantation.

난소과자극 증후근의 예측인자와 임상 양상에 관한 연구

송지홍(Ji Hong Song),유근재(Keun Jai Yoo),송인옥(In Ok Song),백은찬(Eun Chan Paik),최범채(Bum Chae Choi),궁미경(Mi Kyoung Koong),손일표(Il Pyo Son),전종영(Jong Young Jun),강인수(Inn Soo Kang),박인서(In Sou Park) 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.11

Objeetive: Ovarian hyperstimulation syndrome (OHSS) is one of the well known complication of conttolled ovarian hyperstimulation. Though there have been numerous protocols for the prevention of OHSS, it has not been completely preventable until now. This study was performed to identify clinical predictors for early and late OHSS. Methods: A retrospective analysis of all IVF cycles in 1993 up to June 1996 was performed. OHSS was diagnosed using the criteria of Rabau modified by Schenker. All cases of OHSS reported in this study presented with marked ovarian enlargement, ascites, oliguria, hemoconcentration and electrolyte disturbance. Ovarian stimulation was carried out using a combination of gonadotrophin releasing hormone-agonist, follicle-stimulation hormone and human menopausal gonadotrophin. 27 patients has moderate or severe OHSS presenting 3-7 days post-human chorionic gonadotrophin (hCG), and 21 patients had severe OHSS presenting 12-17 days post-hCG. Results: No patient with early OHSS went onto develop late OHSS, and no patient with late OHSS had demonstrated early OHSS. Logistic regression showed that early OHSS was predicted by the number of oocytes retrieved and the estradiol concentration on the day hCG injection (P<0.05). Late OHSS was predicted by the transferred embryos, B-hCG on 14 day after hCG injection (P<0.05). Conclusion: Early OHSS was an acute effect of the hCG administered prior to egg retrieval in women with high estradiol and large number of retrieved oocytes. Our analysis of the risk factors for early OHSS indicates that cryopreservation of all embryos will not alter the risk of early OHSS even though it should prevent late OHSS. Late OHSS was induced by the rising serum concentration of hCG produced by the early pregnancy, the number of transferred embryos must be adjusted carefully, since it was associated with multiple gestation.