습관성 유산환자에서 정맥내 면역글로불린 치료의 효과

송지홍(Ji Hong Song),백은찬(Eun Chan Paik),전종영(Jong Young Jun),강인수(Inn Soo Kang),노건웅(Keun Woong Noh),조동희(Dong Hee Cho) 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.11

N/A The aim of this study was to evaluate the efficacy of intravenous immunoglobulin treatment for recurrent spontaneous abortion. Immunologic causes in either alloimmune or autoimmune type have been suggested for more than 80% of these patients. Various immunotherapy including paternal leukocyte transfusion has been used, but there is controversy on its efficacy and side-effects. The proposed immunomodulatory mechanism of intravenous immunoglobulin includes passive transfer of blocking or anti-idiotype antibody, blockade of Fc receptors, enhancement of supressor T-cell function, down regulation of B cell function. In this study, we used intravenous immunoglobulin for the prevention of spontaneous abortion. Five patients with a history of two or more spontaneous abortions were enrolled in this study. Other etiologic factors such as anatomical, chromosomal, hormonal factors were excluded. Three of them were positive for anti-cardiolipin antibody (ACA). When the pregnancy was diagnosed at about five weeks of gestation, 30 g intravenous immunoglobulin was administered and continued up to 28 weeks with three weeks. Ongoing pregnancy beyond 20 weeks was considered successful. Four among five patients (80%) was successful in maintaining pregnancy now ongoing 20, 31, 33, 39 weeks. One patient with ACA positive had abartion due to anembryonic pregnancy. No adverse reaction was observed during the treatment. From these preliminary data, it is suggested that intravenous immunoglobulin treatment may be effective in maintaining pregnancy in patients with unexplained recurrent spontaneous abortion, Further studies are needed to clarify the its immunomodulatory mechanism and establish a more simplified protocol limiting the use at certain critical period of time.

난소기능평가를 위한 Gonadotropin Releasing Hormone Agonist Stimulation Test (GAST)의 효용성에 관한 연구

김미란,송인옥,연혜정,최범채,백은찬,궁미경,손일표,이진우,강인수,Kim, Mee-Ran,Song, In-Ok,Yeon, Hye-Jeong,Choi, Bum-Chae,Paik, Eun-Chan,Koong, Mi-Kyoung,Song, Il-Pyo,Lee, Jin-Woo,Kang, Inn-Soo 대한생식의학회 1999 Clinical and Experimental Reproductive Medicine Vol.26 No.2

Objectives: The aims of this study are 1) to determine if GAST is a better indicator in predicting ovarian response to COH compared with patient's age or basal FSH level and 2) to evaluate its role in detecting abnormal ovarian response. Design: Prospective study in 118 patients undergoing IVF-ET using GnRH-a short protocol during May-September 1995. Materials and Methods: After blood sampling for basal FSH and estradiol $(E_2)$ on cycle day two, 0.5ml (0.525mg) GnRH agonist ($Suprefact^{(r)}$, Hoechst) was injected subcutaneously. Serum $E_2$ was measured 24 hours later. Initial $E_2$ difference $({\Delta}E_2)$ was defined as the change in $E_2$ on day 3 over the baseline day 2 value. Sixteen patients with ovarian cyst or single ovary or incorrect blood collection time were excluded from the analysis. The patients were divided into three groups by ${\Delta}E_2$; group A (n=30):${\Delta}E_2$<40 pg/ml, group B (n=52): 40 pg/ml${\leq}{\Delta}E_2$<100 pg/ml, group C (n=20): ${\Delta}E_2{\leq}100$ pg/ml. COH was done by GnRH agonist/HMG/hCG and IVF-ET was followed. Ratio of $E_2$ on day of hCG injection over the number of ampules of gonadotropins used ($E_2hCGday$/Amp) was regarded as ovarian responsiveness. Poor ovarian response and overstimulation were defined as $E_2$ hCGday less than 600 pg/ml and greater than 5000 pg/ml, respectively. Results: Mean age $({\pm}SEM)$ in group A, B and C were $33.7{\pm}0.8^*,\;31.5{\pm}0.6\;and\;30.6{\pm}0.5^*$, respectively ($^*$: p<0.05). Mean basal FSH level of group $A(11.1{\pm}1.1mlU/ml)$ was significantly higher than those of $B(7.4{\pm}0.2mIU/ml)$ and C $(6.8{\pm}0.4mIU/ml)$ (p<0.001). Mean $E_2hCGday$ of group A was significantly lower than those of group B or C, i.e., $1402.1{\pm}187.7pg/ml,\;3153.2{\pm}240.0pg/ml,\;4078.8{\pm}306.4pg/ml$ respectively (p<0.0001). The number of ampules of gonadotropins used in group A was significantly greater than those in group B or C: $38.6{\pm}2.3,\;24.2{\pm}1.1\;and\;18.5{\pm}1.0$ (p<0.0001). The number of oocytes retrieved in group A was significantly smaller than those in group B or C: $6.4{\pm}1.1,\;15.5{\pm}1.1\;and\;18.6{\pm}1.6$, respectively (p<0.0001). By stepwise multiple regression, only ${\Delta}E_2$ showed a significant correlation (r=0.68, p<0.0001) with $E_2HCGday$/Amp, while age or basal FSH level were not significant. Likewise, only ${\Delta}E_2$ correlated significantly with the number of oocytes retrieved (r=0.57, p<0.001). All four patients whose COH was canceled due to poor ovarian response belonged to group A only (Fisher's exact test, p<0.01). Whereas none of 30 patients in group A (0%) had overstimulation, 14 patients among 72 patients (19.4%) in group B and C had overstimulation (Fisher's exact test, p<0.01). Conclusions: These data suggest that initial $E_2$ difference after GAST may be a better prognostic indicator of ovarian response to COH than age or basal FSH level. Since initial $E_2$ difference demonstrates significant association with abnormal ovarian response such as poor ovarian response necessitating cycle cancellation or overstimulation, GAST may be helpful in monitoring and consultation of patients during COH in IVF-ET cycle.

근이양증 가계에서의 PEP-PCR을 이용한 착상전 유전자진단

최수경,이은호,이호준,전진현,강인수,백은찬,류현미,전종영,Choi, Soo-Kyung,Lee, En-Ho,Lee, Ho-Joon,Jun, Jin-Hyun,Kang, Inn-Soo,Paik, Eun-Chan,Ryu, Hyun-Mee,Jun, Jong-Young 대한생식의학회 1996 Clinical and Experimental Reproductive Medicine Vol.23 No.1

General PCR technique alone has a limitation for preimplantation genetic diagnosis(PGD) using single blastomere. Recntly developed primer extension preamplification(PEP) technology amplifies the whole genome and thus, simultaneous multiple locus analysis became possible. In this study, we report the efficacy of PEP-PCR for PGD in three muscular dystrophy carriers undergoing IVF-ET. A total of 37 blastomeres were obtained from 40 embryos at six to eight cell stage in three IVF cycles in two DMD and one BMD carriers. Whole genome from single blastomeres were amplified using I5-base oligonucleotide random primers. PCR amplified products of exon 45 in the dystrophin gene and alphoid X/Y loci for gender determination were analysed by 2% metaphor gel electrophoresis. A total of 37 PEP-PCR replicates from 37 single blastomeres from 40 embryos and 37 blanks were performed. We obtained the reliable results for exon 45 and alphoid X/Y. Transfer of female embryos and unaffected male embryo was attempted in three couples. Unfortunately, pregnancy was not achieved in these cases. PEP-PCR is a reliable and efficient PGD method in multiple locus analysis using single blastomere.

일반적인 체외수정 방법과 세포질내 정자주입술로 얻어진 배아의 동결-융해 후 이식의 결과

김정욱,한미현,변혜경,전진현,손일표,궁미경,백은찬,강인수,이호준,Kim, Jeong-Wook,Han, Mi-Hyun,Byun, Hye-Kyung,Jun, Jin-Hyun,Son, Il-Pyo,Koong, Mi-Kyoung,Paik, Eun-Chan,Kang, Inn-Soo,Lee, Ho-Joon 대한생식의학회 1997 Clinical and Experimental Reproductive Medicine Vol.24 No.1

Intracytoplasmic sperm injection (ICSI) recently has been utilized widely as the most successful technique to overcome the unfertilization problem in cases of severe male infertility in couples who could not be treated by conventional IVF. Recently, indications of ICSI have been extended further and more fertilized oocytes become available. Thus, it is necessary to examine the efficiency of freezing the surplus embryos obtained from ICSI. We compared the survival rate and the future outcome of cryopreserved embryos obtained either after conventional IVF or ICSI during the same period. After ICSI or IVF, five best-quality embryos from each patient were transferred in the stimulation cycle and the surplus pronuclear (PN) stage oocytes or multicellular embryos were cryopreserved by slow freezing protocol with 1,2-propanediol (PROH) as a cryoprotectant. A total of 792 embryos from ICSI trial were thawed and 65.2% (516/792) survived. The survival rates of PN stage oocyte, multicellular embryo and PN + multicellular embryo were 63.5%, 68.2%, 64.0%, respectively. After 111 transfers, 34 pregnancies were achieved, corresponding to a clinical pregnancy rate of 30.6% per transfers. We thawed 1033 embryos from IVF trials and 57.5% (594/1033) survived. In IVF cycle, the survival rates of PN stage oocyte, multicellular embryo and PN + multicellular embryo were 58.2%, 65.2%, 40.2%, respectively. Thirty eight clinical pregnancies were established after 134 transfers, corresponding to a pregnancy rate of 28.4% per transfer. The cleavage rate of thawed PN stage oocytes from ICSI trial (61.3%) was significantly higher than those from conventional IVF (53.4%). The developmental rates of good embryo (${\geqq}$ grade II) in thawed PN stage oocytes obtained from conventional IVF and ICSI were 63% and 65%, respectively. We concluded that PN stage oocytes, multicellular embryos resulting from ICSI procedure can be successfully frozen/thawed with reasonable clinical pregnancy rates comparable to those of IVF.

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

N/A 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.

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

N/A 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.