• 대한생식의학회:학술대회논문집
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• 대한불임학회 2001년도 제41차 추계학술대회
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• pp.76-76
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• 2001

• Clinical and Experimental Reproductive Medicine
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• 제24권3호
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• pp.399-405
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• 1997

Progesterone is necessary for successful pregnancy and had immunosuppressive properties. Peripheral blood mononuclear cells (PBMC) from many women with unexplained recurrent spontaneous abortion responded to trophoblast extract in vitro by prolifertion and releasing soluble, heat-labile factors that are toxic to mouse embryos (embryotoxic factors). Accumulating evidence suggests that T Helper (Th)-1 type immunity to trophoblast is correlated with embryotoxic factor production and is associated with pregnancy loss, while Th2-type immunity is associated with successful gestation. The objective of this study was to determine whether progesterone can inhibit Th1-type cytokine secretion (IFN-${\gamma}$, TNF-${\alpha}$) by trophoblast-activated peripheral blood mononuclear cells from 23 nonpregnant women (age 25-35) with unexplained recurrent abortion (median 5, range 3 to 15)who otherwise produce embryotoxic factors in response to trophoblast. We also determined whether progesterone affected Th2-type cytokines (IL-4, IL-10) in this system in vitro and if IL-10 (1,500 pg/mL) could inhibit Th1-type immunity to trophoblast. IFN-${\gamma}$ was detected in 17 of 23 (74%) trophoblast stimulated PBMC culture supernatants ($77.94{\pm}23.79$ pg/mL) containing embryotoxic activity. TNF-${\alpha}$ was detected in 19 (83%) of these same supernatants ($703.15{\pm}131.36$ pg/mL). In contrast, none of the supernatants contained detectable levels of IL-4 or IL-10. Progesterone ($10^{-5}$, $10^{-7}$, $10^{-9}$M) inhibited Th1-type immunity in a dose dependent manner, but had no effect on Th2-type cytokine secretion. The inhibitory effects of progesterone were abrogated with RU486, but did not affect Th2-type cytokine secretion in trophoblast-activated cell cultures. IL-10, like progesterone also inhibited Th1-type cytokine secretion but had no effect on Th2-type cytokines. These data suggest that therapies designed to suppress Th1-type cytokine secretion in women with recurrent abortion who have evidence of Th1-type immunity to trophoblast may be efficacious in preventing pregnancy loss and should be tested in appropriately designed clinical trials.

• Clinical and Experimental Reproductive Medicine
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• 제29권3호
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• pp.215-222
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• 2002

Objective : Previous studies have suggested that hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR C677T) mutations are associated with increased risk of recurrent spontaneous abortion (RSA). Recently, a second site polymorphism in MTHFR, 1298A-->C, which changes a glutamic acid into an alanine residue, was shown to be associated with a decreased enzyme activity. We tested whether the variant alleles of MTHFR C677T and A1298C are risk factor (biomarker) for RSA. Materials and Methods: We analyzed DNA from a case-control study in the Korean DNA was extracted from blood samples of 118 patients with RSA and 123 healthy fertile patients as the controls. MTHFR variant alleles were determined by a PCR-restriction fragment length polymorphism assay. Results: We found no evidence for an association between 677TT genotype and risk of RSA (OR=1.95, 95% CI=$0.84{\sim}4.50$, p=0.12). However, the MTHFR 1298AC (OR=0.36, 95% CI=$0.20{\sim}0.63$, p=0.0004) and 1298AC+CC (OR=0.35, 95% CI=$0.20{\sim}0.61$, p=0.0002) genotypes were lower among 118 RSA cases compared with 123 controls, conferring a 2.8-fold decrease in risk of RSA, respectively. Moreover, the combined genotypes of MTHFR 677CC/1298AC (OR=0.30, 95% CI=$0.10{\sim}0.88$, p=0.029) and 677CT/1298AC (OR=0.77, 95% CI=$0.60{\sim}0.99$, p=0.043) also showed significantly lower risk than those with MTHFR 677CC/1298AA type. Conclusion: MTHFR 1298AC, MTHFR 677CC/1298AC and 677CT/1298AC genotypes may represent genetic markers for the protection of RSA at least in Korean women.

• 대한생식의학회:학술대회논문집
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• 대한불임학회 2004년도 제47차 추계학술대회
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• pp.98-98
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• 2004

• Clinical and Experimental Reproductive Medicine
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• 제24권3호
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• pp.293-300
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• 1997

The aim of present study was to determine the efficacy of immunotherapy with paternal lymphocytes for unexplained infertility. It has been apparent that reproductive success may be affected by the presence of abnormal autoantibodies. Unexplained infertility and repeated pregnancy wastage has been reported in the presence of abnormal autoantibodies. These data suffest that abnormal immune function may be an important pathologic entity contributing subfertility in patients with unexplained infertility. Therefore, immunotherapy may be a possible treatment modality for patients with unexplained infertility. Some investigators have reported that a proportion of infertile couples with repeatedly unsuccessful ET showed close histocompatibility similar to those of spontaneous recurrent abortion. Recently, it has been noted that immunotherapy with paternal lymphocytes achieves a high efficacy in preventing subsequent abortion in women with primary recurrent abortion of unknown cause, which was mediated by immune reaction including blocking antibody. To substantiate the hypothesis, we applied immunotherapy preceding Peritoneal Oocyte and Sperme transfer (POST) to 43 patients, 47 cycles of 82 patients, 89 cycles with at least three previous IUI failure from April, 1993 to February, 1995. There were no significant differences between treatment and control group in clinical response and hormonal response to controlled hyperstimulation. there was no significant difference between treatment and control group in pregnant rates per cycles (42.6% versus 28.6%), but a significantly lower abortion rate per pregnancy in treatment group, with 10.0% (2/20) compared with 50.03% (6/12) in control group. This study may suggest that immune therapy for patients with unexplained infertility with paternal lymphocytes might be beneficial.

• Journal of Yeungnam Medical Science
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• 제13권1호
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• pp.141-145
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• 1996

Habitual pregnancy loss has been defined as three or more consecutive spontaneous abortions. The rate of recurrent pregnancy loss is 2% to 5% of reproducible women. Half of this failure can be explained by genetic, hormonal, infectious, and anatomic factors. And eighty percent of the unexplained failures are proposed to have an immunologic cause. The antiphospholipid antibodies are characterized by prolonged phospholipid-dependent coagulation test (known as APTT or Russel viper venom), thrombosis, thrombocytopenia, and fetal loss. The association of antiphospholipid antibodies with one or more of these characteristic clinical features has been termed the antiphospholipid syndrome. We have experienced a case of successful live birth after treated a woman with heparin and aspirin who has experienced spontaneous abortion four times with antiphospholipid antibodies and present it with the review of literature.

• Clinical and Experimental Reproductive Medicine
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• 제30권3호
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• pp.233-240
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• 2003

연구목적: 본 연구에서는 정상 환자와 습관성 유산 질환 환자에서 유래된 융모막 조직 내에서의 면역억제유전자들의 발현 양상에 대해 알아보고자 하였다. 연구재료 및 방법: 임신 6주와 8주의 습관성 유산 질환 환자와 정상 환자로부터 융모막 조직을 채취하였다 (Normal N=6; RSA N=6). 면역조직화학적 분석을 통해서 조직을 관찰하고 세포가 살아있음을 확인한 후에, 역전사 중합효소연쇄반응을 통해서 면역억제유전자인 placenta protein 14 (PP14), indoleamine 2, 3-dioxygenase (IDO) 그리고 mucin1 (MUC1) 유전자의 발현 정도를 비교하였다. GAPDH 발현에 기준한 면역억제유전자 발현을 정량 분석하여 Student's t-test를 시행하였고, p<0.05를 유의성이 있는 것으로 판정하였다. 결 과: 습관성 유산 질환 환자의 경우, 임신 6주와 8주의 융모막 조직에서의 면역억제유전자 (PP14, IDO, MUC1) 발현이 현저하게 낮은 양상을 보이고 있었다. 습관성 유산과 면역억제유전자의 발현이 통계학적으로 유의성 있는 연관성을 가지고 있다는 것이 확인되었다. 결 론: 면역억제유전자 (PP14, IDO, MUC1)의 발현이 습관성 유산 질환 환자에서 특이적으로 낮게 나타나는 것으로 보아 습관성 유산 질환의 진단과 치료 연구 방안에 이 유전자들의 발현이 이용될 수 있을 것으로 사료된다.

• 대한한의학회지
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• 제19권2호
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• pp.17-35
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• 1998

Medication used during pregnancy may affect the growth of fetus and maintenance of pregnancy so that it may cause fetal deformity or abortion. Before 1940 it was recognized that only genetic factor could affect the incidence of fetal deformity and the teratogen was protected by placenta barrier. But since the report that Thalidomide caused phocomelia was announced in l962 and 1962, it was acknowledged that the placenta barrier was imperfect. In oriental medical care, there were so many prescription used during pregnancy for nausea, threatened abortion, recurrent spontaneous abortion and it was acknowledged that those medication did not harm both maternity and fetus. Most of them are composed of the material that was not classified as prohibition during pregnancy. But we thought that it should be demonstrated through objective methods that these materials do not affect the incidence of fetal deformity or abortion and have the effect of preventing abortion and maintenance of pregnancy. As the first step of that study we researched 78 prescription and each materials, their kinds and using frequency, used for illness and symptoms during pregnancy written in Dongeuibokam(東醫寶鑑) so that we got to know the tendency about what materials are used for each illness and symptoms.

• Clinical and Experimental Reproductive Medicine
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• 제20권2호
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• pp.149-156
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• 1993

Human chorionic gonadotropin(hCG) and intravenous immunoglobulin(IVIG) treatment were attempted as a novel therapeutic approach for unexplained recurrent spontaneous abortion(RSA). Forty-four and 3 women with a history of RSA were treated with hCG and IVIG, respectively, during pregnancy. Of these patients, serum blocking factor assay was performed before and after each treatment, in 15 patients; 12 cases with hCG and 3 cases with IVIG. The results were as follows: 1. Of 44 women who receive hCG during pregnancy, 24 delivered healthy infants at term, 10 patients suffered repeat abortion, and 10 women are still pregnant under 28 weeks. Over all success rate of hCG treatment was 70.6% (24/34). Although there is no statistical significance, absolute serm blocking level was decreased after treatment(N=12). 2. Of 3 women who receive IVIG during pregnancy, all 3 women are still pregnant under 28 weeks. Serum blocking level was increased after treatment, however, this increment was not statistically significant. Although no conclusion could be extracted from the patients who received IVIG, the therapeutic effect of hCG is comparable to that of the other therapeutic regimens, such as allogeneic leukocytes. It was postulated that actual etiology of unknown RSA would be classified as hormonal origin although combined etiologies are common in Korean women.

• 대한생식의학회:학술대회논문집
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• 대한생식의학회 2007년도 제53차 추계학술대회 초록집
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• pp.101-101
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• 2007