• Clinical and Experimental Reproductive Medicine
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• 제25권2호
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• pp.115-122
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• 1998

The maintenance of a viable pregnancy has long been viewed as an immunological paradox. The deveolping embryo and trophoblast are immunologically foreign to the maternal immune system due to their maternally inherited genes products and tissue-specific differentiation antigens (Hill & Anderson, 1988). Therefore, speculation has arisen that spontaneous abortion may be caused by impaired maternal immune tolerance to the semiallogenic conceptus (Hill, 1990). Loss of recall antigen has been reported in immunosuppressed transplant recipients and is associated with graft survival (Muluk et al., 1991; Schulik et al., 1994). Progesterone $(10^{-5}M)$ has immunosuppressive capabilities (Szekeres-Bartho et al., 1985). Previous study showed that fertile women, but not women with unexplained recurrent abortion (URA), lose their immune response to recall antigens when pregnant (Bermas & Hill, 1997). Therefore, we hypothesized that immunosuppressive doses of progesterone may affect proliferative response of lymphocytes to trophoblast antigen and alloantigen. Proliferative responses using $^3H$-thymidine ($^3H$-TdR) incorporation of peripheral blood mononuclear cells (PBMCs) to the irradiated allogeneic periperal blood mononuclear cells as alloantigen, trophoblast extract and Flu as recall antigen, and PHA as mitogen were serially checked in 9 women who had experienced unexplained recurrent miscarriage. Progesterone vaginal suppositories (100mg b.i.d; Utrogestan, Organon) beginning 3 days after ovulation were given to 9 women with unexplained RSA who had prior evidence of Th1 immunity to trophoblast. We checked proliferation responses to conception cycle before and after progesterone supplementation once a week through the first 7 weeks of pregnancy. All patients of alloantigen and PHA had a positive proliferation response that occmed in the baseline phase. But 4 out of 9 patients (44.4%) of trophoblast antigen and Flu antigen had a positive proliferative response. The suppression of proliferation response to each antigen were started after proliferative phase and during pregnancy cycles. Our data demonstrated that since in vivo progesterone treated PBMCs suppressed more T-lymphocyte activation and $^3H$-TdR incorporation compare to PBMCs, which are not influenced by progesterone. This data suggested that it might be influenced by immunosuppressive effect of progesterone. In conclusion, progesterone may play an important immunological role in regulating local immune response in the fetal-placental unit. Furthermore, in the 9 women given progesterone during a conception cycle, Only two (22%) repeat pregnancy losses occured in these 9 women despite loss of antigen responsiveness (one chemical pregnancy loss and one loss at 8 weeks of growth which was karyotyped as a Trisomy 4). These finding suggested that pregnancy loss due to fetal aneuploidy is not associated with immunological phenomena.

• Clinical and Experimental Reproductive Medicine
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• 제26권2호
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• pp.265-269
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• 1999

Thrombocytopenic patients without detectable bound antiplatelet antibody should be diagnosed with idiopathic thrombocytopenic purpura (ITP) if no other cause of their decreased platelet count could be found. More recently the term "autoimmune thrombocytopenic purpura (ATP) has supplanted ITP since the disease is related to the production of autoantibodies against one's own platelets. This entity should not be confused with isoimmune thrombocytopenic purpura (also called alloimmune thrombocytopenic purpura). In this cases maternal antiplatelet antibodies directed against the PLA 1 antigen on the fetal platelets causes severe fetal and neonatal thrombocytopenia in a situation analogous to Rheusus disease. Antibodies to the negatively charged phospholipids, lupus anticoagulant, and anticardiolipin have been linked to adverse pregnancy events. Pregnant women possessing these antibodies have an increased risk of spontaneous abortion, stillbirths, intrauterine fetal growth retardation, preterm birth, and arterial and venous thrombosis. Antiphospholipid antibodies decrease or may even disappear between pregnancies only to recur with increased activity in a subsequent pregnancy and lead to loss. We have experienced a case of antiphospholipid syndrome associated with autoimmune thrombocytopenic purpura in patient with recurrent spontaneous abortion. So we report this case with a brief review of literatures.

• Clinical and Experimental Reproductive Medicine
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• 제48권3호
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• pp.203-210
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• 2021

We performed a systematic review and meta-analysis to evaluate whether intralipid administration improved the outcomes of in vitro fertilization. Online databases (PubMed, Cochrane Library, Medline, and Embase) were searched until March 2020. Only randomized controlled trials (RCTs) that assessed the role of intralipid administration during in vitro fertilization were considered. We analyzed the rates of clinical pregnancy and live birth as primary outcomes. Secondary outcomes included the rates of chemical pregnancy, ongoing pregnancy, and missed abortion. We reviewed and assessed the eligibility of 180 studies. Five RCTs including 840 patients (3 RCTs: women with repeated implantation failure, 1 RCT: women with recurrent spontaneous abortion, 1 RCT: women who had experienced implantation failure more than once) met the selection criteria. When compared with the control group, intralipid administration significantly improved the clinical pregnancy rate (risk ratio [RR], 1.48; 95% confidence interval [CI], 1.23-1.79), ongoing pregnancy rate (RR, 1.82; 95% CI, 1.31-2.53), and live birth rate (RR, 1.85; 95% CI, 1.44-2.38). However, intralipid administration had no beneficial effect on the miscarriage rate (RR, 0.75; 95% CI, 0.48-1.17). A funnel plot analysis revealed no publication bias. Our findings suggest that intralipid administration may benefit women undergoing in vitro fertilization, especially those who have experienced repeated implantation failure or recurrent spontaneous abortion. However, larger, well-designed studies are needed to confirm these findings.

• 대한한방부인과학회지
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• 제20권4호
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• pp.160-174
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• 2007

Purpose: The purpose of this study was to investigate about missed abortion pathophysiology, diagnosis, medical treatment and to research the trend of the study related to missed abortion. Methods: We referred a PubMed site by using search word of "missed abortion"(Limits: 3 Year, only items with abstracts, Human). Results: 37 journals with 49 papers were searched. Conclusion: 1. The study of missed abortion pathophysiology was the following. The first was that important pathologies such as molar pregnancy and placental trophoblastic disease can be diagnosed by routine histopathologic analysis of product of conception following first-trimester spontaneous miscarriages. The second was that coelomic fluid leptin concentration in missed abortion is higher than in normal. The third was that adenosine deaminae activity in serum and placenta of patients with anembryonic pregnancies and missed abortions was low. The forth was that Leptotrichia amnionii sp. nov. was the etiopathogenetic factor in missed abortion. 2. Transvaginal ultrasound assessment of irregular vaginal bleeding is effective in diagonosis of missed abortion. 3. There were medical therapy with misoprostol, mifepristone or anti progesterone for missed abortion. Misoprostol was administrated oral(sublingual) and vaginal.

• Clinical and Experimental Reproductive Medicine
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• 제28권2호
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• pp.105-110
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• 2001

Objective: To evaluate the abnormality of protein S in patients with recurrent spontaneous abortion due to antiphospholipid syndrome. Material and Method: Antigen and activity of protein S were analyzed by enzyme immunoassay and clotting method, respectively. Results: Of 18 patients with antiphospholipid syndrome, 4 patients were found to have no abnormality of protein S. There were 14 cases of protein S abnormality. Among them, there were 8 cases of type 1, 1 case of type 2, and 5 cases of type 3 protein S deficiency. Conclusion: So in the workup of patients with recurrent spontaneous abortion due to antiphospholipid syndrome, the evaluation for protein S is required.

• Clinical and Experimental Reproductive Medicine
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• 제18권2호
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• pp.223-231
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• 1991

During the years 1984 to 1989, in order to determine of chromosome abnormalities are associated with recurrent spontaneous abortions, cytogenetic studies were performed 384 couples. Abnormal karyotypes were found in 51(13.3%) couples. There was no apparent relation with the number of abortions. The abnormalities were as follows: 17(4.4%) balanced translocation; 15(3.9%) mosaicisms; 17(4.4%) pericentric inversion; 2(0.5%) addition or isochromosome. Chromosome abnormalities were observed in 34(67%) of the wives and 17(33%) of the husbands. In addition, we detected polymorphic variants of chromosomes in 89(23.2%) subjects. Reciprocal translocations(13/17) were more common than the robertsonian type(4/17). All of the mosaicisms were associated with the sex chromosomes in 10 females and 5 males subjects. Pericentric inversions were most common in chromosome 9. Compared to previously studied general populations, significantly higher frequencies of translocations, mosaicisms and inversions were found in couples with repetitive spontaneous abortion. This suggests that couples should have chromosome studies after two or more abortions.

• 대한한방부인과학회지
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• 제29권3호
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• pp.78-90
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• 2016

Objectives: The purpose of these cases is to report the effects of Korean medicine on two women with recurrent miscarriage.Methods: One women who had recurrent miscarriage with myoma uteri was 39 years old. She was treated with herbal medicine and acupuncture until intrauterine pregnancy (IUP) 14 wks. the other who had recurrent miscarriage with adenomyosis was 40 years old. she was also treated with these until IUP 11 wks.Results: After treatment, one women delivered successfully by normal full term spontaneous delivery. The other succeeded in normal pregnancy and she is 15 weeks pregnant.Conclusions: Two cases show that Korean Medicine has effects on recurrent miscarriage with old age and underlying diseases.

• Clinical and Experimental Reproductive Medicine
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• 제32권2호
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• pp.113-119
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• 2005

Objective: The purposes of this study were to investigate the types and the incidences of chromosomal abnormalities, and to provide an explanation for the genetic causations of recurrent spontaneous abortions in Korean population. Methods: Cytogenetic studies were carried out in 535 couples with at least two spontaneous first trimester abortions from January 1981 to December 2003. For karyotype analysis, we used modified Moorhead method by Giemsa staining and Giemsa-Trypsin-Giemsa banding Results: The overall incidence of chromosome abnormality was 32 out of 535 cases (5.98%). There were 25 cases (4.67%) of translocation and 7 cases (1.31%) of inversion. In translocation, 5 cases (0.93%) of Robertsonian translocation and 20 cases (3.74%) of reciprocal translocation were observed. In inversion, 6 cases (1.12%) of inversion of chromosome 9 and one case (0.19%) of inversion of chromosome 18 were found. Conclusion: In this study, overall chromosomal abnormality rate in couples with recurrent spontaneous abortions is much higher than that in the general population. So, chromosomal analysis should be offered for the prognostic information in genetic counseling such as prenatal diagnosis in couples with repetitive reproductive failure.

• Clinical and Experimental Reproductive Medicine
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• 제32권3호
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• pp.217-222
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• 2005

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.

• Clinical and Experimental Reproductive Medicine
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• 제31권3호
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• pp.183-190
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• 2004

Objectives: Methylenetetrahydrofolate reductase (MTHFR) mutation are commonly associated with hyperhomocysteinemia, and through their defects in homocysteine metabolism, they have been implicated as a risk factor for recurrent spontaneous abortion. Recent report describe that 28-bp tandem repeat polymorphism in thymidylate synthase enhancer region (TSER) that influence enzyme activity would affect plasma homocysteine level. We have investigated the relationship between TSER genotype and plasma homocysteine level in 54 patients with recurrent spontaneous abortion. Methods: Plasma homocysteine level was measured by fluorescent polarizing immunoassay. MTHFR mutation (C677T and A1298C) was identified by PCR-restriction fragment length polymorphism assay and TSER mutation was analyzed by PCR method. The data were analyzed using the program SAS 8.2 for Windows. Results: Total homocysteine level was significantly higher in MTHFR 677TT genotype ($9.80{\pm}3.87{\mu}mol/L$) than MTHFR 677CC genotype ($8.14{\pm}1.74{\mu}mol/L$) in Korean patients with unexplained recurrent spontaneous abortion (p=0.0143). However, the plasma homocysteine level was not significantly different in the MTHFR 1298AA ($8.42{\pm}2.65{\mu}mol/L$) and 1298CC ($6.09{\pm}0.32{\mu}mol/L$; p=0.2058) and, TSER 2R2R ($8.61{\pm}1.68{\mu}mol/L$) and 3R3R ($8.05{\pm}2.81{\mu}mol/L$; p=0.9319) mutant genotypes, respectively. In this study, we found the combination effects of TSER and MTHFR C677T genotypes. Plasma homocysteine levels were the highest ($11.47{\pm}4.66{\mu}mol/L$) in individuals with TSER 3R3R ($8.05{\pm}2.81{\mu}mol/L$) and MTHFR 677TT ($9.80{\pm}3.87{\mu}mol/L$) genotypes. Individuals with a combination of both TSER 2R2R/2R3R and MTHFR 677CC/CT genotypes ($7.69{\pm}1.77{\mu}mol/L$) had lower plasma homocysteine levels than TSER 2R2R ($8.61{\pm}1.68{\mu}mol/L$) and MTHR 677CC ($8.14{\pm}1.74{\mu}mol/L$) genotypes, respectively. The effect of MTHFR polymorphism in the homocysteine metabolism appears to be stronger than that of TSER polymorphism. Conclusion: Although statistically not significant, we found the elevated level of plasma homocysteine in combined genotypes with TSER and MTHFR (C677T and A1298C) in Korean patients with unexplained habitual abortion. In this study, we reported the possibility that TSER polymorphism is a genetic determinant of plasma homocysteine levels in the Korean patients as well as MTHFR C677T polymorphism. A large prospective study is needed to verify our findings.