Masato Arakawa

Chromosome analysis of aborted conceptuses of recurrent aborters positive for anticardiolipin antibody

OBJECTIVE To elucidate the relationship between anticardiolipin antibody and recurrent abortion. DESIGN Prospective clinical study. SETTING Institutional practice in which patients with recurrent abortion were registered at the outpatient clinic for infertility of Niigata University Hospital. PATIENT(S) Five hundred sixty-one patients with recurrent abortions and 148 patients who were not recurrent aborters and who had experienced sporadic abortion. INTERVENTION(S) Aborted conceptuses for chromosome analyses were collected from the patients. MAIN OUTCOME MEASURE(S) The positive rate of anticardiolipin antibody was assessed in patients with recurrent abortion. Chromosome analyses of aborted conceptuses were performed in 10 patients with positive anticardiolipin antibody who had experienced another pregnancy that resulted in repeated abortion. Similar analyses of aborted conceptuses from 148 sporadic early abortions (controls) were performed. RESULT(S) The incidence of chromosome abnormalities in anticardiolipin antibody-positive recurrent aborters was 20.0% (2 of 10 cases), which was significantly lower than that of patients with sporadic abortion (60.1%, 89 of 148 cases). CONCLUSION(S) The low incidence of chromosome abnormalities in aborted conceptuses of patients with positive anticardiolipin antibody suggests that this antibody is strongly implicated in the genesis of recurrent abortions.

Treatment for patients with recurrent abortion with positive antiphospholipid antibodies using a traditional Chinese herbal medicine

Twelve patients with recurrent abortion who had shown positive antiphospholipid antibodies were treated through the administration of a Japanese modified traditional Chinese herbal medicine Sairei-To (Chan ling-Tang) The patients had experienced a total of 27 spontaneous abortions in their previous pregnancies and had no other pregnancy history except for one patient. The patients were treated with 9.0 g of Sairei-To per day before their next pregnancy. The positive value of antiphospholipid antibodies returned to negative in 9 patients out of 12 patients through the treatment. Out of 12 patients, in 10 patients, their new pregnancy continued uneventfully and delivered an offspring (Success rate: 83.3%). Thus, the current treatment was considered to be an effective therapy for patients with recurrent abortion who were found to be positive for antiphospholipid antibodies.

Relationship between MLR blocking antibodies and the outcome of the third pregnancy in patients with two consecutive spontaneous abortions

To determine the relationship between mixed lymphocyte culture reaction (MLR) blocking antibodies (BAbs), immunological humoral factors, which generated in pregnant women and the outcome of pregnancy, the natural outcome of the third pregnancy in fifty-five patients with primary twice consecutive abortion was evaluated, and MLR-BAbs in sera were examined during their third pregnancy. The third pregnancy in 39 of 55 patients (70.9%) continued successfully, and remaining 16 patients (29.1%) experienced repeated abortion at the first trimester. Out of these 55 patients, MLR-BAbs were examined in 27 (17 with successful outcome and 10 with repeated abortion). The positive rate of MLR-BAbs was 82.4% in patients with successful outcome (15 of 17 cases), and that in patients with repeated abortion was 10% (one of 10 cases). The positive rate of MLR-BAbs was significantly higher in the successful pregnancy group compared with that in the repeated abortion group (p < 0.001). The blocking effect on MLR significantly increased along with the prenatal course in patients with successful outcome. Thus, MLR-BAbs are strongly associated with the outcome of pregnancy in patients with primary twice consecutive spontaneous abortions.

Anti-cardiolipin antibody and anti-cardiolipin beta-2-glycoprotein I antibody in patients with recurrent fetal miscarriage

To elucidate the association between anticardiolipin antibody (aCL-Ab) or anti-cardiolipin beta-2-glycoprotein I-antibody (aCL-beta-2-GP I-Ab) and recurrent fetal miscarriage, the positive rates of aCL-Ab were assessed in 667 patients with recurrent fetal miscarriages and those of aCL-beta-2-GP I-Ab were assessed in 208 patients. The rates were then compared with the control group. The positive rate of aCL-Ab in the patients group (17.4%) was significantly higher than that in the control group (4.0%). The rate of aCL-Ab was especially high in patients who had experienced two or more fetal miscarriages including at least one or more intrauterine fetal deaths during the second or third trimester (41.3%). The positive rate of aCL-beta-2-GP I-Ab in patients with recurrent fetal miscarriage (3/208 cases, 1.4%) was not significantly different from the control group (0/100 cases, 0%). However, the rate of aCL-beta-2-GP I-Ab was significantly higher in patients who had experienced two or more fetal miscarriages including at least one or more intrauterine fetal deaths during the second or third trimester (8.3%) compared with the control group. In conclusion, the implication of aCL-Ab in the genesis of recurrent fetal miscarriage was confirmed. It was suggested that aCL-beta-2-GP I-Ab was associated with the generation of intrauterine fetal death, although it had little association with the genesis of recurrent fetal miscarriage during the first trimester.

HLA Antigens in patients with severe preeclampsia

The distribution of human leucocyte antigens (HLA) was analyzed in 35 patients with severe preeclampsia and compared with that in the general population in the Niigata district of Japan. The frequency of patients with HLA CW7 was significantly higher than that of the general population of this area (p < 0.05, Chi-square test). The frequency of those with HLA-DR6 (DR6, DR13 and DR14) was also significantly greater compared with the general population (P < 0.05, Chi-square test), while that of those with DR4 was significantly lower (P < 0.05, Chi-square test). The compatibility of HLA antigens in spouses was also analyzed in 20 patient couples and 26 normal fertile couples, and there was no significant difference. Thus it is suggested that HLA antigen systems might be involved in the genesis of preeclampsia.

Possible susceptibility of the HLA-DPB1*0402 and HLA-DPB1*04 alleles to unexplained recurrent abortion: analysis by means of polymerase chain reaction-restricted fragment length polymorphism method.

Takakuwa K, Hataya I, Arakawa M, Kikuchi A, Higashino M, Yasuda M, Kurabayashi T, Tanaka K. Possible susceptibility of the HLA‐DPB1*0402 and HLA‐DPB1*04 alleles to unexplained recurrent abortion – analysis by means of polymerase chain reaction–restricted fragment length polymorphism method. AJRI 1999; 42:233–239

Suppressive effect of anticardiolipin antibody on the proliferation of human umbilical vein endothelial cells

OBJECTIVE To determine whether sera that show a positive anticardiolipin test result have a suppressive effect on the proliferation of endothelial cells collected from human umbilical veins. DESIGN Retrospective in vitro study. SETTING University hospital outpatient clinic for the treatment of infertility. PATIENT(S) Thirteen patients with recurrent fetal miscarriages who were positive for anticardiolipin antibody and 14 patients with recurrent miscarriages who were negative for anticardiolipin antibody. INTERVENTION(S) Serum was obtained from each patient. MAIN OUTCOME MEASURE(S) Suppressive effect of the sera on the culture of human umbilical vein endothelial cells. RESULT(S) The proliferation of human umbilical vein endothelial cells decreased significantly in cultures that contained sera showing positive anticardiolipin antibody activity that had been collected from patients with recurrent fetal miscarriages. CONCLUSION(S) The results strongly suggest that anticardiolipin antibody has a suppressive effect on the proliferation of human umbilical vein endothelial cells.

Polymorphism of the β3-adrenergic-receptor gene associated with maternal body weight gain and fetal body weight

Objective: To investigate whether the polymorphism of the β3‐adrenergic‐receptor (β3‐AR) gene was associated with the maternal and fetal conditions during pregnancy. Method: The association between the genotypes of β3‐AR and clinical phenotypes during pregnancy was analyzed in 92 women (a total of 126 pregnancies). Result: The overall frequency of the Trp64Arg β3‐AR allele in 92 pregnant Japanese women was 20.7%. In 125 pregnancies, excluding one homozygote (51 heterozygote group and 74 wild‐type group), a significant difference in the maternal body weight gain during pregnancy was observed between the heterozygote group and wild‐type group. The heterozygote group had significantly higher neonatal body weights, neonatal body weight index values and placental weights compared with the wild‐type group. Conclusion: The Trp64Arg heterozygous mutation in the β3‐AR gene is associated with not only the increase in the body weight of pregnant Japanese women but also the increase in the weights of their neonate and placentas.