Masahiko Higashino

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.

Is an additional vaccination necessary for a successful second pregnancy in unexplained recurrent aborters who were successfully immunized with their husband's lymphocytes before the first pregnancy?

PROBLEM: Is an additional immunotherapy necessary or not for patients who have obtained successful results after initial immunotherapy?

A typical case of reproductive autoimmune failure syndrome in which a patient experienced recurrent abortion, preeclampsia, and intrauterine growth retardation

In the past few years a new concept concerning reproductive failure caused by autoimmune mechanisms has been recognized and accepted as a reproductive autoimmune failure syndrome (RAFS). I RAFS was first reported to include spontaneous abortion, endometriosis, and unexplained infertility, Recently, preeclampsia and intrauterine growth retardation have also been included in RAFS.2-4 In this report, the clinical course of a patient who was considered to be a typical case of RAFS is described, and the possibility of prophylactic therapy for patients of RAFS is discussed.

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.

Successful prenatal treatment of congenital heart block with ritodrine administered transplacentally.

Abstract Congenital heart block (CHB) is rather rare, and a poorer prognosis has been documented in fetuses with a ventricular rate <55 beats per minutes (bpm), in which therapeutic interventions during pregnancy have been warranted. We present a case of CHB associated with maternal anti-SSA/Ro antibody, diagnosed at 28 weeks’ gestation. Fetal echocardiography revealed atrioventricular dissociation, with an atrial rate of 170 bpm and a ventricular rate of 54 bpm. To increase the fetal heart rate, maternal intravenous ritodrine infusion was undertaken, fetal ventricular rate was rapidly increased to 65 bpm. The pregnancy successfully continued until term, and a female infant weighing 2919 g was delivered by cesarean section with Apgar scores of 8 and 8 and 1 and 5 min. The infant is now 12 months of age and growing normally on oral terbutaline without pacing. In a case of fetal heart block, maternal administration of ritodrine may be a therapeutic intervention to improve the fetal and neonatal prognosis.

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.

Significant Compatibility Does Not Exist at the HLA-DQB Gene Locus in Couples With Unexplained Recurrent Abortions

ABSTRACT: The polymerase chain reaction‐restricted fragment length polymorphism (PCR‐RFLP) method was used for both examining compatibility at the HLA‐DQB1 gene locus and determining HLA‐DQ antigen polymorphism in spouses of unexplained recurrent abortions. Genomic DNA samples were prepared from peripheral mononuclear cells from patient and control couples. Two hundred and thirty base pair fragments of the second exon of the HLA‐DQB genes were selectively amplified. Amplified DNAs were digested with the restriction endonucleases, Fok I, Hae III, Hha I, Rsa I and Sau3A I, and subjected to electrophoresis in a polyacrylamide gel. The RFLPs showed that habitual aborters and their husbands had neither significantly frequent alleles nor shared common alleles at the HLA‐DQB locus when compared to the control group.

Studies on the human leukocyte antigen class I antigens in Japanese patients with macroscopically diagnosed endometriosis.

An increasing number of reports suggest that endometriosis is associated with abnormal immune function, although the etiology of the disease remains undefined. The human leukocyte antigen system (HLA) is known to play a role in the etiology of a number of diseases. This study examines the possible association between the HLA system and endometriosis. Fifty-five patients diagnosed with endometriosis by laparoscopic examination were typed for HLA class I antigens – HLA-A, -B, and -C antigens – using the standard microlymphocytotoxity technique of Terasaki. The frequency of HLA-B 54 and that of HLA-Cw7 were significantly higher in the patient population than in the control population. No significant difference was found between the two groups in the frequencies of the other HLA-class I antigens. The results of this study may implicate the HLA system in the development of endometriosis.

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

Trizygotic pregnancy consisting of two fetuses and a complete hydatidiform mole with dispermic androgenesis

A triplet pregnancy in a 23-year-old woman was terminated at 15 weeks of gestation because of her severe hypertension, lung edema, and secondary hyperthyroidism. The pregnancy consisted of a hydatidiform mole with a 46,XY karyotype and two fetuses each with 46,XX and a 46,XY karyotype. To determine the zygosity and genetic origin of the mole and fetuses, PCR- and computer-assisted genotyping were performed at 27 CA-repeat marker loci that were distributed evenly over the genome. As a result, genotypes of the three pregnancy products were distinct from each other, indicating that the triplets were trizygotic. The mole lacked any maternal alleles but inherited both of the paternal alleles and/or one paternal allele in duplicate. This, along with the XY sex chromosome constitution, indicated that the mole resulted from dispermic androgenesis. The mother developed a persistent trophoblastic tumor thereafter.