Search

Infertility is defined as a reproductive disorder in which pregnancy is established, but normal fetal growth can never be achieved due to pregnancy loss. The pathogenesis of this disorder must be understood accurately to obtain optimal results in its management. Although genetic, anatomic and hormonal factors have been implicated as to its cause, a substantial proportion of cases remain unexplained. Recently, an immunologic etiology for this disorder has been proposed for many couples with infertility due to unexplained causes. Author has evaluated patients with infertility according to two immunologic aspects, namely "autoimmune" and "alloimmune", and assessed them pathophysiologically and clinically. [Autoimmune abnormality] Autoimmune diseases, especially SLE, have been associated with pregnancy loss, with autoantibody abnormalities being speculated to be causally related to this reproductive disorder. Especially among various autoantibodies, author noticed an antiphospholipid antibody (aPL) that has been associated with micro-thrombosis, and performed the enzyme-linked immunosorbent assay. Pathophysiological evaluations performed were as follows: 1. Inhibitory effect of aPL on prostacyclin production in cultured vascular endothelial cells. 2. Existence of aPL in the elute from placental tissue. Clinical evaluations were as follows: 1. Frequency of aPL positivity among patients with infertility. 2. Correlation between frequency of aPL positivity at the placental site and the outcome of pregnancy. 3. Correlation between the selected modes of medical therapy (e.g., administration of prednisolone, aspirin, etc.) in aPL-positive cases and the outcome of pregnancy. Based on the results of the above evaluations, it was suggested that IgG-aPL can be considered a useful diagnostic and prognostic variable in women with infertility. Moreover, it was considered that the inhibition of prostacyclin production due to aPL might disturb utero-placental circulation by vasoconstriction and local vascular thrombosis in the placenta and thus lead to pregnancy loss. It was confirmed that the combination of immunosuppressive and anticoagulant therapy is, to a certain extent, an effective treatment for aPL-positive pregnant women. [Alloimmune abnormality] When normal pregnancy is viewed from an immunological standpoint, there arises a basic question of how the fetus escapes immunological rejection despite being allograft. Explanations have been based on various mechanisms of maternal immunity and some experiments were therefore attempted to elucidate the immunological mechanisms. Points of evaluation were as follows: 1. Blocking activity of serum utilizing the mixed lymphocyte reaction with lymphocytes of the husband as stimulators and those of the wife as responders. 2. Detection of HLA-class II antibody, cold-B cell antibody, and anti-idiotype antibody as blocking antibodies in the serum.(ABSTRACT TRUNCATED AT 400 WORDS)

Two hundred and forty-nine healthy women at 36 weeks gestation and 38 women with pregnancy induced hypertension (PIH) underwent urinalysis for urinary calcium excretion to obtain the calcium/creatinine ratio. This ratio was significantly lower in the women with PIH than in the healthy pregnant women, and it was especially low in those with PIH who had no family history of hypertension. Three hundred forty-eight healthy women at 20 weeks of gestation underwent urinalysis to determine their calcium/creatinine ratio as a means to predict PIH in patients showing no symptoms. In the primiparous group with no family history 58% of the patients with a low calcium/creatine ratio eventually developed PIH. Using a receiver operator curve, we calculated a predictive threshold calcium value for PIH of 0.06 at six month's pregnancy. Thus urinary calcium excretion may be a useful early marker for PIH.

The C100-3 antibodies to HCV can be examined with a Chiron kit but only the antibody to non-structure-4 can be. The antibodies in sera of pregnant women were examined by a passive hemagglutination method (PHA), which is one of the second generation kits used in detecting antibodies to the hepatitis C virus. We studied the percentage of pregnant women in our hospital with antibodies to HCV, and tried to compare the C100-3 antibodies with PHA results in pregnant women. The results are as follows. 1) In the sera of 235 pregnant women both the PHA antibody and the C100-3 antibody were examined. Two women (0.85%) had the C100-3 antibody and 4 (1.7%) had the PHA antibody. 2) Two women positive for both PHA and C100-3 antibodies were positive for PCR during pregnancy. But 2 women positive for PHA only were negative for PCR during pregnancy and positive after delivery. So 4 women positive for PHA had HCV RNA. 3) Next, the sera of 1,198 pregnant women were examined by the PHA method, and nine women were positive. Only four of the 9 were positive for C100-3. 4) It is speculated that the positive rate for anti-HCV antibodies in the sera of pregnant women in Nagoya city is 0.75%. 5) There were 3 cases that were negative for PCR during pregnancy and positive after delivery. So it is speculated that HCV can be activated after delivery.

Immunotherapy (immunization twice at 5 and 7 weeks of gestation with X-irradiated 200ml total blood or 1-200 x 10(6) mononuclear cells from the husband) was performed on 200 women without autoimmune abnormalities but experiencing habitual abortions of unknown causes between August, 1982 and September, 1990. One hundred fifty-seven babies were eventually born alive. The oldest offspring was 7 yrs 4 mos in August, 1991. We investigated the safety of the immunotherapy in terms of its effects on the women, conditions during pregnancy/labor and conducted long-term follow-up on offspring. Among 190 women whose pregnancy terminated by September, 1990, 152 cases gave birth, including 5 sets of twins. The successful rate was 80.0%. There were no complications among the 200 cases, only 2 small-for-dates babies (1.3%) among 157 babies born alive, and 1 baby born dead in the 3rd trimester, but that was not directly related with immunotherapy. Tsumori-Inage Infant Mental Development Test found no abnormalities (3 yrs and over). At 3 yrs, and only 1 child scored under the mean--2 standard deviation in height and weight. Thus, the safety of the immunotherapy was confirmed by long-term follow-up of both mother and child in which no notable complications resulting from immunotherapy with the husband's X-irradiated cells could be found.

There is strong evidence that anti-phospholipid antibodies is implicated in thrombosis and recurrent fetal death. In recent years, it has been suggested that anti-phosphatidylethanolamine (PE) antibody is an important antibody of this type. In the present study, we established a sensitive enzyme linked immunosorbent assay (ELISA) to detect anti-PE antibodies and examined the relationship between the anti-PE antibody level in serum and recurrent abortion. The improvement of the assay was made by treating PE with 1.0% acetic acid in methanol solution prior to its application to the microplates. This treatment markedly increased the antigenicity of PE. Using this modified ELISA, anti-PE antibodies in 10 patients with a history of recurrent fetal loss were measured before and after therapy during the last period of their pregnancies. IgG anti-PE antibodies were detected in all 10 patients. Four patients exhibiting high titers of IgG anti-PE antibody experienced subsequent intrauterine fetal death (IUFD), while the other 6 patients, whose titers of IgG anti-PE antibody had decreased with therapy, had live births. These results suggest that this modified ELISA for estimating IgG anti-PE antibody is a valuable tool for the diagnosis and prognosis of patients with recurrent fetal loss.

This study was carried out to clarify the effect of pregnancy on chronic glomerulonephritis (CGN). Fifteen patients with CGN diagnosed by renal biopsy were studied throughout 17 pregnancies. The following criteria were adopted: 1) Creatinine clearance (Ccr) over 70 ml/min and serum creatinine (s-Cr) 1.2 mg/dl or less. 2) Blood pressure lower than 140/90 mmHg when not receiving any medicine. 3) No evidence of active progress of nephropathy. In two patients excluded from the criteria, renal function was adversely affected, but there was no evidence that pregnancy affected the natural course of the underlying renal disease. In the patients to which the criteria were applied, the outcome of pregnancy and renal function were good. In conclusion, we recognized that there was no relationship between the body weight of the newborn and maternal serum albumin but that there was a significant correlation between serum uric acid and body weight (r = -0.67). These results show that serum uric acid is a useful indicator of placental dysfunction and fetal growth. In the patients with preeclampsia, the serum uric acid concentration was higher than in the CGN group (8.95 +/- 2.58 mg/dl vs 5.88 +/- 1.49 mg/dl: Scheffe method p less than 0.001). There was no significant difference between the CGN and normal control (5.88 +/- 1.49 mg/dl vs 4.51 +/- 0.68: Scheffe method p less than 0.1). Uric acid serves to distinguish CGN and preeclampsia.

This is the first report on the use of the Nd-YAG laser in performing tubal end to end anastomosis in rabbit. At first, the optimal intensity of laser exposure was evaluated using histological preparations of tubal ampullary tissues which were exposed in various conditions. It was determined that the most suitable condition was 12 watts/cm2 of energy density of 0.2 second duration and a 0.6mm focal spot. Subsequently, these treatment conditions were applied practically to end end anastomosis of severed tubal ampulla of three rabbits. Four weeks later, the second laparotomy was done to confirm the restoration of tubal patency by chromopertubation in vivo, and to excise the restored tube to study the reconstruction of luminal epithelium histologically by scanning electron microscope. Proven by chromopertubation in vivo, tubal patency was restored in 4 out of 6 tubal samples, but in two, tubes were dehisced at the anastomosed line. By scanning electron microscopic observation of tubal samples in which patency was restored some injury to mucosal epithelial cells was seen at the anastomosed site. It is concluded that the Nd-YAG laser technique is useful in tubal end to end anastomosis of rabbit and accurate placement of tubal stumps is essential to the proper restoration of tubal patency.

For the purpose of studying immunogenetic factors related to disease susceptibility to cervical carcinoma (squamous cell carcinoma), HLA-A,B and DR typings were performed by the standard microlymphocytotoxicity test using about 240 typing antisera in 66 Japanese patients with cervical carcinoma and 206 healthy individuals. The results obtained were as follows: 1) The patients had a significant association with HLA-Bw46 (gene frequency = 6.3%, relative risk = 3.9, p less than 0.025), compared with the controls (g.f. = 1.7%). 2) The patients had a significant association with HLA-DRw8 (g.f. = 17.3%, r.r. = 2.3, p less than 0.05), compared with the controls (g.f. = 8.9%). 3) When the patients with cervical carcinoma were divided into two groups, i.e. 53 patients with invasive carcinoma of the cervix and 13 patients with carcinoma in situ of the cervix, the former had a more significant association with both HLA-Bw46 (g.f. = 6.8%, r.r. = 4.3) and HLA-DRW8 (g.f. = 19.2%, r.r. = 2.6) than the total patients, compared with the controls. However, the latter showed only a negligible association when compared with the controls. 4) The significant linkage disequilibrium between HLA-Bw46 and HLA-DRw8 was found in the patients with cervical carcinoma (haplotype frequency = 0.059, delta = 0.047, p less than 0.002), but not in the controls (h.f. = 0.0097, delta = 0.0075). 5) On the other hand, the significant linkage disequilibrium between HLA-A2 and HLA-Bw46 was found in both the patients and the controls.

The T/t complex in the mouse is considered to be a gene locus that brings about neural tube defects. This locus is found to exist near the H-2 complex, which is the MHC of the mouse. Accordingly, it is conceivable that there exists a T/t-like complex near the HLA complex in humans. Studies on the HLA-A, -B, -DR, -DRw52, -53 and DQ loci of parents with anencephalus and affected offspring were undertaken with the aim of revealing the relationship between anencephalus and the HLA complex. The following results were obtained: The gene frequency of HLA-DR5 in a mother with anencephalus was significantly higher than in controls. HLA-DR materno-paternal compatibility was significantly higher than in control couples. An increase in HLA-DR, -DRw52, -53 and DQ homozygosity were observed among the affected offspring. These results indicated that there may exist an anencephalus immunogenetic factor in the HLA-D region.

Renal involvement associated with preeclampsia is well investigated, especially from the aspect of glomerular lesion and coagulation. On the other hand, only a few studies on tubular dysfunction during normal pregnancy and preeclampsia have been reported. The first study was carried out to clarify and estimate the chronological changes in tubular function. Pregnant women without obvious tubular dysfunction and toxemia (group A) were investigated using serum Cl, Na minus Cl (Na-Cl index), uric acid and urinary beta 2-microglobulin (u-beta-MG) at the 10th, 20th, 30th and 36th weeks of gestation. The second study was carried out to determine the significance of tubular dysfunction accompanied by preeclampsia. Patients with severe preeclampsia (group B) and normal pregnancy (group C) were examined by the same index of tubular dysfunction. The diagnosis of severe preeclampsia was confirmed with hypertension (over 170/110 mmHg), proteinuria (beyond 3 g/day) and severe edema. The following results were obtained: Urinary beta-MG and serum Cl increased during the third trimester in group A, but the Na-Cl index decreased. The serum uric acid concentration increased during the third trimester in group A. Tubular dysfunction was evident during the third trimester in normal pregnancy. Every index of tubular dysfunction including u-beta-MG, serum Cl, Na-Cl index and uric acid in group B was significantly higher than in group C. In group B, 4 fetuses died and 7 out of 15 cases required Cesarean sections. The critical line of tubular dysfunction for fetal prognosis was Cl 110 mEq/l, Na-Cl index 28 mEq/l, uric acid 6.0 mg/dl and u-beta-MG 1,000 micrograms/l.(ABSTRACT TRUNCATED AT 250 WORDS)