Role of Indoleamine 2,3-Dioxygenase and Tryptophan 2,3-Dioxygenase in Patients with Recurrent Miscarriage.

PROBLEM: An indoleamine 2,3-dioxygenase (IDO) and a tryptophan 2,3-dioxygenase (TDO) lead to dysfunction of T cell and immunological tolerance between fetus and mother in early pregnancy. We investigated the role of IDO and TDO in patients with recurrent miscarriage. METHODS OF STUDY: Cervical mucus, decidua, and villi were surgically collected from patients with recurrent miscarriage from April 2010 to March 2013. Samples of cervical mucus were divided into two groups: the delivery group and the miscarriage group. The samples of cervical mucus in the miscarried group and tissue of villi and decidua were divided into normal chromosome group (normal chromosome analysis of villi) and abnormal chromosome group (abnormal chromosome analysis of villi). We performed immunohistochemistry, SDS-PAGE, and Western Blot analysis and measured the activity of IDO and TDO. RESULTS: The activity of IDO and TDO in cervical mucus was not significantly different between the delivery group and the miscarriage group, and between the normal chromosome group and abnormal chromosome group. The expression of TDO in villi and decidua was not significantly different between the normal chromosome group and the abnormal chromosome group. The activity of IDO and TDO in villi and decidua was not significantly different between the normal chromosome group and the abnormal chromosome group. The expression of IDO in villi was significantly higher in the normal chromosome group than in the abnormal chromosome group. CONCLUSION: Our results suggest that the difference of expression of IDO and dysfunctional activation of IDO in villi may play an important role in unexplained recurrent miscarriage.

Two cases of prenatally diagnosed sacrococcygeal teratoma type I with different clinical features.

Sacrococcygeal teratoma (SCT) is a rare congenital disease and prognostic factors have not been entirely established. We report two cases of fetal SCT with different clinical courses. Case 1 was a cystic, slow growing tumor with mild vascularity. The tumor was removed one week after delivery at 35 weeks, and there was no recurrence at 1.5-year follow-up. Case 2 was a solid, rapid growing tumor with rich vascularity. Cesarean section was performed due to severe fetal hydrops and mirror syndrome in the mother at 27 weeks. The tumor had ruptured and was removed soon after delivery to control bleeding, but the baby died the next day. Our cases suggest that solid component and rich vascularity might correlate with poor prognosis.

Prenatal findings of omphalocele-exstrophy of the bladder-imperforate anus-spinal defects (OEIS) complex.

Omphalocele-exstrophy of the bladder (cloaca)-imperforate anus-spinal defects (OEIS) complex describes a rare grouping of more commonly occurring component malformations. We report two cases of OEIS complex diagnosed prenatally by ultrasound and magnetic resonance imaging (MRI). In both cases, OEIS complex was suspected by conventional sonography in the second trimester, and fetal MRI was performed at 27 and 32 weeks of gestation. Conventional sonography revealed low abdominal wall mass, spina bifida, absent bladder and ambiguous genitalia, but those findings were inconclusive. Using fetal MRI, we were able to detect omphalocele, imfraumbilical mass connected to gut tract, absent bladder, ambiguous external genitalia and spinal defect. Our findings suggest that fetal MRI is a useful tool for prenatal diagnosis of OEIS complex. MRI helps prenatal counseling and planning of postnatal early treatment strategy.

A Case of Microangiopathic Antiphospholipid-Associated Syndromes during Pregnancy: Review of the Literature.

Microangiopathic antiphospholipid-associated syndromes (MAPSs) are reported as encompassing several conditions mainly affecting the microvasculature of selected organs: the liver in HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet); kidney, brain, and skin in TTP (thrombotic thrombocytopenic purpura). It is predominant in patients with catastrophic antiphospholipid syndrome (APS). A recent report suggests that APS is not only a thrombotic disease but also associated with microangiopathic features, and it can explain the greater prevalence of HELLP syndrome in these patients. We here report a case of MAPS during pregnancy associated with systemic lupus erythematosus (SLE) in early second trimester.

Prenatal diagnosis of familial lethal hypophosphatasia using imaging, blood enzyme levels, chorionic villus sampling and archived fetal tissue.

Hypophosphatasia is an inheritable disorder characterized by defective bone mineralization and a deficiency of tissue-nonspecific alkaline phosphatase (TNSALP) activity. Screening for mutations in the TNSALP gene allows genetic counseling and prenatal diagnosis of the disease in families with severe forms of hypophosphatasia. A 33-year-old, gravida 4, para 3 Japanese woman was referred to Nagoya City University Hospital for prenatal genetic counseling because of two previous occurrences of fetal bone anomalies. The molecular examination showed that the fetus was homozygous for the TNSALP gene mutation c.1559delT, each parent being heterozygous. Genetic counseling was offered and at the next pregnancy, chorionic villus sampling was performed, whereupon genetic analysis confirmed that the fetus did not carry the familial mutation c.1559delT. Postnatal molecular genetic analysis using the cord tissue can provide a diagnosis of lethal hypophosphatasia and prenatal genetic diagnosis of the TNSALP gene allows time for parental counseling and delivery planning.

Glycogen storage disease type Ia (GSD Ia) during pregnancy: report of a case complicated by fetal growth restriction and preeclampsia.

Glycogen storage disease type Ia (GSD Ia) leads to disturbed glycogenolysis and gluconeogenesis due to a deficiency in the enzyme glucose-6-phosphatase. A patient with GSD Ia showed hypoglycemia and proteinuria without dietary management since early pregnancy. The patient's condition was complicated by hypertension with increase in proteinuria at 22 weeks of gestation. In spite of administration of antihypertensive drugs and dietary management, the disease became more severe with deterioration in the fetal status and inhibition of fetal growth. Thus, a cesarean section was performed at 26 weeks of gestation. The delivered male infant weighing 412 g died at 2 days after birth. The patient's blood pressure had normalized within 3 months after delivery, while proteinuria persisted.

Antiphosphatidylethanolamine antibodies might not be an independent risk factor for further miscarriage in patients suffering recurrent pregnancy loss.

The prevalence of antiphosphatidylethanolamine antibodies (aPEs) is higher in recurrent pregnancy loss patients than that in women with normal pregnancy. We conducted a cohort study to examine the predictive value of aPE for recurrent pregnancy loss and to determine its clinical significance. We examined plasma protein dependent (P+) and independent (P-) aPE IgG and IgM antibodies in 367 women with two or more unexplained consecutive pregnancy losses. We also examined conventional antiphospholipid antibodies (aPL) such as beta2-glycoprotein I-dependent anticardiolipin antibodies (beta2GPI-dependent aCL), lupus anticoagulant with reference to the dilute activated partial thromboplastin time (aPTT) and the diluted Russell's viper venom time (RVVT). Subsequent pregnancy outcome without medication was examined, and patients with and without aPE were compared. Totals of 37 (10.1%), 14 (3.8%), 23 (6.3%), 6 (1.6%), 9 (2.5%), 10 (2.7%) and 50 (13.6%) of the 367 patients were, respectively, positive for P+aPE IgG, P-aPE IgG, P+aPE IgM, P-aPE IgM, beta2GPI-dependent aCL, lupus anticoagulant by RVVT and LA by aPTT. The patients with aPE differed from patients with beta2GPI-dependent aCL or lupus anticoagulant by RVVT. No difference in live birth rate was apparent between positive and negative aPE patients with no medication. The areas under the curves for each ROC curve for the four aPEs were 0.535, 0.612, 0.546 and 0.533, respectively, so there was no significant variation in diagnostic capacity. We did not obtain any evidence that aPE elevation is an independent risk factor to predict further miscarriage in recurrent pregnancy loss patients.

Prenatal diagnosis of persistent cloaca.

We report four cases of persistent cloaca diagnosed at 32-33 weeks of gestation. In cases of persistent cloaca, serial prenatal ultrasonography shows transient fetal ascites, enlarged cystic structures arising from the fetal pelvis. Our four cases of persistent cloaca were diagnosed prenatally. Persistent cloaca should be considered in any female fetus presenting with hydronephrosis and a large cystic lesion arising from the pelvis as assessed by ultrasound and magnetic resonance imaging. Neither pulmonary hypoplasia nor severe oligohydramnios were found in any of our four cases, and they each had a good prognosis. Prenatal diagnosis allows time for parental counseling and delivery planning at a tertiary care center for neonatal intensive care and pediatric surgery.

Live birth rate according to maternal age and previous number of recurrent miscarriages.

PROBLEM: In Japan, marital age and women's age at the first pregnancy are continuing to increase year by year. However, information concerning subsequent live birth rate according to maternal age and number of previous recurrent miscarriages is limited. METHOD OF STUDY: We studied a total of 1250 unexplained patients suffering two or more consecutive miscarriages. We examined the live birth rate at the first pregnancy and the cumulative success rate for birth of at least one child after examination. RESULTS: The live birth rate of women in their 40s was 58.1%, which was similar to that of women who were 35-39 years old (58.4%) at the first pregnancy, as found after examination. From logistic regression, women's age and the number of previous miscarriages independently decreased the live birth rate in subsequent pregnancies (p(s)) as well as cumulative pregnancies (p(c)), as follows: logit (p(s)) = 3.964 - 0.0652 x (age) - 0.408 x (previous number of miscarriages), logit(p(c)) = 6.806 - 0.1130 x (age) - 0.514 x (previous number of miscarriages). CONCLUSION: The information concerning the live birth rate can be given to each patient before subsequent pregnancy.