Hyaluronan-binding protein 2 (HABP2) gene variation in women with recurrent miscarriage.

BACKGROUND: Idiopathic recurrent miscarriage, defined as three or more consecutive miscarriages, is a distressing early pregnancy complication. Although, the etiology of recurrent miscarriage is still unknown, an aberrant regulation of the endometrial receptivity marker hyaluronan-binding protein 2 (HABP2) has been suggested. The objective of the present study was to investigate the effect of genetic variations of HABP2 in women with idiopathic recurrent miscarriage compared to fertile women. METHODS: This study was designed as a case-control study. In total, 165 women who had three or more consecutive miscarriages and 289 fertile women were included in the study. Polymorphisms in the HABP2 gene were analyzed using TaqMan SNP Genotyping Assays. Three polymorphisms in the HABP2 gene, rs1157916, rs2240879 and rs7080536 (Marburg I) were studied. RESULTS: Polymorphism in HABP2 showed no significant difference in women with recurrent miscarriage compared to fertile women, except for rs1157916 minor A allele that was more prevalent among RM patients (p = 0.058). Significantly higher live birth rate was observed among women with three to four miscarriages compared to those with more miscarriages (p = 0.001). CONCLUSIONS: Variations in the HABP2 gene did not seem to be involved in the etiology of recurrent miscarriage, while, the number of previous miscarriages had an impact on the live birth rate.

Incidence of Subclinical Hypothyroidism and Hypothyroidism in Early Pregnancy.

BACKGROUND: Untreated and subclinical hypothyroidism (SCH) has been associated with adverse pregnancy complications such as increased risk of miscarriage, hypertension, preeclampsia, and preterm delivery. However, in Sweden, screening for thyroid dysfunction during pregnancy is only recommended for women with a high risk of thyroid disease. Therefore, the aim of this study was to determine the incidence of clinical and SCH in women in the first trimester of pregnancy. MATERIALS AND METHODS: In this prospective study, 1298 pregnant women were divided into three groups: one unselected general screening group (n = 611), one low-risk group comprising women without risk factors for thyroid disorder (n = 511), and one high-risk group comprising women with an inheritance or suspicion of thyroid disease or undergoing treatment for thyroid disease (n = 88). Serum was obtained up to gestational week 13, and thyrotropin (TSH) was analyzed. RESULTS: The incidences of thyroid dysfunction in the three screening groups were 9.8% in the general screening group, 9.6% in the low-risk group, and 10.2%, p = 0.948, in the high-risk group. In the women with known hypothyroidism on levothyroxine treatment, 50.6% had serum TSH levels above 2.0 mIU/L. CONCLUSIONS: High-risk screening is not useful in predicting which women are at risk of thyroid disease in early pregnancy since ∼10% of women with SCH or hypothyroidism could not be diagnosed in this way.

Association between trefoil factor 3 gene variants and idiopathic recurrent spontaneous abortion.

Trefoil factor 3 (TFF3) gene is an inflammatory mediator expressed in human endometrium during the window of implantation. The aim of this study was to evaluate the possible genetic association of TFF3 variants in recurrent spontaneous abortion. Women with a history of recurrent spontaneous abortion (n = 164) and healthy pregnant women (n = 143) were genotyped for five TFF3 polymorphisms (rs225439 G/A, rs533093 C/T, rs225361 A/G, rs11701143 T/C and rs77436142 G/C). In addition, haplotypes formed within the gene were analysed. Within the recurrent spontaneous abortion group, women who at some point had given birth and childless women had 4.19 ± 1.75 and 5.34 ± 3.42 consecutive spontaneous abortions, respectively. Women who had experience recurrent spontaneous abortions had a lower allele frequency of the rs11701143 promoter region minor C allele compared with fertile women (0.02 versus 0.05, P = 0.015). Patients with rs225361 AG genotype had significantly more successful pregnancies before spontaneous abortion than those with homozygous AA and GG genotypes (P = 0.014). No significant differences in haplotype frequencies between patients and controls were detected. Possible genetic risk factors identified that might contribute to the pathogenesis of idiopathic recurrent spontaneous abortion were TFF3 gene variants.

The histidine-rich glycoprotein A1042G polymorphism and recurrent miscarriage: a pilot study.

BACKGROUND: Histidine-rich glycoprotein (HRG) has previously been shown to have an impact on implantation and fertility. The aim of this study was to investigate if there is an association between the HRG A1042G single nucleotide polymorphism (SNP) and recurrent miscarriage. METHODS: The study was designed as a case-control study and the women were included at University Hospitals in Sweden. 186 cases with recurrent miscarriage were compared with 380 pregnant controls with no history of miscarriage. Each woman was genotyped for the HRG A1042G SNP. RESULTS: The results indicated that the frequency of heterozygous HRG A1042G carriers was higher among controls compared to cases (34.7% vs 26.3%; p<0.05). In a bivariate regression analysis, a negative association was found between recurrent miscarriage and heterozygous A/G carriers both in the entire study population (OR 0.67, 95% CI 0.45 - 0.99; p<0.05) as well as in a subgroup of women with primary recurrent miscarriage (OR 0.37, 95% CI 0.16 - 0.84; p<0.05). These results remained even after adjustment for known confounders such as age, BMI and thyroid disease (OR 0.36, 95% CI 0.15 - 0.84; p<0.05). CONCLUSIONS: Women who are heterozygous carriers of the HRG A1042G SNP suffer from recurrent miscarriage more seldom than homozygous carriers. Thus, analysis of the HRG A1042G SNP might be of importance for individual counseling regarding miscarriage.

Histidine-rich glycoprotein gene polymorphism in patients with recurrent miscarriage.

Association between the histidine-rich glycoprotein (HRG) C633T single nucleotide polymorphism (SNP) and recurrent miscarriage was investigated in a case-control study. The cases constituted 187 women with recurrent miscarriage that were compared with 395 controls who had delivered a child and had no history of miscarriage. Blood samples were collected from each woman, genomic DNA was extracted and genotyped for the HRG C633T SNP. In the whole study population, the percentage of miscarriage was the same, regardless of genotype (C/C 31.2%, C/T 32.9% and T/T 32.5%). However, an association between homozygous T/T carriers and recurrent miscarriage was detected in a subgroup of women with primary recurrent miscarriage (odds ratio 2.44, 95% CI 1.01-5.92). Our results indicate an important role for the HRG C633T SNP in the occurrence of recurrent miscarriage.

Phosphodiesterase 8B gene polymorphism in women with recurrent miscarriage: a retrospective case control study.

BACKGROUND: Recurrent miscarriage affects approximately 1% of all couples. There is a known relation between hypothyroidism and recurrent miscarriage. Phosphodiesterase 8B (PDE8B) is a regulator of cyclic adenosine monophosphate (cAMP) with important influence on human thyroid metabolism. Single nucleotide polymorphism (SNP) rs 4704397 in the PDE8B gene has been shown to be associated with variations in serum Thyroid Stimulating Hormone (TSH) and thyroxine (T4) levels. The aim of this study was to investigate whether there is an association between the SNP rs 4704397 in the PDE8B gene and recurrent miscarriage. METHODS: The study was designed as a retrospective case control study. 188 cases with recurrent miscarriage were included and compared with 391 controls who had delivered at least once and with no history of miscarriage or assisted reproduction. RESULTS: No difference between cases and controls concerning age was found. Bivariate associations between homozygous A/A (OR 1.57, 95% CI 0.98-2.52) as well as G/G carriers (OR 1.52, 95% CI 1.02-2.25) of SNP rs 4704397 in PDE8B and recurrent miscarriage were verified (test for trend across all 3 genotypes, p=0.059). After adjustment for known confounders such as age, BMI and smoking the association between homozygous A/A (AOR 1.63, 95% CI 1.01-2.64, p=0.045) and G/G (AOR 1.52, 95% CI 1.02-2.27, p=0.039) carriers of SNP rs 4704397 in PDE8B and recurrent miscarriage remained. CONCLUSIONS: Our findings suggest that there is an association between homozygous A/A as well as homozygous G/G carriers of SNP rs 4704397 in PDE8B and recurrent miscarriage.

Receptors for thyroid-stimulating hormone and thyroid hormones in human ovarian tissue.

Dysfunction in thyroid regulation can cause menstrual and ovulatory disturbances, the mechanism of which is not clear. The distribution and activity of the thyroid-stimulating hormone (TSHR), and the thyroid hormone receptors (TR) alpha1, alpha2 and beta1 in human ovarian tissue and in granulosa cells was studied using immunohistochemistry, reverse-transcriptase polymerase chain reaction (RT-PCR), quantitative PCR and immunoassays. Strong immunostaining of TSHR, TRalpha1 and TRbeta1 was observed in ovarian surface epithelium and in oocytes of primordial, primary and secondary follicles, with minimal staining in granulosa cells of secondary follicles. Granulosa cells of antral follicles expressed TSHR, TRalpha1 and TRbeta1 proteins. Messenger RNA for all receptors was present in ovarian tissue. Mature human granulosa cells expressed transcripts for 5' deiodinases types 2 and 3, but not type 1, indicating the possibility of conversion of peripheral thyroid hormone thyroxin (T(4)). Granulosa cells stimulated with TSH showed a significant increase in cAMP concentrations after 2 h of culture (P = 0.047), indicating activation through TSHR. Stimulation with T(4) resulted in increased extracellular signal-regulated kinase 1 and 2 activation after 10, 30, 60 min and 24 h. These data demonstrate that TSH and thyroid hormone receptors may participate in the regulation of ovarian function.

Non-hydropic intrauterine fetal death more than 5 months after primary parvovirus B19 infection.

AIMS: Clinical follow-up of possible fetal complications associated with maternal parvovirus B19 infection is usually recommended during the 2-3 months after primary infection. RESULTS: A case of late intrauterine fetal death associated with at least 5 months of maternal parvovirus B19 viremia and in the presence of B19 IgG and IgM is described. CONCLUSIONS: The time of clinical and laboratory follow-up after maternal parvovirus B19 infection may need to be revised if prolonged viremia is more common than previously described.

[Cooperation reduces the risks of thyroid disease in pregnancy. Also mild maternal hypothyroidism can threaten the neurological development of the fetus]. / Samarbete minskar riskerna vid sköldkörtelsjukdom och graviditet. Aven mild hypotyreos hos modern kan hota fostrets neurologiska utveckling.

A history of thyroidal disease in a pregnant mother requires special attention. Untreated, or not adequately treated, hypothyreosis in a pregnant mother is likely to affect the neurological development of the fetus negatively. The authors refer the discussion on the need for screening for hypothyroidism in early pregnancy, but stress the need for everybody dealing with these patients (general practitioners, midwives, gynecologists, pediatricians and endocrinologists), to recognize women at risk and inform their patients on the need of careful monitoring of thyroid supplementation in case of pregnancy. On the other hand, women with Graves' disease should be carefully assessed for the presence of TRAK-antibodies, and be subject to specialist maternal care. Their babies risk neonatal thyreotoxicosis and need careful attention.

Detection of human parvovirus B19 infection in first-trimester fetal loss.

OBJECTIVE: To investigate the frequency of parvovirus B19 infection in first-trimester fetal loss, as measured by B19 DNA polymerase chain reaction in placental tissue in a prospective descriptive study from a nonendemic area. METHODS: Placental tissues from first-trimester fetal losses were examined for presence of B19 DNA by polymerase chain reaction in a prospective study during 30 months. For comparison, placental tissues from second-trimester fetal losses, as well as from full-term normal pregnancies, were also studied. RESULTS: B19 DNA was detected by polymerase chain reaction in one of 36 (3%) placental tissues from first-trimester fetal losses. In second-trimester fetal losses, eight of 64 (12%) samples were B19 DNA positive. None of the 53 placental tissues from full-term normal pregnancies were B19 DNA positive. In first-trimester fetal losses, maternal serum from the B19 DNA-positive sample was B19 immunoglobulin (Ig)G positive but B19 IgM negative. In second-trimester fetal losses, six of six tested B19 DNA-positive samples were both B19 IgG and IgM positive. CONCLUSION: The frequency of first-trimester fetal loss associated with parvovirus B19 infection was low, 3%, during a nonepidemic period in Sweden, as measured by B19 DNA-specific polymerase chain reaction in placental tissue.