Critical analysis of intravenous immunoglobulin therapy for recurrent miscarriage. (25/515)

Critical analysis of intravenous immunoglobulin therapy for recurrent miscarriage An alloimmune abnormality is believed to be the cause of recurrent miscarriage in couples in whom no other cause can be identified. Because of its immunosuppressive properties, intravenous immunoglobulin (IVIG) is used as a treatment for this disorder. The purpose of this study was to determine whether IVIG improves the chance of successful pregnancy in women with recurrent miscarriage by using individual patient data from efficacy trials. Detailed information on each patient enrolled in these trials was obtained to evaluate the efficacy of IVIG and investigate the effect of clinical variability on pregnancy outcome. Data from 125 patients in the IVIG group and 115 patients in the placebo group were available for analysis. Although the number of previous miscarriages and female age were both negative prognostic factors for successful outcome, there was no significant improvement in successful pregnancy or live birth rate with IVIG. Subgroup analyses indicated that timing of IVIG administration may be important. The results of the present study highlight the importance of stratification for known confounders, so that the role of IVIG can be evaluated in more detail. The collective evidence thus far indicates that IVIG does not have a therapeutic effect that is clinically meaningful.  (+info)

Recurrent pregnancy loss and autoantibody profile in autoimmune diseases. (26/515)

OBJECTIVE: To explore the association of non-organ-specific autoimmune responses against three distinct Ro antigen-related reactivities (Ro52, Ro60, p57) with a history of pregnancy loss in women with autoimmune disorders. Materials and methods. Seventy unselected anti-Ro/SSA-positive women were studied in a retrospective cohort study. Forty anti-Ro/SSA-positive women were age matched to an equal number of women with autoimmune disorders who were anti-Ro/SSA negative in a case-control study. The association of reactivities against three distinct antigen specificities (Ro52, Ro60, p57) with recurrent pregnancy loss was investigated. Independence and modification of these associations from the effect of antithyroglobulin, antithyroid peroxidase and anticardiolipin antibodies were also examined. RESULTS: In the cohort study, reactivity against each of the three antigen specificities (Ro52, Ro60, p57) was independently associated with a history of recurrent pregnancy loss. In the case-control study, the effects were still independent and were not modified when other autoantibodies were considered. In particular, the number of reactivities against Ro52, Ro60 and p57 peptides, and the presence of antithyroglobulin antibodies, were independent predictors of recurrent pregnancy loss (odds ratios 3.35 per each additional reactivity and 5.54 in the presence of antithyroglobulin; P=0.002 and 0.025, respectively). CONCLUSIONS: In women with autoimmune disorders, a history of recurrent pregnancy loss is independently associated with reactivity against each of the three antigen specificities (Ro52, Ro60, p57) and also with the presence of antithyroglobulin antibodies, suggesting that cumulative autoimmune responses against these non-organ-specific and organ-specific antigens correlate with the risk of stillbirth and spontaneous abortion.  (+info)

The prognostic value of anti-paternal antibodies and leukocyte immunizations on the proportion of live births in couples with consecutive recurrent miscarriages. (27/515)

Anti-paternal antibodies directed towards paternal leukocytes have been used to predict the prognosis for the subsequent pregnancy in women with consecutive recurrent miscarriages (CRM) and also to determine if the patient has become immune after paternal leukocyte immunization. The predictive value is controversial, as these antibodies are not essential for pregnancy to develop, and only occur in a minority of parous women. This study tried to determine the predictive value of these antibodies when assessed separately for women with five or more abortions and compared to women with three or four abortions. The patients were assessed separately so that the higher live birth rate in the latter group would not obscure meaningful results in the former group with a poor prognosis. Antibody production, whether spontaneous, or induced by immunization, raised the live birth rate in primary and tertiary aborters with three, four, five or more abortions. Anti-paternal antibodies increased the proportion of live births from 18.5 to 53. 7% (P /= 5 CRM and 3-4 CRM respectively. Both immunization with paternal leukocytes per se and the ability to express anti-paternal antibodies were associated with an increased proportion of live births in the next pregnancy. Multivariate analysis showed that that the odds ratio for a live birth was approximately four times greater in women who were immunized and produced anti-paternal antibodies than in control patients. The lack of anti-paternal antibodies at initial testing could serve as a marker for the benefit of immunization with paternal leukocytes; the subsequent presence as a prognostic marker for the subsequent pregnancy.  (+info)

Prospective evaluation of the risk conferred by factor V Leiden and thermolabile methylenetetrahydrofolate reductase polymorphisms in pregnancy. (28/515)

Factor V (FV) Leiden and thermolabile methylenetetrahydrofolate reductase (MTHFR) are 2 common polymorphisms that have been implicated in vascular thrombosis. We determined whether these mutations predicted an adverse outcome in pregnancy. Second, we looked for an interaction between these 2 mutations in patients with recurrent fetal loss or thrombosis in pregnancy. Primigravid subjects at their booking visit to the National Maternity Hospital (Holles Street, Dublin, Ireland) were screened for the polymorphisms. Thermolabile MTHFR and FV Leiden genotypes were detected by either restriction fragment length polymorphism or heteroduplex capillary chromatography. The carrier frequency of FV Leiden in the screened primigravid population was 2.7% (allele frequency 1.36%), all being heterozygous for the mutation. This value was lower than expected from previous studies in European populations. Forty-nine percent of the screened population (289 of 584) were heterozygous for thermolabile MTHFR, and 10.6% were homozygous (62 of 584). The frequency of the 2 polymorphisms was no higher in those who subsequently developed preeclampsia (n=12) or intrauterine growth retardation (n=9), and none of the screened population developed thrombosis. However, the frequency of FV Leiden was higher in patients who subsequently miscarried after the first trimester of pregnancy (allele frequency of 5.5%, P=0.0356). Among those positive for FV Leiden, 3 of 27 miscarried, compared with 24 of 572 of FV Leiden-negative patients (11% versus 4.2%). No interaction was found between the 2 mutations in the control or patient populations. In patients with a prior history of venous thrombosis, the carrier rate of FV Leiden was increased (4 of 33, allele frequency of 7.6%, P=0. 0115). In contrast, the carrier frequency for thermolabile MTHFR was no higher, and there was no interaction between the 2 mutations. Neither mutation occurred at a significantly higher frequency in patients with a prior history of recurrent fetal loss. In conclusion, FV Leiden is a risk factor for thrombosis in pregnancy and possibly for second-trimester miscarriage independent of thermolabile MTHFR. However, prospective analysis suggests that the risk conferred by FV Leiden is low in a primigravid population. The thermolabile MTHFR genotype was not implicated in any adverse outcome.  (+info)

Factor V leiden and prothrombin G20210A mutations, but not methylenetetrahydrofolate reductase C677T, are associated with recurrent miscarriages. (29/515)

The aim of this study was to investigate the relationship between recurrent miscarriages and factor V Leiden, prothrombin G20210A and C677T methylenetetrahydrofolate reductase (MTHFR) mutations. In this case-control study the prevalence of factor V Leiden, prothrombin G20210A and C677T methylenetetrahydrofolate reductase mutations was determined in a consecutive series of 80 recurrent miscarriage patients and 100 controls. Fifteen of 80 recurrent miscarriage patients and four out of 100 controls carried the factor V Leiden mutation (19 versus 4%, P = 0.003, odds ratio 5.5, 95% confidence interval (CI): 1.7-17). Seven of 80 recurrent miscarriage patients and two of 100 controls were carriers of the prothrombin G20210A mutation (9 versus 2%, P = 0.038, odds ratio 4.6, 95% CI: 0.9-23.2). Six of 80 recurrent miscarriage women and 15 of 100 controls were homozygotes for the C677T MTHFR mutation (8 versus 15%, P = 0.134, odds ratio: 0.4, 95% CI: 0.1-1.2). Our results suggest that the presence of factor V Leiden and prothrombin G20210A polymorphism, but not MTHFR C677T homozygosity, could be additional risk factors for recurrent miscarriages. Furthermore, it was suggested that the prevalence of factor V Leiden and prothrombin G20210A mutations is more prominent in second trimester, primary fetal losses and it is independent of the existence of additional pathology predisposing to recurrent fetal losses.  (+info)

Non-invasive exclusion of fetal aneuploidy in an at-risk couple with a balanced translocation. (30/515)

A pregnant woman who was a carrier for a balanced chromosome translocation [46,XX, t(1;6) (p31;q14)] and who had had six miscarriages, declined invasive testing but agreed to non-invasive prenatal diagnosis by analysis of fetal cells in maternal blood. Monoclonal antibody (Mab) against the zeta (z) and gamma (gamma) chains of embryonic and fetal haemoglobin were used to identify fetal nucleated erythrocytes (FNRBC). There were no FNRBC detected at 7 weeks, one anti-z-positive FNRBC was detected at 11 weeks, and 12 anti-gamma-positive FNRBC were detected at 20 weeks. Fluorescent in-situ hybridization was performed using probes for chromosomes X, Y, 1 and 6 to identify fetal gender and the presence of an unbalanced chromosomal translocation. A tentative prenatal diagnosis was made of a female fetus disomic for chromosomes 1 and 6. A female infant with a 46,XX karyotype was born at term. This is the first attempt of exclusion of a chromosome translocation using fetal cells isolated from maternal blood. There is an advantage of using fetal cells isolated from maternal blood for non-invasive prenatal diagnosis in couples who have a history of multiple miscarriages due to a parental translocation, and who decline invasive testing in a pregnancy that continues to the second trimester.  (+info)

Polycystic ovaries and recurrent miscarriage--a reappraisal. (31/515)

The prevalence of polycystic ovaries (PCO) was established amongst 2199 consecutive women (median age 33 years; range 19-46) with a history of recurrent miscarriage (median 3; 3-14). A diagnosis of PCO was made if the ovarian volume was enlarged (>9 ml), there were >/=10 cysts of 2-8 mm in diameter in one plane and there was increased density of the stroma. In a cohort study, the prospective pregnancy outcome of 486 of the women scanned who were antiphospholipid antibody negative and who received no pharmacological treatment during their next pregnancy was studied. The prevalence of PCO was 40.7% (895/2199). The livebirth rate was similar amongst women with PCO (60.9%; 142/233) compared to that amongst women with normal ovarian morphology (58.5%; 148/253; not significant). Neither an elevated serum luteinizing hormone concentration (>10 IU/l) nor an elevated serum testosterone concentration (>3 nmol/l) was associated with an increased miscarriage rate. Polycystic ovarian morphology is not predictive of pregnancy loss amongst ovulatory women with recurrent miscarriage conceiving spontaneously. The search for a specific endocrine abnormality that can divide women with PCO into those with a good and those with a poorer prognosis for a future successful pregnancy continues.  (+info)

Cytokine production by maternal lymphocytes during normal human pregnancy and in unexplained recurrent spontaneous abortion. (32/515)

It has been proposed that successful pregnancy is a T helper 2-type phenomenon, and that T helper (Th)1-type reactivity is deleterious to pregnancy. The objective of this study was to compare the concentrations of Th1 and Th2 cytokines produced by peripheral blood mononuclear cells from women undergoing unexplained recurrent spontaneous abortion (RSA) with those produced during normal pregnancy at a similar gestational stage. The control group consisted of 24 women with a history of successful pregnancies and the abortion group comprised of 23 women with a history of unexplained RSA. Blood from the control group was obtained at the end of the first trimester as gestational age controls for the abortion group from whom blood was collected at the time of abortion. Phytohaemagglutinin-stimulated peripheral blood cell culture supernatants were analysed for concentrations of cytokines. Significantly higher concentrations of Th2 cytokines were produced by the first trimester normal group than by the RSA group, while significantly higher concentrations of Th1 cytokines were produced by the abortion group as compared to first trimester normal pregnancy, indicating a distinct Th2-bias in normal pregnancy and a Th1-bias in unexplained RSA.  (+info)