Kinue Katano

β2-Glycoprotein I-dependent anticardiolipin antibodies as a predictor of adverse pregnancy outcomes in healthy pregnant women

Our aim was to elucidate prospectively whether beta 2-glycoprotein I-dependent anticardiolipin antibodies (beta 2GPI-dependent aCL; autoimmune type) can predict an adverse pregnancy outcome in healthy pregnant women and whether beta 2GPI-dependent aCL should be applied for routine screening of the pregnant population. A prospective cohort study was performed on 1600 healthy pregnant women from whom blood samples were obtained at about week 10 of gestation. We used a modified enzyme-linked immunosorbent assay with which to divide the subjects into three study groups: beta 2GPI-independent aCL positive, beta 2GPI-dependent aCL positive and aCL negative. Their subsequent pregnancy outcomes were ascertained and the three study groups were compared statistically for the following poor pregnancy outcomes: intrauterine fetal death (IUFD) after 12 gestational weeks, intrauterine growth retardation (IUGR) and pre-eclampsia. The total number of patients eligible for this study was 1125. The prevalence of beta 2GPI-dependent aCL positive was eight (0.7%), beta 2GPI-independent aCL positive was 17 (1.5%) and aCL negative was 1100 (97.8%). Beta 2-GPI-dependent aCL positivity was significantly associated with poor pregnancy outcome: 25.0% of beta 2GPI-dependent aCL-positive and 0.5% of aCL-negative patients experienced IUFD [relative risk 52.4; 95% confidence interval (CI), 12.7-216.3; P = 0.0009]; 37.5% of beta 2GPI-dependent aCL-positive and 2.9% of aCL-negative patients experienced IUGR (relative risk 18.4; 95% CI, 4.6-74.0; P = 0.001); and 50.0% of beta 2GPI-dependent aCL-positive and 4.0% aCL-negative patients experienced pre-eclampsia (relative risk 22.1; 95% CI, 5.7-85.7; P = 0.0002). In contrast, beta 2GPI-independent aCL did not show any significant association with such adverse pregnancy outcomes. beta 2GPI-dependent aCL are significantly highly associated with adverse pregnancy outcomes in healthy pregnant women and can be used for prediction purposes, whereas beta 2GPI-independent aCL cannot. Our results suggest that routine screening for beta 2GPI-dependent aCL should be introduced for the general pregnant population.

Abnormal embryonic karyotype is the most frequent cause of recurrent miscarriage

BACKGROUND We previously found that a normal karyotype in a previous miscarriage is a predictor of subsequent miscarriage. However, the prevalence of recurrent miscarriage caused by an abnormal embryonic karyotype has not yet been reported, since embryonic karyotype is not typically analyzed during conventional examinations. METHODS A total of 482 patients who underwent both embryonic karyotype determination and conventional examinations for recurrent miscarriage were enrolled in this study. The distribution of the causes and the live birth rate for each cause were examined. RESULTS The total percentage of subjects in whom conventional causes of recurrent miscarriage could be detected was 29.5%. The prevalence of the abnormal embryonic karyotype was 41.1% in the subjects in whom no conventional causes of miscarriage could be identified. The prevalence of recurrent miscarriage of truly unexplained cause, that is, of subjects without conventional causes in whom the embryonic karyotype was ascertained to be normal, was 24.5%. Among the patients in whom the first determination revealed an abnormal embryonic karyotype, 76.2% (32/42) showed an abnormal embryonic karyotype in the repeat determination as well. The cumulative live birth rate (71.9%) in women with recurrent miscarriages caused by the abnormal embryonic karyotype was significantly higher than that (44.7%) in women with recurrent miscarriages associated with the embryonal euploidy. CONCLUSION An abnormal embryonic karyotype was found to represent the commonest cause of recurrent miscarriage, and the percentage of cases with recurrent miscarriage of truly unexplained cause was limited to 24.5%.The two groups should be distinguished for both clinical and research purposes.

Factor XII but not protein C, protein S, antithrombin III, or factor XIII is a predictor of recurrent miscarriage.

OBJECTIVE To investigate whether a decrease in the values of protein C (PC), protein S (PS), antithrombin III (ATIII), factor XII (FXII), or factor XIII (FXIII) has predictive value for subsequent miscarriages. DESIGN Prospective study. SETTING Nagoya City University Medical School. PATIENT(S) A total of 536 patients with a history of two or more first-trimester miscarriages. INTERVENTION(S) One hundred and twelve patients treated with low-dose aspirin were excluded from the analysis. MAIN OUTCOME MEASURE(S) The subsequent pregnancy outcome of 424 patients was compared for abnormal and normal levels of each parameter. RESULT(S) There were no differences in the subsequent miscarriage rates between abnormal and normal values of PC, PS, ATIII, and FXIII. However, the rate with abnormal FXII is significantly higher than that with normal FXII. CONCLUSION(S) A decrease in FXII (but not in PC, PS, ATIII, or FXIII) predicts subsequent miscarriage in patients with a history of first-trimester recurrent miscarriages.

Elevation of Transforming Growth Factor-β1 Is Associated with Recurrent Miscarriage

To investigate the significance of transforming growth factor-β1 (TGF-β1) in reproduction we have compared plasma levels in normal pregnant women and patients suffering miscarriages. We examined 188 normal pregnant women and 12 pregnant women with miscarriages. Eight women with severe recurrent miscarriages (mean ± SD of previous number of miscarriages; 10.4 ± 2.4 times) were also examined before conception; 34 nonpregnant women served as controls. Plasma TGF-β1 level increased with the gestational week and returned within the normal range 1 month after delivery. The levels among pregnant women with miscarriages (mean ± SD; 2.44 ± 0.83 ng/ml) were significantly higher than those of pregnant controls (1.74 ± 0.95 ng/ml) of matched gestational weeks; levels among nonpregnant women with severe recurrent miscarriages were extremely elevated (4.1 ± 3.04 ng/ml) compared to the control value (1.34 ± 0.59 ng/ml). These data suggest that TGF-β1 may be necessary to maintain pregnancy but also may be a risk factor for recurrent miscarriages.

IgG anti-laminin-1 autoantibody and recurrent miscarriages.

PROBLEM: The present study assesses the clinical significance of anti‐laminin‐1 auto‐antibodies (auto‐Abs) in recurrent miscarriages.
 METHOD OF STUDY: A total of 207 recurrent aborters with a history of two or more consecutive first‐trimester miscarriages were tested for the presence of anti‐laminin‐1 Abs, β2‐glycoprotein I‐dependent anticardiolipin Abs, lupus anticoagulants, anti‐DNA Abs, and anti‐nuclear Abs, before they had conceived again. Recurrent aborters then were followed up during subsequent pregnancies and their outcomes were evaluated relative to their blood test results prior to pregnancy.
 RESULTS: Fifty‐five (31.1%) women out of 177 recurrent aborters were positive for IgG anti‐laminin‐1 auto‐Abs. The levels of IgG anti‐laminin‐1 auto‐Abs in recurrent aborters were significantly higher than those in healthy pregnant women and in healthy non‐pregnant women (P=0.0043 and 0.0073, respectively). The live birth rate of subsequent pregnancies in IgG anti‐laminin‐1 auto‐Abs‐positive recurrent aborters was significantly lower than the IgG anti‐laminin‐1 auto‐Abs‐negative recurrent aborters (P=0.0320). There were no specifically significant relationships observed between IgG anti‐laminin‐1 auto‐Abs and other tested auto‐Abs.
 CONCLUSION: IgG anti‐laminin‐1 auto‐Abs are associated with recurrent miscarriages and the subsequent pregnancy outcome of recurrent aborters.

Low Serum M-CSF Levels Are Associated with Unexplained Recurrent Abortion

PROBLEM: The purpose of this study was to determine whether the serum macrophage‐colony stimulating factor (M‐CSF) level is associated with early pregnancy loss in unexplained recurrent spontaneous abortion (RSA) patients.

Uterine anomaly and recurrent pregnancy loss.

Women with recurrent pregnancy loss have a 3.2 to 6.9% likelihood of having a major uterine anomaly and a 1.0 to 16.9% chance of having an arcuate uterus. Bicornuate and septate uterine have a negative impact on reproductive outcomes and are associated with subsequent euploid miscarriage. The impact of an arcuate uterus on pregnancy outcome remains unclear. There are no definitive criteria to distinguish among the arcuate, septate, and bicornuate uteri. The American Fertility Society classification of Müllerian anomalies is the most common standardized classification of uterine anomalies. According to estimates, 65 to 85% of patients with bicornuate or septate uteri have a successful pregnancy outcome after metroplasty. However, 59.5% of the patients with such anomalies have a successful subsequent pregnancy without surgery, with a cumulative live birthrate of 78.0%. There is no case-control study to compare live birthrates in women who had surgery compared with those who did not. Strict criteria to distinguish between the bicornuate and septate uterus should be established. Further study is needed to confirm the benefits of metroplasty.

Peripheral natural killer cell activity as a predictor of recurrent pregnancy loss: a large cohort study.

OBJECTIVE To determine the predictive value of preconceptional peripheral blood natural killer (pNK) cell activity in patients with recurrent pregnancy loss (RPL). DESIGN Cohort study. SETTING University department. PATIENT(S) A total of 552 patients with a history of two to six consecutive miscarriages. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) The predictive value of preconceptional pNK cell activity for subsequent miscarriage was analyzed using multivariable logistic regression analysis, with age, number of previous miscarriages, and presence/absence of previous live births and bed rest as covariates. RESULT(S) Age and number of previous miscarriages, but not high pNK cell activity, were found to be independent risk factors for a subsequent miscarriage. No effect of bed rest and previous live birth on the likelihood of live birth was observed (odds ratios 1.28 [95% confidence interval 0.81-2.02] and 0.91 [0.52-1.59], respectively). CONCLUSION(S) Elevated pNK cell activity was found to not be an independent risk factor for subsequent miscarriage. Clinicians should not measure the plasma NK activity as a systematic recurrent pregnancy loss examination, because its clinical significance is yet to be established.

Are serum progesterone levels predictive of recurrent miscarriage in future pregnancies

OBJECTIVE To examine the predictive value of midluteal serum P as a marker of a luteal phase defect (LPD) in future pregnancies of recurrent aborters. DESIGN Prospective analysis. SETTING Nagoya City University Hospital. PATIENT(S) One hundred ninety-seven women with a history of two consecutive first trimester abortions, none of whom had any other medical problems or an identifiable cause of recurrent miscarriages, such as uterine anomalies or evidence of antiphospholipid antibodies. None of the study subjects received any medication for miscarriage or infertility. MAIN OUTCOME MEASURE(S) A midluteal phase single serum P level < 10 ng/mL was used as the criterion for a potential LPD: those whose subsequent pregnancy was successful and those in which failure was the end result. RESULT(S) Of the 197 patients, 46 (23.4%) demonstrated LPD without other endocrine abnormalities and 38 (19.3%) recurrent aborters suffered another abortion, with figures for LPD-negative and LPD-positive patients of 20.5% (31/151) and 15.2% (7/46), respectively. There was no statistically significant difference between the two groups. CONCLUSION(S) Progesterone, E2, and the P/E2 ratio may not predict future pregnancy loss in recurrent aborters.

A case of successful conservative chemotherapy for intramural pregnancy.

OBJECTIVE To describe a rare case of intramural pregnancy diagnosed with the use of magnetic resonance imaging (MRI) and conservatively managed. DESIGN Case report. SETTING Department of obstetrics and gynecology in a university hospital. PATIENT A 33-year-old healthy patient with a history of a partial mole after 3 years of primary unexplained infertility. INTERVENTION(S) Laparoscopic and transvaginal local injections of methotrexate. MAIN OUTCOME MEASURE(S) Transvaginal ultrasound (US) and MRI findings. RESULT Treatment was successful, with no complications, and the patients reproductive potential was preserved. CONCLUSION(S) Early detection of intramural pregnancy with the use of transvaginal US is important, and MRI is a useful, noninvasive imaging modality. Chemotherapy with methotrexate is an effective treatment that allows preservation of reproductive potential.