Mayumi Ogasawara

Embryonic karyotype of abortuses in relation to the number of previous miscarriages

OBJECTIVE To examine the frequency of chromosomal abnormalities in products of conception from patients with recurrent miscarriages in relation to the number of previous miscarriages. DESIGN Retrospective analysis. SETTING Nagoya City University Medical Hospital. PATIENT(S) A total of 1,309 women with a history of 2-20 consecutive first-trimester abortions. INTERVENTION(S) Chromosomal analysis performed on products of conception with use of a standard G-banding technique. MAIN OUTCOME MEASURE(S) The frequencies of abnormal and normal embryonic karyotypes for each number of previous abortions were studied. The subsequent pregnancy outcome of patients whose previous miscarriages were karyotyped were studied along with the predictive value of karyotyping of previous miscarriages for subsequent miscarriages. RESULT(S) The miscarriage rate increased with the number of previous spontaneous abortions. The frequency of abnormal embryonic karyotypes significantly decreased and that of normal embryonic karyotypes significantly increased with the number of previous abortions. Among 71 patients whose embryonic karyotypes were normal, 44 aborted subsequently, and 23 of 60 patients whose embryonic karyotypes were abnormal aborted subsequently. Patients with a previous normal embryonic karyotype aborted more frequently than those with an abnormal karyotype. CONCLUSION(S) The frequency of normal embryonic karyotypes significantly increases with the number of previous abortions, and a normal karyotype in a previous pregnancy is a predictor of subsequent miscarriage.

Preconceptional natural-killer-cell activity as a predictor of miscarriage

There is no immunological test for the prospective identification of alloimmune causes of miscarriage. We investigated whether activity of natural killer cells was predictive of subsequent abortion in women who had had unexplained recurrent abortions and had received no treatment. 24 women with high preconceptional NK activity, defined as mean plus 1 SD of NK activity of 47 controls, had a significantly higher abortion rate in the next pregnancy than 44 women with normal levels of NK activity (71 vs 20%; relative risk 3.5; 95% CI 1.8-6.5). The preconceptional evaluation of NK activity in women with recurrent miscarriages may thus be predictive of the risk of pregnancy loss at the next conception.

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.

Distributions of endometrial NK cells, B cells, T cells, and Th2/Tc2 cells fail to predict pregnancy outcome following recurrent abortion.

PROBLEM: To evaluate the ability of immunophenotypes of endometrial leukocytes from patients with histories of recurrent abortion to predict outcome of subsequent pregnancy.

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.

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.

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.

Successful Uterine Steroid Therapy in a Case with a History of Ten Miscarriages

A woman experienced ten unexplained first trimester miscarriages. Uterine steroid therapy was performed just before her 11th pregnancy. Prednisolone was inserted into the uteral cavity before ovulation and her 11th pregnancy resulted in success. Our experience in this case confirms the potential usefulness of this treatment for patients with unexplained recurrent miscarriages.

Prevalence of autoantibodies in patients with recurrent miscarriages.

PROBLEM: It is well known that the prevalence of several autoantibodies is higher in patients with recurrent miscarriages than in normal women. However, links between individual autoantibodies are unclear. The present study focuses on the possible association between β2‐glycoprotein I (β2‐GPI)‐dependant anticardiolipin antibody (aCL), lupus anticoagulant (LA), and antinuclear antibody (ANA) in patients with recurrent miscarriages.