Tamao Kitaori

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.

Midline uterine defect size is correlated with miscarriage of euploid embryos in recurrent cases

OBJECTIVE To compare subsequent pregnancy outcomes after two or more miscarriages in patients with and without congenital uterine anomalies. DESIGN Case-control study. SETTING Nagoya City University Hospital. PATIENT(S) A total of 42 patients with a bicornuate or septate uterus and 1528 with normal uteri. INTERVENTION(S) No surgery. MAIN OUTCOME MEASURE(S) The cumulative success rate for birth, abnormal chromosome karyotype rate in aborted concepti, and the predictive values of the height of the defect/length of the remaining uterine cavity ratio (D/C ratio). RESULT(S) Of the total of 1676 patients, 54 (3.2%) had congenital uterine anomalies; 25 (59.5%) of the 42 patients with a bicornuate or septate uterus had a successful first pregnancy after examination, while this was the case for 1096 (71.7%) of the 1528 with normal uteri. There was no difference in the cumulative live-birth rate (78.0% and 85.5%) within the follow-up period. However, the rates for an abnormal chromosome karyotype in aborted concepti in cases with and without uterine anomalies were 15.4% (two of 13) and 57.5% (134 of 233), respectively, with the latter being significantly higher. The D/C ratio in the miscarriage group was also significantly greater than that for the live-birth group. CONCLUSION(S) Congenital uterine anomalies have a negative impact on reproductive outcome in couples with recurrent miscarriage and are associated with further miscarriage with a normal embryonic karyotype. The D/C ratio was found to have a predictive value for further miscarriages in recurrent cases.

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.

Frequency of recurrent spontaneous abortion and its influence on further marital relationship and illness: The Okazaki Cohort Study in Japan

Aims:  The aim of this study was to examine the influence of recurrent spontaneous abortion (RSA) on marital relationships, and the association between past/present illness and RSA.

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 Russells 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.

The polycystic ovary syndrome does not predict further miscarriage in Japanese couples experiencing recurrent miscarriages.

Problem  It has been a matter of controversy whether the polycystic ovary syndrome (PCOS) is actually a causal factor of miscarriages because of the absence of internationally established criteria. We, therefore, in this study investigated whether PCOS and a polycystic ovary (PCO) morphology have predictive value for subsequent miscarriages using new International and Japanese criteria.

Genotyping analysis for the 46 C/T polymorphism of coagulation factor XII and the involvement of factor XII activity in patients with recurrent pregnancy loss.

Background Established causes of recurrent pregnancy loss (RPL) include antiphospholipid syndrome, uterine anomalies, parental chromosomal abnormalities, particularly translocations and abnormal embryonic karyotype. A systematic review concluded that coagulation factor XII (FXII) deficiency was associated with RPL. However, it could not be established whether the 46 C/T SNP of FXII or low activity of FXII was a risk factor for RPL, because of the small sample size. Methods and Findings We conducted a cross-sectional and cohort study in 279 patients with two or more unexplained consecutive pregnancy losses and 100 fertile women. The association between the lupus anticoagulant (LA) activity and FXII activity was examined. The frequency of the CC, CT and TT genotypes and the FXII activity were also compared between the patients and controls. Subsequent miscarriage rates among the CC, CT, TT genotypes and according to the FXII activity was examined. LA was associated with reduced FXII activity. The CT, but not the TT, genotype was confirmed to be a risk factor for RPL in the cross-sectional study using multivariate logistic regression analysis (OR, 2.8; 95% CI, 1.37–5.85). The plasma FXII activity in the patients was similar to that in the controls. Neither low FXII activity nor the CT genotype predicted the subsequent pregnancy outcome in the cohort study. On the other hand, and intermediate FXII activity level of 85–101% was predictive of subsequent miscarriage. Conclusions Low FXII activity was not associated with RPL. The FXII gene was found to be one of the significant susceptibility genes for RPL, similar to the FV Leiden mutation. However, the clinical influence of the CT genotype might be relatively small, because the presence/absence of this genotype did not have any predictive value for the subsequent pregnancy outcome. This was the first study indicating the influence of FXII 46C/T on further pregnancy outcomes.

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.

Japanese single women have limited knowledge of age-related reproductive time limits.

This article describes the results of an anonymous survey distributed at several universities in Nagoya Japan to single women containing questions addressing attitudes toward marriage occupation childbirth and knowledge about infertility miscarriage and age-related reproductive time limits. The findings from the study imply that without knowing their reproductive limits many Japanese women may lose their capacity for conception; thus increased efforts are need to educate Japanese women about the influence of age on fertility. Copyright

ORIGINAL ARTICLE: The Polycystic Ovary Syndrome Does Not Predict Further Miscarriage in Japanese Couples Experiencing Recurrent Miscarriages

Problem  It has been a matter of controversy whether the polycystic ovary syndrome (PCOS) is actually a causal factor of miscarriages because of the absence of internationally established criteria. We, therefore, in this study investigated whether PCOS and a polycystic ovary (PCO) morphology have predictive value for subsequent miscarriages using new International and Japanese criteria.