Mayumi Sugiura-Ogasawara

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.

Genetic Factors as a Cause of Miscarriage

Aneuploidy in the conceptus or fetus, occurs in 5-10% of all pregnancies and is a common reproductive problem in humans. Most aneuploid conceptuses die in utero, resulting in early pregnancy loss. Causes of recurrent miscarriage may include abnormal chromosomes in either partner, particularly translocations, antiphospholipid antibodies and uterine anomalies. Chromosomal aberrations in parents are a major pre-disposing factor and causative of abortion if carried over to the embryo. The transmission rate in the embryo can be speculated to be about 50%. Embryo morphology, developmental rates, and maternal age are correlated with chromosomal abnormalities. Translocation in either partner is one of the most important causes of recurrent miscarriage and the prognosis of subsequent pregnancy in couples with abnormal embryonic karyotype is poorer than that in couples with normal chromosome karyotypes. As for parents whose karyotypes are normal, 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. Recently, many kinds of genetic polymorphisms have also been found to be associated with recurrent miscarriages. In contrast, preimplantation genetic diagnosis for aneuploidy screening is sometimes performed in patients with unexplained recurrent miscarriages. We review genetic factors as a cause of miscarriage.

No association of C677T methylenetetrahydrofolate reductase and an endothelial nitric oxide synthase polymorphism with recurrent pregnancy loss

Problem:  It is controversial whether polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and the endothelial nitric oxide synthase (eNOS) are associated with recurrent pregnancy loss.

Psychosocial predictors of successful delivery after unexplained recurrent spontaneous abortions: a cohort study

Objective:  To examine psychosocial predictors of successful pregnancy after recurrent spontaneous abortions (RSA).

PCBs, Hexachlorobenzene and DDE are not Associated with Recurrent Miscarriage

Problem:  A case‐control study was designed to evaluate any associations between high exposure to polychlorinated biphenyls (PCB), hexachlorobenzene (HCB) and the 1,1,1,‐trichloro‐2,2‐bis (p‐chlorophenyl) ethane (DDT) metabolite 1,1‐dichloro‐2,2‐bis (p‐chlorophenyl) ethylene (DDE) and recurrent miscarriage and immunoendocrine abnormalities.

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.

Subsequent pregnancy outcomes in recurrent miscarriage patients with a paternal or maternal carrier of a structural chromosome rearrangement

AbstractInformation concerning the prognosis of subsequent pregnancies in patients with reciprocal translocations is limited. This study was performed to determine the percentage success rate with first pregnancies after ascertainment of a carrier status. A total of 2,382 couples with a history of two or more consecutive miscarriages were studied in multicenters. The prevalence of an abnormal chromosome in either partner was examined, and subsequent success rates were compared between cases with and without an abnormal karyotype in either partner. A total of 129 couples (5.4%) had an abnormal karyotype in one partner excluding inversion 9 in 44 men and in 85 women. Thus, 2,253 couples had a normal karyotype in both partner. Eighty-five (3.6%) had translocations, 13 being Robertsonian translocations. Twenty-nine of the 46 cases (63.0%) who became pregnant with reciprocal translocations in either partner experienced a live birth with natural conception. In contrast, 950 of 1,207 cases (78.7%) with normal chromosomes had successful live births, the difference being significant (P = 0.019). No infant with an unbalanced translocation was found in 29 cases of successful pregnancy following recurrent miscarriage. Pregnancy prognosis was worsened with either maternal or paternal reciprocal translocations. Explanation of the success rate with natural conception should be provided before the subsequent pregnancy after ascertainment of carrier status.

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.

Uterine Cervical Inflammatory Cytokines, Interleukin-6 and -8, as Predictors of Miscarriage in Recurrent Cases

Inflammatory changes frequently occur in cases of second trimester miscarriage or pre‐term delivery, but little attention has been paid to this association with recurrent miscarriage. As interleukin‐6 and interleukin‐8 are inflammatory cytokines reported to be associated with bacterial vaginosis, intrauterine infections, and pre‐term delivery, we here investigated whether they might have predictive value for spontaneous abortion in recurrent cases.

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.