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The incidence of chromosomal abnormalities in twin pregnancies is not well-studied. In this retrospective study, we investigated the frequency of chromosomal abnormalities in twin pregnancies and compared the incidence of chromosomal abnormalities in dichorionic diamniotic (DD) and monochorionic diamniotic (MD) twins. We used data from 57 clinical facilities across Japan. Twin pregnancies of more than 12 weeks of gestation managed between January 2016 and December 2018 were included in the study. A total of 2899 and 1908 cases of DD and MD twins, respectively, were reported, and the incidence of chromosomal abnormalities in one or both fetuses was 0.9% (25/2899) and 0.2% (4/1908) in each group (p= 0.004). In this study, the most common chromosomal abnormality was trisomy 21 (51.7% [15/29]), followed by trisomy 18 (13.8% [4/29]) and trisomy 13 (6.9% [2/29]). The incidence of trisomy 21 in MD twins was lower than that in DD twins (0.05% vs. 0.5%, p= 0.007). Trisomy 21 was less common in MD twins, even when compared with the expected incidence in singletons (0.05% vs. 0.3%, RR 0.15 [95% CI 0.04–0.68]). The risk of chromosomal abnormality decreases in twin pregnancies, especially in MD twins.

The data collected by nation-wide study of noninvasive prenatal genetic testing (NIPT) for trisomy 21 from 21,610 pregnant women with advanced maternal age in Japan were reported. Among 188 NIPT-positive cases, 180 cases were true positive. The incidence of aneuploidy according to maternal age was estimated using a state-space model. Although, the frequency of trisomy increased exponentially with maternal age as previously reported, the maternal age-specific risk for trisomy 21 that was based on the clinical performance of NIPT was lower than the predicted risk in previous Western cohorts based on the data from invasive prenatal testing (Bayesian two-sided tail-area probability P= 0.0156). The empirical positive predictive value (PPV) of NIPT is likely to turn out higher than that of the theoretical PPV calculated from the sensitivity/specificity of the test and the incidence of trisomy 21 from this study.

The purpose of this study is to summarize the results from a survey on awareness of genetic counseling for pregnant women who wish to receive non-invasive prenatal testing (NIPT) in Japan. As a component of a clinical study by the Japan NIPT Consortium, genetic counseling was conducted for women who wished to receive NIPT, and a questionnaire concerning both NIPT and genetic counseling was given twice: once after pre-test counseling and again when test results were reported. The responses of 7292 women were analyzed. They expressed high satisfaction with the genetic counseling system of the NIPT Consortium (94%). The number of respondents who indicated that genetic counseling is necessary for NIPT increased over time. Furthermore, they highly valued genetic counseling provided by skilled clinicians, such as clinical geneticists or genetic counselors. The vast majority (90%) responded that there was sufficient opportunity to consider the test ahead of time. Meanwhile, women who received positive test results had a poor opinion and expressed a low-degree satisfaction. We confirmed that the pre-test genetic counseling that we conducted creates an opportunity for pregnant women to sufficiently consider prenatal testing, promotes its understanding and has possibilities to effectively facilitate informed decision making after adequate consideration. A more careful and thorough approach is considered to be necessary for women who received positive test results.

The purpose of this noninvasive prenatal testing (NIPT) study was to compare the fetal fraction of singleton gestations by gestational age, maternal characteristics and chromosome-specific aneuploidies as indicated by z-scores. This study was a multicenter prospective cohort study. Test data were collected from women who underwent NIPT by the massively parallel sequencing method. We used sequencing-based fetal fraction calculations in which we estimated fetal DNA fraction by simply counting the number of reads aligned within specific autosomal regions and applying a weighting scheme derived from a multivariate model. Relationships between fetal fractions and gestational age, maternal weight and height, and z-scores for chromosomes 21, 18 and 13 were assessed. A total of 7740 pregnant women enrolled in the study, of which 6993 met the study criteria. As expected, fetal fraction was inversely correlated with maternal weight (P<0.001). The median fetal fraction of samples with euploid result (n=6850) and trisomy 21 (n=70) were 13.7% and 13.6%, respectively. In contrast, the median fetal fraction values for samples with trisomies 18 (n=35) and 13 (n=9) were 11.0% and 8.0%, respectively. The fetal fraction of samples with trisomy 21 NIPT result is comparable to that of samples with euploid result. However, the fetal fractions of samples with trisomies 13 and 18 are significantly lower compared with that of euploid result. We conclude that it may make detecting these two trisomies more challenging.

To review the prevalence of congenital uterine anomalies and pregnancy outcomes in patients with these anomalies.

Although recent studies in patients with paternal uniparental disomy 14 [upd(14)pat] and other conditions affecting the chromosome 14q32.2 imprinted region have successfully identified underlying epigenetic factors involved in the development of upd(14)pat phenotype, several matters, including regulatory mechanism(s) for RTL1expression, imprinting status of DIO3and placental histological characteristics, remain to be elucidated. We therefore performed molecular studies using fresh placental samples from two patients with upd(14)pat. We observed that RTL1expression level was about five times higher in the placental samples of the two patients than in control placental samples, whereas DIO3expression level was similar between the placental samples of the two patients and the control placental samples. We next performed histological studies using the above fresh placental samples and formalin-fixed and paraffin-embedded placental samples obtained from a patient with a maternally derived microdeletion involving DLK1, the-IG-DMR, the MEG3-DMR and MEG3. Terminal villi were associated with swollen vascular endothelial cells and hypertrophic pericytes, together with narrowed capillary lumens. DLK1, RTL1 and DIO3 proteins were specifically identified in vascular endothelial cells and pericytes, and the degree of protein staining was well correlated with the expression dosage of corresponding genes. These results suggest that RTL1as-encoded microRNA functions as a repressor of RTL1expression, and argue against DIO3being a paternally expressed gene. Furthermore, it is inferred that DLK1, DIO3 and, specially, RTL1 proteins, play a pivotal role in the development of vascular endothelial cells and pericytes.

Premature ovarian failure (POF) is defined as the cessation of ovarian function under the age of 40 years and is characterized by amenorrhea, hypoestrogenism, and elevated serum gonadotropin concentrations. POF affects 1 of all women and occurs in approximately 0.1 before the age of 30 years. To date, mutations associated with POF have been identified in a small number of genes, including those encoding inhibin (INHA), the FSH receptor and the LH/chorio gonadotrophin receptor. Germ cell specific genes such as Gdf9, Bmp15, and Rfpl4 may also play important roles in human oogenesis. Transcription factors that regulate oocyte gene expression in animal models and include Nobox, Taf4b, Figla, Lhx8, Sohlh1 and Sohlh2 are likely to be key mediators of fertility in humans. In this review, after summarizing the general background on human POF, we focus on insights gained from the animal models with regards to mammalian folliculogenesis. Studies in animal models provide new candidate genes for ovarian failure in humans.

ABSTRACT The aim of the present study was to compare the rates of fetal cells obtained after separation from maternal blood by magnetic activated cell sorting (MACS) using different fetal specific antibodies, and to evaluate the potential role of this method in the prenatal diagnosis of fetal trisomies. Peripheral blood samples were obtained from 42 women carrying chromosomally normal fetuses and from 4 women with aneuploid fetuses (2 cases of 47,XX,+18 and 2 of 47,XY,+21) at 9–20 weeks of gestation. After fetal cells were enriched by MACS with three different monoclonal antibodies (GPA, CD71, CD14), fluorescence in situ hybridization (FISH) with chromosome X, and Y‐specific probes was performed to detect the rates of fetal cells in the samples sorted. FISH with chromosome 13‐, 18‐, and 21‐specific probes was carried out to compare proportions of cells with three‐signal nuclei in chromosomally normal and abnormal groups. In male infants, X‐and Y‐positive cells were detected in 80%, 73.3%, and 66.6% of samples after the separation by antibodies CD14, GPA, and CD71, respectively. The percentage of nuclei with three signals was increased in pregnancies with trisomy, ranging between 2% and 5.18%. Pregnancies with normal fetuses showed 0 to 3.7% of nuclei with three signals. The data demonstrate that fetal cell detection varies depending on the antibodies used for cell sorting. This study provides further evidence on the feasibility of screening for fetal chromosomal abnormalities by enriching maternal blood for fetal cells and using FISH.

ABSTRACT We report here the results of fetal cell enrichment from maternal blood in 58 pregnant women by the use of magnetic activated cell sorting (MACS) with erythroblast‐specific and/or maternal cell specific antibodies. Two approaches were compared; one‐step MACS to enrich CD71+ (a membrane‐bound marker) or GPA+ (another marker, glycophorin A) fetal cells versus two‐step MACS to deplete CD14+ maternal cells and subsequently to enrich fetal (CD71+ or GPA+) cells. The existence of fetal cells was ensured by both FISH with Y‐specific probes and karyotyping of respective anuniotic and/or chorionic vullus cells, the results being applied for comparison of detection rate for XY fetuses between the two MACS procedures.

To determine whether expression of secretory leukocyte protease inhibitor is affected in tissue and peritoneal fluid of women with ovarian endometriomas treated with GnRH analogues.

Objective: To determine whether expression of secretory leukocyte protease inhibitor is affected in tissue and peritoneal fluid of women with ovarian endometriomas treated with GnRH analogues.

Initial approaches to prenatal diagnosis from fetal karyotyping involved application of standard cytogenetic techniques. However, when fetal samples, such as chorionic villus cells or amniocytes are used, small chromosome rearrangements cannot be easily identified because they lack a distinct banding pattern. We report here two cases with minute chromosome rearrangements detected prenatally by fluorescence in situ hybridization. The use of this technique allowed precise identification of fetal chromosome abnormalities, demonstrating its usefulness for characterizing conditions that would be difficult to diagnose correctly with conventional banding methods alone. © 1998 John Wiley & Sons, Ltd.

Initial approaches to prenatal diagnosis from fetal karyotyping involved application of standard cytogenetic techniques. However, when fetal samples, such as chorionic villus cells or amniocytes are used, small chromosome rearrangements cannot be easily identified because they lack a distinct banding pattern. We report here two cases with minute chromosome rearrangements detected prenatally by fluorescence in situ hybridization.

Preterm infants have a high risk of neonatal white matter injury (WMI) caused by hypoxia-ischemia. Cell-based therapies are promising strategies for neonatal WMI by providing trophic substances and replacing lost cells. Using a rat model of neonatal WMI in which oligodendrocyte progenitors (OPCs) are predominantly damaged, we investigated whether insulin-like growth factor 2 (IGF2) has trophic effects on OPCs in vitroand whether OPC transplantation has potential as a cell replacement therapy. Enhanced expression of Igf2mRNA was first confirmed in the brain of P5 model rats by real-time polymerase chain reaction. Immunostaining for IGF2 and its receptor IGF2 R revealed that both proteins were co-expressed in OLIG2-positive and GFAP-positive cells in the corpus callosum (CC), indicating autocrine and paracrine effects of IGF2. To investigate the in vitroeffect of IGF2 on OPCs, IGF2 (100 ng/ml) was added to the differentiation medium containing ciliary neurotrophic factor (10 ng/ml) and triiodothyronine (20 ng/ml), and IGF2 promoted the differentiation of OPCs into mature oligodendrocytes. We next transplanted rat-derived OPCs that express green fluorescent protein into the CC of neonatal WMI model rats without immunosuppression and investigated the survival of grafted cells for 8 weeks. Although many OPCs survived for at least 8 weeks, the number of mature oligodendrocytes was unexpectedly small in the CC of the model compared with that in the sham-operated control. These findings suggest that the mechanism in the brain that inhibits differentiation should be solved in cell replacement therapy for neonatal WMI as same as trophic support from IGF2.

Since the advance online publication of this article, the authors of the above paper have noticed errors in the list of authors and affiliations. The article with correct author information now appears in this issue.

Placental growth factor (PlGF) is a secreted glycoprotein that is expressed in endothelial and epithelial cells as well as in some tumors. The investigators thought that the concentration of PlGF, which is an angiogenic actor, might be elevated in the peritoneal fluid of women with endometriosis. PlGF concentrations were measured with an enzyme-linked immunosorbent assay in 35 women with endometriosis and 24 control women with ovarian cystadenoma who were scheduled for surgery. All participants had regular menstrual cycles. The 2 groups were matched for parity. Peritoneal fluid from women with endometriosis contained significantly higher concentrations of PlGF than that from control women. Median levels were 189 and 88 pg/mL, respectively. Levels varied significantly with the stage of endometriosis (Fig. 1) and were significantly higher in the presence of peritoneal implants classified as red lesions. In both groups, concentrations of PlGF were significantly higher in the secretory phase of the menstrual cycle than in the proliferative phase. These findings suggest that the production of PlGF is sensitive to cyclical changes in ovarian steroid concentrations and could contribute to an important degree to the development of endometriosis, particularly in patients having red lesions. It seems possible that PlGF in peritoneal fluid promotes neovascularization.