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Research Question: What is the prevalence of triplet and quadruplet pregnancies after single embryo transfer (SET) in Japan., Design: A retrospective observational study was conducted on 274,605 pregnancies after 937,848 SET cycles in registered assisted reproductive technology (ART) data from the Japanese ART national registry database between 2007 and 2014. A questionnaire survey of ART centres was also conducted. Data on pregnancies with embryo division into three or more after SET were analysed., Results: According to the Japanese ART national registry database, SET resulted in 109 triplet pregnancies (0.04% of pregnancies), and the questionnaire reports from 31 centres revealed 33 triplet and one quadruplet pregnancies. After exclusion of 20 duplicated cases, 122 triplet and one quadruplet pregnancies included 46 monochorionic (one gestational sac [37.4%]), 18 dichorionic (two gestational sacs [14.6%]) and 59 trichorionic pregnancies (three gestational sacs [48.0%]). Compared with singleton pregnancies, patients with monozygotic triplet or quadruplet pregnancies were less frequently diagnosed with unexplained infertility (P = 0.004), more often received gonadotrophin injections for ovarian stimulation in 39 cases with information available (P = 0.021) and underwent more blastocyst transfers and assisted hatching (P = 0.002 and P < 0.001, respectively). The proportion of live birth, defined as at least one baby born, excluding induced abortion, was 64.6% (73/116 pregnancies) of monozygotic triplet or quadruplet pregnancies., Conclusions: Combined Japanese ART national registry and survey data revealed 122 triplet and one quadruplet pregnancies, the majority after cryopreserved embryo transfer. Most were conceived after blastocyst transfer and often after assisted hatching, which are potential risk factors for zygotic splitting., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective To evaluate fetal behavioral differences between singleton and twin fetuses before 20 weeks of gestation using four-dimensional (4D) ultrasound. Methods 4D ultrasound was used to examine fetal movements in 58 singleton and 48 twin normal fetuses at 12-19 weeks. The frequencies of eight fetal movements were assessed through 15-min recordings. The fetuses were divided into two gestational age groups (12-13 and 14-19 weeks) to evaluate the changes with advancing gestation in twin versus singleton fetuses. Results Arm and general movements were the most frequent movements in singleton fetuses, whereas only general movement was significantly more frequent than the other seven fetal movements in twin fetuses at 12-13 weeks. At 14-19 weeks, frequencies of arm and leg movements were significantly higher than those of the other six movements in singleton fetuses, while only arm movement was significantly more frequent than the other fetal movements in twin fetuses. Comparisons of fetal movements between singleton and twin fetuses revealed that only arm movement showed a significant difference at 12-13 weeks, while the frequencies of all movements in singleton fetuses were significantly higher than those in twin fetuses at 14-19 weeks. Conclusion Our results suggest that the limitation of available space and crowding of twin fetuses with advancing gestation may have a marked impact on twin fetal movements compared with singleton fetuses, even in the first half of pregnancy. Further studies are needed to assess whether decreased fetal movements in twin pregnancy can affect fetal and neonatal development and maturation before and after birth.

Aim: To assess the frequency of fetal movement and reproducibility of fetal movement counting in normal singleton pregnancies early in the second trimester using four-dimensional (4D) ultrasound., Methods: Twenty-nine singleton pregnancies were studied for 15 min employing 4D ultrasound at 14-16 (19 cases) and 17-19 (10 cases) weeks of gestation. The frequencies of eight fetal movements (head anteflexion, head retroflexion, body rotation, hand to face movement, general movement, isolated arm movement, isolated leg movement and mouthing movement) were evaluated., Results: The most frequent fetal movements were isolated arm movements at 14-16 and 17-19 weeks' gestation. There was a significant difference only in the frequency of mouthing movement between 14-16 and 17-19 weeks' gestation (P<0.05). All fetal movements showed intra- and inter-class correlation coefficients greater than 0.87, with good intra- and inter-observer agreements., Conclusion: The difference in the frequency of mouthing movement at 14-16 and 17-19 weeks' gestation may be due to increasing fetal swallowing because of the increasing amniotic fluid early in the second trimester of pregnancy. To the best of our knowledge, this is the first study on the reproducibility assessment of fetal movement counting using 4D ultrasound. However, the data and their interpretation in the present study should be taken with some degree of caution because of the small number of subjects studied. Further studies involving a larger sample size are needed to assess the reproducibility of fetal movement counting using 4D ultrasound.

Aim: This study aimed to evaluate the ethnic difference in fetal behavior between Asian and Caucasian populations., Methods: Fetal behavior was assesed by Kurjak's antenatal neurodevelopmental test (KANET) using four-dimensional (4D) ultrasound between 28 and 38 weeks of gestation. Eighty-nine Japanese (representative of Asians) and seventy-eight Croatian (representative of Caucasians) pregnant women were studied. The total value of KANET score and values of each parameter (eight parameters) were compared., Results: The total KANET score was normal in both populations, but there was a significant difference in total KANET scores between Japanese (median, 14; range, 10-16) and Croatian fetuses (median, 12; range, 10-15) (P<0.0001). When individual KANET parameters were compared, we found significant differences in four fetal movements (isolated head anteflexion, isolated eye blinking, facial alteration or mouth opening, and isolated leg movement). No significant differences were noted in the four other parameters (cranial suture and head circumference, isolated hand movement or hand to face movements, fingers movements, and gestalt of general movements)., Conclusion: Our results suggest that ethnicity should be considered when evaluating fetal behavior, especially during assessment of fetal facial expressions. Although there was a difference in the total KANET score between Japanese and Croatian populations, all the scores in both groups were within normal range. Our results indicate that ethnical differences in fetal behaviour do not affect the total KANET score, but close follow-up should be continued in some borderline cases.

Objective: To assess the frequency of fetal facial expressions at 20-24 weeks of gestation using four-dimensional (4D) ultrasonography and to determine whether there was any correlation between facial expression and gestational age (20-34 weeks)., Methods: The facial expressions of 23 healthy fetuses were examined using 4D ultrasound at 20-24 weeks. Each fetus was recorded continuously for 15 minutes. The frequencies of mouthing, yawning, smiling, tongue expulsion, scowling, sucking, and blinking were assessed and the data combined with those expressions observed at 25-34 weeks of gestation in two previous studies (n = 34) to determine the correlation between gestational age and each of the facial expressions., Results: Mouthing was significantly more frequent than the other six facial expressions at 20-24 weeks (P < 0.05). Yawning was significantly more frequent than smiling, scowling, and blinking (P < 0.05), and sucking was significantly more frequent than smiling, scowling, and blinking (P < 0.05). The frequency of yawning, smiling, tongue expulsion, scowling, and blinking increased with gestational age (P < 0.05). Mouthing movement and sucking frequencies remained constant between 20 and 34 weeks., Conclusion: Frequencies of complicated facial expressions such as smiling and scowling may increase with advancing gestation owing to the development of the fetal brain and central nervous system., (Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Our objective was to present our experience of fetal facial expressions reconstructed employing the four-dimensional (4D) HDlive rendering mode., Methods: A total of 23 normal fetuses at 18-36 weeks' gestation were studied using the 4D HDlive rendering mode., Results: The 4D HDlive rendering mode provided extraordinarily realistic features of the fetal face. In particular, blinking, mouthing, swallowing, yawning, tongue expulsion, and sucking were clearly noted. Moreover, various realistic fetal emotional expressions such as smiling-like and crying-like movements were recognized. The 4D HDlive rendered images of fetal facial expressions seem to be more readily discernible than those obtained by conventional 4D ultrasonography., Conclusion: Observation of facial expressions using the 4D HDlive rendering mode is considered to reflect the normal and abnormal neurological development of the fetus. Therefore, the 4D HDlive rendering mode may assist in evaluation of fetal brain function, and offer potential advantages relative to conventional 4D ultrasonography.

Objective: To assess the frequency of fetal facial expressions at 25-27 weeks of gestation using 4D ultrasound., Methods: Twenty-four normal fetuses were examined using 4D ultrasound. The face of each fetus was recorded continuously for 15 minutes. The frequencies of tongue expulsion, yawning, sucking, mouthing, blinking, scowling, and smiling were assessed and compared with those observed at 28-34 weeks of gestation in a previous study., Results: Mouthing was the most common facial expression at 25-27 weeks of gestation; the frequency of mouthing was significantly higher than that of the other 6 facial expressions (P<0.05). Yawning was significantly more frequent than the other facial expressions, apart from mouthing (P<0.05). The frequencies of yawning, smiling, tongue expulsion, sucking, and blinking differed significantly between 25-27 and 28-34 weeks (P<0.05)., Conclusion: The results indicate that facial expressions can be used as an indicator of normal fetal neurologic development from the second to the third trimester. 4D ultrasound may be a valuable tool for assessing fetal neurobehavioral development during gestation., (Copyright © 2013 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

To understand a mechanism for the difference in clinical manifestations of congenital cytomegalovirus (CMV) infection between dizygotic twins, the placentas of the dizygotic twins were evaluated for the number of the cells infected with CMV by immunohistochemical and in situ hybridization studies. A Japanese woman with dizygotic twin pregnancy had immunoglobulin M antibodies to CMV at 15 weeks gestation. Intrauterine growth retardation was noted only in the first twin. At birth, CMV was isolated from urine culture in both twins. Clinical manifestations for CMV, such as petechiae, jaundice, hepatosplenomegaly, and deafness were more pronounced in the first twin than in the second twin. Immunohistochemical and in situ hybridization studies showed CMV-positive cells two or three times more densely distributed in the placenta of the first twin compared with the second twin. These data suggest the severity of CMV manifestations of dizygotic twins may be in accord with the number of CMV-positive cells in the placenta.

The prevalence of umbilical cord cysts at 7-13 weeks' gestation is approximately 3%. More than 20% of such cases are complicated by structural defects and/or chromosomal abnormalities such as trisomy 18. These cysts usually have a single cavity and are <5 cm in size. Therefore, when an umbilical cord cyst is detected in the 2nd trimester, the examination of fetal karyotype is recommended. Omphaloceles are also well known to be complicated by many anomalies, especially trisomy 18. We report a case of an omphalocele associated with a large multilobular umbilical pseudocyst (diameter >5 cm) in a patient with a normal karyotype, 46XY. These anomalies were diagnosed by fetal ultrasonography. However, the cyst was difficult to diagnose as an umbilical cord pseudocyst because it was very large and multilobulated. At 38.5 weeks of gestation, the patient was delivered by Cesarean section. The cyst was resected, and the omphalocele was closed by staged surgeries. Pathologic diagnosis of the cyst was the degeneration of Wharton's jelly. This diagnosis was made by the absence of epithelial lining inside the cyst wall, since the existence of epithelial cells correlates with true cysts.

The authors report a case of laryngeal atresia (congenital high airway obstruction syndrome [CHAOS]) that was diagnosed prenatally. The patient underwent successfully tracheostomy by ex utero intrapartum treatment (EXIT). The fetal ultrasonography and magnetic resonance imaging MRI showed a typical CHAOS pattern with expanded hyperechogenic lungs, inverted diaphragms, and a dilated trachea. Recently, 3 cases of prenatally diagnosed CHAOS were reported to be treated successfully by EXIT. The clinical manifestation and course of this case was not similar to these 3 cases. The 3 previous patients did not fare as well during gestation and were delivered earlier than that in our case. In our case, fetal hydrops was seen at 23 gestational weeks, but it gradually subsided and disappeared at 30 gestational weeks. The fetus was stable and well. After delivery at 39 weeks, the baby received respiratory assistance by ventilator assistance. After 3 days, she could breath well on her own. The patient also had chromosome 5p deletion syndrome and perineal groove. More experience in treating CHAOS cases with EXIT to fully estimate its clinical course and prognosis is needed.

A vesicoallantoic cyst in the umbilical cord was detected by fetal ultrasonography at 16 weeks of gestation. The blood flow through the umbilical vessels was evaluated with periodic color Doppler ultrasonographic examinations because compression by the cyst may cause reduction in blood flow and lead to fetal death. After disappearance of the cyst, the infant was delivered vaginally. Retrograde cystography revealed a narrow channel between the bladder and the navel, confirming patent urachus, which was resected without any complications., (Copyright 2003 S. Karger AG, Basel)

Objective: The objective of this study was to determine whether sonographically depicted ovarian tumor growth is fractal, and the mean fractal dimension differs according to stages of the disease and histologic types., Methods: The fractal dimensions of outlines of sonographically depicted solid components in 160 ovarian tumors were measured using a box-counting method., Results: The mean fractal dimensions of the surface of intracystic solid components in serous, mucinous, endometrioid, and clear cell adenocarcinoma were 1.259, 1.243, 1.238, and 1.182, respectively. These values were significantly greater than the topological dimension of a line (=1). The value was significantly higher in stage I or II (1.381) than stage III or IV (1.205) in serous carcinoma (P = 0.02), but not significantly different in clear cell carcinoma (1.187 and 1.172, respectively). In stage I or II, the value of serous carcinoma (1.381) was significantly higher than that of clear cell carcinoma (1.187) (P = 0.03). The value of mucinous cystadenoma of low malignant potential was 1.337, which was also significantly greater than 1. The mean fractal dimensions of outlines of solid tumors in cases with dysgerminoma and thecoma-fibroma were 1.036 and 1.023, respectively. These values were not significantly different from 1., Conclusion: This study shows that the surface of solid components in cystic epithelial ovarian cancers has a fractal structure, and the mean fractal dimension may differ according to stages of the disease and histologic types. Fractal geometry, a vocabulary of irregular shapes, can be useful for describing the pathological architecture of ovarian tumors and for yielding insights into the mechanisms of tumor growth.

An ultrasound examination in a woman at 9 weeks' gestation demonstrated a gestational sac with a live fetus in the left uterine horn which was surrounded by an extremely thin outer lining. An interstitial pregnancy was suspected and laparoscopy was performed. During laparoscopy the purple bulge in the left horn gradually reduced in size and eventually disappeared following the external pressure by the tip of the forceps. We believe this pressure caused contraction of the superficial myometrial fibers resulting in a shift in the location of the gestational sac to the central area of the uterus. The pregnancy continued and on Cesarean section at 34 weeks' gestation, a membranous protrusion of the uterine wall in the left horn was noticed. A myometrial defect caused by an intrauterine intervention in the patient's previous pregnancy was suspected to be the cause of this "movable gestational sac" phenomenon.

Periventricular leukomalacia (PVL) is a major cause of cerebral palsy. However, pathogenetic mechanisms of PVL have not been fully understood. Although it has been postulated that umbilical cord compression is related to the development of PVL, no animal experiments clearly demonstrated an association of umbilical cord occlusion with 'periventricular' white matter lesions. The purpose of this study is to determine whether umbilical cord occlusions could produce periventricular white matter lesions in fetal sheep and to examine how changes in fetal cardiovascular and metabolic variables are related to the induction of brain damage. Fourteen near-term fetal sheep underwent umbilical cord occlusion (3-min total cord occlusions 5 times at 5-min intervals). Dissections performed 24 h after cord occlusion revealed that periventricular white matter lesions were produced in 7 out of 14 sheep fetuses. According to the pattern of brain damage, we classified the fetal sheep into three groups: 5 fetuses with dominant lesions in the periventricular white matter (group I), 4 fetuses with brain lesions in the cerebral cortex and thalamus (group II) and 5 fetuses with no or minimal brain lesions (group III). Group I showed higher blood pressure and higher plasma lipid peroxide levels before cord occlusion compared to the other groups, while group II showed systemic hypotension during cord occlusion. No significant differences in changes in pH, PaCO2, PaO2 and heart rate were found between the three groups. It is speculated that PVL might be produced by an association of preexisting chronic circulatory instability with an acute episode of severe repetitive cord occlusion.

We conducted a chronic preparation experiment involving near term fetal sheep to evaluate the contribution of umbilical cord occlusion to fetal brain injury. In experimental groups (n = 11), complete cord occlusion for 3 min followed by 5 min release, repeated 5 times were performed at 3 days after initial surgery. Instrumental cases without cord occlusion (n = 3) and uninstrumental twins (n = 6) were also examined as controls. Multiple necrotic foci predominantly in the periventricular white matter were found in the fetal brains examined at 1-3 days after cord occlusion. To estimate the contribution of early axonal and glial reaction to brain injury the following immunohistochemical study was performed. In the lesions, coagulation necrosis, axonal swelling and microglial activation were demonstrated with amyloid precursor protein or ionized calcium binding adapter molecule 1 immunohistochemistry. The induction of tumor necrosis factor alpha and inducible nitric oxide synthase were also detected immunohistochemically in the microglia at 1 and 3 days after cord occlusion. In contrast, the reaction of glial fibrillary acidic protein positive astrocytes was faint at 1 day after occlusion, but the induction of cyclooxygenase-2 was observed. These findings suggest the glial reaction of cytokines and free radicals induced by fetal hypoxia may contribute to the occurrence of brain injury.

Thirty-five women with normal menstrual cycles underwent transvaginal and high-frequency (15- or 20-MHz) intrauterine sonographic examinations for the assessment of the endometrium. Five sonographic patterns of endometrium were recognized by both sonographic techniques, but the pattern visualized differed between techniques in 9 women (26%). The higher resolution of intrauterine sonography provided more detail of the endometrium. Our preliminary experience indicates that high-frequency intrauterine sonography enables more detailed visualization of changes in the endometrium during the menstrual cycle than does transvaginal sonography.

A 31-year-old woman, gravida 2 para 1, visited our clinic for routine follow-up at 20 weeks' gestation. Although she had no abdominal pain or pressure, digital vaginal examination revealed dilatation of the internal cervical os of 1.5 cm, and transvaginal sonography demonstrated dynamic changes in the shape of the cervical canal. The patient underwent Shirodkar's operation. Routine postoperative assessment of the cervix with transvaginal sonography showed dynamic dilatation of the upper cervix (above the cerclage), which was accompanied by a sensation of pelvic pressure but no apparent uterine contractions. A healthy male infant weighing 2,980 g was delivered at 38 weeks' gestation.