Effects of Pparγ1 deletion on late-stage murine embryogenesis and cells that undergo endocycle.

Peroxisome proliferator-activated receptor (PPAR) γ1, a nuclear receptor, is abundant in the murine placenta during the late stage of pregnancy (E15-E16), although its functional roles remain unclear. PPARγ1 is encoded by two splicing isoforms, namely Pparγ1canonical and Pparγ1sv, and its embryonic loss leads to early (E10) embryonic lethality. Thus, we generated knockout (KO) mice that carried only one of the isoforms to obtain a milder phenotype. Pparγ1sv-KO mice were viable and fertile, whereas Pparγ1canonical-KO mice failed to recover around the weaning age. Pparγ1canonical-KO embryos developed normally up to 15.5 dpc, followed by growth delays after that. The junctional zone of Pparγ1canonical-KO placentas severely infiltrated the labyrinth, and maternal blood sinuses were dilated. In the wild-type, PPARγ1 was highly expressed in sinusoidal trophoblast giant cells (S-TGCs), peaking at 15.5 dpc. Pparγ1canonical-KO abolished PPARγ1 expression in S-TGCs. Notably, the S-TGCs had unusually enlarged nuclei and often occupied maternal vascular spaces, disturbing the organization of the fine labyrinth structure. Gene expression analyses of Pparγ1canonical-KO placentas indicated enhanced S-phase cell cycle signatures. EdU-positive S-TGCs in Pparγ1canonical-KO placentas were greater in number than those in wild-type placentas, suggesting that the cells continued to endoreplicate in the mutant placentas. These results indicate that PPARγ1, a known cell cycle arrest mediator, is involved in the transition of TGCs undergoing endocycling to the terminal differentiation stage in the placentas. Therefore, PPARγ1 deficiency, induced through genetic manipulation, leads to placental insufficiency.

Examination of a Stillbirth Workup: A Rural Statewide Experience.

OBJECTIVE: The objective of our study was to determine whether recommended assessments were conducted on stillbirths delivered in our predominantly rural state. METHODS: This was a descriptive study of stillbirths delivered in a rural state and included in one site of the Birth Defects Study to Evaluate Pregnancy Exposures stillbirth study. Hospital and fetal death records were examined to determine whether the following areas were evaluated: genetic testing (noninvasive perinatal testing, quad screen, amniocentesis/chorionic villus sampling with karyotype, microarrays, fetal tissue specimen), placenta/membrane/cord sent for pathologic examination, examination of the stillbirth after delivery by the healthcare provider, and fetal autopsy was performed. RESULTS: From July 1, 2015 to June 30, 2020, there were 1108 stillbirths delivered in Arkansas. The most frequent assessments undertaken were placental pathology (72%), genetic testing (67%), fetal inspection (31%), and autopsy (13%). All four assessments were done in 2% of stillbirth cases, three assessments in 27%, two assessments in 47%, one assessment in 14%, and no assessment in 15%. There was no association between stillbirth assessment evaluation by gestational age (<28 weeks and > 28 weeks; P = 0.221); however, there was an overall association between hospital delivery volume with number of components completed (P < 0.0001). Hospitals with >2000 deliveries had a higher proportion of three or four completions compared with those hospitals with <1000 deliveries or 1000 to 2000 deliveries (P = 0.021 and P < 0.0001). CONCLUSIONS: Fetal stillbirth assessment is suboptimal in our rural state, with 15% of stillbirths having no assessment and only 2% having all four assessments. There is no association between stillbirth assessment and gestational age (<28 weeks vs >28 weeks), but there is a correlation between delivery volume and stillbirth assessment.

The relationship between placental characteristics and birthweight discordance in different types of selective intrauterine growth restriction in monochorionic diamniotic twins: A single-center 7 year cohort study.

OBJECTIVE: To clarify the relationships between placental characteristics and birthweight discordance in three types of selective intrauterine growth restriction (sIUGR) in monochorionic diamniotic twins. METHODS: A retrospective cohort study was conducted between april 2013 and april 2020. Associations between placental characteristics and birthweight discordance were evaluated through multiple linear regression analyses with two models for each sIUGR type. Model A was adjusted for gestational age, Model B additionally adjusted for the impact of placental characteristics interacted. RESULTS: In cases of type I sIUGR, birthweight discordance ratio was positively associated with placental territory discordance ratio [(ß = 0.181,95%CI(0.072,0.290), p < 0.05), (ß = 0.239,95%CI(0.125, 0.353), p < 0.05)] under both Model A and Model B. In-type II sIUGR [(ß = -0.012,95%CI(-0.020, -0.004), p < 0.05) (ß = -0.010,95%CI (-0.018, -0.002), p < 0.05)] and type III sIUGR [(ß = -0.011,95%CI (-0.021, -0.001), p < 0.05), (ß = -0.012,95%CI(-0.022, -0.003), p < 0.05)], birthweight discordance ratio was negatively associated with the total diameter of all the anastomoses as calculated with both Model A and Model B. CONCLUSION: Birthweight discordance is primarily related to placental territory discordance in type I sIUGR, whereas vascular anastomoses play important roles for growth-restricted fetal compensation in type II and III sIUGR.

Trisomy 8 mosaicism in the placenta: A Danish cohort study of 37 cases and a literature review.

OBJECTIVE: To evaluate the risk of fetal involvement when trisomy 8 mosaicism (T8M) is detected in chorionic villus samples (CVS). METHODS: A retrospective descriptive study of registered pregnancies in Denmark with T8M in CVS identified through a database search and a review of published cases of T8M found through a systematic literature search and inclusion of cross references. Pregnancies with T8M in CVS and no additional numerical chromosomal aberrations were included. RESULTS: A total of 37 Danish cases and 60 published cases were included. T8M detected in a CVS was associated with fetal involvement in 18 out of 97 pregnancies (18.6% [95%CI: 11.4-27.7]). Eight out of 70 (11.4% [95%CI: 5.1-21.3]) interpreted prenatally to be confined placental mosaicism (CPM) were subsequently found to be true fetal mosaicisms (TFM). CONCLUSION: T8M detected in CVS poses a significant risk of fetal involvement, and examination of amniotic fluid (AF) and/or fetal tissue should be offered. However, a normal result of AF still has a considerable residual risk of fetal involvement. Genetic counselling at an early gestational age is essential, and follow-up ultrasonography should be performed to predict fetal involvement if possible.

Fetal Autopsy-Categories and Causes of Death at a Tertiary Care Center.

BACKGROUND: A fetus is defined from 8 weeks after conception until term while in the uterus. Fetal death is defined as death of the fetus before the complete expulsion or extraction from the mother, irrespective of the duration of pregnancy that is not an induced termination of pregnancy. The causes of fetal death determined after fetal autopsy can be categorized according to the classification proposed by Cunningham and Hollier as fetal, placental, and maternal. METHODS: All fetuses dying in utero, that is, prior to birth, regardless of the gestational age, to the mothers admitted in the Department of Obstetrics and Gynecology along with the respective placentas were received in the Department of Pathology, MGM Medical College, Aurangabad, after an informed and written consent from October 26, 2017, to October 30, 2019, and were included in this study. Clinical details along with obstetric history and antenatal ultrasonographic findings were also recorded. Anthropometric examination of the fetus was performed and evisceration was then done using the Rokitansky technique. Representative sections from each of the organs were taken and kept in tissue cassettes and processed for routine hematoxylin and eosin staining. RESULTS: This study was done on 33 cases of fetal death. Most fetal deaths occurred in the gestational age between 15 and 19 weeks (14 cases [42.42%]) and the least amount during 35 to 39 weeks (2 cases [6.06%]). The cause of death could not be ascertained in 6 cases (18.18%), whereas the maximum cases had fetal factor as the cause of death (15 cases [45.45%]). Maternal causes were seen in only 4 cases (12.12%). Gestational hypertension was seen to be the most common maternal factor associated with fetal death, which comprised 24.24% of cases (8 of 33). Thirteen of the total 33 cases did not have any associated obstetric complication. Of the total 33 fetal deaths, only 7 had associated placental defects on gross examination. Twenty-six placentas did not show any gross abnormality. Of these 7 cases, 5 were seen to have placental infarction. CONCLUSIONS: Fetal autopsy is a valuable and cost-effective modality for the confirmation of cause of fetal death. Fetal autopsy can also prove beneficial to the parents in planning for future pregnancies. Fetal autopsy can serve as the ultimate tool in diagnosing cause of fetal death in cases where no other diagnostic clue is available. Therefore, it should be encouraged and couples to be counseled regarding its importance and clinical utility.

Placental pathology in live births conceived with in vitro fertilization after fresh and frozen embryo transfer.

BACKGROUND: The availability and use of frozen embryos after ovarian hyperstimulation for assisted reproduction has increased with improvement in vitrification techniques and the rise of preimplantation genetic testing. However, there are conflicting data regarding whether obstetric outcomes differ between fresh and frozen embryo transfer cycles. OBJECTIVE: To compare placental pathology from live births arising from fresh and frozen embryo transfer cycles. MATERIALS AND METHODS: A cohort of 1140 live births with placental pathology arising from autologous in vitro fertilization cycles with fresh or frozen programmed transfer performed at MGH Fertility Center between 2004 and 2017 was retrospectively reviewed. An experienced placental pathologist categorized the reported placental pathology as anatomic, infectious, inflammatory, or vascular/thrombotic. Our primary outcomes were differences in these placental pathologies between the 2 groups. Patient demographic, cycle, and birth outcomes were compared with the use of χ2 tests, Student t test, or nonparametric tests, as appropriate. Multivariate logistic regression models were used to compare placental pathology between the fresh and frozen transfer groups. RESULTS: Of the 1140 cycles included in our analysis, 929 arose from fresh embryo transfers (81.3%) and 211 arose from programmed frozen embryo transfers (18.5%). For both transfer types, the average age of the women at time of treatment was 35 years; mean body mass indices were within the normal range (23.6 kg/m2 for fresh transfers and 23.2 kg/m2 for frozen transfers, P = .26), and mean day 3 follicle-stimulating hormone values were 7.1 and 7.0 IU/L (P = .44), respectively. Deliveries occurred on average at 37.5 and 38.0 weeks' gestational age (P = .04) in the fresh versus frozen transfer group, with similar rates of obstetric complications. However, frozen transfers were more likely to be associated with marginal cord insertion (adjusted odds ratio, 1.87; confidence interval, 1.21, 2.91; P = .01), accessory lobe formation (adjusted odds ratio, 2.96; confidence interval, 1.12, 7.79; P = 0.03), subchorionic thrombi (adjusted odds ratio, 3.72; confidence interval, 1.80, 7.71; P < .001), and fetal vascular malperfusion characteristics with cord anomalies (adjusted odds ratio, 2.34; confidence interval, 1.22, 4.46; P = .01). These trends persisted when we analyzed day 5 transfers alone, and single frozen embryo transfers remained associated with increased rates of subchorionic thrombi compared to single fresh embryo transfers. CONCLUSION: Pregnancies arising from frozen embryo transfers demonstrated more anatomic and vascular placental pathology than those from fresh transfers in our cohort of patients, despite similar maternal outcomes. More research is needed to explore how these differences in pathology may influence obstetric and perinatal outcomes.

Prevalence of placental dichotomy, fetal cardiomegaly and starry-sky liver in twin anemia-polycythemia sequence.

OBJECTIVE: To investigate the prevalence of three additional ultrasound markers, placental dichotomy, cardiomegaly and 'starry-sky' liver, in monochorionic twin pregnancy with twin anemia-polycythemia sequence (TAPS). METHODS: All monochorionic twin pregnancies, diagnosed antenatally with TAPS at our center between 2006 and 2019, were reviewed retrospectively for the presence of placental dichotomy, cardiomegaly in the donor twin and a starry-sky liver in the recipient twin. TAPS was diagnosed based on delta middle cerebral artery (MCA) peak systolic velocity (PSV) > 0.5 multiples of the median. The primary outcome was the prevalence of placental dichotomy, cardiomegaly, starry-sky liver and at least one of these markers in both spontaneous and post-laser TAPS. The secondary outcome was the prevalence of these ultrasound markers according to the antenatal stage of TAPS. RESULTS: A total of 91 monochorionic twin pregnancies with TAPS were eligible for analysis. Placental dichotomy was observed in 44% (40/91) of TAPS cases. A total of 70% (64/91) of the TAPS donors developed cardiomegaly and a starry-sky liver was identified in 66% (53/80) of the TAPS recipients. The prevalence of cardiomegaly and starry-sky liver was roughly comparable between spontaneous and post-laser TAPS (69% (33/48) vs 72% (31/43) and 64% (25/39) vs 68% (28/41), respectively). Pregnancies with spontaneous TAPS showed a higher prevalence of placental dichotomy compared with post-laser TAPS (63% (30/48) vs 23% (10/43)). At least one of the three ultrasound markers was detected in 86% (78/91) of TAPS cases, meaning that 14% (13/91) of cases presented solely with discordant MCA-PSV values. There was a trend towards increased prevalence of all three ultrasound markers with increasing antenatal TAPS stage. CONCLUSIONS: Placental dichotomy, fetal cardiomegaly and a starry-sky liver are commonly found in TAPS pregnancy. Investigating the presence of these ultrasound markers can be of additional help in improving antenatal detection of TAPS in monochorionic twin pregnancy. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Intermittent absent and reversed umbilical artery flows in appropriately grown monochorionic diamniotic twins in relation to proximate cord insertion: A harmful combination?

OBJECTIVE: To compare the prevalence of intermittent absent or reversed end-diastolic flow (iAREDF) in the umbilical artery in appropriately grown monochorionic diamniotic (MCDA) pregnancies with and without proximate cord insertion (PCI), and to evaluate pregnancy outcome. METHODS: The prevalence of iAREDF in MCDA pregnancies with PCI (n = 11) was compared with a control group without PCI (n = 33). PCI was defined as a distance between the cord insertions below the fifth percentile. Placental sharing, number, and diameter of anastomoses were assessed by placental examination. Pregnancy outcome was evaluated. RESULTS: iAREDF was present in 7/11 PCI pregnancies, compared with 0/33 in the control group (P ≤ .01). All PCI pregnancies and 94% of controls had arterioarterial (AA)-anastomoses (P = .56), the diameter was larger in the PCI group, respectively 3.3 vs 2.1 mm (P = .03). Three cases with iAREDF had adverse outcome, two resulted in fetal death of which one with brain damage in the co-twin, another underwent early premature emergency section for fetal distress. CONCLUSION: iAREDF occurs in a large proportion of MCDA pregnancies with PCI and is related to the diameter of the AA anastomosis. We hypothesize that iAREDF in appropriately grown MCDA twin pregnancies reflects an unstable hemodynamic balance with an increased risk for fetal deterioration. Whether outcome in these pregnancies can be improved by altered management requires further investigation.

Second-Trimester Ultrasound-Measured Umbilical Cord Insertion-to-Placental Edge Distance: Determining an Outcome-Based Threshold for Identifying Marginal Cord Insertions.

OBJECTIVES: We sought to study potential diagnostic criteria for marginal placental cord insertions as determined by associations with obstetric outcomes. METHODS: This single-center retrospective cohort investigation included singleton gestations delivering from January 1, 2012, to December 31, 2016, and having a standard or detailed fetal ultrasound examination from 18 weeks to 21 weeks 6 days. Cord insertion-to-placental edge distances were used to create a referent comparison group and 3 patient groups: greater than 3.0 cm (comparison); greater than 2.0 to 3.0 cm (group 1); greater than 1.0 to 2.0 cm (group 2); and 1.0 cm or less (group 3). The primary outcome consisted of any one of spontaneous delivery before 37 weeks, fetal growth restriction, oligohydramnios, placental abruption, or intrauterine fetal demise. RESULTS: The numbers of participants and mean distances ± SDs for the comparison group and groups 1 to 3, respectively, were 628 and 4.68 ± 1.17 cm, 106 and 2.52 ± 0.26 cm, 131 and 1.60 ± 0.29 cm, and 77 and 0.36 ± 0.37 cm, respectively. The primary outcome was significantly associated only with cord insertion-to-placental edge distances of 1.0 cm or less (adjusted odds ratio, 3.05; 95% confidence interval, 1.73-5.38). CONCLUSIONS: Marginal cord insertions may be diagnosed when the cord insertion-to-placental edge distance is 1.0 cm or less.

Antenatal Detection of Abnormal Placental Cord Insertion across Different Trimesters: A Prospective Cohort Study.

OBJECTIVES: This article prospectively examines the use of ultrasound for antenatal detection of abnormal placental cord insertion (PCI) and compares the antenatal classification with delivered placental classification. STUDY DESIGN: This prospective cohort study examined 277 singleton pregnancies in a tertiary center. Scans were performed between 10 and 14, 18 and 22, and 32 and 34 weeks where PCI site was identified and its shortest distance to margin measured. Standardized images of delivered placentas were taken and digitally measured. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of antenatal classification compared with delivered placental classification were calculated. RESULTS: Abnormal PCI (distance < 2 cm from margin) was confirmed in 30/277 (11%) placentas at delivery. Note that 102/277 (37%) of PCI sites were classified as abnormal in the first trimester (T1), 43/277 (16%) in the second trimester (T2), and 28/277 (10%) in the third trimester (T3). Sensitivity (73%) and specificity (91%) were highest at T2. The PPVs were low (22% in T1, 51% in T2, and 64% in T3) and the NPVs were high (96% in T1 and 97% in both T2 and T3) for all scans. CONCLUSION: Abnormal PCI can be detected antenatally with optimal agreement with postnatal classification in T2. However, the incidence is overestimated at early scans with low PPVs.

Unr defines a novel class of nucleoplasmic reticulum involved in mRNA translation.

Unr (officially known as CSDE1) is a cytoplasmic RNA-binding protein with roles in the regulation of mRNA stability and translation. In this study, we identified a novel function for Unr, which acts as a positive regulator of placental development. Unr expression studies in the developing placenta revealed the presence of Unr-rich foci that are apparently located in the nuclei of trophoblast giant cells (TGCs). We determined that what we initially thought to be foci, were actually cross sections of a network of double-wall nuclear membrane invaginations that contain a cytoplasmic core related to the nucleoplasmic reticulum (NR). We named them, accordingly, Unr-NRs. Unr-NRs constitute a novel type of NR because they contain high levels of poly(A) RNA and translation factors, and are sites of active translation. In murine tissues, Unr-NRs are only found in two polyploid cell types, in TGCs and hepatocytes. In vitro, their formation is linked to stress and polyploidy because, in three cancer cell lines, cytotoxic drugs that are known to promote polyploidization induce their formation. Finally, we show that Unr is required in vivo for the formation of Unr-containing NRs because these structures are absent in Unr-null TGCs.

Mucolipidosis Type II Affecting 1 Fetus and Placental Disk of a Dichorionic-Diamnionic Twin Gestation: A Case Report and Review of the Literature.

Mucolipidosis type II, also known as I-cell disease, is an autosomal recessive inborn error of metabolism, resulting from loss-of-function mutations in GNPTAB. Affected infants exhibit multiple physical anomalies and developmental delay, and death from disease follows in early childhood. Here we present an instructive case of mucolipidosis type II affecting 1 fetus and placental disk in a dichorionic-diamnionic twin pregnancy delivered at 36-wk gestation. The second twin and placental disk showed no abnormality. On microscopic examination, the affected placenta displayed marked vacuolization of the syncytiotrophoblast and Hofbauer cells, which was confirmed on ultrastructural examination. To our knowledge, this is the first description of placental findings in a twin pregnancy, wherein only 1 twin is affected by an inborn error of metabolism. This provides an opportunity to highlight the placental abnormalities seen in this group of diseases, and to emphasize the role of pathologic examination in early detection of otherwise unsuspected inborn errors of metabolism.

Performance of ultrasound for the visualization of the placental cord insertion.

PURPOSE OF REVIEW: The purpose of this review was to review the literature on the performance of ultrasound for the visualization of the placental cord insertion (PCI) and for the diagnosis of abnormal placental cord insertion (APCI). APCI included both marginal cord insertion (MCI) and velamentous cord insertion (VCI) PCI. RECENT FINDINGS: The overall rate of visualization of the PCI across all trimesters is 90.3% and for those studies routinely using color Doppler, 98.1% (P < 0.0001). Although the visualization was lower with advancing gestational age, it remained high even into the late third trimester. In all studies, where time was reported, the PCI was visualized in most cases in less than 1 min. Ultrasound performed best for the diagnosis of VCI with a sensitivity, specificity and positive predictive value of 100, 99.9 and 85.7%, respectively, with routine use of color Doppler. SUMMARY: Ultrasound is an excellent screening test for the evaluation of PCI across all trimesters. The use of color Doppler increases the rate of visualization and should be routinely used. Ultrasound with color Doppler is also an excellent screening test for the diagnosis of VCI. However, the performance of ultrasound is reduced with the inclusion of MCI.

Role of 2-Dimensional Ultrasound Imaging in Placental and Umbilical Cord Morphometry: Literature and Pictorial Review.

Abnormalities of the placenta and umbilical cord have been associated with adverse pregnancy outcomes. Antenatal detection of placental and umbilical cord abnormalities using ultrasound (US) imaging is now gaining popularity with the advancements in obstetric US. This article reviews the use of 2-dimensional obstetric US as a tool to measure and assess placental and umbilical cord morphometry. It highlights the potential role of placental and umbilical cord morphometry as a valuable component of the screening tool for high risk pregnancies and identifies the need for further research to examine its feasibility.

Placental Findings in Singleton Stillbirths: A Case-control Study.

Aims: This prospective observational study compared placental lesions of stillbirth cases and live birth controls, and aimed to determine the cause of stillbirth. Methods: The study enrolled 85 stillbirths and 85 live births at the time of delivery. Results: There was significantly increased incidence of placental abruption (p = 0.005) and gestational diabetes (p = 0.032) in mothers with stillbirths. Histopathological examination of placenta was significantly abnormal in stillbirths compared with live births (p = 0.004). Delayed villous maturation was significantly more in stillbirths (38.82 vs. 16.47%; p = 0.002). Acute (30.59 vs. 16.47%; p = 0.04) and chronic diffuse villitis (16.47 vs. 4.7%; p = 0.02), chorionic plate acute vasculitis (28.235 vs. 14.11%; p = 0.04) were significantly more in stillbirths. Foetal vascular thrombi in the chorionic plate (30.58 vs. 14.12%; p = 0.02) and avascular villi (24.7 vs. 8.23%; p = 0.006) were significantly more in stillbirths. Conclusion: These abnormal placental patterns could provide information about the etiopathogenisis in stillbirths of unknown aetiology.

Morbidly adherent placenta: One-year case series in a tertiary hospital.

OBJECTIVE: To analyse the clinical characteristics of patients with morbidly adherent placenta (MAP). Findings of this study will be used to identify patients at risk of MAP and to outline the best management strategy to deal with this devastating condition. METHODS: Delivery records in Hospital Sultanah Nur Zahirah, Terengganu from 1st. January 2016 until 31st. December 2016 were reviewed and analysed. RESULTS: Out of the 15,837 deliveries, eight cases of MAP were identified. Six out of eight patients had previous caesarean scar with concomitant placenta praevia, the other two patients had previous caesarean scar with history of placenta praevia in previous pregnancies. Seven out of eight cases were suspected to have MAP based on risk factors. Correct diagnosis was made by ultrasound in five patients, all with histologically confirmed moderate/severe degree of abnormal placentation. The other two cases of 'unlikely MAP', demonstrated segmental MAP intra-operatively with histologically confirmed milder degree of abnormal placentation. Total intraoperative blood loss ranged from 0.8 to 20 litres. Prophylactic internal iliac artery balloon occlusion was associated with significantly less blood loss. CONCLUSION: Antenatal diagnosis is essential in outlining the best management strategy in patients with MAP. Ultrasound may not be accurate in ruling out lower degree of MAP. Apart from having a scarred uterus with concomitant placenta praevia, history of having placenta praevia in previous pregnancy is also a risk factor for MAP. Prophylactic internal iliac artery balloon occlusion is associated with significantly less blood loss and should be considered in cases suspected with MAP.

Inactivation of maternal Hif-1α at mid-pregnancy causes placental defects and deficits in oxygen delivery to the fetal organs under hypoxic stress.

A critical transition occurs near mid-gestation of mammalian pregnancy. Prior to this transition, low concentrations of oxygen (hypoxia) signaling through Hypoxia Inducible Factor (HIF) functions as a morphogen for the placenta and fetal organs. Subsequently, functional coupling of the placenta and fetal cardiovascular system for oxygen (O2) transport is required to support the continued growth and development of the fetus. Here we tested the hypothesis that Hif-1α is required in maternal cells for placental morphogenesis and function. We used Tamoxifen-inducible Cre-Lox to inactivate Hif-1α in maternal tissues at E8.5 (MATcKO), and used ODD-Luciferase as a reporter of hypoxia in placenta and fetal tissues. MATcKO of Hif-1α reduced the number of uterine natural killer (uNK) cells and Tpbpa-positve trophoblast cells in the maternal decidua at E13.5 -15.5. There were dynamic changes in all three layers of E13.5-15.5 MATcKO placenta. Of note was the under-development of the labyrinth at E15.5 associated with reduced Ki67 and increased TUNEL staining consistent with reduced cell proliferation and increased apoptosis. Labyrinth defects were particularly evident in placentas connected to effectively HIF-1α heterozygous null embryos. MATcKO had no effect on basal ODD-Luciferase activity in fetal organs (heart, liver, brain) at any stage, but at E13.5-15.5 resulted in enhanced induction of the ODD-Luciferase hypoxia reporter when the dam's inspired O2 was reduced to 8% for 4 hours. MATcKO also slowed the growth after E13.5 of fetuses that were effectively heterozygous for Hif-1α, with most being non-viable at E15.5. The hearts of these E15.5 fetuses were abnormal with reduction in size, thickened epicardium and mesenchymal septum. We conclude that maternal HIF-1α is required for placentation including recruitment of uNK and trophoblast cells into the maternal decidua and other trophoblast cell behaviors. The placental defects render the fetus vulnerable to O2 deprivation after mid-gestation.

Placental Chorioangioma with Nonimmune Hydrops Fetalis.

A 38-year-old woman was found to have a large placental chorioangioma. The fetus was studied using ultrasound. The pregnancy became complicated by hydrops fetalis, polyhydramnios, and abruptio placenta. The infant delivered at 29 weeks' gestational age. The neonatal course was complicated by nonimmune hydrops fetalis, respiratory distress syndrome, anemia, pulmonary hemorrhage, intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia. The infant was discharged home with breastfeeding and off oxygen at 50 days of life. This case represents the multidisciplinary approach to the pregnancy complicated by a large placental chorioangioma and the resulting premature neonate with nonimmune hydrops fetalis.

Failed manual removal of the placenta after vaginal delivery.

PURPOSE: A retained placenta after vaginal delivery where manual removal of placenta fails is a clinical challenge. We present six cases that illustrate the heterogeneity of the condition and discuss the etiology and terminology as well as the clinical management. METHODS: Members of the European Working group on Abnormally Invasive Placenta (EW-AIP) were invited to report all recent cases of retained placenta that were not antenatally suspected to be abnormally adherent or invasive, but could not be removed manually despite several attempts. RESULTS: The six cases from Denmark, The Netherlands and the UK provide examples of various treatment strategies such as ultrasound-guided vaginal removal, removal of the placenta through a hysterotomy and just leaving the placenta in situ. The placentas were all retained, but it was only possible to diagnose abnormal invasion in the one case, which had a histopathological diagnosis of increta. Based on these cases we present a flow chart to aid clinical management for future cases. CONCLUSION: We need properly defined stringent terminology for the different types of retained placenta, as well as improved tools to predict and diagnose both abnormally invasive and abnormally adherent placenta. Clinicians need to be aware of the options available to them when confronted by the rare case of a retained placenta that cannot be removed manually in a hemodynamically stable patient.

Twin-to-Twin Transfusion Syndrome: A Case Report.

PURPOSE: To present a case of twin-to-twin transfusion syndrome (TTTS), followed by discussion of the etiology, pathophysiology, prenatal diagnosis, management, complications, prognosis, and family considerations. METHODS: A literature review was conducted using MEDLINE, PubMed, CINAHL, ProQuest, and Google Scholar. The search resulted in 593 articles; 25 relevant articles were chosen. RESULTS: Approximately 1 of every 250 cases of monochorionic twins acquire TTTS. The progression of TTTS is unpredictable; nontreatment and early onset have been associated with >90 percent mortality of both twins. Neurodevelopmental impairment, preterm birth, renal hypoperfusion, growth restriction, cardiomyopathy, and hydrops fetalis have been associated with TTTS. LIMITATIONS: A paucity of research and case reports exists, limiting recommendations for optimal diagnosis, management, and treatment regimens. IMPLICATIONS FOR PRACTICE: TTTS is unpredictable in progression; earlier identification of chorionicity, diagnosis of TTTS, and improvement of treatment and management have the potential to improve the mortality and morbidity outcomes associated with TTTS.