Pregnancy Outcomes and Obstetrical Complications of Twin Pregnancies with Endometriosis: A Single-Center Cohort Study.

PURPOSE: There are many studies regarding the increased relationship between pregnancy outcomes of singleton with endometriosis. However, there was limited evidence of twin pregnancies with endometriosis. This study aimed to compare the pregnancy outcomes and complications in twin pregnancies with or without endometriosis in a single institution. MATERIALS AND METHODS: From January 2011 to July 2022, a retrospective analysis of twin pregnancies was conducted. The endometriosis group included patient with histological or visual confirmation before pregnancy or during cesarean section. Pregnancy outcomes and complications were compared between the two groups. RESULTS: Out of 1714 patients examined, 127 (7.4%) were included in the endometriosis group. Maternal body mass index (BMI) was lower in the endometriosis group (p<0.001). There were no significant differences in maternal age, mode of conception, chorionicity, and pregnancy outcomes, such as gestational age at delivery (p=0.835) and the preterm birth rate (p=0.579). The endometriosis group had a significantly higher rate of obstetrical complication: small for gestational age (SGA) <10% (p=0.029). However, after adjustment for BMI, the endometriosis group showed no statistical significance in obstetrical complications, including SGA (adjusted odds ratio, 1.568; 95% confidence interval, 0.984-2.499; p=0.059). CONCLUSION: Twin pregnancies with endometriosis were not related to adverse effects on pregnancy outcomes and obstetrical complications. To confirm these outcomes, further large prospective studies are required.

A Novel Paradigm for Non-Invasive Prenatal Genetic Screening: Trophoblast Retrieval and Isolation from the Cervix (TRIC).

As the prevalence of pregnancies with advanced maternal age increases, the risk of fetal chromosomal abnormalities is on the rise. Therefore, prenatal genetic screening and diagnosis have become essential elements in contemporary obstetrical care. Trophoblast retrieval and isolation from the cervix (TRIC) is a non-invasive procedure that can be utilized for prenatal genetic diagnosis. The method involves the isolation of fetal cells (extravillous trophoblasts) by transcervical sampling; along with its non-invasiveness, TRIC exhibits many other advantages such as its usefulness in early pregnancy at 5 weeks of gestation, and no interference by various fetal and maternal factors. Moreover, the trophoblast yields from TRIC can provide valuable information about obstetrical complications related to abnormal placentation even before clinical symptoms arise. The standardization of this clinical tool is still under investigation, and the upcoming advancements in TRIC are expected to meet the increasing need for a safe and accurate option for prenatal diagnosis.

Combined Model-Based Prediction for Non-Invasive Prenatal Screening.

The risk of chromosomal abnormalities in the child increases with increasing maternal age. Although non-invasive prenatal testing (NIPT) is a safe and effective prenatal screening method, the accuracy of the test results needs to be improved owing to various testing conditions. We attempted to achieve a more accurate and robust prediction of chromosomal abnormalities by combining multiple methods. Here, three different methods, namely standard Z-score, normalized chromosome value, and within-sample reference bin, were used for 1698 reference and 109 test samples of whole-genome sequencing. The logistic regression model combining the three methods achieved a higher accuracy than any single method. In conclusion, the proposed method offers a promising approach for increasing the reliability of NIPT.

Advanced Strategy of Trophoblasts Retrieval and Isolation from the Cervix (TRIC): Comparison of Two HLA-G Antibodies for Immunomagnetic Isolation of Trophoblasts.

Trophoblasts retrieval and isolation from the cervix (TRIC) is a non-invasive method which enables analysis of fetal genetic information from the extravillous trophoblast cells (EVTs). The aim of this study was to compare the efficacy of the HLA-G antibodies­G233 and 4H84­in isolating EVT cells and provide an optimized protocol of TRIC. We analyzed EVTs from 23 pregnant women in between 5 to 20 weeks of gestation who underwent invasive prenatal testing. Two HLA-G antibodies­G233 and 4H84­were used in a subgroup of 11 and 12 samples for immunomagnetic isolation. Cells with ß-hCG expression were counted to compare the rate of isolated trophoblast cells. The rate of ß-hCG positive cells was significantly different between the G233 and the 4H84 by immunefluorescence microscopy (p < 0.001). The percentage of ß-hCG expressing cells in G233 and 4H84 groups were 62.4 ± 8.24% and 82.6 ± 7.1%, respectively (p < 0.001). The average fetal cell positive rate was 14.1 ± 3.78 in the G233 group while it was 25.8 ± 3.9 in the 4H84 group by fluorescence in situ hybridization (FISH) (p = 0.011). Immunoisolation of trophoblast cells using 4H84 HLA-G antibody was more efficient in capturing EVT cells than using G233 for successful clinical application of TRIC.

Defective Uteroplacental Vascular Remodeling in Preeclampsia: Key Molecular Factors Leading to Long Term Cardiovascular Disease.

Preeclampsia is a complex hypertensive disorder in pregnancy which can be lethal and is responsible for more than 70,000 maternal deaths worldwide every year. Besides the higher risk of unfavorable obstetric outcomes in women with preeclampsia, another crucial aspect that needs to be considered is the association between preeclampsia and the postpartum cardiovascular health of the mother. Currently, preeclampsia is classified as one of the major risk factors of cardiovascular disease (CVD) in women, which doubles the risk of venous thromboembolic events, stroke, and ischemic heart disease. In order to comprehend the pathophysiology behind the linkage between preeclampsia and the development of postpartum CVD, a thorough understanding of the abnormal uteroplacental vascular remodeling in preeclampsia is essential. Therefore, this review aims to summarize the current knowledge of the defective process of spiral artery remodeling in preeclampsia and how the resulting placental damage leads to excessive angiogenic imbalance and systemic inflammation in long term CVD. Key molecular factors in the pathway-including novel findings of microRNAs-will be discussed with suggestions of future management strategies of preventing CVD in women with a history of preeclampsia.

Neuromyelitis optica (NMO)-IgG-driven organelle reorganization in human iPSC-derived astrocytes.

Neuromyelitis optica (NMO) is an autoimmune disease that primarily targets astrocytes. Autoantibodies (NMO-IgG) against the water channel protein, aquaporin 4 (AQP4), are a serologic marker in NMO patients, and they are known to be responsible for the pathophysiology of the disease. In the brain, AQP4 is mainly expressed in astrocytes, especially at the end-feet, where they form the blood-brain barrier. Following the interaction between NMO-IgG and AQP4 in astrocytes, rapid AQP4 endocytosis initiates pathogenesis. However, the cellular and molecular mechanisms of astrocyte destruction by autoantibodies remain largely elusive. We established an in vitro human astrocyte model system using induced pluripotent stem cells (iPSCs) technology in combination with NMO patient-derived serum and IgG to elucidate the cellular and functional changes caused by NMO-IgG. Herein, we observed that NMO-IgG induces structural alterations in mitochondria and their association with the endoplasmic reticulum (ER) and lysosomes at the ultrastructural level, which potentially leads to impaired mitochondrial functions and dynamics. Indeed, human astrocytes display impaired mitochondrial bioenergetics and autophagy activity in the presence of NMO-IgG. We further demonstrated NMO-IgG-driven ER membrane deformation into a multilamellar structure in human astrocytes. Together, we show that NMO-IgG rearranges cellular organelles and alter their functions and that our in vitro system using human iPSCs offers previously unavailable experimental opportunities to study the pathophysiological mechanisms of NMO in human astrocytes or conduct large-scale screening for potential therapeutic compounds targeting astrocytic abnormalities in patients with NMO.

Clinical implications of placenta-derived angiogenic/anti-angiogenic biomarkers in pre-eclampsia.

Pre-eclampsia (PE) is a devastating systemic disease which results in maternal hypertension with multi-organ failure due to angiogenic imbalance, characterized by lack of circulating pro-angiogenic factors and excess of anti-angiogenic factors. These factors are crucial for understanding the pathophysiology of PE since they serve as a critical link from placental dysfunction to the clinical syndrome of systemic endothelial dysfunction in the disease. Moreover, utilizing these angiogenic/anti-angiogenic biomarkers can be helpful in risk stratifying and the early detection of PE, which allows for timely intervention to improve maternal and neonatal outcomes. In this review, we summarize updated perspectives of the angiogenic imbalance in PE with detailed characterization of key factors involved in the pathogenesis and how the developed biomarkers can be used in clinical settings as diagnostic tools and as possible therapeutic targets of PE.

Twin pregnancies with uterine fibroids are not at increased risk for obstetric complications: single center cohort study.

BACKGROUND: Twin pregnancies with uterine fibroid(s) (UFs) may not be at increased risk for obstetric complications compared to those without UFs. However, there was no reported comparison study with obstetric outcomes and complications of twin pregnancy after myomectomy. We aimed to compare the pregnancy outcomes in twin pregnancies with or without uterine fibroid(s), and also compared in patients with previous myomectomy history in Korean women. METHODS: A cohort of twin pregnancies delivered in a single institution between January 2011 and March 2019 were retrospectively analyzed. UFs group was defined by the presence of UFs during pregnancy (≥1 fibroid, measuring ≥2 cm or multiple fibroids regardless of the size). Previous myomectomy group included patients with history of abdominal or laparoscopic or hysteroscopic myomectomy of ≥1 fibroid, measuring ≥2 cm or multiple fibroids whatever the size. Patients with monochorionic monoamniotic twins, myoma less than 2 cm in size, missed abortion or intrauterine fetal death (IUFD) of one fetus before 14 weeks, history of previous conization, and uterine anomalies were excluded. Pregnancy outcomes and obstetric complications were compared. RESULT: A total 1388 patients were included in this study, 191 (13.8%) had UFs and 89 (6.4%) had a history of myomectomy. Maternal age was younger in non-UFs group and primiparity was more common in UFs group (p < 0.001, and p = 0.019). No significant differences were found in the gestational age at delivery (p = 0.657), delivery before 37 weeks (p = 0.662), delivery before 34 weeks (p = 0.340), and sum of birth weight of twin (p = 0.307). There were also no statistical differences in rates of obstetrical complications, such as preeclampsia, gestational diabetes mellitus, placenta previa, placenta abruption, cerclage, small for gestational age, IUFD, postpartum hemorrhage and peripartum transfusion or ICU care. These obstetrical outcomes and complications showed no statistical differences between UFs group and previous myomectomy group. CONCLUSION: In patients with twin pregnancies, the presence of UFs or history of previous myomectomy did not relate to negative effects on pregnancy outcomes and obstetrical complications.

Unexpected uterine smooth muscle tumor of uncertain malignant potential and sarcoma: A single center cohort study in South Korea.

OBJECTIVE: To evaluate the risk of encountering unexpected uterine smooth muscle tumors of uncertain malignant potential (STUMPs) or sarcomas during surgical treatment of mesenchymal tumors of the uterus using morcellation. MATERIAL AND METHODS: Data were collected retrospectively from subjects who were pathologically diagnosed with uterine leiomyoma or its variants, STUMP or other premalignant mesenchymal tumors of uterus, or sarcoma during surgical treatment between July 2014 and June 2017. RESULTS: A total of 3785 women were investigated; 2824 laparoscopic procedures (74.6%) were performed, and an electronic power morcellator was used in 1636 patients (43.2%). Sixteen women (0.42%) were diagnosed with STUMP and 14 (0.37%) were diagnosed with uterine sarcoma. The incidence rate of unexpected STUMP or uterine sarcoma was 0.61% (23 of 3785 women); unexpected STUMP in 13 (0.34%), and unexpected sarcoma was in 10 (0.26%). Moreover, the unexpected leiomyosarcoma rate was 0.08% (3 in 3785). The rate of unintended morcellation of STUMPs was relatively high at 0.26% (10 in 3785), however, that for uterine sarcomas was 0.05% (2 in 3785). CONCLUSION: The risks of unintended morcellation were very low for sarcomas and STUMPs, although the risk of the latter was approximately 5-fold that of the former. To reduce the unintended dissemination of tumors, patients suspected of having malignancies should be provided adequate information regarding their treatment options as well as their associated risks. Meanwhile, improved preoperative screening methods for STUMP and sarcoma should be established.

Successful in vitro fertilization pregnancy and delivery after a fertility-sparing laparoscopic operation in a patient with a papillary thyroid carcinoma arising from a mature cystic teratoma.

Malignant transformation of ovarian mature cystic teratomas is rare, and papillary thyroid cancer occurs in 0.1%-0.3% of ovarian teratomas that undergo malignant transformation. We describe a case of successful in vitro fertilization pregnancy and delivery after a fertility-sparing laparoscopic operation in a patient with papillary thyroid carcinoma arising from a mature cystic teratoma.