Normal Pregnancy Research Articles

P-165 Artificial removal of the zona pellucida at the pronuclear stage in patients with poor quality embryos with severe fragmentation

Abstract Study question Is artificial removal of the zona pellucida (ZP) at the pronuclear stage effective in patients with poor quality embryos with severe fragmentation? Summary answer Artificial removal of the ZP at the pronuclear stage significantly improved culture results in patients with poor quality embryos with severe fragmentation. What is known already In 2020, Yumoto et al. first reported that artificial removal of the ZP (ZP-free) at the pronuclear stage decreased the rate of fragmentation and improved the culture outcomes of 3 pronuclei (3PN) embryos reaching to the good blastocysts. Therefore, the ZP may not always be necessary for normal embryonic development after the pronuclear stage. The same group presented at the 37th ESHRE meeting in 2021, that the blastocyst transfer after ZP-free embryo of 2 pronuclei (2PN) resulted in normal pregnancy in two patients with poor-quality embryos resulting in live births. Study design, size, duration This study included 211 of 2PN embryos from 46 cycles for 30 couples obtained between July 2021 and December 2022, whose previous oocyte retrieval cycle showed massive cytoplasmic fragmentation at the first cleavage confirmed by a time-laps incubator (TLI). Average age of women was 38.8years. The embryos with artificial removal of the ZP at the pronuclear stage were cultured in a TLI up to 7 days. All blastocysts were cryopreserved for future embryo transfer cycles. Participants/materials, setting, methods All participants provided written informed consent, and Institutional Review Board approval was obtained. Artificial removal of the ZP at the pronuclear stage was performed by following procedure. 1) Embryos were placed in 0.125M sucrose-containing HEPES for cytoplasm shrinking. 2) The ZP without adhesion was removed with a laser system. 3) Ooplasms were completely separated from ZP by blowing the medium to adhesion point like a jet car wash. 4) ZP-free embryo was obtained. Main results and the role of chance Day 3 embryos were divided into 3 groups using the Veeck’s classification: 8 cell embryos with grade 2 or higher were defined as good, embryos with grade 4 or 5 regardless of the number of cells were defined as poor, and others were defined as fair. We compared the culture results of ZP-free cycle and previous oocyte retrieval cycle (ZP-intact). For day 3 embryos, good, fair and poor grade were 19.4% (41/211), 62.6% (132/211) and 18.0% (38/211) in ZP-free embryos compared with 2.9% (15/561), 37.4% (210/561), and 59.9% (336/561) in the past, respectively (p < 0.001). Good-quality blastocysts were defined as 3BB or more on day 5 by the Gardner’s classification. As to the blastocysts, blastocysts development and good-quality blastocysts rates were 45.0% (95/211) and 27.0% (57/211) in ZP-free embryos compared with 23.0% (112/488) and 6.8% (33/488) in the past, respectively (p < 0.001). Of these, 30 embryo transfers were performed resulting in 11 clinical pregnancies. We had 3 live births without any congenital anomalies and one miscarriage. One was delivered at 33 weeks of gestation with caesarian section, one mother had gestational diabetes. Limitations, reasons for caution This study was retrospective study without any control group and was conducted at only single fertility center. It is necessary to conduct sibling oocytes study to demonstrate the effectiveness of ZP-free culture, and to create criteria who are benefit from ZP-free culture. Moreover, safety of ZP-free culture should be evaluated. Wider implications of the findings ZP-free culture reduced fragments and improved culture outcomes in patients with poor quality embryos with severe fragmentation. ZP-free culture might bring light to the patients who have difficulty obtaining good-quality embryos with severe fragmentation. Trial registration number Not Applicable

Clinical chorioamnionitis at term is characterized by changes in the plasma concentration of CHCHD2/MNRR1, a mitochondrial protein

Objective Mitochondrial dysfunction was observed in acute systemic inflammatory conditions such as sepsis and might be involved in sepsis-induced multi-organ failure. Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 2 (CHCHD2), also known as Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1), a bi-organellar protein located in the mitochondria and the nucleus, is implicated in cell respiration, survival, and response to tissue hypoxia. Recently, the reduction of the cellular CHCHD2/MNRR1 protein, as part of mitochondrial dysfunction, has been shown to play a role in the amplification of inflammatory cytokines in a murine model of lipopolysaccharide-induced systemic inflammation. The aim of this study was to determine whether the plasma concentration of CHCHD2/MNRR1 changed during human normal pregnancy, spontaneous labor at term, and clinical chorioamnionitis at term. Methods We conducted a cross-sectional study that included the following groups: 1) non-pregnant women (n = 17); 2) normal pregnant women at various gestational ages from the first trimester until term (n = 110); 3) women at term with spontaneous labor (n = 50); and 4) women with clinical chorioamnionitis at term in labor (n = 25). Plasma concentrations of CHCHD2/MNRR1 were assessed by an enzyme-linked immunosorbent assay. Results 1) Pregnant women at term in labor with clinical chorioamnionitis had a significantly higher plasma CHCHD2/MNRR1 concentration than those in labor without chorioamnionitis (p = .003); 2) CHCHD2/MNRR1 is present in the plasma of healthy non-pregnant and normal pregnant women without significant differences in its plasma concentrations between the two groups; 3) there was no correlation between maternal plasma CHCHD2/MNRR1 concentration and gestational age at venipuncture; and 4) plasma CHCHD2/MNRR1 concentration was not significantly different in women at term in spontaneous labor compared to those not in labor. Conclusions CHCHD2/MNRR1 is physiologically present in the plasma of healthy non-pregnant and normal pregnant women, and its concentration does not change with gestational age and parturition at term. However, plasma CHCHD2/MNRR1 is elevated in women at term with clinical chorioamnionitis. CHCHD2/MNRR1, a novel bi-organellar protein located in the mitochondria and the nucleus, is released into maternal plasma during systemic inflammation.

LncRNA landscape and associated ceRNA network in placental villus of unexplained recurrent spontaneous abortion

BackgroundUnexplained recurrent spontaneous abortion (URSA) is one of the most challenging conditions frustrates women of childbearing age profoundly. The gene expression patterns and biological characteristics of placental villus in patients with URSA remain largely unknown. The aim of our study was to identify potential lncRNAs as well as their action mechanisms in URSA.MethodThe ceRNA microarray was used to identify the mRNA and lncRNA expression profiles of URSA patients and normal pregnancy. Functional enrichment analyses for differentially expressed mRNAs in URSA were performed. Protein-protein interaction analysis of differentially expressed mRNAs was performed to identify hub genes and key modules. Subsequently, the co-dysregulated ceRNA network of URSA was established, and the enrichment analyses for the mRNAs in the ceRNA network was implemented. qRT-PCR was performed to validated the expression of key ENST00000429019 and mRNAs in URSA.ResultsWe found that URSA placental villus have distinct mRNA and lncRNA expression profiles through ceRNA microarray, with a total of 347 mRNAs and 361 lncRNAs differentially expressed compared with controls. The functional enrichment analysis revealed that ncRNA processing, DNA replication, cell cycle, apoptosis, cytokine-mediated signaling pathway, ECM-receptor interaction were the potentially disrupted pathways in URSA patients. Then we constructed a co-dysregulated ceRNA network and found differentially expressed mRNAs were regulated by a small fraction of hub lncRNAs. Finally, we found a key network of ENST00000429019 and three cell proliferation or apoptosis related key mRNAs (CDCA3, KIFC1, NCAPH), and validated their expression and regulation in tissue and cellular levels.ConclusionsThis study identified a key ceRNA network, which might take part in URSA and correlate with cell proliferation and apoptosis. Optimistically, this study may deepen our apprehensions about the underlying molecular and biological causes of URSA and provide an important theoretical basis for future therapeutic strategies for patients with URSA.

Coagulation Profile Study in Pregnancy Induced Hypertension

Abstract Background & Aims: Hypertensive disorders represent the most common medical complication of pregnancy. Hypertensive disorders remains leading cause of direct maternal and fetal mortality. Coagulation profile study in pregnancy induced hypertension helps inearly diagnosis of pregnancy induced hypertension and assessing the severity of pregnancy induced hypertension at earlier stage and help to prevent severe complications like disseminated intravascular coagulation and HELLP syndrome. To estimate platelet count, prothrombin time and activated partial thromboplastin time in pregnancy induced hypertension. To estimate above parameters in normal pregnancy. To compare above parameters between normotensive women and women with pregnancy induced hypertension. Material and Method: 100 newly diagnosed patients of pregnancy induced hypertension and 100 normal healthy controls were included in the study. After taking consent, their blood samples were collected. These samples were transported to the laboratory and processed without delay for prothrombin time, activated partial thromboplastin time and platelet count. The results of these parameters were noted, compared and analysed statistically. Result:In our study, we observe that pregnancy induced hypertension is common in primipara. There was a statistically significant difference between study group and control group for all three parameters(p<0.001). Comparison between each study group and control group showed significant difference (p<0.05) between prothrombin time and activated partial thromboplastin time . Prothrombin time and activated partial thromboplastin time showed significant increase value when compared to normal group although the mean value are normal or near normal in range. Conclusions: It can be concluded from this study that the pregnancy induced hypertension causes a significantchanges in haematological parameters. These parameters should be regularly monitored to prevent serious complications like disseminated intravascular coagulation and HELLP syndrome, hence to decrease morbidity and mortality. Keywords: - Pregnancy induced hypertension, Disseminated intravascular coagulation, activated partial thromboplastin time , prothrombin time.

Two-Compartment Perfusion MR IVIM Model to Investigate Normal and Pathological Placental Tissue.

Perfusion and diffusion coexist in the placenta and can be altered by pathologies. The two-perfusion model, where f1 and, f2 are the perfusion-fraction of the fastest and slowest perfusion compartment, respectively, and D is the diffusion coefficient, may help differentiate between normal and impaired placentas. Investigate the potential of the two-perfusion IVIM model in differentiating between normal and abnormal placentas. Retrospective, case-control. 43 normal pregnancy, 9 fetal-growth-restriction (FGR), 6 small-for-gestational-age (SGA), 4 accreta, 1 increta and 2 percreta placentas. Diffusion-weighted-echo planar imaging sequence at 1.5 T. Voxel-wise signal-correction and fitting-controls were used to avoid overfitting obtaining that two-perfusion model fitted the observed data better than the IVIM model (Akaike weight: 0.94). The two-perfusion parametric-maps were quantified from ROIs in the fetal and maternal placenta and in the accretion zone of accreta placentas. The diffusion coefficient D was evaluated using a b ≥ 200 sec/mm2 -mono-exponential decay fit. IVIM metrics were quantified to fix f1 + f2 = fIVIM . ANOVA with Dunn-Sidák's post-hoc correction and Cohen's d test were used to compare parameters between groups. Spearman's coefficient was evaluated to study the correlation between variables. A P-value<0.05 indicated a statistically significant difference. There was a significant difference in f1 between FGR and SGA, and significant differences in f2 and fIVIM between normal and FGR. The percreta + increta group showed the highest f1 values (Cohen's d = -2.66). The f2 between normal and percreta + increta groups showed Cohen's d = 1.12. Conversely, fIVIM had a small effective size (Cohen's d = 0.32). In the accretion zone, a significant correlation was found between f2 and GA (ρ = 0.90) whereas a significant negative correlation was found between fIVIM and D (ρ = -0.37 in fetal and ρ = -0.56 in maternal side) and f2 and D (ρ = -0.38 in fetal and ρ = -0.51 in maternal side) in normal placentas. The two-perfusion model provides complementary information to IVIM parameters that may be useful in identifying placenta impairment. 2 TECHNICAL EFFICACY STAGE: 1.

Paradoxical expression of NRP1 in decidual stromal and immune cells reveals a novel inflammation balancing mechanism during early pregnancy.

To investigate the balancing mechanisms between decidualization-associated inflammation and pregnancy-related immunotolerance. Decidual samples from women with normal pregnancy (n = 58) or unexplained spontaneous miscarriage (n = 13), peripheral blood from normal pregnancy and endometria from non-pregnancy (n = 10) were collected. Primary endometrial stromal cells (ESCs), decidual stromal cells (DSCs), decidual immune cells (DICs) and peripheral blood mononuclear cells (PBMCs) were isolated. The plasmid carrying neuropilin-1 (NRP1) gene was transfected into ESC for overexpression. To induce decidualization in vitro, ESCs were treated with a combination of 10nM estradiol, 100nM progesterone and 0.5mM cAMP. Anti-Sema3a and anti-NRP1 neutralizing antibodies were applied to block the ligand-receptor interactions. RNA-seq analysis was performed to identify differentially expressed genes in DSCs and DICs, and NRP1 expression was verified by Western blotting and flow cytometry. The secretion of inflammatory mediators was measured using a multifactor cytometric bead array. The effects of Sema3a-NRP1 pathway on DICs were determined by flow cytometry. Statistical differences between groups were compared using the T test and one way or two-way ANOVA. Combined with five RNA-seq datasets, NRP1 was the only immune checkpoint changing oppositely between DSCs and DICs. The decreased expression of NRP1 in DSCs allowed intrinsic inflammatory responses required for decidualization, while its increased expression in DICs enhanced tolerant phenotypes beneficial to pregnancy maintenance. DSC-secreted Sema3a promoted immunosuppression in DICs via NRP1 binding. In women with miscarriage, NRP1 was abnormally elevated in DSCs but diminished in decidual macrophages and NK cells. NRP1 is a multifunctional controller that balances the inflammatory states of DSCs and DICs in gravid uterus. Abnormal expression of NRP1 is implicated in miscarriage.

Взаємозв’язок різних триместрів вагітності і ризику COVID-19

у статті узагальнено питання в рамках наукової дискусії щодо взаємозв’язку різних триместрів вагітності і ризику COVID-19. Основна мета цього дослідження це оцінка впливу ризику COVID-19 від часу зараження, а саме від різних триместрів, зрозуміти ризики ускладнень на різних термінах вагітності, оцінити вплив триместру інфікування COVID-19 на прогресування захворювання, визначити чи збільшується частота прогресування захворювання COVID-19 зі збільшенням терміну вагітності. Завдяки детальному вивченню літературних джерел, їхній систематизації та підходів до вирішення проблеми, було виявлено, що спалах пандемії COVID-19 у США призвів до понад 97 мільйонів заражень і понад 1,06 мільйона смертей. Зареєстровано приблизно 182 000 випадків захворювання серед вагітних жінок, і 285 випадків материнської смерті. Нормальна вагітність в основному пов'язана зі зниженням функціональної залишкової ємності легень на 20-30 % і збільшенням споживання кисню на 20 %. В результаті інфекції нижніх дихальних шляхів погано переносяться, особливо в третьому триместрі. Актуальність дослідження даної патології полягає в тому, що вагітні мають вищий ризик інфікування коронавірусом 2 (SARS‑CoV‑2) у важкій або критичній формі порівняно з жінками того ж віку. Крім того, ця невідповідність посилилася під час сплеску варіанту Дельта. Підвищений ризик несприятливих наслідків для новонароджених і матерів пов’язаний із тяжким перебігом COVID-19 під час вагітності. Однак мало відомо про вплив часу зараження під час вагітності на такі ризики, тому це може призвести до помилок у лікуванні таких вагітних, що перешкоджає своєчасному, правильному лікуванню і профілактиці. У дослідженні використано методи бібліографічного та контент-аналізу літератури, порівняльного підходу та синтезу, а також семантичного групування відносно особливостей взаємозв’язку різних триместрів вагітності і ризику COVID-19. Усі документи, знайдені на різноманітних офіційних веб-сайтах були проаналізовані, а зібрану інформацію порівняли і згрупували. В статті наведено результати досліджень, які показали, що частота прогресування захворювання COVID-19 не відрізняється від триместру діагностики. Захворювання середнього, важкого або критичного ступеня розвивається майже у 10% вагітних, інфікованих вірусом SARS-CoV-2. Ці результати підкреслюють важливість профілактичних заходів, включаючи вакцинацію проти COVID-19 до або якомога раніше під час вагітності. Оскільки рівень вакцинації серед вагітних зростає, необхідні подальші дослідження, щоб зрозуміти прогресування захворювання. Подібним чином тяжкість захворювання та прогресування слід вивчати далі в умовах розвитку медичної терапії та еволюції нових варіантів SARS-CoV-2 і рецидивуючої інфекції. Тому необхідно й надалі досліджувати це питання, щоб отримати дані, орієнтовані на пацієнта та економічну ефективність. Результати даного дослідження можуть бути цікавими для лікарів первинної ланки, гінекологів та терапевтів

Late Postpartum Posterior Reversible Encephalopathy Syndrome: Case Series and Literature Review

Abstract Posterior reversible encephalopathy syndrome (PRES) is a reversible neurological entity characterized by seizures, headache, visual symptoms and other focal neurological findings. It is caused by wide variety of causes ultimately leading to vasogenic cerebral edema of occipital and parietal lobes of the brain. Prompt and early diagnosis of PRES is key in reducing the risk of permanent neurological sequelae. Occurrence of PRES during pregnancy or early postpartum period is well known. However, occurrence of PRES between 48 hours and one month postpartum in women who had normal pregnancy and delivery and no signs of preeclampsia is rare. In this case series we present three cases of PRES that occurred in young women during late postpartum period. All these three patients were normotensive during antenatal and early puerperal period but developed hypertension and vision loss in late puerperium. The prompt diagnosis and management of symptoms resulted in complete reversal of the symptoms with no permanent neurological deficit. Posterior reversible encephalopathy syndrome (PRES) is a reversible neurological entity characterized by the presence of white matter edema affecting the occipital and parietal lobes. The predominantly affected area of the cerebral cortex determines presentation in the patient. The reversibility of these symptoms is one of the hallmarks of the disease. Diffusion-weighted MRI is the gold standard in diagnosis of PRES as it helps to distinguish between vasogenic edema from cytotoxic edema. Prompt diagnosis and initiation of early treatment may lead to complete recovery with no residual neurological deficit.

Fetal Cerebellar Area: Ultrasound Reference Ranges at 13-39 Weeks of Gestation.

The present study aims to provide prenatal 2-dimensional ultrasonographic (2D-US) nomograms of the normal cerebellar area. This is a prospective cross-sectional analysis of 252 normal singleton pregnancies, ranging from 13 to 39 weeks of gestation. The operator performed measurements of the fetal cerebellar area in the transverse plane using 2D-US. The relationship between cerebellar area and gestational age (GA) was determined through regression equations. A significant, strong positive correlation was investigated between the cerebellar area with GA (r-value = 0.89), and a positive correlation indicates that with increasing GA, the cerebellar area increased in all the participants of the study. Several 2D-US nomograms of the normal cerebellar area were provided, and an increase of 0.4% in the cerebellar area each week of GA was reported. We presented information on the typical dimensions of the fetal cerebellar area throughout gestation. In future studies, it could be evaluated how the cerebellar area changes with cerebellar abnormalities. It should be established if calculating the cerebellar area in addition to the routine transverse cerebellar diameter may help in discriminating posterior fossa anomalies or even help to identify anomalies that would otherwise remain undetected.

Evaluating the characteristics of myocardial work by two-dimensional echocardiography during pre-eclampsia pregnancy.

This study aimed to analyze the changes in myocardial work (MyW) properties and the correlation of MyW with cardiovascular and clinical indices during the pre-eclampsia (PE) pregnancy. Standard two-dimensional and speckle-tracking echocardiography were sequentially performed on 77 women with PE and 89 with normal pregnancy. Four components of MyW: global myocardial work index (GWI), constructive work (GCW), wasted work (GWW), and work efficiency (GWE) were measured. The significant increased GWI, GCW and GWW were observed, while GWW elevated more than GCW with consequently resulting the decline in GWE among PE cases. Although there was a diverse relationship between MyW components and LV morphological as well as functional indices, MyW parameters were significantly correlated with the grades of arterial hypertension and the incidence of adverse outcome of PE. With the hypertension stages, GWI, GCW and GWW gradually increased but GWE decreased. Meanwhile, the higher GWI and GCW and the lower GWE, the more adverse events occurred in PE group. In conclusion, during the PE pregnancy, GWI, GCW and GWW increase, while GWW elevates more than GCW, which leads to the decrease in GWE. Moreover, the changes in MyW are associated with the hypertension grades and the poor prognosis in PE. The non-invasive manner for MyW assessment provides a new perspective on the myocardial biomechanics, cardio-metabolic conditions and pathophysiological changes in the condition of PE.

Differences in Average Serum Cortisol Levels and Serum 25 Hydroxyvitamin D Levels in Preeclampsia and Normal Pregnancy

According to the World Health Organization, hypertension ranks second as the direct cause of maternal death in pregnancy; namely gestational hypertension (14%). Causes of maternal death in 2021 related to hypertension in pregnancy totaling 1,077 cases. Preeclampsia involves a number of biological processes that affect immune dysfunction, placental implantation, abnormal angiogenesis, excessive inflammation and high oxidative stress reactions and diseases related to maternal vascularization or blood vessels are possible contributing causes. Research with a case-control design was conducted at RSUP Dr. M. Djamil, RSIA Siti Hawa, and RSIA Cicik Padang from February 2021–August 2022. Preeclampsia and normal pregnancy research samples consisted of 27 case samples and 27 control samples. Serum cortisol levels and serum 25-hydroxyvitamin D levels were examined by the ELISA method. The Independent Sample T-Test was used to analyze the data. The mean difference in serum cortisol levels in preeclampsia was 48.70 ± 15.23 µg/dL, higher than that in normal pregnancy, 38.62 ± 8.27 µg/dL (p-value = 0.004, p &lt;0.05). Differences The mean serum level of 25 Hydroxyvitamin D in preeclampsia was 13.63 ± 6.12 ng/ml, lower than that in normal pregnancy, 14.49 ± 3.94 ng/ml (p-value =0.539, p&gt;0.05). The study concluded that there were differences in cortisol levels in preeclamptic pregnancies with normal pregnancies and there were no differences in serum levels of 25 Hydroxyvitamin D in preeclamptic pregnancies with normal pregnancies

First-Trimester Screening for Miscarriage or Stillbirth-Prediction Model Based on MicroRNA Biomarkers.

We evaluated the potential of cardiovascular-disease-associated microRNAs to predict in the early stages of gestation (from 10 to 13 gestational weeks) the occurrence of a miscarriage or stillbirth. The gene expressions of 29 microRNAs were studied retrospectively in peripheral venous blood samples derived from singleton Caucasian pregnancies diagnosed with miscarriage (n = 77 cases; early onset, n = 43 cases; late onset, n = 34 cases) or stillbirth (n = 24 cases; early onset, n = 13 cases; late onset, n = 8 cases; term onset, n = 3 cases) and 80 selected gestational-age-matched controls (normal term pregnancies) using real-time RT-PCR. Altered expressions of nine microRNAs (upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-26a-5p, miR-146a-5p, and miR-181a-5p and downregulation of miR-130b-3p, miR-342-3p, and miR-574-3p) were observed in pregnancies with the occurrence of a miscarriage or stillbirth. The screening based on the combination of these nine microRNA biomarkers revealed 99.01% cases at a 10.0% false positive rate (FPR). The predictive model for miscarriage only was based on the altered gene expressions of eight microRNA biomarkers (upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-26a-5p, miR-146a-5p, and miR-181a-5p and downregulation of miR-130b-3p and miR-195-5p). It was able to identify 80.52% cases at a 10.0% FPR. Highly efficient early identification of later occurrences of stillbirth was achieved via the combination of eleven microRNA biomarkers (upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-146a-5p, and miR-181a-5p and downregulation of miR-130b-3p, miR-145-5p, miR-210-3p, miR-342-3p, and miR-574-3p) or, alternatively, by the combination of just two upregulated microRNA biomarkers (miR-1-3p and miR-181a-5p). The predictive power achieved 95.83% cases at a 10.0% FPR and, alternatively, 91.67% cases at a 10.0% FPR. The models based on the combination of selected cardiovascular-disease-associated microRNAs had very high predictive potential for miscarriages or stillbirths and may be implemented in routine first-trimester screening programs.

Comparison of clinical outcomes and biochemical markers in normal and preeclamptic pregnancies: a prospective cohort study

Background Preeclampsia (PreE), the de novo onset of hypertension and proteinuria at 20 weeks of gestation, is a leading cause of maternal and fetal morbidity and mortality. This study compared inflammatory biomarkers in PreE and normal pregnancies using paired samples of mothers and neonates. Methods Twenty normal pregnant and 27 PreE patients were monitored for biomarkers, neonatal outcomes, and placental morphologies. Fetal and maternal serum levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble endoglin (sENG), and soluble fms-like tyrosine kinase-1 (sFLT-1) were measured by enzyme-linked immunosorbent assay. Results Placental thickness was 25 mm in early PreE subjects compared to 32 mm in late PreE subjects (P < 0.05). Placental volume was 296 cm3 in early PreE compared to 393 cm3 in late PreE (P < 0.05). The average hospital stay for PreE babies was longer (20 ± 5 days) compared to babies from normal pregnancies (2 ± 1 days; P < 0.05). PreE babies had a lower Ponderal index (2.28 ± 0.3) than those from normal pregnancies (2.95 ± 0.2; P < 0.05). sENG and sFLT-1 had cord values like the maternal values, while VEGF and PlGF did not. Conclusion PreE alters the intrauterine environment by activating chemical mediators that result in maternal and fetal complications.

Comparative study between oxytocin and combination of tranexamic acid and ethamsylate in reducing intra-operative bleeding during emergency and elective cesarean section after 38 weeks of normal pregnancy

ObjectiveCesarean Section (CS) is associated with an increased risk of hemorrhage. Many drugs are used to decrease this risk. We aim to compare the combination of ethamsylate and tranexamic acid, oxytocin, and placebo in women undergoing CS.MethodsWe conducted a double-blinded, randomized, placebo-controlled trial between October and December 2020 in four university hospitals in Egypt. The study included all pregnant women in labor without any complications who accepted to participate in the study between October and December 2020. The participants were divided into three groups. The subjects were randomly allocated to receive either oxytocin (30 IU in 500 ml normal saline during cesarean section), combined one gram of tranexamic acid with 250 mg of ethamsylate once before skin incision, or distilled water. Our main outcome was the amount of blood loss during the operation. The secondary outcomes were the need for blood transfusion, hemoglobin and hematocrit changes, hospital stay, operative complications, and the need for a hysterectomy. The one-way ANCOVA test was used to compare the quantitative variables between the three groups while the Chi-square test was used to compare the qualitative variables. Post hoc analysis then was performed to compare the difference between every two groups regarding the quantitative variables.ResultsOur study included 300 patients who were divided equally into three groups. Tranexamic acid with ethamsylate showed the least intra-operative blood loss (605.34 ± 158.8 ml) compared to oxytocin (625.26 ± 144.06) and placebo (669.73 ± 170.69), P = 0.015. In post hoc analysis, only tranexamic acid with ethamsylate was effective in decreasing the blood loss compared to placebo (P = 0.013); however, oxytocin did not reduce blood loss compared to saline (P = 0.211) nor to tranexamic acid with ethamsylate (P = 1).Other outcomes and CS complications showed no significant difference between the three groups except for post-operative thrombosis which was significantly higher in the tranexamic and ethamsylate group, P < 0.00001 and the need for a hysterectomy which was significantly increased in the placebo group, P = 0.017.ConclusionThe combination of tranexamic acid and ethamsylate was significantly associated with the least amount of blood loss. However, in pairwise comparisons, only tranexamic acid with ethamsylate was significantly better than saline but not with oxytocin. Both oxytocin and tranexamic acid with ethamsylate were equally effective in reducing intra-operative blood loss and the risk of hysterectomy; however, tranexamic acid with ethamsylate increased the risk of thrombotic events. Further research with a larger number of participants is needed.Trial registrationThe study was registered on Pan African Clinical Trials Registry with the following number: PACTR202009736186159 and was approved on 04/09/2020.

Intra-abdominal umbilical venous diameter and abdominal circumference discordance at 15-20weeks' gestation: simple markers in transverse abdominal plane to predict adverse pregnancy outcomes in monochorionic diamniotic twins.

This study aimed to investigate the association between simple markers in fetal abdominal plane, intra-abdominal umbilical venous diameter (DIUV) and abdominal circumference (AC) discordance at 15-20weeks' gestation, and adverse pregnancy outcomes in monochorionic diamniotic (MCDA) twins. We performed a retrospective analysis of MCDA twins with two live fetuses examined at 15-20weeks from Jun 2020 to Dec 2021 at Beijing Obstetrics and Gynecology Hospital. Measurement of fetal AC and DIUV was performed according to standard protocols. Twin pregnancies with major fetal structural anomalies, chromosomal abnormalities, miscarriage, and twin reversed arterial perfusion sequence were excluded. DIUV and AC discordance in MCDA twins with an adverse pregnancy outcome was compared with a normal pregnancy outcome. Furthermore, the performance of DIUV and AC discordance in predicting adverse pregnancy outcomes in MCDA twins was assessed. A total of 105 women with MCDA twin pregnancies were enrolled, contributing 179 visits. Adverse pregnancy outcomes occurred in 33.3% (35/105) of cases in our study. The intra-observer and inter-observer intraclass correlation coefficient (ICC) of both AC and DIUV were very good or excellent. There was no statistical difference in AC and DIUV discordance (%) between 15-16, 17-18, and 19-20weeks (χ2 = 3.928, P = 0.140; χ2 = 2.840, P = 0.242). Both AC and DIUV discordance were greater in twins with adverse pregnancy outcomes than that in twins with normal pregnancy outcome at each pregnancy periods. Both AC discordance (OR 1.2, 95% CI 1.1-1.3) and DIUV discordance (OR 1.2, 95% CI 1.1-1.2) were associated with adverse pregnancy outcomes. The AUC for predicting adverse pregnancy outcomes by AC discordance was 0.75 (95% CI 0.68-0.83), with a sensitivity of 58.7% (95% CI 51.9-64.5) and a specificity of 86.2% (95% CI 81.7-88.4). The AUC for predicting adverse pregnancy outcomes by DIUV was 0.78 (95% CI 0.70-0.86), with sensitivity and specificity of 65.1% (95% CI 58.1-70.3) and 86.2% (95% CI 81.7-88.4), respectively. The AC discordance and DIUV discordance could predict adverse pregnancy outcomes in MCDA twins. When these simple markers occurred, intensive surveillance was recommended.

Trophoblast PR-SET7 dysfunction induces viral mimicry response and necroptosis associated with recurrent miscarriage

Recurrent miscarriage (RM) is a distressing pregnancy complication. While the etiology of RM remains unclear, growing evidence has indicated the relevance of trophoblast impairment to the pathogenesis of RM. PR-SET7 is the sole enzyme catalyzing monomethylation of H4K20 (H4K20me1) and has been implicated in many pathophysiological processes. However, how PR-SET7 functions in trophoblasts and its relevance to RM remain unknown. Here, we found that trophoblast-specific loss of Pr-set7 in mice led to defective trophoblasts, resulting in early embryonic loss. Mechanistic analysis revealed that PR-SET7 deficiency in trophoblasts derepressed endogenous retroviruses (ERVs), leading to double-stranded RNA stress and subsequent viral mimicry, which drove overwhelming interferon response and necroptosis. Further examination discovered that H4K20me1 and H4K20me3 mediated the inhibition of cell-intrinsic expression of ERVs. Importantly, dysregulation of PR-SET7 expression and the corresponding aberrant epigenetic modifications were observed in the placentas of RM. Collectively, our results demonstrate that PR-SET7 acts as an epigenetic transcriptional modulator essential for repressing ERVs in trophoblasts, ensuring normal pregnancy and fetal survival, which sheds new light on potential epigenetic causes contributing to RM.

Placental damage comparison between preeclampsia with COVID-19, COVID-19, and preeclampsia: analysis of caspase-3, caspase-1, and tumor necrosis factor-alpha expression

Some studies have reported that preeclampsia with coronavirus disease 2019 (COVID-19) significantly increases the risk of adverse perinatal outcome until near to three-fold over the normal pregnancy. Preeclampsia pathophysiology in theory, increases the perinatal mortality and morbidity starting from placental injury which is also believed to share the common pathway with COVID-19 infection. Major typical placental injuries for these matters could be apoptotic, necrotic, or pyroptotic. This study aimed to compare placental damage between those three conditions above in those three typical injuries. This was an observational analytic study with cross-sectional setting. Seventy-two pregnant women admitted to hospital consecutively with diagnosis of preeclampsia with COVID-19, Preeclampsia only and COVID-19 only. Diagnosis for preeclampsia was following FIGO criteria with at least one of the severe features. COVID-19 eligible for this study was PCR test confirmative with moderate to severe clinical degree. Placenta were taken after the delivery, and parameters were quantified with immunohistochemistry test for caspase-3, caspase-1, and TNF-alpha representing apoptotic, pyroptotic, and necrotic pathway respectively. Pregnancy with double complications, preeclampsia, and COVID-19, significantly has the highest placental damage on apoptotic, pyroptotic, and necrotic pathway shown from the caspase-3, caspase-1, and TNF-alpha expression in placenta (p <0.05). Moderate to severe degree of COVID-19 resulting higher placental damage compared to preeclampsia in all the three forms (p <0.05). Apoptotic process was the most prominent among other pathways. Preeclampsia with COVID-19 infection showed significant placental damage, with major changes related were apoptosis, inflammation, and necrosis. This data support poor perinatal outcome of pregnancy having preeclampsia and COVID-19 at the same time.

Evaluation of a New Model for Human Chorionic Gonadotropin Rise in Pregnancies of Unknown Viability.

To evaluate the performance of a new human chorionic gonadotropin (hCG) threshold model to classify pregnancies as viable or nonviable using a longitudinal cohort of individuals with pregnancy of unknown viability. The secondary objective was to compare the new model with three established models. This is a single-center, retrospective cohort study of individuals seen at the University of Missouri from January 1, 2015, until March 1, 2020, who had at least two consecutive quantitative hCG serum levels with an initial level greater than 2 milli-international units/mL and 5,000 milli-international units/mL or less, with the first interval between laboratory draws no greater than 7 days. Prevalence of correct classification of viable intrauterine pregnancies, ectopic pregnancies, and early pregnancy losses was evaluated with a new proposed hCG threshold model and compared with three established models describing minimum expected rates of hCG rise for a viable intrauterine pregnancy. Of an initial cohort of 1,295 individuals, 688 patients met inclusion criteria. One hundred sixty-seven individuals (24.3%) had a viable intrauterine pregnancy; 463 (67.3%) had an early pregnancy loss; and 58 (8.4%) had an ectopic pregnancy. A new model based on the total additive percent rise of hCG at 4 and 6 days after initial hCG (70% or greater and 200% or greater rise, respectively) was created. The new model was able to correctly identify 100% of viable intrauterine pregnancies while minimizing incorrect classification of early pregnancy losses and ectopic pregnancies as normal pregnancies. At 4 days after initial hCG, 14 ectopic pregnancies (24.1%) and 44 early pregnancy losses (9.5%) were incorrectly classified as potentially normal pregnancies. At 6 days after initial hCG, only seven ectopic pregnancies (12.1%) and 25 early pregnancy losses (5.6%) were incorrectly classified as potentially normal pregnancies. In established models, up to nine intrauterine pregnancies (5.4%) were misclassified as abnormal pregnancies and up to 26 ectopic pregnancies (44.8%) and 58 early pregnancy losses (12.5%) were incorrectly classified as potentially normal pregnancies. The proposed new hCG threshold model optimizes a balance between identifying potentially viable intrauterine pregnancies and minimizing misdiagnosis of ectopic pregnancies and early pregnancy losses. External validation in other cohorts is needed before widespread clinical use.

Fetal-maternal interactions during pregnancy: a 'three-in-one' perspective.

A successful human pregnancy requires the maternal immune system to recognize and tolerate the semi-allogeneic fetus, allowing for appropriate trophoblasts invasion and protecting the fetus from invading pathogens. Therefore, maternal immunity is critical for the establishment and maintenance of pregnancy, especially at the maternal-fetal interface. Anatomically, the maternal-fetal interface has both maternally- and fetally- derived cells, including fetal originated trophoblasts and maternal derived immune cells and stromal cells. Besides, a commensal microbiota in the uterus was supposed to aid the unique immunity in pregnancy. The appropriate crosstalk between fetal derived and maternal originated cells and uterine microbiota are critical for normal pregnancy. Dysfunctional maternal-fetal interactions might be associated with the development of pregnancy complications. This review elaborates the latest knowledge on the interactions between trophoblasts and decidual immune cells, highlighting their critical roles in maternal-fetal tolerance and pregnancy development. We also characterize the role of commensal bacteria in promoting pregnancy progression. Furthermore, this review may provide new thought on future basic research and the development of clinical applications for pregnancy complications.

RETRACTED ARTICLE: Exposure to pesticide components causes recurrent pregnancy loss by increasing placental oxidative stress and apoptosis: a case–control study

We investigated the plasma levels of pesticides components namely polychlorinated biphenyls (PCBs), dieldrin, dichlorodiphenyldichloroethylene (DDE), ethion, malathion, and chlorpyrifos in recurrent pregnancy loss (RPL) cases, and tested their associations with placental oxidative stress (OS) biomarkers [nitric oxide (NO.), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), and superoxide dismutase (SOD)] and with placental apoptotic/antiapoptotic indices (Bcl-2 and caspase-3), and evaluated their possible cut-off points to distinguish RPL cases. The study recruited 101 pregnant women divided into; G1 [n = 49, control, normal 1st-trimester pregnancy, normal obstetric history with at least one previous normal live birth], G2 [n = 26, cases with missed abortion (< 3 abortions) before 24 weeks of gestation], and G3 [n = 26, cases with missed abortion (≥ 3 abortions) before 24 weeks of gestation]. The plasma pesticide levels were analyzed by gas chromatography-mass spectrometry. Plasma human chorionic gonadotrophin (HCG), placental OS, Bcl-2, and caspase-3, were analyzed by their corresponding methods and kits. Plasma PCBs, DDE, dieldrin, and ethion levels were significantly higher in RPL cases than in normal pregnancies (p ≤ 0.001). These levels correlated positively with placental OS and apoptosis and negatively with plasma HCG levels. Also, these levels were reliable markers of risk to RPL. Malathion and chlorpyrifos were not detected in any of the study’s participants. Pesticides may be risk factors in cases of spontaneous RPL cases. They are associated with an increasing placental OS and placental apoptosis. Specific measures should be taken to decrease maternal exposure to these pollutants’ sources, especially in underdeveloped and developing countries.