Uterine Artery Research Articles

Biomarkers in the prediction of complications in pregnancy after assisted reproductive technology.

To compare the temporal changes in mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) across gestation between assisted reproductive technology (ART) pregnancies complicated with great obstetrical syndromes (GOS) or gestational diabetes (GDM) ± large-for-gestational-age (LGA) fetus, and uncomplicated ART pregnancies. This was a prospective longitudinal study of 143 women with singleton pregnancies who conceived through ART at the Department of Obstetrics and Gynecology, Prince of Wales Hospital, the Chinese University of Hong Kong, Hong Kong SAR between December 2017 and January 2020. The participants were followed up at 6-6+3, 11-13+6, 20-24+6, 30-34+6, and 35-37+6 weeks for the measurement of MAP, UtA-PI, PlGF, and sFlt-1. A linear mixed-effects analysis was performed to compare the biomarkers in the GOS, GDM ± LGA, and uncomplicated groups across gestation. Thirty-three (23.1%) and fifty-five (31.5%) women were diagnosed with GOS and GDM ± LGA, respectively. The GOS group had higher estimated marginal mean log10 MAP mulitples of the median (MoM) across gestation, compared with the uncomplicated group (0.00771 vs -0.02022; P < 0.001), when adjusting for clinical visits and days of embryo transfer. The absolute mean log10 MAP MoM in the GOS group was found to be significantly higher than that of the uncomplicated group at all clinical visits from 6 weeks onwards. Furthermore, the estimated marginal mean log10 PlGF MoM was significantly lower in the GOS group across gestation, compared with the uncomplicated group (-0.04226 vs 0.05566; P = 0.010). The significant difference in log10 PlGF MoM was observed from 11-13+6 to 30-34+6 week of gestation (P < 0.05). However, no significant differences in the estimated marginal means of log10 UtA-PI MoM and log10 sFlt-1 MoM between GOS and uncomplicated groups were observed. GDM ± LGA group had a lower estimated marginal mean log10 PlGF MoM throughout pregnancy compared with the uncomplicated group (-0.01536 vs 0.05572; P = 0.032). In the individual visit analysis, the significant difference was observed at the 20-24+6 and 35-37+6 weeks visits (P < 0.05). There were no significant differences in estimated marginal mean log10 MoM of MAP, UtA-PI, and sFlt-1 between GDM ± LGA and uncomplicated groups during pregnancy. Our study has revealed that among pregnancies conceived through ART, GOS is associated with higher MAP and lower PlGF from early gestation until late third trimester, while GDM ± LGA is associated with lower PlGF during the second half of pregnancy. The same degree of differences in MAP and PlGF persists from early until late gestation in the GOS group and these findings highlight the importance of early screening during the first trimester to identify women who are at risk for developing GOS following ART procedures. Lastly, the potential of PlGF in predicting the development of GDM from the second trimester of pregnancy requires further investigation.

Maternal Preconception Omega-6, Omega-3, and Omega-6:Omega-3 Intake and Uterine Artery Indices in Mid-Gestation.

Maternal preconception diet influences pregnancy health and fetal outcomes. We examined the relationship between preconception fatty acid (FA) intake and uterine artery indices in mid-gestation in a large, heterogeneous cohort of nulliparous individuals. This is a secondary analysis of the nuMom2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be) study. Dietary ω-6 and ω-3 FA intake was assessed with food frequency questionnaires and uterine artery indices were obtained via Doppler studies in the second trimester. For our primary outcome of pulsatility index (PI) > 1.6, we compared proportions by each dichotomous FA exposure and tested differences with chi-square test. For PI > 1.6, odds ratio for the unfavorable FA quartile compared with remaining quartiles for the exposures were 0.96 to 1.25, p = 0.157 (ω-6 FA); 0.97 to 1.26, p = 0.124 (ω-3 FA); 0.87 to 1.14, p = 1.00 (ω-6:ω-3 FA ratio). No significant associations between self-reported maternal preconception ω-6 and ω-3 FA intake and uterine artery Doppler indices measured during the second trimester were observed. · Maternal diet impacts pregnancy health/fetal outcomes.. · ω-3 and ω-6 FA intake influences cardiovascular health.. · FA intake may affect blood flow to fetoplacental unit.. · Results are limited by inadequate adherence to dietary recommendations..

Gestational exposure to air pollutants perturbs metabolic and placenta-fetal phenotype

Air pollution (AP) is detrimental to pregnancies including increasing risk factors of gestational diabetes mellitus. We hypothesized that exposure to AP causes cardiovascular and metabolic disruption thereby altering placental gene expression, which in turn affects the placental phenotype and thereby embryonic/fetal development. To test this hypothesis, we investigated the impact of intra-nasal instilled AP upon gestational day 16–19 maternal mouse cardiovascular and metabolic status, placental nutrient transporters, and placental-fetal size and morphology. To further unravel mechanisms, we also examined placental total DNA 5’-hydroxymethylation and bulk RNA sequenced gene expression profiles. AP exposed pregnant mice and fetuses were tachycardic with a reduction in maternal left ventricular fractional shortening and increased uterine artery with decreased umbilical artery systolic peak velocities. In addition, they were hyperglycemic, glucose intolerant and insulin resistant, with changes in placental glucose (Glut3) and fatty acid (Fatp1 & Cd36) transporters, and a spatial disruption of cells expressing Glut10 that imports L-dehydroascorbic acid in protecting against oxidative stress. Placentas revealed inflammatory cellular infiltration with associated cellular edema and necrosis, with dilated vascular spaces and hemorrhage. Placental and fetal body weights decreased in mid-gestation with a reduction in brain cortical thickness emerging in late gestation. Placental total DNA 5’-hydroxymethylation was 2.5-fold higher, with perturbed gene expression profiles involving key metabolic, inflammatory, transcriptional, cellular polarizing and processing genes and pathways. We conclude that gestational exposure to AP incites a maternal inflammatory response resulting in features mimicking maternal gestational diabetes mellitus with altered placental DNA 5’-hydroxymethylation, gene expression, and associated injury.

Prediction of Pregnancy Outcomes in Women with Threatened Abortion Using Ultrasound Parameters, Uterine Artery Doppler, and Serum Progesterone Levels: A Prospective Cohort Study

Prediction of Pregnancy Outcomes in Women with Threatened Abortion Using Ultrasound Parameters, Uterine Artery Doppler, and Serum Progesterone Levels: A Prospective Cohort Study

Placental Protein 13: Vasomodulatory Effects on Human Uterine Arteries and Potential Implications for Preeclampsia

Placental protein 13 (PP13) exhibits a plasma concentration that increases gradually during normal gestation, a process that is disrupted in preeclampsia, which is characterized by elevated vascular resistance, reduced utero-placental blood flow, and intrauterine growth restriction. This study investigated PP13’s role in vascular tone regulation and its molecular mechanisms. Uterine and subcutaneous arteries, isolated from both pregnant and non-pregnant women, were precontracted with the thromboxane analogue U46619 and exposed to PP13 using pressurized myography. The molecular mechanisms were further investigated, using specific inhibitors for nitric oxide synthase (L-NAME+LNNA at 10−4 M) and guanylate cyclase (ODQ at 10−5 M). The results showed that PP13 induced vasodilation in uterine arteries, but not in subcutaneous arteries. Additionally, PP13 counteracted U46619-induced vasoconstriction, which is particularly pronounced in pregnancy. Further investigation revealed that PP13’s mechanism of action is dependent on the activation of the nitric oxide–cGMP pathway. This study provides novel insights into the vasomodulatory effects of PP13 on human uterine arteries, underscoring its potential role in regulating utero-placental blood flow. These findings suggest that PP13 may be a promising candidate for improving utero-placental blood flow in conditions such as preeclampsia. Further research and clinical studies are warranted to validate PP13’s efficacy and safety as a therapeutic agent for managing preeclampsia.

Placental Protein 13: Vasomodulatory Effects on Human Uterine Arteries and Potential Implications for Preeclampsia

Placental protein 13 (PP13) exhibits a plasma concentration that increases gradually during normal gestation, a process that is disrupted in preeclampsia, which is characterized by elevated vascular resistance, reduced utero-placental blood flow, and intrauterine growth restriction. This study investigated PP13’s role in vascular tone regulation and its molecular mechanisms. Uterine and subcutaneous arteries, isolated from both pregnant and non-pregnant women, were precontracted with the thromboxane analogue U46619 and exposed to PP13 using pressurized myography. The molecular mechanisms were further investigated, using specific inhibitors for nitric oxide synthase (L-NAME+LNNA at 10−4 M) and guanylate cyclase (ODQ at 10−5 M). The results showed that PP13 induced vasodilation in uterine arteries, but not in subcutaneous arteries. Additionally, PP13 counteracted U46619-induced vasoconstriction, which is particularly pronounced in pregnancy. Further investigation revealed that PP13’s mechanism of action is dependent on the activation of the nitric oxide–cGMP pathway. This study provides novel insights into the vasomodulatory effects of PP13 on human uterine arteries, underscoring its potential role in regulating utero-placental blood flow. These findings suggest that PP13 may be a promising candidate for improving utero-placental blood flow in conditions such as preeclampsia. Further research and clinical studies are warranted to validate PP13’s efficacy and safety as a therapeutic agent for managing preeclampsia.

Influence of Cesarean Section Scar on the Mean Pulsatility Index of the Uterine Artery Doppler between 20 and 34 Weeks of Gestation

AbstractThe aim of this study was to assess the influence of the cesarean section scars on the mean pulsatility index (PI) of the uterine artery Doppler between 20 and 34 weeks of gestation. A secondary objective was to assess the association between previous cesarean section and adverse maternal/perinatal outcomes.A retrospective cohort study was conducted with pregnant women who had their deliveries between March 2014 and February 2023. PI of the uterine arteries Doppler was performed transvaginally between 20–24 weeks and transabdominally between 28–34 weeks. The following variables were considered adverse perinatal outcomes: birth weight &lt; 10th percentile for gestational age, preeclampsia, premature birth, placental abruption, perinatal death, postpartum hemorrhage, neonatal intensive care unit (NICU) admission.A total of 479 pregnant women were included in the final statistical analysis, being that 70.6% (338/479) had no (Group I) and 29.4% (141/479) had at least one previous cesarean section (Group II). Pregnant women with a previous cesarean had higher median of mean PI (1.06 vs. 0.97, p = 0.044) and median MoM of mean PI uterine arteries Doppler (1.06 vs. 0.98, p = 0.037) than pregnant women without previous cesarean section at ultrasound 20–24 weeks. Pregnant women with a previous cesarean section had higher median of mean PI (0.77 vs. 0.70, p &lt; 0.001) and mean MoM PI uterine arteries Doppler (1.08 vs. 0.99, p &lt; 0.001) than pregnant women without previous cesarean section at ultrasound 28–34 weeks. Pregnant women with ≥ 2 previous cesarean sections had a higher median of mean PI uterine arteries Doppler than those with no previous cesarean sections (1.19 vs. 0.97, p = 0.036). Group II had a lower risk of postpartum hemorrhage (aPR 0.31, 95% CI 0.13–0.75, p = 0.009) and composite neonatal outcome (aPR 0.66, 95% CI 0.49–0.88, p = 0.006). Group II had a higher risk of APGAR score at the 5th minute &lt; 7 (aPR 0.75, 95% CI 1.49–51.29, p = 0.016).The number of previous cesarean sections had a significant influence on the mean PI uterine arteries Doppler between 20–24 and 28–34 weeks of gestation. Previous cesarean section was an independent predictor of postpartum hemorrhage and APGAR score at the 5th minute &lt; 7. Pregnancy-associated arterial hypertension and number of previous deliveries influenced the risk of composite neonatal outcome, but not the presence of previous cesarean section alone.

Expression of Concern: Uterine artery embolization versus surgery for symptomatic uterine fibroids: a randomized controlled trial and a meta-analysis of the literature.

Expression of Concern: Uterine artery embolization versus surgery for symptomatic uterine fibroids: a randomized controlled trial and a meta-analysis of the literature.

Uterine Artery Embolization: A Case Report on Primary Postpartum Hemorrhage Management

Uterine Artery Embolization: A Case Report on Primary Postpartum Hemorrhage Management

Placental biophysical model for prediction of early onset fetal growth restriction in first and second trimester of pregnancy: A prospective cohort study

IntroductionTo assess the placental biometry, placental biomarkers and uterine artery Doppler in each trimester of pregnancy for prediction of early-onset fetal growth restriction (EO FGR). MethodsIn this prospective cohort study placental biometry; biomarkers PAPP-A, sFLT-1, and PlGF along with the uterine artery blood flow evaluation was done serially at 11–14, 20–24 and 28–32 weeks of gestation. The above parameters were compared between women with early onset FGR and controls. ResultsOut of 1008 fully followed cases, the small for gestational age fetuses were 227/1008 (22.5 %), and EO FGR were 84/1008(8.3 %).The placental length, volume, and PlGF levels were significantly lower, whereas the uterine artery PI(Ut PI) was significantly higher at all time points among cases. The sFLT-1 level showed a significant increase among cases, whereas it decreased among controls from the first to the second trimester. The detection rate using PV/UtA PI was 60 % in the first trimester and 66.7 % in the second trimester at 30 % FPR. ConclusionThe PV/Ut PI in first and the second trimester was a good marker for the prediction of pregnancies at increased risk of developing EO FGR.

A prediction model for stillbirth based on first trimester pre-eclampsia combined screening.

To evaluate the accuracy of combined models of maternal biophysical factors, ultrasound, and biochemical markers for predicting stillbirths. A retrospective cohort study of pregnant women undergoing first-trimester pre-eclampsia screening at 11-13 gestational weeks was conducted. Maternal characteristics and history, mean arterial pressure (MAP) measurement, uterine artery pulsatility index (UtA-PI) ultrasound, maternal ophthalmic peak ratio Doppler, and placental growth factor (PlGF) serum were collected during the visit. Stillbirth was classified as placental dysfunction-related when it occurred with pre-eclampsia or birth weight <10th percentile. Combined prediction models were developed from significant variables in stillbirths, placental dysfunction-related, and controls. We used the area under the receiver-operating-characteristics curve (AUC), sensitivity, and specificity based on a specific cutoff to evaluate the model's predictive performance by measuring the capacity to distinguish between stillbirths and live births. There were 13 (0.79%) cases of stillbirth in 1643 women included in the analysis. The combination of maternal factors, MAP, UtA-PI, and PlGF, significantly contributed to the prediction of stillbirth. This model was a good predictor for all (including controls) types of stillbirth (AUC 0.879, 95% CI: 0.799-0.959, sensitivity of 99.3%, specificity of 38.5%), and an excellent predictor for placental dysfunction-related stillbirth (AUC 0.984, 95% CI: 0.960-1.000, sensitivity of 98.5, specificity of 85.7). Screening at 11-13 weeks' gestation by combining maternal factors, MAP, UtA-PI, and PlGF, can predict a high proportion of stillbirths. Our model has good accuracy for predicting stillbirths, predominantly placental dysfunction-related stillbirths.

O-226 Effects of preventive uterine artery occlusion during laparoscopic myomectomy on ovarian reserve markers: a randomized controlled trial

Abstract Study question Does definitive occlusion of uterine arteries have a short or long term impact on anti-Müllerian hormone (AMH) levels in reproductive age women undergoing laparoscopic myomectomy? Summary answer Preventive uterine artery occlusion during laparoscopic myomectomy does not impact AMH levels in reproductive age women. What is known already Uterine leiomyoma are the most common benign tumours in women of reproductive age. For symptomatic women willing to retain their uterus, especially for a future pregnancy, the current gold standard is the myomectomy for subserous/intramural leiomyoma. Temporary or definitive occlusion of uterine arteries can be performed to control bleeding during surgery but its impact on ovarian reserve markers is still unknown. A single randomized trial with a one-year follow-up demonstrated that temporary bilateral uterine artery occlusion during laparoscopic myomectomy slightly decreased AMH levels at day-2 after surgery but has no impact thereafter 3, 6 and 12 months postoperatively. Study design, size, duration We conducted a randomized controlled trial with a two-year follow-up evaluating the effect of definitive occlusion of uterine arteries on ovarian reserve via sequential measures of anti-Müllerian hormone (AMH) levels. Fifty-eight women with symptomatic leiomyoma type FIGO 3-6 scheduled for laparoscopic myomectomy at were included between July 2015 and October 2021. Participants/materials, setting, methods Patients were randomized into: the intervention group (laparoscopic myomectomy with preventive occlusion of uterine arteries) and the control group (laparoscopic myomectomy without occlusion of uterine arteries) ). AMH evaluated at T0 and followed at 1 month (T1), 3 months (T3), 6 months (T6), 12 months (T12) and 24 months (T24) after surgery. Intraoperative blood loss, leiomyoma recurrence and adenomyosis occurrence were also evaluated comparing pre- and post-operative findings. Finally, pregnancies and live births were monitored. Main results and the role of chance Women in both groups did not differ in their baseline characteristics in terms of age, body mass index, ethnicity, parity, wish to become pregnant, hormonal treatment, leiomyoma number and size, baseline haemoglobin levels, bleeding symptoms baseline AMH levels and antral follicular count (AFC). The mean operative time was similar in between both groups. Mean blood loss during surgery was on average 138 (±104)ml in the intervention group versus 436 (±498)ml in controls (p &amp;lt; 0.001). The difference in haemoglobin between before and after surgery was significantly higher in the control group 21.8 (±12.7)g/l compared with the intervention group 14.8 (±8.9)g/l (p = 0.02). Regarding clinical symptoms, most patients had decreased menstrual flow at the last follow-up visit (24 months) compared to baseline in both group improvement of dysmenorrhea followed the same trend with a reduction in pain levels in both groups. Risk of leiomyoma recurrence was found similar between both groups. Most importantly, AMH levels were similar between groups at all times (T1, T3, T6, T12 and T24) and non-inferiority of preventive occlusion was demonstrated with a non-inferiority margin of -3.5pmol/L (0.5 ng/ml). The pregnancy rate was not different between groups. Limitations, reasons for caution Our sample size was calculated to detect a clinically relevant difference of at least two-third of the standard deviation in AMH levels, but we cannot exclude a smaller impact on AMH with a different sample size. Wider implications of the findings Preventive uterine artery occlusion during laparoscopic myomectomy does not impact ovarian reserve markers and can be safely used to control perioperative bleeding. Trial registration number NCT02563392

O-290 Reduced uterine artery pulsatility index (UtAPI) in artificial frozen embryo transfer pregnancies leads to underestimation of 1st-trimester preeclampsia risk. An analysis of over 30,000 pregnancies

Abstract Study question Does the mode of conception (spontaneous, ovulation induction, fresh or frozen embryo transfer) impact Uterine Artery Pulsatility Index (UtAPI) values in 1st-trimester preeclampsia screening? Summary answer A significant reduction in UtAPI during 1st-trimester screening is observed in artificial frozen embryo transfer (AC-FET) pregnancies, resulting in underestimated preeclampsia risk. What is known already Accumulating evidence indicates that AC-FET cycles are associated with an increased risk of preeclampsia. Uterine artery (UtA) Doppler is a crucial biomarker for first-trimester preeclampsia screening, along with maternal factors and serum biomarkers, identifying “high-risk” patients. Guidelines strongly recommend the administration of aspirin(150mg/day) in these women, owing to robust evidence demonstrating a 40% reduction in the incidence of preeclampsia. Despite small studies suggesting a lower UtAPI after frozen ET, no previous studies explored the impact of the type of endometrial preparation in UtAPI Doppler or its influence on estimating preeclampsia risk Study design, size, duration This is a retrospective single-center study including 33880 singleton pregnancies (spontaneous or after ART) who underwent the 1st-trimester ultrasound screening at our University Hospital between January 2010 - May 2023. Overall, 33880 pregnancies were included: 29709 spontaneous, 429 ovulation induction, 1015 fresh ET and 2727 after frozen ET pregnancies (326/2727 in NC-FET and 2401 in AC-FET). Participants/materials, setting, methods The study included only singleton pregnancy for which a first trimester ultrasound (11+0- 13+6 wks) with UtA Doppler was performed. The primary aim of the study was to assess whether there was an association between the mode of conception and the UtA Doppler and whether UtAPI differed according to the type the endometrial preparation for FET. Continuous variables were expressed as mean ± SD. ANOVA test and multivariate regression analysis were performed. Main results and the role of chance Overall, the 1st-trimester UtAPI in pregnancies conceived after AC-FET was 1,036±0,160 [CI95%:0,723;1,349], after NC-FET 1,354±0,162 [CI95%:1,037;1,671], Fresh-ET 1,418 ±0,161 [CI95%:1,104;1,733], OI 1,413±0,162 [CI95%:1,096;1,730] and spontaneous pregnancies 1,373 ± 0,160 [CI95%:1,060;1,686]. A multivariable regression analysis, adjusting for confounding factors (age, weight, smoking, and oocyte donation), demonstrated that the value of uterine artery UtAPI is significantly lower when artificial cycle for frozen embryo transfer is performed compared with spontaneous pregnancies (-0,337 ± 0,014 [CI95%:-0,378;-0,297]), ovulation induction (-0,377 ± 0,028 [CI95%:-0,455; -0,298]) Fresh-ET (-0,383 ±0,021 [CI95%:-0,442; -0,323]), and NC-FET (-0,318 ± 0,029[CI95%:-0,401; -0,23]). On the contrary none of the other modes of conception are different in terms of UtAPI as compared with spontaneous pregnancies. Among screened patients, the number of patients classified at high risk for preeclampsia was significantly lower in pregnancies following AC-FET 7.8%(156/2002) as compared to NC-FET 15.9%(46/289), fresh-ET 11.0%(58/527), ovulation induction 10.5%(26/248) and spontaneous pregnancies (1452/15624) p &amp;lt; 0.001. Nonetheless, despite the lower number of high-risk patients in the AC-FET group, the actual incidence of PE was more than three times higher in AC-FET group 5.2%(125/2401) as compared with spontaneous 1.5%(431/29709), ovulation induction 1.4%(6/429) or NC-FET pregnancies 1.5%(5/326) and more than two times higher when compared to fresh-ET pregnancies 2.3%(23/1015) p &amp;lt; 0.001. Limitations, reasons for caution Despite employing a robust methodology with a substantial sample size and multivariate statistical analysis to address confounding factors, it’s essential to acknowledge the possibility of residual bias. However, its impact on the presented outcomes is anticipated to be minimal. Wider implications of the findings Existing 1st-trimester preeclampsia screening calculators overlook the notably lower UtAPI in AC-FET pregnancies, as discovered in our study. This poses a threat of underestimating high-risk patients and neglecting prophylactic aspirin. Algorithms should be adjusted to accurately assess risk for those undergoing AC-FET Trial registration number Not applicable

Uterine Artery Doppler in the Second Trimester as a Predictor of Preeclampsia in High Risk Pregnancy

Abstract Background Preeclampsia is a multisystem disorder of pregnancy which is a major cause of maternal and fetal morbidity and mortality worldwide. The cardinal clinical features of the condition are hypertension and proteinuria occurring after 20 weeks gestation in women who were not previously known to be hypertensive. Aim of the Work The aim of the work was to evaluate the role of uterine artery Doppler in the second trimester as a predictor of preeclampsia in high risk pregnancy. Patients and Methods We included 80 pregnant females in the second trimester at high risk pregnancy in our study, uterine artery Doppler ultrasound was done in the second trimester and the patients were followed up in the third trimester for blood pressure measurement and diagnosis of PE. Results Our results revealed correlation between high indices of uterine arteries and development of PE. Conclusion Our study revealed that we can use uterine artery Doppler as a reliable method to predict preeclampsia.

P-321 Uterine fibroids secrete vasodilatory factors that induce their response via the opioid pathway

Abstract Study question Do uterine fibroids produce vasoactive factors that could affect vasculature and induce fibroid associated symptoms? Summary answer Ex vivo secretions from uterine fibroids induce a vasodilatory response in rat mesenteric arteries that is mediated via the opioid receptor pathway. What is known already Uterine fibroids (leiomyoma) are a common but clinically neglected gynaecological condition, where benign smooth muscle tumours arise from the myometrium and cause heavy menstrual bleeding (HMB), pain and infertility. Fibroids affect up to one in two women of reproductive age and are the main reason for failure of both medical and surgical treatments in women with HMB. Fibroids are proposed to affect the systemic vasculature system, with angiogenic growth factors and abnormal vasculature implicated in fibroid pathophysiology. However, the precise mechanism of fibroid induced HMB has yet to be fully elucidated. Study design, size, duration Fibroid and myometrium biopsies were prospectively collected from 13 patients undergoing MyoSure, myomectomy or hysterectomy for the treatment of HMB associated with fibroids at Liverpool Women’s Hospital, a tertiary referral centre. The collection and use of human tissue was ethically approved, and all participants gave informed written consent. Tissue biopsies were incubated in a basal medium for 24 hours. Conditioned medium was collected and used for wire myography assays to examine vascular reactivity. Participants/materials, setting, methods Second order mesenteric arteries from female Wistar rats were mounted on a wire myograph system and toned with uridine triphosphate (UTP) before being exposed to control (non-conditioned), normal myometrium (n = 4) or fibroid (n = 9) conditioned medium. Vascular activity was measured relative to UTP induced vasoconstriction. To determine the mediatory factors of observed vasoreactivity, inhibitors of well characterised pathways were systematically tested in the presence of conditioned medium. Main results and the role of chance Fibroid conditioned medium caused a marked dilation of UTP induced vasoconstriction in rat mesenteric arteries, which was significantly greater than that induced by non-conditioned, or control myometrium conditioned medium. Blockage of ATP-sensitive potassium (KATP) channels with PNU37883A completely inhibited fibroid induced vasodilation. However, blockage of other potassium channels did not inhibit dilation, suggesting that a KATP-mediated PKA-dependent pathway is being stimulated. To test the potential involvement of endothelial-derived nitric oxide synthase in vasodilation, vessels were treated with the inhibitor L-NAME, which partially blocked fibroid induced vasodilation. The specificity of nitric oxide synthase inhibition was confirmed by treating vessels with acetylcholine or carbachol, which induced vasodilation via activation of nitric oxide synthase. In the presence of L-NAME, the vasodilatory effects of acetylcholine and carbachol were blocked, thus confirming inhibitor specificity. An adenosine receptor inhibitor, theophylline, had no effect on fibroid induced vasodilation, thus ruling out the adenosine pathway. Blockage of bradykinin and adrenergic receptors also failed to prevent fibroid induced dilation in mesenteric arteries. However, blocking opioid receptors with naloxone completely inhibited vasodilation in the presence of fibroid conditioned medium. These findings suggest that fibroid induced vasodilation is mediated via endothelial nitric oxide synthase and an unknown opioid compound. Limitations, reasons for caution This study was performed using excised tissue in an ex vivo environment, which may not fully simulate the fibroid secretome in vivo. Although rat mesenteric arteries are a well-established model, human uterine arteries may be more appropriate to study fibroid induced vasoreactivity. Wider implications of the findings Fibroids are responsible for up to half of all hysterectomies and healthcare costs run into the billions globally. This study demonstrates that fibroid secreted factors can impact vasoreactivity, which has important connotations for disease pathophysiology regarding HMB. Targeting vasoactive compounds produced by fibroids may be a future novel treatment option. Trial registration number NA

Prophylactic Radiologic Interventions for Postpartum Hemorrhage Control in Women With Placenta Accreta Spectrum Disorder: A Systematic Review and Meta-analysis.

To quantify the association between prophylactic radiologic interventions and perioperative blood loss during cesarean delivery in women with placenta accreta spectrum disorder through a systematic review and network meta-analysis. On January 3, 2023, a literature search was conducted in PubMed, EMBASE, Cochrane Library, and Web of Science. We also checked ClinicalTrials.gov retrospectively. Prophylactic radiologic interventions to reduce bleeding during cesarean delivery involved preoperative placement of balloon catheters, distal (internal or common iliac arteries) or proximal (abdominal aorta), or sheaths (uterine arteries). The primary outcome was volume of blood loss; secondary outcomes were the number of red blood cell units transfused and adverse events. Studies including women who received an emergency cesarean delivery were excluded. Two authors independently screened citations for relevance, extracted data, and assessed the risk of bias of individual studies with the Cochrane Risk of Bias in Non-randomized Studies of Interventions tool. From a total of 1,332 screened studies, 50 were included in the final analysis, comprising 5,962 women. These studies consisted of two randomized controlled trials and 48 observational studies. Thirty studies compared distal balloon occlusion with a control group, with a mean difference in blood loss of -406 mL (95% CI, -645 to -167). Fourteen studies compared proximal balloon occlusion with a control group, with a mean difference of -1,041 mL (95% CI, -1,371 to -710). Sensitivity analysis excluding studies with serious or critical risk of bias provided similar results. Five studies compared uterine artery embolization with a control group, all with serious or critical risk of bias; the mean difference was -936 mL (95% CI, -1,522 to -350). Reported information on adverse events was limited. Although the predominance of observational studies in the included literature warrants caution in interpreting the findings of this meta-analysis, our findings suggest that prophylactic placement of balloon catheters or sheaths before planned cesarean delivery in women with placenta accreta spectrum disorder may, in some cases, substantially reduce perioperative blood loss. Further study is required to quantify the efficacy according to various severities of placenta accreta spectrum disorder and the associated safety of these radiologic interventions. PROSPERO, CRD42022320922.

Alpha 1,3 N-Acetylgalactosaminyl Transferase (GTA) Impairs Invasion Potential of Trophoblast Cells in Preeclampsia.

Preeclampsia (PE) is a pregnancy-specific disorder associated with shallow invasion of the trophoblast cells and insufficient remodeling of the uterine spiral artery. Protein glycosylation plays an important role in trophoblast cell invasion. However, the glycobiological mechanism of PE has not been fully elucidated. In the current study, employing the Lectin array, we found that soybean agglutinin (SBA), which recognizes the terminal N-acetylgalactosamine α1,3-galactose (GalNAc α1,3 Gal) glycotype, was significantly increased in placental trophoblast cells from PE patients compared with third-trimester pregnant controls. Upregulating the expression of the key enzyme α1,3 N-acetylgalactosaminyl transferase (GTA) promoted the biosynthesis of terminal GalNAc α1,3 Gal and inhibited the migration/invasion of HTR8/SVneo trophoblast cells. Moreover, the methylation status of GTA promoter in placental tissues from PE patients was lower than that in the third trimester by methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) analysis. Elevated GTA expression in combination with the DNA methylation inhibitor 5-azacytidine (5-AzaC) treatment increased the glycotype biosynthesis and impaired the invasion potential of trophoblast cells, leading to preeclampsia. This study suggests that elevated terminal GalNAc α1,3 Gal biosynthesis and GTA expression may be applied as the new markers for evaluating placental function and the auxiliary diagnosis of preeclampsia.

Short-term effects of antenatal betamethasone on fetal cardiovascular and circulation status: A quasi-experimental observational (before-after) study

Background: The administration of antenatal corticosteroid is a standard treatment to reduce the rate of perinatal mortality and morbidity; however, there is limited evidence regarding the potential effects of betamethasone on the constriction of the ductus arteriosus (DA). Objective: This study aimed to investigate the short-term effects of antenatal betamethasone on fetal cardiovascular and circulation status. Materials and Methods: This quasi-experimental observational (before-after) study was conducted on 32 singleton fetuses. The participants were healthy pregnant women with a diagnosis of placenta accreta spectrum who were eligible for 2 doses of betamethasone and referred to prenatal care clinic, Vali-E-Asr hospital; Tehran, Iran from January 2021-May 2022. The results of fetal echocardiography and Doppler sonography were compared before and after the administration of antenatal corticosteroid therapy. Results: Following betamethasone injection, significant increases were observed in peak systolic and diastolic velocity of the DA without constriction of the DA (p &lt; 0.001, p = 0.002 respectively). However, no significant changes were observed in right ventricular function, tricuspid valve function, Doppler of ductus venous, and peak systolic velocity of the aortic isthmus (p &gt; 0.05). Doppler examination of the uterine, umbilical, and middle cerebral arteries also showed no significant changes (p &gt; 0.05). Conclusion: Considering the benefits of antenatal corticosteroid therapy, its administration seems reasonable in preterm births. The transient changes in ductal blood flow are not prohibitive. Key words: Betamethasone, Premature birth, Ultrasonography, Doppler, Echocardiography, Fetus.

Short-term effects of antenatal betamethasone on fetal cardiovascular and circulation status: A quasi-experimental observational (before-after) study

Background: The administration of antenatal corticosteroid is a standard treatment to reduce the rate of perinatal mortality and morbidity; however, there is limited evidence regarding the potential effects of betamethasone on the constriction of the ductus arteriosus (DA). Objective: This study aimed to investigate the short-term effects of antenatal betamethasone on fetal cardiovascular and circulation status. Materials and Methods: This quasi-experimental observational (before-after) study was conducted on 32 singleton fetuses. The participants were healthy pregnant women with a diagnosis of placenta accreta spectrum who were eligible for 2 doses of betamethasone and referred to prenatal care clinic, Vali-E-Asr hospital; Tehran, Iran from January 2021-May 2022. The results of fetal echocardiography and Doppler sonography were compared before and after the administration of antenatal corticosteroid therapy. Results: Following betamethasone injection, significant increases were observed in peak systolic and diastolic velocity of the DA without constriction of the DA (p &lt; 0.001, p = 0.002 respectively). However, no significant changes were observed in right ventricular function, tricuspid valve function, Doppler of ductus venous, and peak systolic velocity of the aortic isthmus (p &gt; 0.05). Doppler examination of the uterine, umbilical, and middle cerebral arteries also showed no significant changes (p &gt; 0.05). Conclusion: Considering the benefits of antenatal corticosteroid therapy, its administration seems reasonable in preterm births. The transient changes in ductal blood flow are not prohibitive. Key words: Betamethasone, Premature birth, Ultrasonography, Doppler, Echocardiography, Fetus.

Acquired uterine artery pseudoaneurysm: a rare iatrogenic complication following cesarean delivery at complete cervical dilatation.

Acquired uterine artery pseudoaneurysm: a rare iatrogenic complication following cesarean delivery at complete cervical dilatation.