Uterine Artery Resistance Index Research Articles

Values of ultrasound elastography and progesterone receptor proteins for diagnosis and prognostic evaluation of uterine fibroid.

We aimed to study the values of ultrasound elastography (UE) and progesterone receptor (PR) proteins for the diagnosis and prognostic evaluation of uterine fibroid (UF). A total of 200 UF patients treated from January 2020 to June 2023 were selected as a UF group, and another 100 healthy women as a healthy group. Routine ultrasound parameters uterine artery pulsatility index (PI), resistance index (RI), and UE parameter strain ratio (SR) were obtained. The relative protein expressions of PRA and PRB in the peripheral blood were detected by Western blotting. The differences in these parameters and relative protein expressions of PRA and PRB were compared. The UF patients were divided into a cure group (n = 159) and a recurrence group (n = 41) according to their prognosis. The protein expressions of PRA and PRB in the UF group were higher than those in the healthy group (p < 0.05). In the recurrence group, PI and RI were lower, while SR and the protein expressions of PRA and PRB were higher than those in the cure group (p < 0.05). Age at menarche < 13 years old, intramural fibroid, PI, RI, SR, PRA, and PRB were risk factors for recurrence in UF patients (p < 0.05). The efficiency of combination of ultrasound and UE parameters, PRA and PRB for the diagnosis and prognostic evaluation of UF was significantly higher than that of any single indicator ( p < 0.05). Ultrasound and UE parameters combined with PR proteins have high efficiency for the diagnosis and prognostic evaluation of UF.

Correlation Between Serum Markers and Midluteal Phase Doppler Assessment of Uterine Arterial Blood Flow in Unexplained Recurrent Pregnancy Loss.

This study aimed to determine changes in uterine artery Doppler parameters in unexplained recurrent pregnancy loss (URPL) and to explore serum markers possibly associated with them. This retrospective case-control study included 107 URPL women and 107 control women. The mean pulsatility index (PI), resistive index (RI), and systolic-to-diastolic values for uterine arteries in URPL women were significantly higher than those in the controls (P < 0.05). The cutoff values of PI and RI differentiating the women with URPL from the controls were confirmed by ROC and Youden's index. Given a PI cutoff value of 2.6, the prevalence of URPL was significantly elevated in the high-PI group (74.58%) compared with that in the low-PI group (40.65%, P < 0.0001), with sensitivity and specificity of 63% and 69%, respectively. With an RI cutoff value of 0.86, the prevalence of URPL in the high-RI group (65.28%) was significantly elevated compared with that in the low-RI group (42.25%, P = 0.001), with sensitivity and specificity of 66% and 75%, respectively. The levels of serum D-dimers and anticardiolipin antibody (ACA)-IgM in URPL women were significantly higher than those in the controls. A positive correlation existed between the levels of ACA-IgM and uterine artery RI in URPL women (r = 0.43, P < 0.01). These results indicated that URPL women may be at a relatively high risk of a prothrombotic state, and the increased ACA-IgM deserves attention for its role in the elevated uterine artery Doppler parameters in URPL women.

Intact NOX2 in T Cells Mediates Pregnancy-Induced Renal Damage in Dahl SS Rats.

Hypertensive disorders of pregnancy are associated with increased risk for cardiovascular disease, renal disease, and mortality. While the exact mechanisms remain unclear, T cells and reactive oxygen species have been implicated in its pathogenesis. We utilized Dahl salt-sensitive (SS), SSCD247-/- (Dahl SS CD247 knockout rat; lacking T cells), and SSp67phox-/- (Dahl SS p67phox [NOX2 (NADPH [nitcotinamide adenine dinucleotide phosphate] oxidase 2)] knockout rat; lacking NOX2) rats to investigate these mechanisms in primigravida and multigravida states. We assessed blood pressure and renal damage phenotypes in SS, SSCD247-/-, and SSp67phox-/- rats during primigravida and multigravida states. To investigate the contribution of NOX2 in T cells, we performed adoptive transfers of splenocytes or cluster of differentiation (CD)4+ T cells from either SS or SSp67phox-/- donors into SSCD247-/- recipients to determine pregnancy-specific alterations in phenotype. Multigravida SS rats developed significant pregnancy-induced renal damage and renal functional impairment associated with elevated maternal mortality rates, whereas deletion of T cells or NOX2 garnered protection. During primigravida states, this attenuation in renal damage was observed, with the greatest protection in the SSp67phox-/- rat. To demonstrate that NOX2 in T cells contributes to adverse pregnancy phenotypes, adoptive transfer of SS splenocytes into SSCD247-/- rats resulted in significant pregnancy-induced renal damage, whereas transfer of SSp67phox-/- splenocytes garnered protection. Specifically, the transfer of SS CD4+ T cells resulted in pregnancy-induced proteinuria and increases in uterine artery resistance index, an effect not seen with the transfer of SSp67phox-/- CD4+ T cells. T cells and NOX2-derived reactive oxygen species, thus, contribute to end-organ damage in both primigravida and multigravida pregnancies in the SS rat leading to increases in maternal mortality.

Abstract P191: Progesterone Supplementation Ameliorates the Maternal Syndrome of Preeclampsia in the Dahl Salt-Sensitive Rats

Introduction: Preeclampsia (PreE) is characterized by new onset hypertension after 20 weeks of gestation. PreE is associated with activated CD4+ T cells, inflammation, autoantibodies to angiotensin II type 1 receptor (AT1-AA) and hypertension. To date, the best treatment remains early delivery of the feto-placental unit. Hypothesis: This study was designed to test the hypothesis that progesterone, in the form of 17-hydroxyprogesterone caproate (17-OHPC), reduces inflammation and blood pressure in the Dahl Salt-Sensitive (Dahl S) rat model of PreE. Methods: A subset of pregnant Sprague-Dawley (SD) and Dahl S rats were injected with 17-OHPC (3.32mg/kg, human dose equivalent) or vehicle (saline) at day 15 (GD15) of gestation. On GD 18, Uterine Artery Resistance Index (UARI) was measured by Doppler Ultrasound and carotid catheters were inserted for mean arterial blood pressure (MAP) measurement on GD19. Circulating and placental populations of CD4+ T cells were quantified by flow cytometry. TNF-alpha and IL-6 were measured by ELISA and AT1-AA were quantified by the chronotropic responses to angiotensin II type 1 receptor-mediated stimulation of cultured neonatal rat cardiomyocytes. Results are reported as means ± standard error means (SEM) and statistically significant when p &lt; 0.05. Results: MAP was 105±5 mmHg in SD+ vehicle rats (n=6), 104±4 in SD+17-OHPC rats (n=6), 136±3 in Dahl S+ saline rats (p &lt;0.05, n=11), which improved to 125±4 in DS+17-OHPC rats (p &lt;0.05, n=7). Pup and Placenta weights were 2.1± 0.1, 0.6 ± 0.1 g in SD+ vehicle rats and reduced to 1.4±0.1 (p&lt;0.05), 0.5±0.1 g in Dahl S +vehicle. UARI was 0.5 ±0.1 in SD+ vehicle rats (n=6) and 0.5 ±0.1 in in SD+17-OHPC (n=6), 0.7±0.1 in Dahl S+ vehicle rats (n=6, p&lt;0.05), which reduced to 0.5±0.1 in Dahl S+17-OHPC (n=7, p&lt;0.05). TNF-alpha and IL-6 levels (n=4-5/group) were 3.0±1.0, 45±11 pg/mL in SD+ vehicle rats, 11.0±1.2, 78±21 in Dahl S+ vehicle rats, which reduced to 4.1±1.6 (p&lt;0.05), 62±12 in Dahl S+17-OHPC. Circulating and placental CD4+ T cells were 9.3±3.7 %, 6.4± 1.6 % gate in SD+ vehicle rats (n=4), 38.9 ±2.9, 33.1±4.3 % gate Dahl S+ Saline rats (n=6), which significantly reduced to 26.3 ± 0.1 %, 3.4±1.2 % gate in DahlS+17-OHPC. AT1-AA were -1 ± 2 ΔBPM (beats per minute) in SD+ vehicle rats, 4 ± 1 in Dahl S+ Saline rats and -0.6±2 Dahl S+17-OHPC rats (n=5, p&lt;0.05). Conclusion: Our findings demonstrate that 17-OHPC ameliorates the maternal syndrome in the Dahl Salt-Sensitive rat model of PreE.

Abstract 16: A Novel H2 Relaxin B-Chain-Only Peptide Variant B7-33 Improves The Pathophysiology Of Placental Ischemia In The Reduced Uterine Perfusion Pressure Rat Model Of Preeclampsia

Background: Preeclampsia (PE) is a hypertensive pregnancy disorder, which occurs in approximately 10% of all gestations. The literature suggests the potential therapeutic role of H2 relaxin in PE. A novel H2 relaxin B-chain-only peptide variant B7-33 (27 amino acids without any disulfide bonds) has recently been developed. Objective: The goal of this study was to test the hypothesis that a novel H2 relaxin B-chain-only peptide variant B7-33 could improve the pathophysiology of placental ischemia in the Reduced Uterine Perfusion Pressure (RUPP) rat model of PE. Methods: The efficacy of B7-33 was evaluated in the RUPP model as described previously. RUPP rats are randomly assigned to 4 groups (N=8/group): 1) vehicle, 2) B733; 3) B733-Fc; and 4) B733-HSA. Rats are dosed twice weekly (i.v.) from GD10 to GD 20. On GD 18, rats are anesthetized with isoflurane, and carotid arterial catheters are inserted into the carotid artery, tunneled under the skin, and externalized at the back of the neck. On the following day, mean arterial pressure (MAP) is monitored with a pressure transducer (Cobe III Tranducer CDX Sema) and recorded continuously for 30 min. On GD18, uterine artery resistance index (UARI) of rats is measured by Doppler sonography. The nitric oxide bioavailability, soluble fms-like tyrosine kinase-1 (sFlt-1), and TNF-α) were measured by commercially available kits. Statistical comparisons were performed using analysis of variance with Duncan’s post hoc test. Results: The RUPP rats have increased MAP (122.2 ± 8.1 mm Hg), plasma TNF-α (223 ±11.4 pg/mL), and plasma sFlt-1(863 ±18.2 pg/mL) along with decreased NO index (14±2 µM) compared to normal pregnancy: MAP (102 ± 5.2 mm Hg); plasma TNF-α (28 ± 4.1 pg/mL); plasma sFlt-1(244 ± 9.4 pg/mL) and NO index (26 ±4.1 µM). Treatment with B733 and B7-33 fusion proteins significantly (*p&lt;0.05) lowers MAP, plasma TNF-α, and plasma sFlt-1 and increased NO index back to that of normal pregnancy. The B7-33 data are consistent with earlier data with serelaxin in the RUPP model. All fusions tested ameliorate hypertension in the RUPP animals. B7-33 normalizes BP and proteinuria in the DOCA rat model of preE. Conclusion: The conclusion of the study is that both B7-33 and B7-33 fusion proteins demonstrate efficacy in attenuating the symptoms of PE including hypertension and inflammation in RUPP model. We conclude that B7-33 is an ideal candidate for development as a novel therapeutic in preE.

Abstract 68: Soluble FMS-Like Tyrosine Kinase 1 induces Vascular Endothelial Dysfunction in Pregnant Female Mice

Preeclampsia (PE) is a hypertensive disorder of pregnancy clinically characterized by hypertension and increased risk of fetal growth restriction. Elevated levels of anti-angiogenic soluble fms-like tyrosine kinase 1 (sFlt-1) is a well-known hallmark of PE. In addition, emerging clinical evidence indicates that vascular endothelial dysfunction is a mediator of PE. Although these two facets of PE are associated, whether sFlt-1 is a crucial mediator in endothelial dysfunction in PE is unknown. We previously showed that the placenta-derived hormone leptin, whose levels characteristically increase in PE patients, induces the features of PE in pregnant mice, notably endothelial dysfunction. Novel preliminary data also shows that sFlt-1 induces an increase in placental leptin production, however, what remains to be explored is whether this pathway mediates endothelial dysfunction in PE pregnant mice. Therefore, we hypothesize that in pregnant mice, sFlt-1 induces vascular endothelial dysfunction via increasing leptin production. We bred BALB/c female mice for timed pregnancy (12-14 wk old). On gestational day (GD)11, pregnant females were implanted with subcutaneous (sc.) minipumps containing either sFlt-1 (1.2 µg/day, n=5) or saline (n=6). Uterine artery resistance index (UARI) was measured at GD17 via Doppler ultrasound. At GD18, vascular reactivity was measured in 2nd-order mesenteric arteries by wire myography. Our data showed that sFlt-1 increased UARI compared to sham mice ([PSV-EDV]/PSV; Mean±SEM;0.61±0.01 vs. 0.45±0.01, t test, p=0.0007). In addition, sFlt-1 reduced endothelial-dependent relaxation to acetylcholine (concentration-response, 1nM-10µM, 2-way ANOVA w/RM, p&lt;0.0001), indicating endothelial dysfunction. sFlt-1 also reduced smooth muscle relaxation responses to sodium nitroprusside (p&lt;0.05). To test whether sFlt-1 induces leptin production, we bred BALB/c mice as described above. At GD12, mice were treated with either sFlt-1 (sc.10 µg) or saline (n=6/group). After 24 h, mice were euthanized, and plasma and subcutaneous adipose tissue were collected. Our data showed an increase in plasma leptin in sFlt-1 group (ng/mL;5.0 ±0.2 vs. 2.9±0.1, t test, p&lt;0.0001) and an upregulation in placental leptin gene expression (normalized to 18S; fold change to control; 7.8±1.8 vs. 1.1±0.3, t test, p&lt;0.05). In conclusion, our data indicates that sFlt-1 induces vascular endothelial dysfunction and increases leptin plasma levels and gene expression in preeclampsia.

IL-33 Signaling Inhibition Leads to a Preeclampsia-Like Phenotype in Pregnant Rats.

Preeclampsia (PE) is a hypertensive pregnancy disorder that is a leading cause of maternal and fetal morbidity and mortality characterized by maternal vascular dysfunction, oxidative stress, chronic immune activation, and excessive inflammation. No cure exists beyond delivery of the fetal-placental unit and the mechanisms driving pathophysiology are not fully understood. However, aberrant immune responses have been extensively characterized in clinical studies and shown to mediate PE pathophysiology in animal studies. One pathway that may mediate aberrant immune responses in PE is deficiencies in the IL-33 signaling pathway. In this study, we aim to investigate the impact of IL-33 signaling inhibition on cNK, TH17, and TReg populations, vascular function, and maternal blood pressure during pregnancy. In this study, IL-33 signaling was inhibited using two different methods: intraperitoneal administration of recombinant ST2 (which acts as a decoy receptor for IL-33) and administration of a specific IL-33 neutralizing antibody. Maternal blood pressure, uterine artery resistance index, renal and placental oxidative stress, cNK, TH17, and TReg populations, various cytokines, and pre-proendothelin-1 levels were measured. IL-33 signaling inhibition increased maternal blood pressure, uterine artery resistance, placental and renal oxidative stress. IL-33 signaling inhibition also increased placental cNK and TH17 and renal TH17 cells while decreasing placental TReg populations. IL-33 neutralization increased circulating cNK and TH17s and decreased circulating TRegs in addition to increasing pre-proendothelin-1 levels. Data presented in this study demonstrate a role for IL-33 signaling in controlling vascular function and maternal blood pressure during pregnancy possibly by mediating innate and adaptive immune inflammatory responses, identifying the IL-33 signaling pathway as a potential therapeutic target for managing preeclampsia.

Role of Uterine Artery Doppler Study Between 11 and 14 Weeks as a Predictor of Preeclampsia.

Introduction Preeclampsia is a serious complication marked by antepartum hemorrhage, resulting in severe maternal and fetal complications. Predicting this condition using placental dysfunction assessments, such as uterine artery Doppler ultrasound, is challenging due to the placenta's evolving structural and biochemical characteristics throughout different stages of pregnancy. Objectives To determine the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the uterine artery Doppler Pulsatility Index (PI) and Resistive Index (RI) in predicting preeclampsia. To compare the Doppler ultrasound measurements between normal pregnancies and those that develop preeclampsia. To assess the diagnostic accuracy of uterine artery Doppler ultrasound in predicting gestational hypertension in addition to preeclampsia. Methodology Conducted as a prospective study, 116 antenatal mothers with computed gestational ages and scan gestational ages between 11 and 14 weeks, and a previous history of preeclampsia were included. Subjects with chronic hypertension or multiple gestations were excluded. Participants underwent uterine artery Doppler screening, during which the PI and RI were measured upon obtaining three consecutive similar waveforms, and the mean PI of the left and right arteries was calculated. The outcomes of patients with normal pregnancies and those who developed preeclampsia were compared. Data were entered into Microsoft Excel (Microsoft® Corp., Redmond, WA, USA) and analyzed using IBM SPSS Statistics for Windows, Version 23 (Released 2015; IBM Corp., Armonk, NY, USA). Results The mean PI among participants was 1.75 (±0.38), with a range from 1 to 2.75. The mean RI was 0.58 (±0.08), ranging from 0.45 to 0.8. The cutoff for the mean PI in predicting preeclampsia was 2.27, which showed a sensitivity of 92.9%, specificity of 97.1%, PPV of 81.47%, NPV of 99.01%, and a diagnostic accuracy of 96.59% (area under the curve (AUC): 0.982). The cutoff for the mean RI for predicting preeclampsia was 0.695, with a sensitivity of 85.7%, specificity of 98%, PPV of 85.47%, NPV of 98.04%, and diagnostic accuracy of 96.52% (AUC: 0.965). In predicting gestational hypertension, the cutoff for the mean PI was 1.975, with a sensitivity of 80%, specificity of 82.9%, PPV of 17.41%, NPV of 98.92%, and diagnostic accuracy of 82.78% (AUC: 0.848). The cutoff for the mean RI in predicting gestational hypertension was 0.615, showing a sensitivity of 80%, specificity of 80.2%, PPV of 15.4%, NPV of 98.89%, and diagnostic accuracy of 80.19% (AUC: 0.767). Conclusion The research demonstrated that aberrant readings in uterine Doppler ultrasound, specifically in the PI and RI, possess strong overall validity in forecasting the occurrence of preeclampsia.

Progesterone Supplementation Improves the Maternal Syndrome of Superimposed Preeclampsia in the Dahl Salt Sensitive Rats

Introduction: Preeclampsia (PE) is characterized by new onset of hypertension after 20 weeks of gestation. It affects 5-7% of all pregnancies in the U.S., and is associated with reduced fetal weight, inflammation and hypertension (HTN). Importantly, 30% of HTN disorders in pregnancy are caused by chronic HTN that is present prior to pregnancy which increases the risk of superimposed PE (SIPE). The mechanisms responsible for the pathogenesis of PE and SIPE are unclear and currently the only treatment is early delivery of the fetus. Progesterone is important for the establishment and maintenance of pregnancy. We have previously shown that progesterone supplementation with 17-hydroxyprogesterone caproate (17-OHPC) improves inflammation, fetal weight and blood pressure in the preclinical RUPP rat model of PE, however the mechanism for this in SIPE is still unknown. Hypothesis: This study was designed to test the hypothesis that 17-OHPC reduces inflammation while improving maternal blood pressure in the preclinical pregnant Dahl Salt Sensitive (DS) rat model of SIPE. Methods: 17-OHPC (3.32mg/kg) or vehicle (Saline) was administrated intraperitoneally on gestation day (GD) 15 to normal pregnant (NP) Sprague-Dawley (SD) and pregnant Dahl Salt Sensitive (DS) rats. On GD 18, Uterine Artery Resistance Index (UARI) was measured by Vevo Doppler Ultrasound and carotid catheters were inserted. On GD 19, mean arterial blood pressure (MAP) and samples were collected. All data are expressed as mean ± standard error means (SEM). Results: MAP was 105±5 mmHg in SD+ Saline rats (n=7) and 105±4 mmHg in SD+17-OHPC rats (n=4), 137±3 mmHg in DS + Saline rats (p&lt;0.05, n=11), which improved to 125±4 mmHg in DS+17-OHPC rats (p&lt;0.05, n=7). Pup and Placenta weights were 2.1± 0.1 g, 0.6 ± 0.1 g in SD + saline rats and significantly reduced to 1.4±0.1 g, 0.5±0.1 g in DS+ Saline rats (p&lt;0.05). Neither placental weight nor pup weight was affected by 17-OHPC. UARI was 0.5 ±0.1 in SD+ Saline rats (n=6) and 0.5 ±0.1 in in SD+17-OHPC (n=4), 0.7±0.1 in DS+Saline rats (n=6, p&lt;0.05), which reduced to 0.5±0.1 in DS+17-OHPC (n=7, p&lt;0.05). TNF-alpha levels were 3.0±1.0 pg/mL in SD+ Saline rats, 11.0±1.2 in DS + Saline rats, which reduced to 4.1±1.6 in DS+17-OHPC (n=4, p&lt;0.05). Importantly, circulating and placental CD4+ T cells were 9.3±3.7 % Gate and 6.4± 1.6 % Gate in SD+ Saline rats (n=4), 38.9 ±2.9 % Gate and 33.1±4.3 % Gate in DS + Saline rats (n=6), which significantly reduced to 26.3 ± 0.1 % Gate and 3.4±1.2 % Gate in DS + 17-OHPC. Conclusion: Collectively, our findings demonstrate that 17-OHPC reduces inflammation and hypertension in the Dahl Salt Sensitive rat model of SIPE. Supported by NIH P20GM121334. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Pathologic maternal and neonatal outcomes associated with programmed embryo transfer: potential etiologies and strategies for prevention.

In the first of two companion papers, we comprehensively reviewed the recent evidence in the primary literature, which addressed the increased prevalence of hypertensive disorders of pregnancy, late-onset or term preeclampsia, fetal overgrowth, postterm birth, and placenta accreta in women conceiving by in vitro fertilization. The preponderance of evidence implicated frozen embryo transfer cycles and, specifically, those employing programmed endometrial preparations, in the higher risk for these adverse maternal and neonatal pregnancy outcomes. Based upon this critical appraisal of the primary literature, we formulate potential etiologies and suggest strategies for prevention in the second article. Comprehensive review of primary literature. Presupposing significant overlap of these apparently diverse pathological pregnancy outcomes within subjects who conceive by programmed autologous FET cycles, shared etiologies may be at play. One plausible but clearly provocative explanation is that aberrant decidualization arising from suboptimal endometrial preparation causes greater than normal trophoblast invasion and myometrial spiral artery remodeling. Thus, overly robust placentation produces larger placentas and fetuses that, in turn, lead to overcrowding of villi within the confines of the uterine cavity which encroach upon intervillous spaces precipitating placental ischemia, oxidative and syncytiotrophoblast stress, and, ultimately, late-onset or term preeclampsia. The absence of circulating corpus luteal factors like relaxin in most programmed cycles might further compromise decidualization and exacerbate the maternal endothelial response to deleterious circulating placental products like soluble fms-like tyrosine kinase-1 that mediate disease manifestations. An alternative, but not mutually exclusive, determinant might be a thinner endometrium frequently associated with programmed endometrial preparations, which could conspire with dysregulated decidualization to elicit greater than normal trophoblast invasion and myometrial spiral artery remodeling. In extreme cases, placenta accreta could conceivably arise. Though lower uterine artery resistance and pulsatility indices observed during early pregnancy in programmed embryo transfer cycles are consistent with this initiating event, quantitative analyses of trophoblast invasion and myometrial spiral artery remodeling required to validate the hypothesis have not yet been conducted. Endometrial preparation that is not optimal, absent circulating corpus luteal factors, or a combination thereof are attractive etiologies; however, the requisite investigations to prove them have yet to be undertaken. Presuming that in ongoing RCTs, some or all adverse pregnancy outcomes associated with programmed autologous FET are circumvented or mitigated by employing natural or stimulated cycles instead, then for women who can conceive using these regimens, they would be preferable. For the 15% or so of women who require programmed FET, additional research as suggested in this review is needed to elucidate the responsible mechanisms and develop preventative strategies.

Effectiveness of Sanatorium Treatment Programs for Women with Chronic Endometritis: a Prospective Randomized Study

INTRODUCTION. The problem of recurrent antibiotic-resistant urogenital infections is increasing, and standard therapy is becoming ineffective. Sanatorium-resort treatment of chronic inflammatory diseases of the pelvic organs in women allows us to solve these problems with the help of natural and preformed physical factors.&#x0D; AIM. To study the clinical effectiveness of comprehensive sanatorium treatment programs in patients with chronic endometritis.&#x0D; MATERIALS AND METHODS. A prospective randomized trial included 73 patients, aged 35 ± 10 years, diagnosed with chronic endometritis. The control group (n = 25) received «basic» therapy with amplipulstherapy, sodium chloride baths. The comparison group (n = 24) received «basic» therapy and manual therapy. The main group (n = 24) received «basic» therapy, high-intensity pulsed magnetic field and manual therapy. Diagnostic criteria: immunohistochemical examination of the endometrium, echographic examination, dopplerometry of pelvic vessels, laser Doppler flowmetry.&#x0D; RESULTS AND DISCUSSION. After treatment, an increase in the uterine arterial perfusion index was noted in all groups compared with baseline values. The median indicator increased in the study groups by 2.36 times, 2.4 times, and 2.6 times, respectively (p 0.05). The decrease in the maximum peak speed in the comparison group and the main group exceeded the indicators of the control group (p 0.001). The systolic-diastolic ratio decreased in the comparison group and the main group (p 0.05). A decrease in stagnation in the venular microcirculation, a normotonic type of microcirculation, improvement in endothelial function (p 0.01) were revealed in the main group.&#x0D; CONCLUSION. An algorithm has been developed. In case of endometrial hypoplasia, decreased uterine perfusion, increased uterine artery resistance index, «basic» therapy is recommended, including sodium chloride baths and amplipulstherapy. With an increase in the maximum peak blood flow rate, an increase in the systolic-diastolic ratio, it is necessary to add a course of manual therapy to the «basic» therapy. When detecting violations of venous outflow, it is recommended to include high-intensity pulsed magnetic therapy.

IL-33 supplementation improves uterine artery resistance and maternal hypertension in response to placental ischemia.

Preeclampsia (PE), a leading cause of maternal/fetal morbidity and mortality, is a hypertensive pregnancy disorder with end-organ damage that manifests after 20 wk of gestation. PE is characterized by chronic immune activation and endothelial dysfunction. Clinical studies report reduced IL-33 signaling in PE. We use the Reduced Uterine Perfusion Pressure (RUPP) rat model, which mimics many PE characteristics including reduced IL-33, to identify mechanisms mediating PE pathophysiology. We hypothesized that IL-33 supplementation would improve blood pressure (BP), inflammation, and oxidative stress (ROS) during placental ischemia. We implanted intraperitoneal mini-osmotic pumps infusing recombinant rat IL-33 (1 µg/kg/day) into normal pregnant (NP) and RUPP rats from gestation day 14 to 19. We found that IL-33 supplementation in RUPP rats reduces maternal blood pressure and improves the uterine artery resistance index (UARI). In addition to physiological improvements, we found decreased circulating and placental cytolytic Natural Killer cells (cNKs) and decreased circulating, placental, and renal TH17s in IL-33-treated RUPP rats. cNK cell cytotoxic activity also decreased in IL-33-supplemented RUPP rats. Furthermore, renal ROS and placental preproendothelin-1 (PPET-1) decreased in RUPP rats treated with IL-33. These findings demonstrate a role for IL-33 in controlling vascular function and maternal BP during pregnancy by decreasing inflammation, renal ROS, and PPET-1 expression. These data suggest that IL-33 may have therapeutic potential in managing PE.NEW & NOTEWORTHY Though decreased IL-33 signaling has been clinically associated with PE, the mechanisms linking this signaling pathway to overall disease pathophysiology are not well understood. This study provides compelling evidence that mechanistically links reduced IL-33 with the inflammatory response and vascular dysfunction observed in response to placental ischemia, such as in PE. Data presented in this study submit the IL-33 signaling pathway as a possible therapeutic target for the treatment of PE.

Application value of ultrasound elastography for screening of early pregnancy cervical insufficiency: a retrospective case-control study.

This study aimed to investigate changes in the cervical strain rate (SR), cervical length (CL), and uterine artery blood flow parameters during early pregnancy in women with cervical insufficiency and evaluate the clinical efficacy of these markers for screening of cervical insufficiency in early pregnancy. This retrospective study in 60 pregnant women with cervical insufficiency and 100 normal pregnant women was conducted between September 2021 and January 2023 and measured ultrasound parameters of the cervix during early pregnancy. The cervical SR, CL, and uterine artery resistance index (RI) were measured in both groups at 11-14 weeks of gestation. Strain elastography represented by the SR was used to assess the hardness of the internal and external cervical openings. During early pregnancy, the SR at the internal and external cervical openings were significantly higher in the cervical insufficiency group than those in the normal pregnancy group (SR I: 0.19 ± 0.018% vs. 0.16 ± 0.014%; SR E: 0.26 ± 0.028% vs. 0.24 ± 0.025%; p < .001). The CL was significantly shorter in the cervical insufficiency group than that measured in the normal pregnancy group (34.3 ± 2.9 mm vs. 35.2 ± 1.99 mm; p = .036), while cervical blood perfusion was also poorer in the cervical insufficiency group than that in the normal pregnancy group (uterine artery RI: 0.76 ± 0.07 vs. 0.74 ± 0.05; p = .048). Receiver operating characteristic (ROC) curve analysis showed that the optimal critical values for diagnosing cervical insufficiency were 0.17% for SR I, 0.25% for SR E, 33.8 mm for CL, and 0.78 for uterine artery RI. Of these parameters, the ROC curve for SR I had the largest area under the curve [AUC = 0.89 (p < .001)], with the highest sensitivity (78%) and specificity (82%). Multivariate logistic regression analysis demonstrated that the SR at the internal cervical opening (OR 17.47, 95% confidence interval (CI) 5.08-60.08; p < .001) and CL (OR 5.05, 95% CI 1.66-15.32; p = .004) still showed significant differences between the two groups. Cervical elastography is an effective tool for screening early pregnancy cervical insufficiency. The SR at the internal cervical opening is a valuable indicator for screening cervical insufficiency and has superior clinical efficacy for screening for this condition compared to that of CL and the uterine artery blood flow index.

Correlation of uterine artery Doppler flow velocimetry and β-human chorionic gonadotropin levels during postmolar evacuation surveillance: A pilot study in a tertiary hospital

BACKGROUND: During postmolar evacuation surveillance, beta-human chorionic gonadotropin (β-hCG) regression levels can predict invasive disease while Doppler ultrasound can assess in vivo tumor neovascularization and quantify uterine blood supply. As an ancillary tool to β-hCG monitoring, ultrasound can detect the early presence of viable trophoblastic tissues and identify patients at risk of developing postmolar gestational trophoblastic Neoplasia (PMGTN). OBJECTIVE: The objective of this study was to correlate uterine artery Doppler ultrasound with β-hCG levels during pre- and postmolar evacuation surveillance among patients with complete mole. MATERIALS AND METHODS: A cohort of patients with sonographic diagnosis of complete hydatidiform mole and managed with suction curettage in the same institution were prospectively followed up after evacuation. The pre- and postmolar evacuation surveillance period was at days 1, 7, 14, 21, 28, and 35. Monitoring of serum β-hCG levels was based on the standard regression curve. For Doppler ultrasound parameters, monitoring of the systolic/diastolic (S/D) ratio, pulsatility index (PI), resistance index (RI), and peak systolic velocity (PSV) was based on its relationship with its serum β-hCG levels. The ultrasound images generated were archived and reviewed by the authors. Descriptive and inferential statistics were utilized to analyze median differences. For the correlation of uterine artery Doppler flow parameters, analysis for the test of difference used Pearson correlation and multiple linear regression analysis for the odds ratio. RESULTS: Sixteen of the 23 enrolled patients completed the protocol (16 of 23, 69.50%). A majority had spontaneous remission (13; 81%) while 3 cases (19%) presented increasing and plateauing β-hCG levels. The pre- and post evacuation median β-hCG levels showed a significant decrease (P = 0.001). As post evacuation β-hCG levels decreased, PSV also decreased (r = 0.478, P = 0.061) while Doppler parameters, RI, PI, and S/D ratio increased. However, when post evacuation β-hCG levels rose or plateaued, Doppler parameters decreased. These changes had statistical correlation (all P &lt; 0.05). Moreover, the magnitude of the relationship for β-hCG and Doppler parameters was moderate and ranged from 0.524 to 0.581. Among the Doppler parameters, the S/D ratio and RI of the right uterine artery strongly predicted a rise in β-hCG levels. The odds ratio of predicting increased β-hCG levels and risk of gestational trophoblastic neoplasia by the right S/D ratio were − 2683.67 (confidence interval [CI] = −271.692–5095.655; P = 0.034) and by the right RI − 66,193.34 (CI = −161,818.107–29,431.433; P = 0.046). Notably, Doppler parameter changes appeared early at day 14 up to day 35 and before the appearance of abnormal β-hCG regression patterns. CONCLUSION: There is a strong correlation between uterine artery Doppler flow changes and β-hCG levels during postmolar evacuation surveillance. The inverse relationship of the S/D ratio, PI and RI, and β-hCG regression patterns confirms spontaneous remission of the disease. For patients with abnormal β-hCG patterns, this relationship is altered. The Doppler changes become erratic, unpredictable, and significantly decreased. These changes were detected as early as 2 weeks post evacuation. Thus, the use of ultrasound as an adjunct to β-hCG post evacuation surveillance can predict abnormal β-hCG regression patterns and identify patients at risk of developing postmolar gestational trophoblastic neoplasia (PMGTN).

Added Value of Mean Blood Pressure and Placental Growth Factor in the Early Detection of Pre-eclampsia among Gabonese Women.

To evaluate the use of the Foetal Medicine Foundation (FMF) algorithm in routine practice for early pre-eclampsia (PE) screening in Libreville. We conducted a cohort study on pregnant women within their 11-13 + 6 weeks of gestation (WG). We had measured mean blood pressure (MBP), placental growth factor (PlGF), soluble Fms-like tyrosine kinase 1, Uterine Artery Pulsatility Index (UtA-PI) and resistance index (UtA-RI). Statistical analyses were considered significant for P < 0.05. There were 30 participants. At the first quarter (T1), 36.7% of them were at high risk of PE according to the FMF algorithm and were consequently prescribed aspirin (100 mg/d). By the end of the observation period, we have found a 13% incidence of PE. MBP was higher in the higher risk PE group than in the lower risk group as early as the T1 (90 ± 6 vs. 81 ± 6 mmHg; P = 0.0007, threshold is >86 mmHg/area under the curve (AUC) = 0.86; P = 0.0012). It was the same for PlGF (58 ± 24 vs. 88 ± 38 pg/ml; P = 0.03; threshold is <71.98 pg/ml/AUC = 0.73; P = 0.03). At the second quarter (20-27 WG), biochemical markers did not change between the two groups. UtA-RI, UtA-PI and notch were unconclusive individually, but they are still very important for FMF algorithm application. Early detection of PE using the FMF algorithm is possible in routine practice in Gabon. MBP and PlGF levels at T1 seem to be very significant. However, the present study must continue to obtain the larger cohorts that would achieve more conclusive statistical analyses.

Comparison of Doppler ultrasound indices of uterine artery and sub endometrial blood supply in frozen embryo transfer with and without repeated implantation failure: A cross-sectional study.

Background: Uterine blood supply has been identified as a potential factor in implantation failure. Objective: This study aimed to investigate Doppler indices in the uterine artery, including vascular flow and resistance, as well as the amount of sub-endometrial blood supply in women with a history of repeated implantation failure (RIF) compared to the non-RIF group. Materials and Methods: This cross-sectional study was conducted with 139 women candidates for frozen embryo transfer in Yazd Reproductive Sciences Institute, Yazd, Iran from February to July 2023. Group A (n = 68) included women with a history of more than 2 RIF, and group B (n = 71) included women candidates for implantation for the first time without RIF. Doppler ultrasound indices of uterine artery and sub-endometrium, including sub-endometrial flow, uterine artery flow, uterine artery resistance, and peak systolic velocity, were recorded. Results: No significant differences were observed in uterine artery Doppler pulsatility index and peak systolic velocity between groups, but the uterine artery resistance index was significantly higher in the A group (p 0.001). A significant difference was observed in the perfusion area between groups. 60/68 women in the group A had endometrial perfusion in areas 2 and 3 (p 0.001). Conclusion: Our study revealed that women with RIF exhibited higher resistance index in sub-endometrial arteries compared to the non-RIF group.

The Comparison Between The Effect of Different Medical Drugs used To Improve Endometrial Receptivity in patients with Thin Poorly Vascularized Endometrium

In a perfect world, the peak of receptivity of the endometrial lining would occur simultaneously with the entry into the uterine cavity of a healthy blastocyst, which would then be able to adhere, attach, invade, and develop protected until the time of delivery. This would be the ideal scenario. The study was carried out on 200 infertile women who have thin , poorly vascularized endometrium, those patients were divided into five groups ; 40 patients in each group, group A received esterofem oral, group B received vagifem vaginal tablets, group C received sildenafil citrate gel, group D received pentoxifylline oral and group E received 4 grams of pentoxifylline vaginal gel. The endometrial thickness, vascularity zones, sub endometrial flow, and both uterine arteries resistance and pulsatility indices were assessed at the middle of the menstrual cycle (day 11–14) on a monthly basis for six cycles or until a positive pregnancy test was obtained. Pentoxifylline vaginal gel, pentoxifylline+ vitamin E capsule, and sildenafil vaginal gel have improved the vascularity indeces of endometrium and uterine arteries, while the vagifem and esterofem were less effective in terms of improving the vascularity indeces of endometrium and uterine arteries. The study also showed that 57.5% of women succeed to get pregnant after six months of receiving pentoxifylline vaginal gel, 35% of women succeed to get pregnant after six months of Pentoxifylline+vit E, while 22.5% of women succeed to get pregnant after six months of sildenafil, about 10% of women got pregnant after six months of vagifem, and finally 2.5% of women got pregnant after six months of receiving estrofem tablets. It was discovered that pentoxifylline vaginal gel, pentoxifylline tablet plus vitamin E capsule, and sildenafil vaginal gel were able to improve the vascularity index of the endometrium, the uterine arteries and endometrial thickness, and enhance the pregnancy rates in patients with thin poorly vascularized endometrium

The Role of Uterine Artery Pulsatility and Resistance Index in Detection of Pre-invasive Cervical Lesions

The Role of Uterine Artery Pulsatility and Resistance Index in Detection of Pre-invasive Cervical Lesions

Abstract 022: Il-33 Supplementation Improves Vascular Function And Maternal Hypertension In Response To Placental Ischemia

Preeclampsia (PE), a leading cause of maternal/fetal morbidity and mortality, is a hypertensive pregnancy disorder with end-organ damage that manifests after 20 weeks of gestation. PE is characterized by chronic immune activation and endothelial dysfunction. Clinical studies report reduced IL-33 signaling in PE. We use the R educed U terine P erfusion P ressure (RUPP) rat model, which mimics many PE characteristics including reduced IL-33, to identify mechanisms mediating PE pathophysiology. We hypothesized IL-33 supplementation would improve blood pressure (BP), inflammation, and oxidative stress (ROS) during placental ischemia. We implanted i.p. mini-osmotic pumps infusing recombinant rat IL-33 (1 μg/kg/day) into normal pregnant (NP) and RUPP rats from gestation day 14-19. We assessed maternal BP, cytolytic NK (cNK) and T H 17 cells, cNK cell activity, ROS, preproendothelin-1 (PPET) expression, and uterine artery resistance index (UARI). MAP (mmHg) was 104±4 in NP vs 124±7 in RUPP (p&lt;0.05 vs NP) and lowered to 108±10 in RUPP+IL-33 (p&lt;0.05 vs RUPP, n=8/group). Circulating cNKs (% gated) were 0.9±0.2% in NP vs 3.9±1.1% in RUPP (p&lt;0.05 vs NP) and decreased to 1.1±0.6% in RUPP+IL-33 (p&lt;0.05 vs RUPP, n=8/group). Circulating T H 17s (%CD4 + T cells) were 1.0±0.6% in NP vs 7.2±0.5% in RUPP (p&lt;0.05 vs NP) and 0.8±0.4% in RUPP+IL-33 (p&lt;0.05 vs RUPP, n=8/group). Renal T H 17s, placenta cNKs and T H 17s followed similar trends. cNK cell activity (fold change) was 3.92±0.6 fold higher in RUPP vs NP (p&lt;0.05 vs NP) and decreased to -0.24±0.1 in RUPP+IL-33 (p&lt;0.05 vs RUPP, n=3/group). Renal ROS (relative light units/min/mg protein) was 452±33 in NP vs 676±44 in RUPP (p&lt;0.05) and decreased to 258±50 in RUPP+IL-33 (p&lt;0.05 vs RUPP, n=5/group). Placental PPET (fold change) was 2.36±0.4 fold higher in RUPP vs NP (p&lt;0.05) and decreased to 1.22±0.2 in RUPP+IL-33 (p=0.05 vs RUPP, n=6-7/group). UARI (arbitrary units) was 0.71±0.01 in RUPP vs 0.54±0.01 in NP (p&lt;0.05) and was lowered to 0.57±0.02 in RUPP+IL-33 (p&lt;0.05 vs RUPP, n=6/group). These findings demonstrate a role for IL-33 in controlling vascular function and maternal BP during pregnancy by decreasing inflammation, ROS, and PPET expression. These data suggest IL-33 may have therapeutic potential in managing PE.

Abstract 064: CD4+ T Cells Mediate Pregnancy-induced Renal Damage In The Dahl SS In A Process Dependent Upon NADPH Oxidase 2 (NOX2)

Previous work from our lab demonstrated that adoptive transfer of Dahl SS splenocytes into rats lacking T cells (SS CD247-/- ) led to significant renal damage and impairment in uterine artery blood flow during pregnancy. In contrast, transfer of SS p67phox-/- splenocytes, which lack the ability to generate NOX2-derived ROS, did not amplify pregnancy-induced renal damage. It is unknown what cell type in splenocytes mediates these effects. The present study tested the hypothesis that adoptive transfer of Dahl SS CD4+ T cells would induce a preeclamptic-like phenotype in the SS CD247-/- in a process dependent on NOX2. CD4+ T cells from Dahl SS or SS p67phox-/- were transferred into SS CD247-/- rats by intraperitoneal injection at postnatal day 5 to investigate the oxidative capacity of CD4+ T cells. Injected SS CD247-/- rats were aged to 10 weeks when they were mated with naïve littermate males. Prior to mating, baseline MAP and protein excretion rates were comparable between the groups (136±6 vs 134±3 mmHg, 33±5 vs 28±3 mg/day, p&gt; 0.05, n=5/group, SS vs SS p67phox-/- , respectively). At the end of the pregnancy, the SS treated rats develop significant proteinuria that is not observed in the rats that received SS p67phox-/- CD4+ T cells (138±14 vs 83±16 mg/day, p&lt; 0.05) despite no difference in MAP. In addition, there was an increase in uterine artery resistance index as assessed by Doppler ultrasound at GD20 in the SS treated relative to SS p67phox-/- (0.70±0.03 vs 0.62±0.02, p &lt;0.05) indicating an impairment in blood flow leading to the placenta. There was a trending reduction in placental efficiency (fetal/placental weight) observed in the rats injected with SS CD4+ T cells versus those injected with SS p67phox-/- CD4+ T cells (3.99±0.3 vs 4.57±0.1, p=0.06) suggesting there is an impairment in placental function. Taken together, the present data suggest a causal role for NOX2 in CD4+ T cells in pregnancy-associated renal damage and impairment of vascular function.