Intrauterine interventions options for preventing recurrence after hysteroscopic adhesiolysis: a systematic review and network meta-analysis of randomized controlled trials.

PURPOSE: Recurrence of adhesions after hysteroscopic adhesiolysis is a challenging clinical problem without a unified management approach. Therefore, we conducted a network meta-analysis that considered both direct and indirect comparisons between interventions to identify optimal strategies for preventing recurrence. METHODS: We searched for research trials published up to July 2023 from PubMed, Embase and the Cochrane Database. We selected randomized controlled trials comparing the use of different interventions for the prevention of adhesion recurrence, with no language or regional restrictions. We used random-effects models to assess odds ratios (OR) and mean difference (MD) with 95% confidence intervals (CI). Adverse events associated with the interventions were also assessed. This study was registered on PROSPERO, CRD42023449068. RESULTS: Data from 21 randomized controlled trials involving 2406 patients were synthesized, including interventions with balloon, amnion, platelet-rich plasma (PRP), intrauterine device (IUD), hyaluronic acid (HA), platelet-rich fibrin (PRF), and granulocyte colony-stimulating factor (G-CSF). The top 5 interventions for change in AFS scores were: PRP + Balloon (MD = 5.44; 95% CI, 2.63-8.25), Amnion + Balloon (MD = 5.08; 95% CI, 2.71-7.44), IUD + Balloon (MD = 4.89; 95% CI, 2.49-7.30), HA + Balloon (MD = 3.80; 95% CI, 1.78-5.82), and G-CSF + Balloon (MD = 3.84; 95% CI, 1.05-6.63). There were no statistically significant differences between interventions in the recurrence rate of moderate-to-severe uterine adhesions and the clinical pregnancy rate. Most interventions were safe. CONCLUSIONS: To our knowledge, this is the most comprehensive network meta-analysis to date of interventions for preventing postoperative intrauterine adhesion recurrence. Our results indicate that PRP + Balloon seems to be the most effective approach.

Higher exogenous gonadotrophin doses increase the risk of small for gestational age singletons after fresh embryo transfers.

RESEARCH QUESTION: A negative relationship has been reported between exogenous gonadotrophin dosage and the live birth rate in IVF. It is unclear whether total gonadotrophin dosage is associated with neonatal outcomes. The effect of exogenous gonadotrophin dosage on neonatal outcomes of singletons after fresh embryo transfer (FET) was investigated. DESIGN: A retrospective cohort study of 2020 live singletons evaluating neonatal outcomes. All patients underwent autologous IVF cycles between 1 August 2016 and 30 April 2020 and delivered a live singleton birth after FET. Patients with polycystic ovary syndrome were excluded. Patients were divided according to total gonadotrophin dose: group 1: ≤1800 IU; group 2: 1801-2500 IU; and group 3: >2500 IU. RESULTS: After adjusting for confounding factors by multiple regression models, the adjusted rate of small for gestational age (SGA) was significantly higher in group 3 (adjusted [a]OR 2.25, 95% CI 1.24 to 4.08). The risk of SGA increased 2.25 times when total gonadotrophin dose exceeded 2500 IU versus gonadotrophin doses below 1800 IU. The hierarchical analysis showed that an increased rate of SGA infants occurred in the GnRH agonist long protocol (aOR 2.09, 95% CI 1.02 to 5.17) and in the antagonist protocol (aOR 2.75, 95% CI 1.05 to 7.22). CONCLUSIONS: For patients without polycystic ovary syndrome, an excessive total gonadotrophin dose during ovarian stimulation, i.e. more than 2500 IU, may negatively affect neonatal outcomes by increasing the SGA rate of singletons after FET. Therefore, total gonadotrophin dose administered during ovarian stimulation should preferably not exceed 2500 IU.

Epigallocatechin-3-gallate (EGCG) attenuates inflammatory responses and oxidative stress in lipopolysaccharide (LPS)-induced endometritis via silent information regulator transcript-1 (SIRT1)/nucleotide oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3) pathway.

The protective effects of epigallocatechin-3-gallate (EGCG) on lipopolysaccharide (LPS)-induced endometritis in vivo and in vitro will be explored in this study. The endometritis model was induced in female BALB/c mice uterus by perfusion with lipopolysaccharide (LPS) and EGCG were administered at 1 h before LPS induction. The primary bovine endometrial epithelial cells (BEECs) were treated with EGCG for 1 h before LPS stimulation. Uterine histopathological changes, myeloperoxidase (MPO) activity, inflammatory cytokine levels and oxidative stress markers were determined. The extent of Bax, Bcl-2, cleaved caspase-3, silent information regulator transcript-1 (SIRT1), nucleotide oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and Caspase1 was detected by Western blot and real-time quantitative PCR assays. The results showed that EGCG significantly reversed the LPS-induced uterine histopathological changes, MPO activity, pro-inflammatory cytokine levels. Additionally, EGCG decreased oxidative stress and reduced cell apoptosis by upregulating SIRT1 expression, downregulating the NLRP3 inflammasome activation. These findings indicated that EGCG exerted its greatest protective effects by blocking inflammatory responses, lowering oxidative stress, and reducing apoptosis via the SIRT1/NLRP3, making its promising candidate treatment for endometritis.

Generating electromagnetic nonuniformly correlated beams.

We develop a method to generate electromagnetic nonuniformly correlated (ENUC) sources from vector Gaussian Schell-model (GSM) beams. Having spatially varying correlation properties, ENUC sources are more difficult to synthesize than their Schell-model counterparts (which can be generated by filtering circular complex Gaussian random numbers) and, in past work, have only been realized using Cholesky decomposition-a computationally intensive procedure. Here we transform electromagnetic GSM field instances directly into ENUC instances, thereby avoiding computing Cholesky factors resulting in significant savings in time and computing resources. We validate our method by generating (via simulation) an ENUC beam with desired parameters. We find the simulated results to be in excellent agreement with the theoretical predictions. This new method for generating ENUC sources can be directly implemented on existing spatial-light-modulator-based vector beam generators and will be useful in applications where nonuniformly correlated beams have shown promise, e.g., free-space/underwater optical communications.

Supraphysiological serum oestradiol negatively affects birthweight in cryopreserved embryo transfers: a retrospective cohort study.

RESEARCH QUESTION: Previous studies have demonstrated a negative relationship between peak oestradiol and low birthweight in IVF. However, it is hard to distinguish which aspect influenced by supraphysiological oestradiol concentrations fundamentally contributes to the low birthweight seen during IVF. This study therefore aimed to investigate whether birthweight was associated with an effect of oestradiol on oocytes. DESIGN: Oocytes are the only component exposed to the high-oestradiol environment in vitrified-warmed embryo transfer (VET) cycles. A retrospective cohort study of 431 infertile women was therefore carried out to evaluate the relationship between peak oestradiol concentration during controlled ovarian stimulation (COS) and birthweight in full-term singletons born after VET. The effect size was calculated using multivariable regression analysis. RESULTS: In this cohort, the mean peak oestradiol concentration was 4186.6 ± 1215.0 pg/ml, the mean number of oocytes retrieved was 11.5 ± 5.4, the mean length of ovarian stimulation was 11.3 ± 2.1 days and the mean birthweight was 3441.8 ± 466.1 g. The results indicated that peak oestradiol concentration was negatively correlated with birthweight in full-term singletons born after VET (adjusted ß -5.0, 95% confidence interval [CI] -9.2 to -0.7). The effect size indicated that for every 100 pg/ml increase in peak oestradiol concentration, birthweight decreased by 5.0 g. The P for trend value was 0.038. CONCLUSIONS: Peak serum oestradiol during COS is negatively associated with birthweight. This model proposes a novel concept as well as new evidence that the effect on birthweight is due to the primary influence of a high oestradiol concentration on oocytes during COS.

Partial regeneration of uterine horns in rats through adipose-derived stem cell sheets.

Severe uterine damage and infection lead to intrauterine adhesions, which result in hypomenorrhea, amenorrhea and infertility. Cell sheet engineering has shown great promise in clinical applications. Adipose-derived stem cells (ADSCs) are emerging as an alternative source of stem cells for cell-based therapies. In the present study, we investigated the feasibility of applying ADSCs as seed cells to form scaffold-free cell sheet. Data showed that ADSC sheets expressed higher levels of FGF, Col I, TGFß, and VEGF than ADSCs in suspension, while increased expression of this gene set was associated with stemness, including Nanog, Oct4, and Sox2. We then investigated the therapeutic effects of 3D ADSCs sheet on regeneration in a rat model. We found that ADSCs were mainly detected in the basal layer of the regenerating endometrium in the cell sheet group at 21 days after transplantation. Additionally, some ADSCs differentiated into stromal-like cells. Moreover, ADSC sheets transplanted into partially excised uteri promoted regeneration of the endometrium cells, muscle cells and stimulated angiogenesis, and also resulted in better pregnancy outcomes. Therefore, ADSC sheet therapy shows considerable promise as a new treatment for severe uterine damage.

Clinical outcomes of frozen embryo versus fresh embryo transfer following in vitro fertilization: a meta-analysis of randomized controlled trials.

PURPOSE: To examine available data from randomized controlled trials to assess if the freeze-all embryo and subsequent frozen-thawed embryo transfer (FET) results in better clinical outcomes than fresh embryo transfer (ET). METHODS: Meta-analysis. RESULTS: We conducted an electronic literature search on PubMed and Embase databases and manually supplemented another 2 articles from relevant citations. Seven studies were finally included in the meta-analysis,including 1141 women who underwent fresh embryo transfer and 1079 who underwent frozen embryo transfer. The results of the meta-analysis suggested that the live birth rate [RR (95% CI) 1.18 (1.08-1.30), P = 0.0003] and clinical pregnancy rate [RR (95% CI) 1.10 (1.02-1.19), P = 0.02] were significantly higher in FET group. Miscarriage rate [RR (95% CI) 0.62 (0.48-0.80), P = 0.0002], and moderate to severe OHSS occurrence rate [RR (95% CI) 0.22 (0.12 to 0.39), P < 0.00001] were significantly lower in FET group. Differences of biochemical pregnancy rate, ongoing pregnancy rate and implantation rate between the two groups did not reach the statistical significance. CONCLUSIONS: Our results suggest that the IVF/ICSI with FET is more efficient and less risky for OHSS compared with ET. However, we should comprehensively inform patients with advantages, disadvantages and potential risks related to embryo cryopreservation, and carefully assess their fertility conditions to make the most beneficial clinical decision.

Modeling random screens for predefined electromagnetic Gaussian-Schell model sources.

In a previous paper [Opt. Express22, 31691 (2014)] two different wave optics methodologies (phase screen and complex screen) were introduced to generate electromagnetic Gaussian Schell-model sources. A numerical optimization approach based on theoretical realizability conditions was used to determine the screen parameters. In this work we describe a practical modeling approach for the two methodologies that employs a common numerical recipe for generating correlated Gaussian random sequences and establish exact relationships between the screen simulation parameters and the source parameters. Both methodologies are demonstrated in a wave-optics simulation framework for an example source. The two methodologies are found to have some differing features, for example, the phase screen method is more flexible than the complex screen in terms of the range of combinations of beam parameter values that can be modeled. This work supports numerical wave optics simulations or laboratory experiments involving electromagnetic Gaussian Schell-model sources.

Changes of Phospholipids in Fetal Liver of Mice Conceived by In Vitro Fertilization.

Environmental influences during early development increase the susceptibility to metabolism diseases in adulthood. Assisted reproductive techniques (ART) expose the gametes or preimplantation embryo to a nonphysiological environment that increases the risk of metabolism diseases in later life. However, the precise underlying causes of ART-related metabolism disease remain unclear. In our previous study, by using a mouse model, we found that ART resulted in placental maldevelopment and dysfunction that led to reduced fetal growth. The lipid metabolism and lipid transporters in the placenta were also affected by ART. Based on these findings, we hypothesized that ART may hamper fetal lipid metabolism, which could predispose to metabolic diseases in later life. In the present examination, by lipidomic analysis, we investigated for the first time the effect of ART on phospholipid profiles in the fetal liver in a mouse model and presented it in a detailed overview. We revealed that ART increased significantly the level of lysophosphatidylcholine (LPC), phosphatidic acid (PA), and lysophosphatidylethanolamine in the livers of fetuses compared with those in the controls. LPC and PA acts as signaling molecules involved in the majority of cellular processes regulating many crucial physiological and pathophysiological processes. LPC has been shown to play a crucial role in the development of atherosclerosis and type 2 diabetes, and an increase in PA can result in insulin resistance. We proposed that changes of LPC and PA may be one of the causes of the changes in glucose metabolism and vascular dysfunction in the mouse model of ART.

Assisted Reproduction Causes Reduced Fetal Growth Associated with Downregulation of Paternally Expressed Imprinted Genes That Enhance Fetal Growth in Mice.

Alteration of intrauterine growth trajectory is linked to metabolic diseases in adulthood. In mammalian and, specifically, human species, pregnancies through assisted reproductive technology (ART) are associated with changes in intrauterine growth trajectory. However, it is still unclear how ART alters intrauterine growth trajectory, especially reduced fetal growth in early to midgestation. In this study, using a mouse model, it was found that ART procedures reduce fetal and placental growth at Embryonic Day 10.5. Furthermore, ART leads to decreased methylation levels at H19, KvDMR1, and Snrpn imprinting control regions in the placentae, instead of fetuses. Furthermore, in the placenta, ART downregulated a majority of parentally expressed imprinted genes, which enhance fetal growth, whereas it upregulated a majority of maternally expressed genes which repress fetal growth. Additionally, the expression of genes that regulate placental development was also affected by ART. ART also downregulated a majority of placental nutrient transporters. Disruption of genomic imprinting and abnormal expression of developmentally and functionally relevant genes in placenta may influence the placental development and function, which affect fetal growth and reprogramming.

Gaussian beam propagation in anisotropic turbulence along horizontal links: theory, simulation, and laboratory implementation.

Experimental and theoretical work has shown that atmospheric turbulence can exhibit "non-Kolmogorov" behavior including anisotropy and modifications of the classically accepted spatial power spectral slope, -11/3. In typical horizontal scenarios, atmospheric anisotropy implies that the variations in the refractive index are more spatially correlated in both horizontal directions than in the vertical. In this work, we extend Gaussian beam theory for propagation through Kolmogorov turbulence to the case of anisotropic turbulence along the horizontal direction. We also study the effects of different spatial power spectral slopes on the beam propagation. A description is developed for the average beam intensity profile, and the results for a range of scenarios are demonstrated for the first time with a wave optics simulation and a spatial light modulator-based laboratory benchtop counterpart. The theoretical, simulation, and benchtop intensity profiles show good agreement and illustrate that an elliptically shaped beam profile can develop upon propagation. For stronger turbulent fluctuation regimes and larger anisotropies, the theory predicts a slightly more elliptical form of the beam than is generated by the simulation or benchtop setup. The theory also predicts that without an outer scale limit, the beam width becomes unbounded as the power spectral slope index α approaches a maximum value of 4. This behavior is not seen in the simulation or benchtop results because the numerical phase screens used for these studies do not model the unbounded wavefront tilt component implied in the analytic theory.

Experimental study of a compressive line sensing imaging system in a turbulent environment.

Turbulence poses challenges in many atmospheric and underwater surveillance applications. The compressive line sensing (CLS) active imaging scheme has been demonstrated in simulations and test tank experiments to be effective in scattering media such as turbid coastal water, fog, and mist. The CLS sensing model adopts the distributed compressive sensing theoretical framework that exploits both intrasignal sparsity and the highly correlated nature of adjacent areas in a natural scene. During sensing operation, the laser illuminates the spatial light modulator digital micromirror device to generate a series of one-dimensional binary sensing patterns from a codebook to encode the current target line segment. A single element detector photomultiplier tube acquires target reflections as the encoder output. The target can then be recovered using the encoder output and a predicted on-target codebook that reflects the environmental interference of original codebook entries. In this work, we investigated the effectiveness of the CLS imaging system in a turbulent environment. The development of a compact CLS prototype will be discussed, as will a series of experiments using various turbulence intensities at the Naval Research Lab's Simulated Turbulence and Turbidity Environment. The experimental results showed that the time-averaged measurements improved both the signal-to-noise radio and the resolution of the reconstructed image in the extreme turbulence environment. The contributing factors for this intriguing and promising result will be discussed.

Numerical modeling of Schell-model beams with arbitrary far-field patterns.

An approach is described for creating random complex screens to be used in computer simulations of arbitrary Schell-model beams with a prescribed far-field intensity distribution. Simulation examples including beam profiles with reflection symmetry and rotational symmetry, flat-top, and pyramidal shapes are presented to verify the proposed approach. A more general scenario with a nonsymmetric far-field beam shape is illustrated to demonstrate the evolution in the free-space propagation from the source plane to the far zone.

SLM-based laboratory simulations of Kolmogorov and non-Kolmogorov anisotropic turbulence.

In this paper, we present a laboratory setup to simulate anisotropic, non-Kolmogorov turbulence. A sequence of numerical phase screens that incorporate the turbulence characteristics were applied to a spatial light modulator placed in the path of a laser beam with a Gaussian intensity profile and the resulting far-field intensity patterns were recorded by a CCD camera. The values of scintillation at the position of the maximum intensity were extracted from the images and compared with theoretical values. Our experimental results show a trend that is in agreement with known theoretical expressions; however, the turbulence rescaling due to anisotropy shows some discrepancy with theory and requires more investigation.

Complex index of refraction estimation from degree of polarization with diffuse scattering consideration.

The estimation of the refractive index from optical scattering off a target's surface is an important task for remote sensing applications. Optical polarimetry is an approach that shows promise for refractive index estimation. However, this estimation often relies on polarimetric models that are limited to specular targets involving single surface scattering. Here, an analytic model is developed for the degree of polarization (DOP) associated with reflection from a rough surface that includes the effect of diffuse scattering. A multiplicative factor is derived to account for the diffuse component and evaluation of the model indicates that diffuse scattering can significantly affect the DOP values. The scattering model is used in a new approach for refractive index estimation from a series of DOP values that involves jointly estimating n, k, and ρ(d)with a nonlinear equation solver. The approach is shown to work well with simulation data and additive noise. When applied to laboratory-measured DOP values, the approach produces significantly improved index estimation results relative to reference values.

Computational approaches for generating electromagnetic Gaussian Schell-model sources.

Two different methodologies for generating an electromagnetic Gaussian-Schell model source are discussed. One approach uses a sequence of random phase screens at the source plane and the other uses a sequence of random complex transmittance screens. The relationships between the screen parameters and the desired electromagnetic Gaussian-Schell model source parameters are derived. The approaches are verified by comparing numerical simulation results with published theory. This work enables one to design an electromagnetic Gaussian-Schell model source with pre-defined characteristics for wave optics simulations or laboratory experiments.

TSG6-Exo@CS/GP Attenuates Endometrium Fibrosis by Inhibiting Macrophage Activation in a Murine IUA Model.

Intrauterine adhesion (IUA) is characterized by the formation of fibrous scar tissue within the uterine cavity, which significantly impacts female reproductive health and even leads to infertility. Unfortunately, severe cases of IUA currently lack effective treatments. This study presents a novel approach that utilizes tumor necrosis factor-(TNF) stimulated gene 6 (TSG6)-modified exosomes (Exos) in conjunction with an injectable thermosensitive hydrogel (CS/GP) to mitigate the occurrence of IUA by reducing endometrium fibrosis in a mouse IUA model. This study demonstrate that TSG6-modified Exos effectively inhibits the activation of inflammatory M1-like macrophages during the initial stages of inflammation and maintains the balance of macrophage phenotypes (M1/M2) during the repair phase. Moreover, TSG6 inhibits the interaction between macrophages and endometrial stromal fibroblasts, thereby preventing the activation of stromal fibroblasts into myofibroblasts. Furthermore, this research indicates that CS/GP facilitates the sustained release of TSG6-modified Exos, leading to a significant reduction in both the manifestations of IUA and the extent of endometrium fibrosis. Collectively, through the successful construction of CS/GP loaded with TSG6-modified Exos, a reduction in the occurrence and progression of IUA is achieved by mitigating endometrium fibrosis. Consequently, this approach holds promise for the treatment of IUA.

Analysis and simulation of a fiber bundle method for creating a partially spatially coherent beam.

A fiber bundle arrangement containing a distribution of fiber lengths has been proposed in the literature to produce a partially spatially coherent beam. Light input to the bundle with limited temporal coherence is translated into limited spatial coherence. Expressions are developed for the bundle pupil autocorrelation function and far-field irradiance pattern. A numerical simulation approach is implemented and results are compared with a speckle-free result. The fiber bundle approach tends to create an irradiance pattern whose average shape matches the pattern produced by a single fiber. A "smoothed" far-field pattern is obtained if the fiber length difference is much greater than the source temporal coherence length.

Scintillation analysis of truncated Bessel beams via numerical turbulence propagation simulation.

Scintillation aspects of truncated Bessel beams propagated through atmospheric turbulence are investigated using a numerical wave optics random phase screen simulation method. On-axis, aperture averaged scintillation and scintillation relative to a classical Gaussian beam of equal source power and scintillation per unit received power are evaluated. It is found that in almost all circumstances studied, the zeroth-order Bessel beam will deliver the lowest scintillation. Low aperture averaged scintillation levels are also observed for the fourth-order Bessel beam truncated by a narrower source window. When assessed relative to the scintillation of a Gaussian beam of equal source power, Bessel beams generally have less scintillation, particularly at small receiver aperture sizes and small beam orders. Upon including in this relative performance measure the criteria of per unit received power, this advantageous position of Bessel beams mostly disappears, but zeroth- and first-order Bessel beams continue to offer some advantage for relatively smaller aperture sizes, larger source powers, larger source plane dimensions, and intermediate propagation lengths.

Platelet-Rich Plasma Improves Pregnancy Outcomes in Moderate to Severe Intrauterine Adhesion: A Retrospective Cohort Study.

The purpose of the present study was to investigate the therapeutic effects of platelet-rich plasma (PRP) in women with moderate to severe intrauterine adhesion (IUA). A retrospective cohort study was conducted at a reproductive medical center between July 2020 and June 2021 to compare the clinical pregnancy rate of two groups (PRP and non-PRP groups) after hysteroscopic adhesiolysis. A multivariate logistic regression analysis and propensity score matching (PSM) were performed to minimize potential bias. According to our inclusion and exclusion criteria, 133 patients were finally enrolled and divided into the PRP group (n = 48) and non-PRP group (n = 85). In the primary comparison, the clinical pregnancy rate in the PRP group was higher than that in the non-PRP group (41.7% vs. 28.2%, p = 0.114), albeit without statistical significance. Multivariate logistic regression analysis was performed, and the results of the adjusted model showed that PRP treatment significantly improved the clinical pregnancy rate (adjusted OR = 3.00, 95% CI = 1.22-7.38, p = 0.017). After PSM, the clinical pregnancy rate was higher in the PRP group than that in the non-PRP group (46.2% vs. 20.5%, p = 0.031). Based on the present study, we concluded that intrauterine perfusion of PRP had great potential in improving the clinical pregnancy rate in patients with moderate to severe IUA. Therefore, we recommend the application of PRP in the treatment of IUA.