Venous Thromboembolism Risk Assessment Models in Obstetrics: A Review of Current Practices and Future Directions.

Pregnancy is a major risk factor for venous thromboembolism (VTE) and its associated complications. The hypercoagulable state in both the antenatal and postnatal periods contributes to thromboembolism and continues to be a leading cause of maternal morbidity and mortality worldwide. The non-specific signs and symptoms of VTE in pregnancy and the lack of specific Risk Assessment Models (RAMs) propose a diagnostic challenge in the obstetric population. This review aims to discuss and compare existing RAMs and highlights the important challenges of using established RAMs in obstetric patients. It also emphasizes the importance of enhancing and individualizing RAMs in obstetrics to improve maternal healthcare. KEY POINTS: · VTE is a major complication of pregnancy, associated with increased maternal morbidity and mortality.. · VTE RAMs lack sensitivity and specificity in stratifying VTE risk in pregnancy.. · Validating VTE RAMs in the obstetric population aims to improve maternal outcomes..

Pulsatile vessel at the posterior bladder wall: A new sonographic marker for placenta percreta.

OBJECTIVE: We investigated using "pulsatile vessels at the posterior bladder wall" as a novel sonographic marker to demonstrate the severity of placenta accreta spectrum (PAS). METHODS: This observational case-control study of 30 pregnant women was performed at Hackensack Meridian Health's Center for Abnormal Placentation in 2020. The case group was made up of women with historically described sonographic signs of PAS and was compared against two control groups: (1) women with uncomplicated placenta previa and (2) women with no evidence of placenta previa sonographically. All patients were evaluated with Color Flow Doppler ultrasound to assess the presence of arterial vessels at the posterior bladder wall. The flow characteristics and resistance indices (RI) were noted in the presence of pulsatile vessels. All patients' placentation was clinically confirmed at delivery. Patients with clinical invasive placentation underwent histopathological diagnosis to confirm disease presence. RESULTS: Hundred percent of subjects in our series with suspected PAS exhibited pulsatile arterial vessels at the posterior bladder wall sonographically with a low RI of 0.38 ± 0.1 at an average of 24.6 ± 5.2 gestational weeks. Cases were histopathologically confirmed to have placenta percreta after delivery. Patients in either of the control groups did not display pulsatile vessels at the posterior bladder wall during antenatal sonographic evaluations and had no clinical evidence of PAS. CONCLUSION: The presence of posterior urinary bladder wall pulsatile arterial vessels with low RI, in addition to traditional sonographic markers increases the suspicion of severe PAS. Thus, these findings allow for the greater opportunity for coordination of patient care prior to delivery.

Exhaustion of racing sperm in nature-mimicking microfluidic channels during sorting.

Fertilization is central to the survival and propagation of a species, however, the precise mechanisms that regulate the sperm's journey to the egg are not well understood. In nature, the sperm has to swim through the cervical mucus, akin to a microfluidic channel. Inspired by this, a simple, cost-effective microfluidic channel is designed on the same scale. The experimental results are supported by a computational model incorporating the exhaustion time of sperm.

Nanoliter droplet vitrification for oocyte cryopreservation.

AIM: Oocyte cryopreservation remains largely experimental, with live birth rates of only 2-4% per thawed oocyte. In this study, we present a nanoliter droplet technology for oocyte vitrification. MATERIALS & METHODS: An ejector-based droplet vitrification system was designed to continuously cryopreserve oocytes in nanoliter droplets. Oocyte survival rates, morphologies and parthenogenetic development after each vitrification step were assessed in comparison with fresh oocytes. RESULTS: Oocytes were retrieved after cryoprotectant agent loading/unloading, and nanoliter droplet encapsulation showed comparable survival rates to fresh oocytes after 24 h in culture. Also, oocytes recovered after vitrification/thawing showed similar morphologies to those of fresh oocytes. Additionally, the rate of oocyte parthenogenetic activation after nanoliter droplet encapsulation was comparable with that observed for fresh oocytes. This nanoliter droplet technology enables the vitrification of oocytes at higher cooling and warming rates using lower cryoprotectant agent levels (i.e., 1.4 M ethylene glycol, 1.1 M dimethyl sulfoxide and 1 M sucrose), thus making it a potential technology to improve oocyte cryopreservation outcomes.

Lensless imaging for simultaneous microfluidic sperm monitoring and sorting.

5.3 million American couples of reproductive age (9%) are affected by infertility, among which male factors account for up to 50% of cases, which necessitates the identification of parameters defining sperm quality, including sperm count and motility. In vitro fertilization (IVF) with or without intra cytoplasmic sperm injection (ICSI) has become the most widely used assisted reproductive technology (ART) in modern clinical practice to overcome male infertility challenges. One of the obstacles of IVF and ICSI lies in identifying and isolating the most motile and presumably healthiest sperm from semen samples that have low sperm counts (oligozoospermia) and/or low sperm motility (oligospermaesthenia). Microfluidic systems have shown potential to sort sperm with flow systems. However, the small field of view (FOV) of conventional microscopes commonly used to image sperm motion presents challenges in tracking a large number of sperm cells simultaneously. To address this challenge, we have integrated a lensless charge-coupled device (CCD) with a microfluidic chip to enable wide FOV and automatic recording as the sperm move inside a microfluidic channel. The integrated system enables the sorting and tracking of a population of sperm that have been placed in a microfluidic channel. This channel can be monitored in both horizontal and vertical configuration similar to a swim-up column method used clinically. Sperm motilities can be quantified by tracing the shadow paths for individual sperm. Moreover, as the sperm are sorted by swimming from the inlet towards the outlet of a microfluidic channel, motile sperm that reach the outlet can be extracted from the channel at the end of the process. This technology can lead to methods to evaluate each sperm individually in terms of motility response in a wide field of view, which could prove especially useful, when working with oligozoospermic or oligospermaesthenic samples, in which the most motile sperm need to be isolated from a pool of small number of sperm.

Vitrification and levitation of a liquid droplet on liquid nitrogen.

The vitrification of a liquid occurs when ice crystal formation is prevented in the cryogenic environment through ultrarapid cooling. In general, vitrification entails a large temperature difference between the liquid and its surrounding medium. In our droplet vitrification experiments, we observed that such vitrification events are accompanied by a Leidenfrost phenomenon, which impedes the heat transfer to cool the liquid, when the liquid droplet comes into direct contact with liquid nitrogen. This is distinct from the more generally observed Leidenfrost phenomenon that occurs when a liquid droplet is self-vaporized on a hot plate. In the case of rapid cooling, the phase transition from liquid to vitrified solid (i.e., vitrification) and the levitation of droplets on liquid nitrogen (i.e., Leidenfrost phenomenon) take place simultaneously. Here, we investigate these two simultaneous physical events by using a theoretical model containing three dimensionless parameters (i.e., Stefan, Biot, and Fourier numbers). We explain theoretically and observe experimentally a threshold droplet radius during the vitrification of a cryoprotectant droplet in the presence of the Leidenfrost effect.

Engineered 3D tissue models for cell-laden microfluidic channels.

Delivery of nutrients and oxygen within three-dimensional (3D) tissue constructs is important to maintain cell viability. We built 3D cell-laden hydrogels to validate a new tissue perfusion model that takes into account nutrition consumption. The model system was analyzed by simulating theoretical nutrient diffusion into cell-laden hydrogels. We carried out a parametric study considering different microchannel sizes and inter-channel separation in the hydrogel. We hypothesized that nutrient consumption needs to be taken into account when optimizing the perfusion channel size and separation. We validated the hypothesis by experiments. We fabricated circular microchannels (r = 400 microm) in 3D cell-laden hydrogel constructs (R = 7.5 mm, volume = 5 ml). These channels were positioned either individually or in parallel within hydrogels to increase nutrient and oxygen transport as a way to improve cell viability. We quantified the spatial distribution of viable cells within 3D hydrogel scaffolds without channels and with single- and dual-perfusion microfluidic channels. We investigated quantitatively the cell viability as a function of radial distance from the channels using experimental data and mathematical modeling of diffusion profiles. Our simulations show that a large-channel radius as well as a large channel to channel distance diffuse nutrients farther through a 3D hydrogel. This is important since our results reveal that there is a close correlation between nutrient profiles and cell viability across the hydrogel.

Microfluidics for cryopreservation.

Minimizing cell damage throughout the cryopreservation process is critical to enhance the overall outcome. Osmotic shock sustained during the loading and unloading of cryoprotectants (CPAs) is a major source of cell damage during the cryopreservation process. We introduce a microfluidic approach to minimize osmotic shock to cells during cryopreservation. This approach allows us to control the loading and unloading of CPAs in microfluidic channels using diffusion and laminar flow. We provide a theoretical explanation of how the microfluidic approach minimizes osmotic shock in comparison to conventional cryopreservation protocols via cell membrane transport modeling. Finally, we show that biological experiments are consistent with the proposed mathematical model. The results indicate that our novel microfluidic-based approach improves post-thaw cell survivability by up to 25% on average over conventional cryopreservation protocols. The method developed in this study provides a platform to cryopreserve cells with higher viability, functionality, and minimal inter-technician variability. This method introduces microfluidic technologies to the field of biopreservation, opening the door to future advancements at the interface of these fields.