Comparative clinical outcome following individualized follitropin delta dosing in Chinese women undergoing ovarian stimulation for in vitro fertilization /intracytoplasmic sperm injection.

BACKGROUND: To compare the efficacy and safety of follitropin delta in its individualized fixed-dose regimen with follitropin alfa in a conventional adjustable dosing regimen in Chinese women.  METHODS: This was a subgroup analysis of the randomized, multi-center, assessor-blind, non-inferiority trial (GRAPE) including 759 Chinese women (aged 20-40 years) recruited in 16 reproductive medicine clinics in China. Women were randomized in a 1:1 ratio to be treated with either follitropin delta dose based on anti-Müllerian hormone (AMH) and body weight or conventional dosing with follitropin alfa following a gonadotropin-releasing hormone (GnRH) antagonist protocol. The primary outcome was ongoing pregnancy rate assessed 10-11 weeks after embryo transfer in the fresh cycle (non-inferiority margin -10.0%). RESULTS: 378 in the follitropin delta group and 381 in the follitropin alfa group were randomized and exposed. Non-inferiority was confirmed with respect to ongoing pregnancy with rates of 31.0% vs. 25.7% for follitropin delta compared to follitropin alfa, estimated mean difference of 5.1% (95% confidence interval (CI) -1.3% to 11.5%). The clinical pregnancy rate (35.4% vs. 31.5%, P = 0.239) and live birth rate (31.0% vs. 25.5%, P = 0.101) were comparable between the follitropin delta group and the follitropin alfa group. Overall, the individualized follitropin delta treatment resulted in fewer oocytes retrieved compared to follitropin alfa treatment (10.3 ± 6.2 vs. 12.5 ± 7.5, P < 0.001), which was mainly due to fewer oocytes (10.5 ± 6.4 vs. 13.9 ± 7.8) in women with AMH ≥ 15 pmol/L. Accordingly there was a lower incidence of early ovarian hyper-stimulation syndrome (OHSS) and/or preventive interventions (6.1% vs. 11.0%, P = 0.013). A daily follitropin delta dose of 10.2 µg (95% CI: 9.3-11.2 µg) was estimated to provide the same number of oocytes retrieved as a starting dose of 150 IU/d of follitropin alfa. CONCLUSION: Follitropin delta in its individualized fixed-dose regimen showed similar efficacy and improved safety compared with follitropin alfa in a conventional adjustable dosing regimen in Chinese women. CLINICAL TRIAL REGISTRATION NUMBER: NCT03296527.

Effects of leukocytospermia on the outcomes of assisted reproductive technology.

Leukocytospermia is one of the common causes of male infertility, and its effects on the clinical outcomes of assisted reproduction are controversial. There are no recommendations for the management of leukocytospermia in cases of assisted reproductive technology (ART). To investigate the impact of leukocytospermia on ART, we retrospectively compared the clinical outcomes in ART couples with or without leukocytospermia and further analysed the impact of the insemination method itself by split insemination treatment in ART couples with leukocytospermia. In this study, leukocytospermia was detected in 133 patients, namely 63 in the conventional in vitro fertilization (IVF) group, 38 in the intracytoplasmic sperm injection (ICSI) group and 32 in the split insemination group. Leukocytospermia has a negative influence on the parameters of semen samples; however, leukocytospermia did not affect the clinical outcomes of IVF or ICSI. Different insemination methods did not affect the fertilization, clinical pregnancy or live birth rates. In the split insemination study, no significant differences in clinical pregnancy and live birth rates between the IVF and ICSI groups were found; however, the numbers of two pronuclei (2PN), available embryos and good-quality embryos in the ICSI group were higher than those in the IVF group. Leukocytospermia may be a risk factor affecting semen parameters, and more attention should be given to IVF insemination. Leukocytospermia has no significant negative effect on the outcomes of ART. ICSI may obtain better embryos than IVF, but it cannot improve the clinical pregnancy and live birth rates.

Neural Style Transfer: A Review.

The seminal work of Gatys et al. demonstrated the power of Convolutional Neural Networks (CNNs) in creating artistic imagery by separating and recombining image content and style. This process of using CNNs to render a content image in different styles is referred to as Neural Style Transfer (NST). Since then, NST has become a trending topic both in academic literature and industrial applications. It is receiving increasing attention and a variety of approaches are proposed to either improve or extend the original NST algorithm. In this paper, we aim to provide a comprehensive overview of the current progress towards NST. We first propose a taxonomy of current algorithms in the field of NST. Then, we present several evaluation methods and compare different NST algorithms both qualitatively and quantitatively. The review concludes with a discussion of various applications of NST and open problems for future research. A list of papers discussed in this review, corresponding codes, pre-trained models and more comparison results are publicly available at: https://osf.io/f8tu4/.

Fluorescence Image Histology Pattern Transformation Using Image Style Transfer.

Confocal laser endomicroscopy (CLE) allow on-the-fly in vivo intraoperative imaging in a discreet field of view, especially for brain tumors, rather than extracting tissue for examination ex vivo with conventional light microscopy. Fluorescein sodium-driven CLE imaging is more interactive, rapid, and portable than conventional hematoxylin and eosin (H&E)-staining. However, it has several limitations: CLE images may be contaminated with artifacts (motion, red blood cells, noise), and neuropathologists are mainly trained on colorful stained histology slides like H&E while the CLE images are gray. To improve the diagnostic quality of CLE, we used a micrograph of an H&E slide from a glioma tumor biopsy and image style transfer, a neural network method for integrating the content and style of two images. This was done through minimizing the deviation of the target image from both the content (CLE) and style (H&E) images. The style transferred images were assessed and compared to conventional H&E histology by neurosurgeons and a neuropathologist who then validated the quality enhancement in 100 pairs of original and transformed images. Average reviewers' score on test images showed 84 out of 100 transformed images had fewer artifacts and more noticeable critical structures compared to their original CLE form. By providing images that are more interpretable than the original CLE images and more rapidly acquired than H&E slides, the style transfer method allows a real-time, cellular-level tissue examination using CLE technology that closely resembles the conventional appearance of H&E staining and may yield better diagnostic recognition than original CLE grayscale images.

Prospects for Theranostics in Neurosurgical Imaging: Empowering Confocal Laser Endomicroscopy Diagnostics via Deep Learning.

Confocal laser endomicroscopy (CLE) is an advanced optical fluorescence imaging technology that has potential to increase intraoperative precision, extend resection, and tailor surgery for malignant invasive brain tumors because of its subcellular dimension resolution. Despite its promising diagnostic potential, interpreting the gray tone fluorescence images can be difficult for untrained users. CLE images can be distorted by motion artifacts, fluorescence signals out of detector dynamic range, or may be obscured by red blood cells, and thus interpreted as nondiagnostic (ND). However, just a single CLE image with a detectable pathognomonic histological tissue signature can suffice for intraoperative diagnosis. Dealing with the abundance of images from CLE is not unlike sifting through a myriad of genes, proteins, or other structural or metabolic markers to find something of commonality or uniqueness in cancer that might indicate a potential treatment scheme or target. In this review, we provide a detailed description of bioinformatical analysis methodology of CLE images that begins to assist the neurosurgeon and pathologist to rapidly connect on-the-fly intraoperative imaging, pathology, and surgical observation into a conclusionary system within the concept of theranostics. We present an overview and discuss deep learning models for automatic detection of the diagnostic CLE images and discuss various training regimes and ensemble modeling effect on power of deep learning predictive models. Two major approaches reviewed in this paper include the models that can automatically classify CLE images into diagnostic/ND, glioma/nonglioma, tumor/injury/normal categories, and models that can localize histological features on the CLE images using weakly supervised methods. We also briefly review advances in the deep learning approaches used for CLE image analysis in other organs. Significant advances in speed and precision of automated diagnostic frame selection would augment the diagnostic potential of CLE, improve operative workflow, and integration into brain tumor surgery. Such technology and bioinformatics analytics lend themselves to improved precision, personalization, and theranostics in brain tumor treatment.

The impact of two different thaw protocols on outcomes of vitrified cleavage-stage embryos transfer.

The objective of this study was to evaluate the gestational results obtained with vitrified-thawed human cleavage-stage embryo by two different thaw protocols. Embryo development was observed to cleavage-stage and embryos were cryopreserved by vitrification on day 3 after oocyte retrieval. 51 cycles were thawed using vitrification warming kit with decreasing concentrations of sucrose in 3 dilutions ( 1.0, 0.5 and 0 mol per L respectively) as group 1, 56 cycles were thawed with decreasing concentrations of sucrose in 5 dilutions ( 0.8, 0.6, 0.33, 0.2 and 0 mol per L respectively) as group 2. Embryo survival (> 50 percent intact blastomeres), complete embryo survival (100 percent intact blastomeres), pregnancy and implantation rates were compared, and development rates the day after thawing were also compared. Multivariate analysis showed a significant difference in embryo immediate morphological survival rate, complete survival and clinical pregnancies rate between the two groups respectively (87.0 vs. 98.6 percent, p=0.000; 71.0 vs 82.0 percent embryo subsequent development rates, mean number of transferred embryos was similar between the two groups. (61.4 vs. 61.3 percent, p=0.502; 2.2 +/ 0.5 vs. 2.4 +/- 0.6, p=0.113). In addition, no differences in implantation rate were observed between two groups (17.7 vs. 25.6 percent, P=0.138). No difference in the multiple pregnancy rates was found among the two groups also.

Successful pregnancy following the transfer of vitrified blastocyst which developed from poor quality embryos on day 3.

BACKGROUND: The selection of pre-embryos for transferred is based on morphological appearance. But some poor quality cleaved embryos also can be cultured to the blastocyst stage and implanted. OBJECTIVE: To assess the clinical pregnancy outcomes of blastocyst transfer which developed from poor quality embryos. MATERIALS AND METHODS: A total of 109 cleaved embryos with poor quality were cultured to day 5/day 6 and 27 (24.8%) blastocysts were collected from the 15 cycles/patients undergoing conventional IVF. All the blastocysts were cooling with fast-freezing. Then the blastocysts were warmed for transfer. RESULTS: All of 25 vitrified blastocysts (92.6%) survived after warming and were transferred to 15 patients. Five of the women became pregnant. CONCLUSION: Our results suggest that vitrified human day 5/day 6 blastocyst transfer which develop from poor quality embryo at day 3 can contribute to increasing cumulative pregnancy rates in assisted reproduction.

Effect of the size of zona pellucida thinning by laser assisted hatching on clinical outcome of human frozen-thawed embryo transfers.

Of 122 consecutive procedures, 31 were not assisted hatching (AH), which served as the control group, 34 were AH with 40 microm thinning of the zona, and 57 were AH with 80 microns of the zona thinning. The pregnancy and implantation rates were significantly higher in 80 microns thinning group compared to control group (40.3 vs. 16.1 percent, P=0.03; 21.5 vs. 7.5 percent, P=0.007, respectively). In addition, the implantation rate was signigicantly higher in 80 microns group than in 40 microns group (21.5 percent vs.9.4 percent, P=0.024). The results indicated that the size of the zona pellucida thinning by laser may influence the pregnancy and implantation rates following frozen-thawed cleaved embryo transfer.

[The role of progesterone in the regulation of gene expression of insulin-like growth factor-I receptor in human decidual stromal cells of early pregnancy in vitro].

OBJECTIVE: To assess the effect of progesterone on the gene expression of insulin-like growth factor-I receptor (IGF-I R) in human decidual stromal cells of early pregnancy in vitro. METHODS: Semiquantitative reverse transcriptase polymerase chain reaction, using beta-ACTIN as internal standard, was applied to determine the levels of IGF-I R mRNA in human decidual stromal cells of early pregnancy in vitro after cultured with different concentrations of progesterone for 72 hours or cultured with 0.1 mumol/L of progesterone for different periods of time. RESULTS: The expression of IGF-I R mRNA was significantly positive in human decidual stromal cells of early pregnancy in vitro. The levels of IGF-I R mRNA were down-regulated by progesterone, and showed significant negative-correlation with the concentration of progesterone (r = -0.680, P < 0.001). The levels of IGF-I R mRNA showed no significant correlation with time when the final concentration of progesterone was 0.1 mumol/L (r = 0.005, P > 0.05). CONCLUSION: Progesterone may play an important role in the regulation of proliferation and decidualization of stromal cells by down-regulating the expression of IGF-I R mRNA in human decidual stromal cells of early pregnancy, which is important for the maintenance of early pregnancy.