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1.
Hum Fertil (Camb) ; 26(4): 824-844, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37980170

ABSTRACT

Ovarian stimulation is a fundamental step in assisted reproductive technology (ART) with the intention of inducing ovarian follicle development prior to timed intercourse or intra-uterine insemination and facilitating the retrieval of multiple oocytes during a single in vitro fertilization (IVF) cycle. The basis of ovarian stimulation includes the administration of exogenous gonadotropins, with or without pre-treatment with oral hormonal therapy. Gonadotropin-releasing hormone agonist or antagonist is given in addition to the gonadotropins to prevent a premature rise of endogenous luteinizing hormone that would in turn lead to premature ovulation. With the advancement in technology, various stimulation protocols have been devised to cater for different patient needs. However, ovarian hyperstimulation syndrome and its serious complications may occur following ovarian stimulation. It is also evident that suboptimal ovarian stimulation strategies may have a negative impact on oogenesis, embryo quality, endometrial receptivity, and reproductive outcomes over recent years. This review describes the various forms of pre-treatment for ovarian stimulation and stimulation protocols, and aims to provide clinicians with the latest available evidence.


Subject(s)
Gonadotropin-Releasing Hormone , Ovulation Induction , Female , Humans , Ovulation Induction/methods , Reproductive Techniques, Assisted , Gonadotropins , Fertilization in Vitro/methods
2.
Hum Reprod Update ; 29(6): 721-740, 2023 Nov 02.
Article in English | MEDLINE | ID: mdl-37336552

ABSTRACT

BACKGROUND: In IVF/ICSI treatment, the process of embryo implantation is the success rate-limiting step. Endometrial scratching has been suggested to improve this process, but it is unclear if this procedure increases the chance of implantation and live birth (LB) and, if so, for whom, and how the scratch should be performed. OBJECTIVE AND RATIONALE: This individual participant data meta-analysis (IPD-MA) aims to answer the question of whether endometrial scratching in women undergoing IVF/ICSI influences the chance of a LB, and whether this effect is different in specific subgroups of women. After its incidental discovery in 2000, endometrial scratching has been suggested to improve embryo implantation. Numerous randomized controlled trials (RCTs) have been conducted, showing contradicting results. Conventional meta-analyses were limited by high within- and between-study heterogeneity, small study samples, and a high risk of bias for many of the trials. Also, the data integrity of several trials have been questioned. Thus, despite numerous RCTs and a multitude of conventional meta-analyses, no conclusion on the clinical effectiveness of endometrial scratching could be drawn. An IPD-MA approach is able to overcome many of these problems because it allows for increased uniformity of outcome definitions, can filter out studies with data integrity concerns, enables a more precise estimation of the true treatment effect thanks to adjustment for participant characteristics and not having to make the assumptions necessary in conventional meta-analyses, and because it allows for subgroup analysis. SEARCH METHODS: A systematic literature search identified RCTs on endometrial scratching in women undergoing IVF/ICSI. Authors of eligible studies were invited to share original data for this IPD-MA. Studies were assessed for risk of bias (RoB) and integrity checks were performed. The primary outcome was LB, with a one-stage intention to treat (ITT) as the primary analysis. Secondary analyses included as treated (AT), and the subset of women that underwent an embryo transfer (AT+ET). Treatment-covariate interaction for specific participant characteristics was analyzed in AT+ET. OUTCOMES: Out of 37 published and 15 unpublished RCTs (7690 participants), 15 RCTs (14 published, one unpublished) shared data. After data integrity checks, we included 13 RCTs (12 published, one unpublished) representing 4112 participants. RoB was evaluated as 'low' for 10/13 RCTs. The one-stage ITT analysis for scratch versus no scratch/sham showed an improvement of LB rates (odds ratio (OR) 1.29 [95% CI 1.02-1.64]). AT, AT+ET, and low-RoB-sensitivity analyses yielded similar results (OR 1.22 [95% CI 0.96-1.54]; OR 1.25 [95% CI 0.99-1.57]; OR 1.26 [95% CI 1.03-1.55], respectively). Treatment-covariate interaction analysis showed no evidence of interaction with age, number of previous failed embryo transfers, treatment type, or infertility cause. WIDER IMPLICATIONS: This is the first meta-analysis based on IPD of more than 4000 participants, and it demonstrates that endometrial scratching may improve LB rates in women undergoing IVF/ICSI. Subgroup analysis for age, number of previous failed embryo transfers, treatment type, and infertility cause could not identify subgroups in which endometrial scratching performed better or worse. The timing of endometrial scratching may play a role in its effectiveness. The use of endometrial scratching in clinical practice should be considered with caution, meaning that patients should be properly counseled on the level of evidence and the uncertainties.


Subject(s)
Fertilization in Vitro , Infertility, Female , Pregnancy , Female , Humans , Fertilization in Vitro/methods , Pregnancy Rate , Sperm Injections, Intracytoplasmic/methods , Embryo Transfer/methods , Birth Rate , Live Birth , Infertility, Female/therapy
3.
Front Neurosci ; 17: 1104419, 2023.
Article in English | MEDLINE | ID: mdl-36968482

ABSTRACT

Neural engineering is an emerging and multidisciplinary field in which engineering approaches are applied to neuroscience problems. Women are underrepresented in engineering fields, and indeed in science, technology, engineering, and mathematics (STEM) fields generally. Underrepresentation of women is particularly notable at later academic career stages, suggesting that even though women are interested in the field, barriers exist that ultimately cause them to leave. Here, we investigate many of the obstacles to women's success in the field of neural engineering and provide recommendations and materials to overcome them. We conducted a review of the literature from the past 15 years regarding the experiences of women in academic careers, as well as reports on the number of women in fields closely related to neural engineering from the National Science Foundation (NSF) and the American Society for Engineering Education (ASEE). Additionally, we interviewed six women in neural engineering who are involved in initiatives and outreach concerning the inclusion and experiences of women in engineering. Throughout the literature and interviews, we identified common themes spanning the role of identity and confidence, professional relationships, career-related hurdles, and personal and professional expectations. We explore each of these themes in detail and provide resources to support the growth of women as they climb within the field of neural engineering.

4.
Hum Genet ; 142(3): 363-377, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36526900

ABSTRACT

Currently, routine genetic investigation for male infertility includes karyotyping analysis and PCR for Y chromosomal microdeletions to provide prognostic information such as sperm retrieval success rate. However, over 85% of male infertility remain idiopathic. We assessed 101 male patients with primary infertility in a retrospective cohort analysis who have previously received negative results from standard-of-care tests. Mate-pair genome sequencing (large-insert size library), an alternative long-DNA sequencing method, was performed to detect clinically significant structural variants (SVs) and copy-number neutral absence of heterozygosity (AOH). Candidate SVs were filtered against our in-house cohort of 1077 fertile men. Genes disrupted by potentially clinically significant variants were correlated with single-cell gene expression profiles of human fetal and postnatal testicular developmental lineages and adult germ cells. Follow-up studies were conducted for each patient with clinically relevant finding(s). Molecular diagnoses were made in 11.1% (7/63) of patients with non-obstructive azoospermia and 13.2% (5/38) of patients with severe oligozoospermia. Among them, 12 clinically significant SVs were identified in 12 cases, including five known syndromes, one inversion, and six SVs with direct disruption of genes by intragenic rearrangements or complex insertions. Importantly, a genetic defect related to intracytoplasmic sperm injection (ICSI) failure was identified in a patient with non-obstructive azoospermia, illustrating the additional value of an etiologic diagnosis in addition to determining sperm retrieval rate. Our study reveals a landscape of various genomic variants in 101 males with idiopathic infertility, not only advancing understanding of the underlying mechanisms of male infertility, but also impacting clinical management.


Subject(s)
Azoospermia , Infertility, Male , Adult , Humans , Male , Azoospermia/genetics , Retrospective Studies , Semen , Infertility, Male/genetics , Testis
5.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 2314-2318, 2022 07.
Article in English | MEDLINE | ID: mdl-36085716

ABSTRACT

Biases in attention to emotional stimuli (i.e., affect-biased attention) contribute to the development and mainte-nance of depression and anxiety and may be a promising target for intervention. Past attempts to therapeutically modify affect-biased attention have been unsatisfactory due to issues with reliability and precision. Electroencephalogram (EEG)-derived steady-state visual evoked potentials (SSVEPS) provide a temporally-sensitive biological index of attention to competing visual stimuli at the level of neuronal populations in the visual cortex. SSVEPS can potentially be used to quantify whether affective distractors vs. task-relevant stimuli have "won" the competition for attention at a trial-by-trial level during neuro-feedback sessions. This study piloted a protocol for a SSVEP-based neurofeedback training to modify affect-biased attention using a portable augmented-reality (AR) EEG interface. During neurofeedback sessions with five healthy participants, signifi-cantly greater attention was given to the task-relevant stimulus (a Gabor patch) than to affective distractors (negative emotional expressions) across SSVEP indices (p<0.000l). SSVEP indices exhibited excellent internal consistency as evidenced by a maximum Guttman split-half coefficient of 0.97 when comparing even to odd trials. Further testing is required, but findings suggest several SSVEP neurofeedback calculation methods most deserving of additional investigation and support ongoing efforts to develop and implement a SSVEP-guided AR-based neurofeedback training to modify affect-biased attention in adolescent girls at high risk for depression.


Subject(s)
Attentional Bias , Augmented Reality , Neurofeedback , Adolescent , Evoked Potentials, Visual , Female , Humans , Reproducibility of Results
6.
Article in English | MEDLINE | ID: mdl-35786558

ABSTRACT

We aim to build a system incorporating electroencephalography (EEG) and augmented reality (AR) that is capable of identifying the presence of visual spatial neglect (SN) and mapping the estimated neglected visual field. An EEG-based brain-computer interface (BCI) was used to identify those spatiospectral features that best detect participants with SN among stroke survivors using their EEG responses to ipsilesional and contralesional visual stimuli. Frontal-central delta and alpha, frontal-parietal theta, Fp1 beta, and left frontal gamma were found to be important features for neglect detection. Additionally, temporal analysis of the responses shows that the proposed model is accurate in detecting potentially neglected targets. These targets were predicted using common spatial patterns as the feature extraction algorithm and regularized discriminant analysis combined with kernel density estimation for classification. With our preliminary results, our system shows promise for reliably detecting the presence of SN and predicting visual target responses in stroke patients with SN.


Subject(s)
Augmented Reality , Brain-Computer Interfaces , Perceptual Disorders , Stroke , Electroencephalography , Humans , Perceptual Disorders/diagnosis , Perceptual Disorders/etiology , Stroke/complications , Stroke/diagnosis
7.
Reprod Biomed Online ; 44(2): 295-303, 2022 02.
Article in English | MEDLINE | ID: mdl-34949538

ABSTRACT

RESEARCH QUESTION: What is the effect of adding an anti-spasmodic drug to an existing ultrasound-guided manual vacuum aspiration (USG-MVA) protocol to alleviate immediate post-procedure abdominal cramping pain in women treated for early pregnancy loss? DESIGN: Double-blind, placebo-controlled, randomized controlled trial conducted between February 2018 and January 2020. Participants were assigned to receive a 1-ml intravenous injection containing 20-mg hyoscine butylbromide (HBB) (n=55) or saline (n =56) as a control immediately before USG-MVA. Primary outcome was reduced abdominal pain after adding a 20-mg dose of HBB to the current pain control regimen. Secondary outcomes were vaginal pain, complications and side-effects, women's pre- and post-procedure psychological state, physiological stress (saliva alpha-amylase) and procedure pain control satisfaction. Two-way mixed ANOVA was used to evaluate the main effects and interactions. RESULTS: VAS abdominal pain scores in the HBB group were 16% lower immediately after and 21% lower 2 h after surgery (not statistically significant). Two-way ANOVA indicated that time (F[1108] = 83.41, P < 0.001) was the only significant main effect for reduced abdominal pain after the procedure and vaginal pain score (F[1108] = 180.1, P < 0.0001) but not drug received. No adverse events were reported. No significant difference was found for psychological state, physiological stress and procedure pain control satisfaction between the two groups. CONCLUSIONS: Anti-spasmodic drugs can help to reduce abdominal cramping pain associated with USG-MVA; HBB produced an insignificant decrease in abdominal pain score. Further studies with longer acting or larger doses of anti-spasmodic drugs are warranted.


Subject(s)
Scopolamine , Vacuum Curettage , Abdominal Pain/chemically induced , Abdominal Pain/drug therapy , Butylscopolammonium Bromide/adverse effects , Butylscopolammonium Bromide/therapeutic use , Double-Blind Method , Female , Humans , Hydrocarbons, Brominated , Pregnancy , Scopolamine/therapeutic use , Ultrasonography, Interventional
8.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 1096-1099, 2021 11.
Article in English | MEDLINE | ID: mdl-34891478

ABSTRACT

Spatial neglect (SN) is a neurological disorder that causes inattention to visual stimuli in the contralesional visual field, stemming from unilateral brain injury such as stroke. The current gold standard method of SN assessment, the conventional Behavioral Inattention Test (BIT-C), is highly variable and inconsistent in its results. In our previous work, we built an augmented reality (AR)-based BCI to overcome the limitations of the BIT-C and classified between neglected and non-neglected targets with high accuracy. Our previous approach included personalization of the neglect detection classifier but the process required rigorous retraining from scratch and time-consuming feature selection for each participant. Future steps of our work will require rapid personalization of the neglect classifier; therefore, in this paper, we investigate fine-tuning of a neural network model to hasten the personalization process.


Subject(s)
Perceptual Disorders , Stroke , Electroencephalography , Functional Laterality , Humans , Perceptual Disorders/diagnosis , Stroke/diagnosis , Visual Fields
9.
Reprod Biomed Online ; 43(2): 310-318, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34193356

ABSTRACT

RESEARCH QUESTION: Is there a difference in the ovarian reserve 1 year post-operatively in those who used a haemostatic sealant or bipolar diathermy for haemostasis during laparoscopic ovarian cystectomy for ovarian endometriomas? DESIGN: This was an extended follow-up observational study of a previous randomized controlled trial where women aged 18 to 40 years with 3-8 cm unilateral or bilateral endometriomas were randomized to receive haemostasis by a haemostatic sealant or bipolar diathermy following ovarian cystectomy. The primary outcome was the ovarian reserve as assessed by antral follicle count (AFC) 1 year post-operatively. Secondary outcomes included the recurrence rate of ovarian endometrioma, the change in anti-Müllerian hormone (AMH) and FSH concentrations, and reproductive outcomes. RESULTS: The significant increase in AFC at 3 months after initial surgery (P = 0.025) in the haemostatic sealant group compared with the diathermy group was sustained at 1 year (P = 0.024) but there was no difference in AMH or FSH concentrations between the groups throughout the follow-up period. The recurrence rate in the FloSeal group was 7.7% (n = 3/39) compared with 22.2% (n = 8/36) in the diathermy group (P = 0.060). The recurrence rate in women who had bilateral lesions was significantly higher than those with unilateral lesions (risk ratio 5.33, interquartile range 1.55-18.38). No difference in reproductive outcomes was found between the two groups. CONCLUSIONS: Applying haemostatic sealant after laparoscopic cystectomy of ovarian endometriomas produces a significantly greater improvement in AFC, which was apparent at 3-month follow-up, and was sustained at 1-year follow-up without compromising the recurrence rate.


Subject(s)
Diathermy/methods , Gelatin Sponge, Absorbable/therapeutic use , Neoplasm Recurrence, Local , Ovarian Cysts/therapy , Ovarian Reserve , Adolescent , Adult , Endometriosis/pathology , Endometriosis/physiopathology , Endometriosis/therapy , Female , Follow-Up Studies , Hemostatic Techniques , Hemostatics/therapeutic use , Hong Kong , Humans , Laparoscopy/methods , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/physiopathology , Ovarian Cysts/pathology , Ovarian Cysts/physiopathology , Ovarian Diseases/pathology , Ovarian Diseases/physiopathology , Ovarian Diseases/therapy , Ovarian Reserve/drug effects , Postoperative Period , Treatment Outcome , Young Adult
10.
Asian J Androl ; 23(2): 150-156, 2021.
Article in English | MEDLINE | ID: mdl-33154201

ABSTRACT

Cryopreservation impairs sperm quality and functions, including motility and DNA integrity. Antioxidant additives in sperm freezing media have previously brought improvements in postthawed sperm quality. Green tea extract (GTE) is widely considered as an excellent antioxidant, and its beneficial role has been proven in other human cells. This study aims to evaluate the GTE as a potential additive in cryopreservation media of human spermatozoa. In part one, the semen of 20 normozoospermic men was used to optimize the concentration of GTE that maintains sperm motility and DNA integrity against oxidative stress, induced by hydrogen peroxide (H2O2). Spermatozoa were treated with GTE at different concentrations before incubation with H2O2. In part two, the semen of 45 patients was cryopreserved with or without 1.0 ng ml-1 GTE. After 2 weeks, the semen was thawed, and the effect on sperm motility and DNA fragmentation was observed. Our data showed that GTE significantly protected sperm motility and DNA integrity against oxidative stress induced by H2O2when added at a final concentration of 1.0 ng ml-1. We found that the addition of 1.0 ng ml-1 GTE to cryopreservation media significantly increased sperm motility and DNA integrity (both P < 0.05). More interestingly, patients with high sperm DNA damage benefited similarly from the GTE supplementation. However, there was no significant change in the reactive oxygen species (ROS) level. In conclusion, supplementing sperm freezing media with GTE has a significant protective effect on human sperm motility and DNA integrity, which may be of clinical interest.


Subject(s)
Cryopreservation , Cryoprotective Agents/pharmacology , DNA/drug effects , Plant Extracts/pharmacology , Semen Preservation , Sperm Motility/drug effects , Spermatozoa/drug effects , Tea , Humans , Hydrogen Peroxide/pharmacology , Male , Oxidants/pharmacology , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Spermatozoa/metabolism
11.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 264-267, 2020 07.
Article in English | MEDLINE | ID: mdl-33017979

ABSTRACT

Spatial neglect (SN) is a neurological syndrome in stroke patients, commonly due to unilateral brain injury. It results in inattention to stimuli in the contralesional visual field. The current gold standard for SN assessment is the behavioral inattention test (BIT). BIT includes a series of penand-paper tests. These tests can be unreliable due to high variablility in subtest performances; they are limited in their ability to measure the extent of neglect, and they do not assess the patients in a realistic and dynamic environment. In this paper, we present an electroencephalography (EEG)-based brain-computer interface (BCI) that utilizes the Starry Night Test to overcome the limitations of the traditional SN assessment tests. Our overall goal with the implementation of this EEG-based Starry Night neglect detection system is to provide a more detailed assessment of SN. Specifically, to detect the presence of SN and its severity. To achieve this goal, as an initial step, we utilize a convolutional neural network (CNN) based model to analyze EEG data and accordingly propose a neglect detection method to distinguish between stroke patients without neglect and stroke patients with neglect.Clinical relevance-The proposed EEG-based BCI can be used to detect neglect in stroke patients with high accuracy, specificity and sensitivity. Further research will additionally allow for an estimation of a patient's field of view (FOV) for more detailed assessment of neglect.


Subject(s)
Brain Injuries , Perceptual Disorders , Stroke , Electroencephalography , Humans , Neural Networks, Computer , Perceptual Disorders/diagnosis , Stroke/complications
12.
Best Pract Res Clin Obstet Gynaecol ; 68: 103-108, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32278628

ABSTRACT

Chronic Hepatitis B virus (HBV) infection is endemic worldwide, and the prevalence is especially high in the Asia-Pacific regions. Despite its high prevalence, the literature regarding the impact of HBV infection on subfertility and fertility treatment remains limited and conflicting. Latest studies do not suggest any detrimental effect of HBV infection on the outcome of IVF/ICSI treatment in women having chronic HBV infection. There is evidence that HBV exists in ovarian tissue including oocyte and follicular fluid, and therefore has the potential risk of transmission to the embryo, which can explain the finding of vertical transmission despite immunoprophylaxis. Most recently, we have observed the evidence of HBV viral replication in female HBV carriers undergoing IVF/ICSI treatment. This raises the question of whether antiviral medication should be administered during ovarian stimulation in IVF/ICSI treatment cycles for women with chronic HBV infection to help reduce the chance of vertical transmission.


Subject(s)
Fertilization in Vitro/methods , Hepatitis B Surface Antigens/analysis , Hepatitis B virus/isolation & purification , Hepatitis B, Chronic/physiopathology , Hepatitis B/complications , Infectious Disease Transmission, Vertical/prevention & control , Infertility , Adult , DNA, Viral/blood , Female , Fertilization in Vitro/statistics & numerical data , Hepatitis B/epidemiology , Hepatitis B virus/genetics , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/transmission , Humans , Ovulation Induction , Pregnancy , Semen Analysis
13.
Dev Cell ; 53(3): 316-329.e5, 2020 05 04.
Article in English | MEDLINE | ID: mdl-32302543

ABSTRACT

All animals have evolved the ability to survive nutrient deprivation, and nutrient signaling pathways are conserved modulators of health and disease. In C. elegans, late-larval starvation provokes the adult reproductive diapause (ARD), a long-lived quiescent state that enables survival for months without food, yet underlying molecular mechanisms remain unknown. Here, we show that ARD is distinct from other forms of diapause, showing little requirement for canonical longevity pathways, autophagy, and fat metabolism. Instead it requires the HLH-30/TFEB transcription factor to promote the morphological and physiological remodeling involved in ARD entry, survival, and recovery, suggesting that HLH-30 is a master regulator of reproductive quiescence. HLH-30 transcriptome and genetic analyses reveal that Max-like HLH factors, AMP-kinase, mTOR, protein synthesis, and mitochondrial fusion are target processes that promote ARD longevity. ARD thus rewires metabolism to ensure long-term survival and may illuminate similar mechanisms acting in stem cell quiescence and long-term fasting.


Subject(s)
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism , Basic Helix-Loop-Helix Transcription Factors/metabolism , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans/growth & development , Cellular Senescence , Gene Expression Regulation , Longevity , Animals , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/genetics , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Caenorhabditis elegans Proteins/genetics , Signal Transduction , Transcriptome
14.
Epilepsia ; 61(4): 810-821, 2020 04.
Article in English | MEDLINE | ID: mdl-32112430

ABSTRACT

OBJECTIVE: Genetic variants in STXBP1, which encodes the conserved exocytosis protein Munc18-1, are associated with a variety of infantile epilepsy syndromes. We aimed to develop an in vivo Caenorhabditis elegans model that could be used to test the pathogenicity of such variants in a cost-effective manner. METHODS: The CRISPR/Cas9 method was used to introduce a null mutation into the unc-18 gene (the C. elegans orthologue of STXBP1), thereby creating a paralyzed worm strain. We subsequently rescued this strain with transgenes encoding the human STXBP1/Munc18-1 protein (wild-type and eight different epilepsy-associated missense variants). The resulting humanized worm strains were then analyzed via behavioral, electrophysiological, and biochemical approaches. RESULTS: Transgenic expression of wild-type human STXBP1 protein fully rescued locomotion in both solid and liquid media to the same level as the standard wild-type worm strain, Bristol N2. Six variant strains (E59K, V84D, C180Y, R292H, L341P, R551C) exhibited impaired locomotion, whereas two (P335L, R406H) were no different from worms expressing wild-type STXBP1. Electrophysiological recordings revealed that all eight variant strains displayed less frequent and more irregular pharyngeal pumping in comparison to wild-type STXBP1-expressing strains. Four strains (V84D, C180Y, R292H, P335L) exhibited pentylenetetrazol-induced convulsions in an acute assay of seizure-like activity, in contrast to worms expressing wild-type STXBP1. No differences were seen between wild-type and variant STXBP1 strains in terms of mRNA abundance. However, STXBP1 protein levels were reduced to 20%-30% of wild-type in all variants, suggesting that the mutations result in STXBP1 protein instability. SIGNIFICANCE: The approach described here is a cost-effective in vivo method for establishing the pathogenicity of genetic variants in STXBP1 and potentially other conserved neuronal proteins. Furthermore, the humanized strains we created could potentially be used in the future for high-throughput drug screens to identify novel therapeutics.


Subject(s)
Disease Models, Animal , Epilepsy/genetics , Munc18 Proteins/genetics , Animals , Animals, Genetically Modified , Caenorhabditis elegans , Caenorhabditis elegans Proteins/genetics , Humans , Mutation , Vesicular Transport Proteins/genetics
15.
J Viral Hepat ; 27(2): 110-117, 2020 02.
Article in English | MEDLINE | ID: mdl-31519044

ABSTRACT

Hepatitis B virus (HBV) can be found in ovarian tissues. This study compared HBV DNA levels in follicular fluid collected during oocyte retrieval with paired serum samples in HBV carriers after ovarian stimulation during IVF treatment for infertility. Sixty-four HBV carrier women referred to the Assisted Reproductive Units of two Hong Kong hospitals were recruited. At oocyte retrieval, the follicular fluid aspirated from the first follicle was collected for study. In 22 women, the first follicular fluid sample from both ovaries was similarly collected and studied. These women were also tested for liver function test and HBeAg. In 28 (43.8%) women, HBV DNA was detected in follicular fluid and the level correlated with serum levels (Spearman's correlation P < .001). There was concordant detection of HBV DNA in both ovaries, and the levels were significantly correlated (Spearman's correlation P = .029). In 40% of women with FF HBV DNA, the follicular fluid:serum ratio was >1.0, suggesting stimulation of HBV replication. These women also had significantly different liver function test results. Increased HBV replication exists in 40% of women with HBV DNA detected in follicular undergoing ovarian stimulation during IVF treatment.


Subject(s)
Carrier State/virology , Fertilization in Vitro/statistics & numerical data , Hepatitis B virus/physiology , Ovary/virology , Virus Replication , Adult , DNA, Viral/blood , Female , Follicular Fluid/virology , Hepatitis B/blood , Hepatitis B/virology , Hong Kong , Humans , Ovulation Induction , Prospective Studies
16.
Trials ; 20(1): 540, 2019 Aug 29.
Article in English | MEDLINE | ID: mdl-31464617

ABSTRACT

BACKGROUND: In Hong Kong, one of six couples is affected by subfertility problems. Male infertility contributes to half of the infertility cases. In male infertility, there is no effective treatment for patients with idiopathic infertility/poor semen parameters. Recent meta-analysis results suggest that a traditional Chinese medicine (TCM) formula - Wuzi Yanzong pill - showed a curative effect on male fertility. However, the heterogeneity of the studies could not draw a definitive conclusion on the therapeutic effect of this formula. The aim of this study is to conduct a well-designed randomized controlled trial to investigate the effect of TCM formula Wuzi Yanzong pill on improving semen qualities in men with suboptimal parameters. METHODS: This study is a double-blinded, randomized placebo-controlled trial conducted in a public hospital in Hong Kong. Participants will be randomized, using computer-generated random numbers, with a 1:1 ratio to either the Wuzi Yanzong pill formula group or the placebo group. Both groups will be administered the drugs for 12 weeks. Participants will have a total of four visits for their semen and blood assessments for a 6-month period, and we will follow up for another 6 months to record their conception outcome. The primary outcome is to compare the total motile sperm count, natural conception rate, and pregnancy outcome to those under placebo treatment. Secondary objectives are sperm functions and assisted reproductive technology outcome. DISCUSSION: To date, there are no studies using the disclosed Wuzi Yanzong formula or double-blinded, randomized trials. The Wuzi Yanzong TCM formula may provide a good clinical solution for subfertile males for which contemporary western medicine has no cure. Therefore, a well-designed randomized trial for evaluating the effect of Wuzi Yanzong TCM formula is urgently needed. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR-INR-17010790 . Registered on 27 February 2017. Centre for Clinical Research and Biostatistics - Clinical Trials Registry, CUHK_CCRB00548 . Registered on 27 February 2017.


Subject(s)
Drugs, Chinese Herbal/administration & dosage , Fertility Agents, Male/administration & dosage , Fertility/drug effects , Infertility, Male/drug therapy , Semen/drug effects , Administration, Oral , Double-Blind Method , Drugs, Chinese Herbal/adverse effects , Equivalence Trials as Topic , Fertility Agents, Male/adverse effects , Hong Kong , Humans , Infertility, Male/diagnosis , Infertility, Male/physiopathology , Male , Prospective Studies , Semen Analysis , Tablets , Time Factors , Treatment Outcome
17.
Eur J Obstet Gynecol Reprod Biol ; 239: 11-15, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31158788

ABSTRACT

OBJECTIVE: To determine the relationship between the presence of detectable HBV DNA in the follicular fluid in HBV carriers with IVF/ICSI treatment outcome. STUDY DESIGN: A prospective observational study conducted in the Assisted Reproductive Unit, a tertiary referral centre affiliated with the Department of Obstetrics and Gynecology, The Chinese University of Hong Kong; and the Union Reproductive Medicine Centre at Union Hospital, Hong Kong. The primary outcome measure was pregnancy rate. Secondary outcome measures were the prevalence of detectable HBV DNA in the follicular fluid, implantation rate, clinical pregnancy rate, ongoing pregnancy rate and live birth rate. RESULTS: HBV DNA was detected in the follicular fluid of 28 (43.8%) of the 64 women, and the mean level in this group in log10 copies/mL (±SD) was 4.36 ± 1.85. Women with detectable follicular fluid HBV DNA were younger, lighter, had longer duration of infertility, higher incidence of detectable serum HBV DNA (OR 4.592, 95% C I 2.333-9.038), and significantly wider range in the number of total fertilized, viable embryos, and blastocyst rate, but no difference in cycle characteristics, stimulation and pregnancy outcomes, although the almost doubled ongoing pregnancy/live birth rate per cycle initiated (60.7% versus 38.9%) failed to reach statistical significance due to the small numbers. CONCLUSION: Our results suggested HBV infection did not appear to be detrimental to the outcome of IVF/ICSI treatment.


Subject(s)
DNA, Viral/isolation & purification , Follicular Fluid/virology , Hepatitis B/complications , Infertility, Female/virology , Sperm Injections, Intracytoplasmic/statistics & numerical data , Adult , Female , Hepatitis B/virology , Humans , Pregnancy , Pregnancy Rate , Prospective Studies
18.
Aust N Z J Obstet Gynaecol ; 59(1): 71-76, 2019 02.
Article in English | MEDLINE | ID: mdl-29672838

ABSTRACT

BACKGROUND: Ultrasound-guided manual vacuum aspiration (USG-MVA) is an effective but underutilised alternative to medical or surgical evacuation of the uterus following first trimester miscarriage. AIMS: To evaluate the efficacy, feasibility and patient acceptability of USG-MVA for treating early pregnancy loss. MATERIAL AND METHODS: We invited patients with early pregnancy losses to participate in this prospective cohort study. We reviewed the medical records of the participants and their visual analogue pain score during MVA. Primary outcomes were efficacy, feasibility and patient acceptability of USG-MVA. Secondary outcomes included the success rate of culture of chorionic villi for chromosomal analysis and complications from the USG-MVA procedure. RESULTS: We included a consecutive series of 35 women who underwent the USG-MVA procedure. The efficacy of USG-MVA in achieving complete evacuation was 97.1%. The procedure was well tolerated and the mean procedure-related pain score was 6.25 out of 10 (SD 1.55). Overall, all patients were satisfied with the procedure. The successful culture rate of chromosomal analysis was 94.3%. There were no major complications. CONCLUSION: USG-MVA is an effective treatment for the management of early pregnancy loss in an out-patient setting. It is an alternative to surgical evacuation under general anaesthesia, particularly for women desiring chromosomal analysis of products of conception. Further studies are required to investigate its health-related and economic benefits in hospital service provision.


Subject(s)
Abortion, Spontaneous/surgery , Patient Satisfaction , Prenatal Care , Ultrasonography, Interventional , Vacuum Curettage , Adult , Female , Hong Kong , Humans , Pregnancy , Pregnancy Trimester, First , Surveys and Questionnaires
20.
Reprod Biomed Online ; 35(1): 28-36, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28476486

ABSTRACT

The benefit of endometrial scratch (ES) prior to embryo transfer is controversial. Systemic analysis has confirmed its potential benefit, especially in women with repeated IVF failures, yet most studies have focused on fresh embryo transfer, and its effect on vitrified-warmed embryo transfer (FET) cycles is yet to be explored. We hereby present our prospective, double-blind, randomized controlled study on the evaluation of the implantation and pregnancy rate after ES prior to natural-cycle FET. A total of 299 patients underwent natural-cycle FET and were randomized to receive ES (n = 115) or endocervical manipulation as control (n = 114) prior to FET cycle, and a total of 196 patients had embryo transfer (93 patients in each group). Our study showed no significant difference in the implantation and pregnancy rate, as well as the clinical and ongoing pregnancy or live birth rates between the two groups. It appears that ES does not have any beneficial effect on an unselected group of women undergoing FET in natural cycles. Further studies on its effect in women with recurrent implantation failure after IVF are warranted.


Subject(s)
Embryo Implantation , Embryo Transfer/methods , Adult , Cryopreservation , Double-Blind Method , Endometrium/surgery , Female , Humans , Pregnancy , Pregnancy Rate
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