Efficacy, feasibility and patient acceptability of ultrasound-guided manual vacuum aspiration for treating early pregnancy loss.

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.

The impact of music therapy on pain and stress reduction during oocyte retrieval - a randomized controlled trial.

RESEARCH QUESTION: Does music therapy help in reducing pain and anxiety in women undergoing transvaginal ultrasound-guided oocyte retrieval (TUGOR)? DESIGN: In this randomized controlled open label study, 209 participants were recruited and randomized into three groups (music group, n = 70; headphone group, n = 70; control group, n = 69). Patients' psychological status was assessed using the visual analogue scale of pain (VAS-P), satisfaction of pain control, state-trait anxiety inventory (STAI), Beck depression inventory (BDI), and general health questionnaire (GHQ). Stress biomarkers, including salivary alpha amylase (sAA) and salivary cortisol (sCort), were measured before and after TUGOR. RESULTS: No significant differences were found in psychological scoring of STAI, BDI, GHQ and the stress biomarkers. Although neither the anxiety scores nor the analgesic requirements differed among the three groups, the visual measure of vaginal pain (median, range) showed music group (20,0-70) was significantly (P = 0.005) lower than headphone group (30,0-90) and control group (30,0-100). The degree of satisfaction with pain control (median, range) in the music group (80,30-100), was significantly (P = 0.001) higher than the headphone group (80,10-100) and control group (70,0-100). CONCLUSION: Music is a simple, inexpensive and effective way to reduce pain score and increase satisfaction with pain control during TUGOR procedure, which may justify its routine use.

Corrigendum to "The Therapeutic Effects of a Traditional Chinese Medicine Formula Wuzi Yanzong Pill for the Treatment of Oligoasthenozoospermia: A Meta-Analysis of Randomized Controlled Trials".

[This corrects the article DOI: 10.1155/2018/2968025.].

The Therapeutic Effects of a Traditional Chinese Medicine Formula Wuzi Yanzong Pill for the Treatment of Oligoasthenozoospermia: A Meta-Analysis of Randomized Controlled Trials.

Oligoasthenozoospermia is a crucial factor in male infertility. Wuzi Yanzong (WZYZ) pill is a popular traditional Chinese medicine (TCM) formula which has been used for male infertility treatment for years. However, its effects on semen quality remain controversial. We conducted a preregistered meta-analysis to assess the effect of WZYZ pill for the therapeutic effects on oligoasthenozoospermia. Five randomized controlled trials including 960 participants were selected from databases of domains in North-East Asian regions, PubMed, Embase, and Cochrane Library. WZYZ pill group yielded a greater mean increment on sperm concentration (5 trials: MD 5.99, 95% CI 2.12-9.85, P = 0.002), sperm motility (5 trials: MD 4.57, 95% CI 0.47-8.68, P = 0.03), sperm morphology (2 trials: MD -1.93, 95% CI -4.87-1.01, P = 0.20), activity of acrosomal enzyme (2 trials: MD 28.27, 95% CI 12.41-44.14, P < 0.01), volume of semen (2 trials: MD 0.56, 95% CI 0.21-0.91, P = 0.002), and a decrement of sperm DNA fragmentation index (2 trials: MD -3.82, 95% CI -6.45--1.19, P = 0.004). However, qualities of selected studies were generally unsatisfactory, and there was inherent heterogeneity among some of the outcomes. Despite these limitations, the WZYZ pill improved sperm quality by improving several semen parameters and decreasing DNA damage in oligoasthenozoospermia patients.

MDSCs drive the process of endometriosis by enhancing angiogenesis and are a new potential therapeutic target.

Endometriosis affects women of reproductive age via unclear immunological mechanism(s). Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid cells with potent immunosuppressive and angiogenic properties. Here, we found MDSCs significantly increased in the peripheral blood of patients with endometriosis and in the peritoneal cavity of a mouse model of surgically induced endometriosis. Majority of MDSCs were granulocytic, produced ROS, and arginase, and suppressed T-cell proliferation. Depletion of MDSCs by antiGr-1 antibody dramatically suppressed development of endometrial lesions in mice. The chemokines CXCL1, 2, and 5 were expressed at sites of lesion while MDSCs expressed CXCR-2. These CXC-chemokines promoted MDSC migration toward endometriotic implants both in vitro and in vivo. Also, CXCR2-deficient mice show significantly decreased MDSC induction, endometrial lesions, and angiogenesis. Importantly, adoptive transfer of MDSCs into CXCR2-KO mice restored endometriotic growth and angiogenesis. Together, this study demonstrates that MDSCs play a role in the pathogenesis of endometriosis and identifies a novel CXC-chemokine and receptor for the recruitment of MDSCs, thereby providing a potential target for endometriosis treatment.

Validation of a high-throughput and robust technique: BACs-on-beads assay (KaryoLite BoBs) for pre-implantation aneuploidy screening.

OBJECTIVE: This study aims to validate the BACs-on-Beads (BoB) technology as a robust and high throughput method for pre-implantation genetic screening (PGS) for aneuploidy. MATERIAL AND METHODS: The performances with respect to the sensitivity, specificity, success rate and detection rate of this technique from new BoBs technology and traditional array chromosomal genomic hybridization (aCGH) were compared. And the use of BoBs as a screening tool for euploid embryos in PGS was evaluated. RESULT: In the first part of validation study, there were total 75 embryos completed PGS by both BoBs and aCGH. The success rate of PGS was 97.4%, and the results showed 100% concordance between BoBs and aCGH for aneuploidy. In the second part, a total 219 embryos were involved. The success rate of PGS by BoBs was 100%. BoBs identified 28% (62/219) euploidy which were further confirmed to be euploidy by aCGH. CONCLUSION: This new strategic approach using BoBs as a first tier PGS screening tool and aCGH as a confirmatory tool can increase the throughput of PGS with a reduced cost and time to meet the demand in high volume units.

The effect of endometrial scratch on natural-cycle cryopreserved embryo transfer outcomes: a randomized controlled study.

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.

Effect of mid-follicular phase recombinant LH versus urinary HCG supplementation in poor ovarian responders undergoing IVF - a prospective double-blinded randomized study.

Luteinizing hormone (LH) is crucial for the development of follicular growth and oocyte maturation, especially in the management of poor ovarian responders (PORs). This study presents the results of a prospective double-blinded randomized study to compare the effect of mid-follicular phase recombinant LH (rLH) supplementation with urinary human chorionic gonadotrophin (uHCG) supplementation when using a fixed gonadotrophin-releasing hormone (GnRH) antagonist protocol in IVF cycles. A total of 49 women with poor ovarian response (POR) according to the Bologna criteria were recruited. This study showed no statistically significant difference in cycle cancellation rates, numbers of oocytes retrieved per cycle initiated, fertilization rates, the numbers of embryos obtained per cycle initiated, implantation, clinical pregnancy and live birth rates, although the live birth rate per cycle initiated in the uHCG group (29.2%) was 3.6 times that of the rLH group (8.0%). Further studies are required to verify if uHCG supplementation produces better clinical outcomes compared with rLH in women with POR.

The changing pattern of uterine contractions before and after fresh embryo transfer and its relation to clinical outcome.

In this prospective cohort study of 286 women undergoing fresh embryo transfer after IVF, uterine contraction frequency and direction were measured before (-5 min), 5 min after (+5 min) and 60 min after (+60 min) embryo transfer. Mean ± SD uterine contraction frequency at -5 min was 1.8 ± 1.1 contractions per min, increasing significantly (P < 0.05) to 2.0 ± 1.1 at +5 min, and returning back to baseline 1.8 ± 1.1 at +60 min. At -5 min, the proportion of women the with retrograde, antegrade, indeterminate direction and absent contractions were 33%, 44%, 17% and 6%; at +5 min, 40%, 42%, 13% and 5%, and at +60 min, 42%, 38%, 14% and 6%. No significant change was observed in the proportion of direction at these three time points. Logistic regression analysis showed live birth rate was significantly reduced in older women (P = 0.035) and in those with higher uterine contraction frequency at +5 min (P = 0.006). Frequency of uterine contraction immediately after embryo transfer (+5 min) seemed to be a significant predictor of IVF outcome and may help to identify women who could benefit from the use of muscle relaxant therapy to improve outcome.

Prenatal detection of 10q22q23 duplications: dilemmas in phenotype prediction.

OBJECTIVES: The phenotype for 10q22q23 duplication is diverse, ranging from intellectual disability and dysmorphism to normal development. Interpreting the clinical significance of the duplication identified in this region is difficult, especially in the prenatal setting. This study aimed to characterize the prenatal findings associated with this submicroscopic imbalance and discuss the dilemmas in predicting the phenotype of 10q22q23 duplications. METHODS: This is a retrospective study of three cases of 10q22q23 duplications diagnosed prenatally by chromosomal microarray analysis. Detailed pregnancy outcome and pediatric follow-up were documented. RESULTS: The genotypic and phenotypic features of the reported cases were discussed. 10q22q23 duplications are associated with an unpredictable and variable phenotypic outcome. Despite there was no phenotype found to be shared by 50% of the duplication cases, congenital heart defects, hypotelorism, and developmental delays including speech and motor delay seem to be more common. CONCLUSIONS: The phenotype of 10q22q23 duplication is highly variable prenatally and postnatally. Identification of additional affected individuals with similar duplications is needed to provide further insights into the pathogenesis of this microduplication. © 2016 John Wiley & Sons, Ltd.

A prospective randomized controlled trial of 3D versus 2D ultrasound-guided embryo transfer in women undergoing ART treatment.

STUDY QUESTION: Does three-dimensional (3D) versus two-dimensional (2D) ultrasound (US) guidance during embryo transfer (ET) increase the ongoing pregnancy rate in women undergoing ART treatment. SUMMARY ANSWER: There is no significant difference in the ongoing pregnancy rate of women undergoing 3D versus 2D US-guided ET. WHAT IS KNOWN ALREADY: Studies have suggested that 3D US may confer additional benefits compared with 2D US during ET, although this has not been tested within the context of an RCT. STUDY DESIGN, SIZE, DURATION: This was a single-blind, single centre prospective RCT performed between April 2015 and April 2016. A total of 481 recruited women were randomised into either a 3D or 2D US-guided ET group. PARTICIPANTS/MATERIALS, SETTING, METHOD: Women younger than 42 years in whom the endometrial cavity could be adequately visualised by US underwent ET in a university ART unit following a standard treatment protocol. All US examinations were performed by a single operator. In both 3D and 2D US groups, the inner catheter tip was aimed at the centre of the uterine cavity. The primary outcome measure was ongoing pregnancy rate, defined as the presence of at least one foetus with heart pulsation at 8 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE: There was no significant difference in the ongoing pregnancy rate between the 3D and 2D US groups (35.4% versus 37.1%, P = 0.70; rate ratio 0.96, 95% confidence interval 0.75-1.21). There were also no significant differences in terms of positive hCG rate, biochemical pregnancy rate, implantation rate, clinical pregnancy rate, miscarriage rate, ectopic pregnancy rate and multiple pregnancy rate. LIMITATIONS, REASONS FOR CAUTION: This study recruited unselected women undergoing routine ET and was therefore not sufficiently powered to assess differences in subsets of women. WIDER IMPLICATIONS OF THE FINDINGS: Although 3D US may be a modern method for demonstrating the ET procedure, it should not be currently recommended as a strategy to improve clinical outcomes in women undergoing ART treatment. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the Health and Medical Research Fund of Hong Kong. The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT02413697. TRIAL REGISTRATION DATE: 4 April 2015. DATE OF FIRST PATIENT'S ENROLMENT: 20 April 2015.

Validation of a robust PCR-based assay for quantifying fragile X CGG repeats.

BACKGROUND: Sizing of FMR1 trinucleotide repeats in the clinical laboratory requires the use of capillary sequencer by PCR, or by a labor intensive measurement using Southern blot method. Our aim was to validate an accurate and robust PCR assay for quantification of CGG repeats. METHODS: We performed an analytical and clinical validation of a new PCR-based method that utilizes a low-cost capillary electrophoresis instrument and the FragilEase™ reagent kit. First, analytical performance was demonstrated on 12 Coriell reference samples comprising normal through full mutations. Subsequently, a cohort of 112 archived clinical DNA samples, enriched for premutation and full mutations, was analyzed. RESULTS: All samples were amplified successfully. Quantification of repeat numbers was interpreted by the use of standards with known repeats. Twenty-five full-mutation samples were successfully amplified with the largest allele size measured at 1380 repeats. The repeat numbers from the new assay were concordant with those obtained with the reference method. The intra-assay (CV<2.5%) and inter-assay imprecision was within 1 CGG repeat. CONCLUSION: This new PCR-based method is reproducible and capable of identifying all Fragile X alleles. It is an accurate and robust method that facilitates Fragile X testing in a broader spectrum of clinical laboratories.

Assessment of the embryo flash position and migration with 3D ultrasound within 60 min of embryo transfer.

STUDY QUESTION: Does the air bubble (embryo flash) position and migration as visualized with 3D ultrasound (US) within 60 min of embryo transfer correlate with clinical outcome following fresh ART transfer cycles? SUMMARY ANSWER: The location of the embryo flash and the direction of its movement at 60 min, but not at 1 or 5 min after transfer, are associated with clinical pregnancy. WHAT IS KNOWN ALREADY: Studies assessing the relation between the pregnancy rate and the position of the catheter tip and/or the position of the air bubbles following embryo transfer show conflicting results to date. STUDY DESIGN, SIZE AND DURATION: This was a prospective cohort study including 277 infertile women undergoing ART between July 2011 and August 2013. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Good prognosis patients undergoing fresh ART cycles within a single tertiary University unit were assessed by 3D US at 1, 5 and 60 min after embryo transfer. The distance of the embryo flash from the fundus was measured at these time points, along with the direction of the embryo flash movement within 60 min of transfer. MAIN RESULTS AND THE ROLE OF CHANCE: Within 60 min of embryo transfer, 76.4% (198/259) of the embryo flashes migrated towards the fundus, 12.4% (32/259) migrated towards the cervix and 11.2% (29/259) remained static. There was no significant association between the embryo position or movement and the pregnancy rate at 1 and 5 min. At 60 min, however, the pregnancy and implantation rates among subjects with embryo flashes located <15 mm from the fundus was significantly higher than those with embryo flashes located >15 mm from the fundus (46.5 and 32.8% versus 25.8 and 18.2%, respectively; P < 0.05). The pregnancy and implantation rates when the embryo flash was seen moving towards the cervix (25.0 and 15.0%) was significantly lower (P < 0.05 and P < 0.01, respectively) compared with those remaining static (55.2 and 37.7%) or moving towards the fundus (45.5 and 32.8%). LIMITATIONS AND REASONS FOR CAUTION: Although the air bubbles seen at the time of embryo transfer are thought to represent the position of the embryo, they are in fact a surrogate marker of the embryo itself, as this cannot be directly visualized by US. WIDER IMPLICATIONS OF THE FINDINGS: Following embryo transfer the majority, but not all, embryo flashes undergo significant migration towards the fundus. The location of the embryo flash and the direction of its movement at 60 min, but not at 1 or 5 min after transfer, is associated with clinical outcome. These findings may challenge the traditional notion that the exact position of the embryo flash immediately following embryo transfer is related to clinical outcome. STUDY FUNDING/COMPETING INTERESTS: The authors have no relevant funding or conflicts of interest to disclose.

Dynamic changes of DNA epigenetic marks in mouse oocytes during natural and accelerated aging.

Aging is a complex time-dependent biological process that takes place in every cell and organ, eventually leading to degenerative changes that affect normal biological functions. In the past decades, the number of older parents has increased significantly. While it is widely recognized that oocyte aging poses higher birth and reproductive risk, the exact molecular mechanisms remain largely elusive. DNA methylation of 5-cytosine (5mC) and histone modifications are among the key epigenetic mechanisms involved in critical developmental processes and have been linked to aging. However, the impact of oocyte aging on DNA demethylation pathways has not been examined. The recent discovery of Ten-Eleven-Translocation (TET) family proteins, thymine DNA glycosylase (TDG) and the demethylation intermediates 5hmC, 5fC and 5caC has provided novel clues to delineate the molecular mechanisms in DNA demethylation. In this study, we examined the cellular level of modified cytosines (5mC, 5hmC, 5fC and 5caC) and Tet/Tdg expression in oocytes obtained from natural and accelerated oocyte aging conditions. Here we show all the DNA demethylation marks are dynamically regulated in both aging conditions, which are associated with Tet3 over-expression and Tdg repression. Such an aberrant expression pattern was more profound in accelerated aging condition. The results suggest that DNA demethylation may be actively involved in oocyte aging and have implications for development of potential drug targets to rejuvenate aging oocytes. This article is part of a Directed Issue entitled: Epigenetics dynamics in development and disease.

Clinical and psychological impact after surgical, medical or expectant management of first-trimester miscarriage--a randomised controlled trial.

BACKGROUND: The management of first-trimester miscarriage has been studied extensively in recent years. However, relatively little attention has been focussed on woman's satisfaction and psychological impact from different treatment modalities. AIM: To investigate the clinical and psychological outcomes of surgical, medical and expectant management of first-trimester miscarriage. MATERIALS AND METHODS: A prospective randomised controlled trial of 180 women suffering miscarriage managed by either surgical evacuation, medical evacuation or expectant management was conducted in a university-affiliated, tertiary referral hospital. The complete miscarriage rate, clinical symptomatology, complications, women's satisfaction and the psychological impact were evaluated. RESULTS: Women in surgical evacuation (98.1%) had a significantly higher complete miscarriage rate when compared with medical evacuation (70%) and expectant management (79.3%). Women who had surgical evacuation had significantly shorter duration of vaginal bleeding, but higher rate of infection. Women who had medical evacuation had significantly more gastrointestinal symptoms. Despite differences in efficacy and complication profile, there was no significant difference in satisfaction among groups. There were no significant differences in terms of psychological well-being, depression scores, anxiety level, fatigue symptoms as measured in General Health Questionnaire-12, Beck Depression Inventory, Spielberger's State Anxiety Inventory and fatigue scale at treatment and four weeks after treatment. However, women with active intervention had greater post-traumatic stress symptoms as measured in Chinese version of Impact of Event Scale-Revised at the time of treatment when compared with women in expectant management. CONCLUSION: Without substantial differences in the clinical and psychological impact between different treatment modalities, a more conservative approach with expectant management for miscarriage may be an option for women.

Comparison in the performance of glucose meters in blood glucose monitoring during pregnancy.

AIMS: To compare the performance of the four latest models of glucose meters in capillary blood glucose monitoring during pregnancy. METHODS: 208 pregnant women with gestational diabetes were recruited. Each subject had simultaneous capillary glucose monitoring by two study glucose meters and venous plasma glucose assay. The performance of four glucose meters was compared using error grid analysis (EGA) and the agreement between the meter readings and plasma glucose by Bland-Altman plot analysis. RESULTS: Elite, Advantage II and CareSens had more than 90% of readings in the acceptable target range of EGA. CareSens had the lowest mean bias by Bland-Altman analysis while Advantage II had the highest proportion of readings within 5% difference from plasma glucose. Readings from all glucose meters except Optium were not influenced by the change in maternal hematocrit levels. CONCLUSIONS: The performance of four study glucose meters appeared very similar.

Cryotherapy as the treatment modality of postcoital bleeding: a randomised clinical trial of efficacy and safety.

BACKGROUND: Postcoital bleeding is a common gynaecological problem that impacts on a woman's quality of life and sexual function. There is little systematic research into its management. AIMS: To assess the efficacy and side-effects of cryotherapy as treatment for postcoital bleeding. METHODS: A prospective randomised controlled trial was conducted in a tertiary referral hospital in Hong Kong. A total of 85 women who presented with postcoital bleeding were recruited, and randomised to cryotherapy or no treatment. The treatment group received cryotherapy with compressed carbon dioxide through a cryoprobe placed on the cervix, and controls had cryoprobe on the cervix without compressed carbon dioxide flow. All recruited women were followed up two weeks, three months and six months to review their symptoms and response to the treatment. RESULTS: The treatment group had a significantly better long-term cure rate and improvement rate. At six months, the cryotherapy group reported a cure rate of 72.1% while that in the control group the cure rate was 50.0% (P = 0.04). The number needed to treat was 5. The mean improvement rate of the cryotherapy group was 82.88% +/- 35.87 but was only 61.62% +/- 55.30 in the control group (P = 0.04). The results were more significant in women with the defined pathological cervix. Apart from the vaginal discharge at second week follow up in the treatment group, there was no statistical significant difference in side-effects and complications among two groups. CONCLUSION: Our study demonstrated that cryotherapy is a safe and an effective treatment for postcoital bleeding.

Comprehensive assessment of serum estradiol impact on selected physiologic markers observed during in-vitro fertilization and embryo transfer cycles.

OBJECTIVE: This investigation assessed the effect of serum estradiol levels on outcomes of in-vitro fertilization and embryo transfer (IVF) cycles. MATERIALS AND METHOD: This was a retrospective cohort study of 1123 IVF cycles comparing impact of estradiol (E(2)) levels on follicular development, fertilization, embryo quality, implantation, pregnancy rate, miscarriage rate, and selected obstetric complications. RESULTS: We found high serum E(2) levels to be significantly associated with increased number of mature follicles and mature oocytes retrieved (p<0.01, for both). E(2) levels were also associated with more viable and good-quality embryos (p<0.01). There was no significant impact of E(2) on oocyte maturation, fertilization rate, embryo quality, or overall pregnancy rates. Moreover, high E(2) levels were significantly associated with higher implantation rates and reduced incidence of miscarriage (p<0.05, for both). CONCLUSION: Within the safety range in clinical practice, our data demonstrate a generally positive effect of high serum E(2) on selected IVF parameters.