Five-year retrospective review of ultrasound-guided manual vacuum aspiration for first-trimester miscarriage.

INTRODUCTION: Manual vacuum aspiration is increasingly accepted as an alternative to medical or surgical evacuation of the uterus after first-trimester miscarriage. This study aimed to assess the efficacy of ultrasound-guided manual vacuum aspiration (USG-MVA) in the management of first-trimester miscarriage. METHODS: This retrospective analysis included adult women with first-trimester miscarriage who underwent USG-MVA in Hong Kong between July 2015 and February 2021. The primary outcome was the efficacy of USG-MVA in terms of complete evacuation of the uterus, without the need for further medical or surgical intervention. Secondary outcomes included tolerance of the entire procedure, the success rate of karyotyping using chorionic villi, and procedural safety (ie, any clinically significant complications). RESULTS: In total, 331 patients were scheduled to undergo USG-MVA for first-trimester miscarriage or incomplete miscarriage. The procedure was completed in 314 patients and well-tolerated in all of those patients. The complete evacuation rate was 94.6% (297/314), which is similar to the rate (98.1%) achieved by conventional surgical evacuation in a previous randomised controlled trial in our unit. There were no major complications. Samples from 95.2% of patients were suitable for karyotyping, which is considerably higher than the rate of suitable samples (82.9%) obtained via conventional surgical evacuation in our previous randomised controlled trial. CONCLUSION: Ultrasound-guided manual vacuum aspiration is a safe and effective method to manage first-trimester miscarriage. Although it currently is not extensively used in Hong Kong, its broader clinical application could avoid general anaesthesia and shorten hospital stay.

The relationship between visceral adiposity and cardiometabolic risk in Chinese women with polycystic ovary syndrome.

OBJECTIVE: To compare the extent to which visceral adiposity, as measured by mesenteric fat thickness, contribute to cardiometabolic risk, especially insulin resistance, in women with PCOS and healthy control. METHODS: This is a cross-sectional study with a total of 190 women with PCOS fulfilling the Rotterdam diagnostic criteria. Women without PCOS were recruited from a previous study, which comprised 416 healthy women controls with normal glucose tolerance. All subjects underwent OGTT, biochemical assessment, and sonographic assessment with measurements of mesenteric, preperitoneal and subcutaneous fat thickness. RESULTS: Mesenteric fat thickness was strongly correlated to cardiometabolic traits including blood pressure, fasting and 2-h glucose, triglycerides, HOMA-IR; and was negatively correlated to HDL-C in both cohorts (all p < 0.01). In PCOS, positive correlation was observed between mesenteric fat thickness and free androgen index (p < 0.01). Compared with controls, the regression line between mesenteric fat and HOMA-IR is much steeper in PCOS (p < 0.01). CONCLUSION: Women with PCOS remain more insulin resistant compared to controls at any given degree of visceral adiposity.

Lifetime risks of hip fracture in patients with type 2 diabetic: Taiwan Diabetes Study.

This study is to estimate the lifetime risks of hip fracture in Chinese patients with type 2 diabetes. INTRODUCTION: The lifetime risks of hip fracture have not been reported across the age spectrum in male adults and female adults with type 2 diabetes. METHODS: A retrospective cohort study was conducted on 25275 men and 27953 women with type 2 diabetes aged 30-100 years old and participated in the National Diabetes Case Management Program in 2002-2004 in Taiwan. Sociodemographic factors, biomarkers, and comorbidity at the baseline and hip fracture events were analyzed with Cox proportional hazards regression models with age as the time scale. RESULTS: Significant differences in the lifetime risks of hip fracture were observed between men and women with type 2 diabetes. The cumulative lifetime incidences (%) of hip fracture at 50, 60, 65, 70, 75, 80, and 85 years old for men were 0.11, 0.40, 0.84, 1.84, 3.82, 8.53, and 16.72, respectively. The corresponding lifetime incidences (%) for women at 50, 60, 65, 70, 75, 80, and 85 years old were 0.05, 0.50, 1.36, 3.89, 9.56, 21.19, and 35.45, respectively. With competing risks, the significant multivariate-adjusted hazard ratio of developing hip fracture included smoking, alcohol drinking, duration of diabetes, type of oral hypoglycemic drugs use (no medication, sulfonylurea only, thiazolidinediones (TZD) only or TZD plus others, other single or multiple oral agents, insulin use, insulin plus oral hypoglycemic drug use), loop diuretics use, use of corticosteroids, normal weight or underweight, hyperlipidemia, and chronic obstructive pulmonary disease. CONCLUSIONS: The gender differences in lifetime hip fracture risk were significant. Thiazolidinediones and insulin use are factors with the greater magnitude of strength of association among those significantly associated with hip fracture.

Single-cell RNA sequencing identifies molecular targets associated with poor in vitro maturation performance of oocytes collected from ovarian stimulation.

STUDY QUESTION: What is the transcriptome signature associated with poor performance of rescue IVM (rIVM) oocytes and how can we rejuvenate them? SUMMARY ANSWER: The GATA-1/CREB1/WNT signalling axis was repressed in rIVM oocytes, particularly those of poor quality; restoration of this axis may produce more usable rIVM oocytes. WHAT IS KNOWN ALREADY: rIVM aims to produce mature oocytes (MII) for IVF through IVM of immature oocytes collected from stimulated ovaries. It is not popular due to limited success rate in infertility treatment. Genetic aberrations, cellular stress and the absence of cumulus cell support in oocytes could account for the failure of rIVM. STUDY DESIGN, SIZE, DURATION: We applied single-cell RNA sequencing (scRNA-seq) to capture the transcriptomes of human in vivo oocytes (IVO) (n = 10) from 7 donors and rIVM oocytes (n = 10) from 10 donors. The effects of maternal age and ovarian responses on rIVM oocyte transcriptomes were also studied. In parallel, we studied the effect of gallic acid on the maturation rate of mouse oocytes cultured in IVM medium with (n = 84) and without (n = 85) gallic acid. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human oocytes were collected from donors aged 28-41 years with a body mass index of <30. RNA extraction, cDNA generation, library construction and sequencing were performed in one preparation. scRNA-seq data were then processed and analysed. Selected genes in the rIVM versus IVO comparison were validated by quantitative real-time PCR. For the gallic acid study, we collected immature oocytes from 5-month-old mice and studied the effect of 10-µM gallic acid on their maturation rate. MAIN RESULTS AND THE ROLE OF CHANCE: The transcriptome profiles of rIVM/IVO oocytes showed distinctive differences. A total of 1559 differentially expressed genes (DEGs, genes with at least 2-fold change and adjusted P < 0.05) were found to be enriched in metabolic processes, biosynthesis and oxidative phosphorylation. Among these DEGs, we identified a repression of WNT/ß-catenin signalling in rIVM when compared with IVO oocytes. We found that oestradiol levels exhibited a significant age-independent correlation with the IVO mature oocyte ratio (MII ratio) for each donor. rIVM oocytes from women with a high MII ratio were found to have over-represented cellular processes such as anti-apoptosis. To further identify targets that contribute to the poor clinical outcomes of rIVM, we compared oocytes collected from young donors with a high MII ratio with oocytes from donors of advanced maternal age and lower MII ratio, and revealed that CREB1 is an important regulator. Thus, our study identified that GATA-1/CREB1/WNT signalling was repressed in both rIVM oocytes versus IVO oocytes and in rIVM oocytes of lower versus higher quality. Consequently we investigated gallic acid, as a potential antioxidant substrate in human rIVM medium, and found that it increased the mouse oocyte maturation rate by 31.1%. LARGE SCALE DATA: Raw data from this study can be accessed through GSE158539. LIMITATIONS, REASONS FOR CAUTION: In the rIVM oocytes of the high- and low-quality comparison, the number of samples was limited after data filtering with stringent selection criteria. For the oocyte stage identification, we were unable to predict the presence of oocyte spindle, so polar body extrusion was the only indicator. WIDER IMPLICATIONS OF THE FINDINGS: This study showed that GATA-1/CREB1/WNT signalling was repressed in rIVM oocytes compared with IVO oocytes and was further downregulated in low-quality rIVM oocytes, providing us the foundation of subsequent follow-up research on human oocytes and raising safety concerns about the clinical use of rescued oocytes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Collaborative Research Fund, Research Grants Council, C4054-16G, and Research Committee Funding (Research Sustainability of Major RGC Funding Schemes), The Chinese University of Hong Kong. The authors have no conflicts of interest to declare.

Embryo migration following ART documented by 2D/3D ultrasound.

Embryos have traditionally been thought to implant at the exact site they are transferred during assisted reproductive technology (ART). The introduction of 2D/3D ultrasound has allowed for mapping of the transfer site using air bubbles as a surrogate marker of embryo location. This study's aim was to compare the location of embryo transfer (ET) on ultrasound to that of embryo implantation. We present four cases of ectopic pregnancy at four sites: tubal, cervical, interstitial and ovarian. We compare the site of implantation on 2D/3D ultrasound at six weeks of pregnancy to that of transfer as assessed on 2D/3D ultrasound. In all four cases, the embryo flash was visualised in the centre of the uterine cavity on ultrasound at ET. At six weeks of pregnancy, the uterine cavity was empty and an ectopic pregnancy was identified. The tubal and ovarian ectopics were managed surgically whilst the cervical and interstitial pregnancies were treated with systemic methotrexate. These cases demonstrate embryo implantation distal to the ultrasound-confirmed site of transfer. These cases provide visually compelling evidence of embryo migration following ET and lend support to the theory that ectopic pregnancy may occur as a result of embryo migration, rather than poor ET technique.

Competing risk analysis on visit-to-visit glucose variations and risk of depression: The Taiwan Diabetes Study.

AIM: Patients with diabetes have higher rates of depression than does the general population, but diabetes management mainly aims to maintain glucose stability. For this reason, our study assessed the relationship between 1-year variations in fasting plasma glucose (FPG) and risk of depression in Chinese patients with type 2 diabetes (T2D). METHODS: This retrospective cohort study was conducted on 32,829 patients aged ≥30 years who were diagnosed with T2D and who participated in the National Diabetes Case Management Program in Taiwan. Their 1-year FPG variation as a predictor was determined by coefficient of variation (CV), whereas depressive events were analyzed by Cox's proportional hazards models. RESULTS: During a mean 8.23 years of follow-up, 1041 new cases of depression were diagnosed. When patients were grouped based on quartiles of FPG-CV, incidence rates were 3.23, 3.49, 3.96 and 4.80 per 1000 person-years in the first, second, third and fourth quartile subgroups, respectively. After adjusting for traditional risk factors, baseline fasting glucose and HbA1c levels, and diabetes complications, FPG-CV was independently linked with incident depression. Hazard ratios of depression for FPG-CV in the fourth vs first quartile subgroups was 1.33 (95% CI: 1.11-1.59), respectively. CONCLUSION: Patients whose 1-year FPG variations were>42.6% had an increased risk of depression, thus suggesting that FPG variations may be a predictor of depression in patients with T2D. Also, glucose variation during outpatient visits may be an indicator for individualized diabetes management in clinical practice.

Reproductive Implications and Management of Congenital Uterine Anomalies: Scientific Impact Paper No. 62 November 2019.

Congenital uterine anomalies (CUAs) are malformations of the womb that develop during fetal life. When a baby girl is in her mother's womb, her womb develops as two separate halves from two tubular structures called 'müllerian ducts', which fuse together before she is born. Abnormalities that occur during the baby's development can be variable from complete absence of a womb through to more subtle anomalies, which are classified into specific categories. While conventional ultrasound is good in screening for CUAs, 3D ultrasound is used to confirm a diagnosis. If a complex womb abnormality is suspected, MRI scanning may also be used, with a combination of laparoscopy in which a camera is inserted into the cavity of the abdomen, and hysteroscopy, when the camera is placed in the womb cavity. As there can be a link between CUAs and abnormalities of the kidney and bladder, scans of these organs are also usually requested. Although CUAs are present at birth, adult women typically do not have any symptoms, although some may experience painful periods. Most cases of CUA do not cause a woman to have difficulty in becoming pregnant and the outcome of pregnancy is good. However, these womb anomalies are often discovered during investigations for infertility or miscarriage. Moreover, depending upon the type and severity of CUA, there may be increased risk of first and second trimester miscarriages, preterm birth, poor growth of the baby in the mother's womb (fetal growth restriction), pre-eclampsia and difficult positioning of the baby for birth (fetal malpresentation). Surgical treatment is only recommended to a woman who has had recurrent miscarriages and has a septate uterus, i.e., the womb cavity is divided by a partition. In this case, surgery may improve her chances for a successful pregnancy, although the risks of surgery, especially scarring of the womb should be considered. However, further evidence from randomised controlled trials are required to provide conclusive evidence-based recommendations for surgical treatment for septate uterus. Surgical treatment for other types of CUAs is not usually recommended as the risks outweigh potential benefits, and evidence for any benefits is lacking. Women with CUAs may be at an increased risk of preterm birth even after surgical treatment for a septate uterus. These women, if suspected to be at an increased risk of preterm birth based on the severity of CUA, should be followed up using an appropriate protocol for preterm birth as outlined in UK Preterm Birth Clinical Network Guidance.1 >.

Do specific ultrasonography features identified at the time of early pregnancy loss predict fetal chromosomal abnormality? - A systematic review and meta-analysis.

To investigate the association of specific ultrasonography features identified during the diagnosis of early pregnancy loss (EPL) and abnormal karyotype. This was a systematic review and meta-analysis conducted in accordance with PRISMA criteria. We searched PubMed, Cochrane and Ovid MEDLINE from 1977 to Jan 2017 to identify the articles that described EPL with karyotype and ultrasonography features. Risk differences were pooled to estimate the chromosomal abnormality rates in ultrasonography features, including pre-embryonic, enlarged yolk sac (YS), short crown rump length (CRL), small gestational sac (GS), symmetrical arrested growth embryo, or gestational sac with only a YS. Quality assessment of included studies was performed using Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklists for Observational Studies (2007 version). Thirteen studies were included in the meta-analysis. Chromosomal abnormality was more likely to occur in embryonic EPL and enlarged YS. On the other hand, short CRL, small GS, symmetrical arrested growth embryo, or gestational sac with only a YS, were not associated with an increased risk of fetal chromosomal abnormality. Ultrasonography features at the time of diagnosis of EPL have limited predictive value of fetal chromosomal abnormality.

Prevention of postoperative adhesion reformation by intermittent intrauterine balloon therapy: a randomised controlled trial.

OBJECTIVE: To compare the efficacy of intermittent intrauterine balloon dilatation versus standard care in the prevention of adhesion reformation. DESIGN: Single-blind randomised controlled trial. SETTING: Hysteroscopic Centre of a tertiary University Hospital. POPULATION: Two hundred patients with moderate to severe (European Society for Gynaecological Endoscopy Grade ≥II) intrauterine adhesions who underwent hysteroscopic adhesiolysis. METHODS: All participants were randomised to a balloon group or a control group postoperatively. The balloon group received intrauterine balloon dilatation therapy at 2 weeks and 6 weeks after surgery, whereas the control group did not. All patients underwent follow-up hysteroscopy at 4 and 8 weeks postoperatively. MAIN OUTCOME MEASURES: The adhesion reformation rate and the Pictorial Blood Loss Assessment Chart scores were analysed. RESULTS: A total of 191 patients successfully completed the study protocol (94 cases for the balloon group and 97 cases for the control group). According to hysteroscopic evaluation at the 8th week, the overall adhesion reformation rate was significantly lower in patients in the balloon group than patients in the control group (20.2% versus 40.2%, respectively; P < 0.05). There was also a significant increase in menstruation flow, as assessed by the Pictorial Blood Loss Assessment Chart score (30 versus 9, respectively; P < 0.001). CONCLUSIONS: Postoperative intermittent intrauterine balloon dilatation therapy can significantly reduce postoperative adhesion reformation and significantly increase menstruation flow. TWEETABLE ABSTRACT: RCT: Postoperative intermittent intrauterine balloon therapy can prevent adhesion reformation after hysteroscopic adhesiolysis.

Presence of Hepatitis B virus DNA in follicular fluid in female Hepatitis B carriers and outcome of IVF/ICSI treatment: A prospective observational study.

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.

Impact of haemostatic sealant versus electrocoagulation on ovarian reserve after laparoscopic ovarian cystectomy of ovarian endometriomas: a randomised controlled trial.

OBJECTIVE: To evaluate the effect of haemostatic sealant compared with bipolar coagulation on ovarian reserve after laparoscopic cystectomy for ovarian endometriomas. DESIGN: Patient-blinded, randomised controlled trial. SETTING: University-affiliated tertiary hospital. POPULATION: Women aged 18-40 years with 3-8 cm unilateral or bilateral endometriomas. METHODS: Ninety-four patients were randomised to receive haemostasis by the application of haemostatic sealant (n = 47) or standard care (n = 47). MAIN OUTCOME MEASURES: Primary outcome was the effect on the antral follicular count 3 months after the operation as it captures the effect on the ovary subjected to treatment. Secondary outcomes included the change in anti-Mullerian hormone, follicular-stimulating hormone and peri-operative outcomes including haemostasis, complications, pain, and satisfaction scores. RESULTS: A total of 94 patients aged 32.36 ± 4.92 years underwent laparoscopic cystectomy for ovarian endometriomas. The average diameter of the endometrioma was 4.21 ± 1.38 cm. The increase in antral follicle count of the affected ovaries at 3 months in the intervention group (+2.36 ± 0.37) was significantly (P = 0.013) higher than that in the control group (+1.08 ± 0.36). Repeated measures analysis of variance revealed significant effect with time (P < 0.001) and of interaction of group × time (P = 0.029) for affected ovary antral follicle count. No significant difference was noted between the two groups with regard to follicular-stimulating hormone, anti-Mullerian hormone, and other secondary outcomes. CONCLUSIONS: Applying haemostatic sealant after laparoscopic cystectomy of ovarian endometriomas produced a greater increase in antral follicle count 3 months after surgery compared with the control group. TWEETABLE ABSTRACT: RCT: Haemostatic sealant in laparoscopic cystectomy of endometriomas increase in the antral follicle count after surgery.

Visit-to-visit blood pressure variability and hip fracture risk in older persons.

We investigated the association between blood pressure variability measured by the coefficient of variation (CV) of blood pressure and hip fracture in older persons with diabetes. After excluding patients with acute complications and comorbidities, a positive association with similar magnitude of strength was found between BP variability and hip fracture, compared with that in the original analysis. INTRODUCTION: Hypertension is a risk factor of osteoporosis and hip fracture, but studies have yet to investigate whether blood pressure variability measured by the CV of blood pressure can predict hip fracture in older persons with diabetes. METHODS: We conducted a retrospective cohort study on 21,160 patients who suffered from type 2 diabetes (age ≥ 50 years) and participated in the National Diabetes Care Management Program in Taiwan. The patients' 1-year variability in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the baseline and subsequent hip fracture incidence for 8.2 years were analyzed. RESULTS: There were 937 recorded incident hip fractures. SBP-CV and DBP-CV were classified based on their tertiles. After multivariate adjustment was conducted, SBP-CV found to be a predictor of hip fracture, and its hazard ratio was 1.18 (95% CI 1.00-1.40) for the third tertile compared with the first tertile. CONCLUSIONS: Our study suggests SBP stability is a predictor for hip fracture incidence in older persons with type 2 diabetes.