Biomarkers in the prediction of complications in pregnancy after assisted reproductive technology.

OBJECTIVES: To compare the temporal changes in mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) across gestation between assisted reproductive technology (ART) pregnancies complicated with great obstetrical syndromes (GOS) or gestational diabetes (GDM) ± large-for-gestational-age (LGA) fetus, and uncomplicated ART pregnancies. METHODS: This was a prospective longitudinal study of 143 women with singleton pregnancies who conceived through ART at the Department of Obstetrics and Gynecology, Prince of Wales Hospital, the Chinese University of Hong Kong, Hong Kong SAR between December 2017 and January 2020. The participants were followed up at 6-6+3, 11-13+6, 20-24+6, 30-34+6, and 35-37+6 weeks for the measurement of MAP, UtA-PI, PlGF, and sFlt-1. A linear mixed-effects analysis was performed to compare the biomarkers in the GOS, GDM ± LGA, and uncomplicated groups across gestation. RESULTS: Thirty-three (23.1%) and fifty-five (31.5%) women were diagnosed with GOS and GDM ± LGA, respectively. The GOS group had higher estimated marginal mean log10 MAP mulitples of the median (MoM) across gestation, compared with the uncomplicated group (0.00771 vs -0.02022; P < 0.001), when adjusting for clinical visits and days of embryo transfer. The absolute mean log10 MAP MoM in the GOS group was found to be significantly higher than that of the uncomplicated group at all clinical visits from 6 weeks onwards. Furthermore, the estimated marginal mean log10 PlGF MoM was significantly lower in the GOS group across gestation, compared with the uncomplicated group (-0.04226 vs 0.05566; P = 0.010). The significant difference in log10 PlGF MoM was observed from 11-13+6 to 30-34+6 week of gestation (P < 0.05). However, no significant differences in the estimated marginal means of log10 UtA-PI MoM and log10 sFlt-1 MoM between GOS and uncomplicated groups were observed. GDM ± LGA group had a lower estimated marginal mean log10 PlGF MoM throughout pregnancy compared with the uncomplicated group (-0.01536 vs 0.05572; P = 0.032). In the individual visit analysis, the significant difference was observed at the 20-24+6 and 35-37+6 weeks visits (P < 0.05). There were no significant differences in estimated marginal mean log10 MoM of MAP, UtA-PI, and sFlt-1 between GDM ± LGA and uncomplicated groups during pregnancy. CONCLUSION: Our study has revealed that among pregnancies conceived through ART, GOS is associated with higher MAP and lower PlGF from early gestation until late third trimester, while GDM ± LGA is associated with lower PlGF during the second half of pregnancy. The same degree of differences in MAP and PlGF persists from early until late gestation in the GOS group and these findings highlight the importance of early screening during the first trimester to identify women who are at risk for developing GOS following ART procedures. Lastly, the potential of PlGF in predicting the development of GDM from the second trimester of pregnancy requires further investigation.

Ultrasonographic placental parameters at 11-13+6 weeks' gestation in the prediction of complications in pregnancy after assisted reproductive technology.

OBJECTIVE: To evaluate the performance of maternal factors, biophysical and biochemical markers at 11-13 + 6 weeks' gestation in the prediction of gestational diabetes mellitus with or without large for gestational age (GDM ± LGA) fetus and great obstetrical syndromes (GOS) among singleton pregnancy following in-vitro fertilisation (IVF)/embryo transfer (ET). MATERIALS AND METHODS: A prospective cohort study was conducted between December 2017 and January 2020 including patients who underwent IVF/ET. Maternal mean arterial pressure (MAP), ultrasound markers including placental volume, vascularisation index (VI), flow index (FI) and vascularisation flow index (VFI), mean uterine artery pulsatility index (mUtPI) and biochemical markers including placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at 11-13 + 6 weeks' gestation. Logistic regression analysis was performed to determine the significant predictors of complications. RESULTS: Among 123 included pregnancies, 38 (30.9%) had GDM ± LGA fetus and 28 (22.8%) had GOS. The median maternal height and body mass index were significantly higher in women with GDM ± LGA fetus. Multivariate logistic regression analysis demonstrated that in the prediction of GDM ± LGA fetus and GOS, there were significant independent contributions from FI MoM (area under curve (AUROC) of 0.610, 95% CI 0.492-0.727; p = 0.062) and MAP MoM (AUROC of 0.645, 95% CI 0.510-0.779; p = 0.026), respectively. CONCLUSION: FI and MAP are independent predictors for GDM ± LGA fetus and GOS, respectively. However, they have low predictive value. There is a need to identify more specific novel biomarkers in differentiating IVF/ET pregnancies that are at a higher risk of developing complications.

Intrauterine adhesion in ultrasound-guided manual vacuum aspiration (USG-MVA) versus electric vacuum aspiration (EVA): a randomised controlled trial.

BACKGROUND: Intrauterine adhesion (IUA) can arise as a potential complication following uterine surgery, as the surgical procedure may damage the endometrial stratum basalis. The objective of this study was to assess and compare the occurrence of IUA in women who underwent ultrasound-guided manual vacuum aspiration (USG-MVA) versus electric vacuum aspiration (EVA) for managing first-trimester miscarriage. METHODS: This was a prospective, single-centre, randomised controlled trial conducted at a university-affiliated tertiary hospital. Chinese women aged 18 years and above who had a delayed or incomplete miscarriage of ≤ 12 weeks of gestation were recruited in the Department of Obstetrics and Gynaecology at the Prince of Wales. Recruited participants received either USG-MVA or EVA for the management of their miscarriage and were invited for a hysteroscopic assessment to evaluate the incidence of IUA between 6 and 20 weeks after the surgery. Patients were contacted by phone at 6 months to assess their menstrual and reproductive outcomes. RESULTS: 303 patients underwent USG-MVA or EVA, of whom 152 were randomised to 'USG-MVA' and 151 patients to the 'EVA' group. Out of the USG-MVA group, 126 patients returned and completed the hysteroscopic assessment, while in the EVA group, 125 patients did the same. The incidence of intrauterine adhesion (IUA) was 19.0% (24/126) in the USG-MVA group and 32.0% (40/125) in the EVA group, showing a significant difference (p < 0.02) between the two groups. No significant difference in the menstrual outcomes at 6 months postoperatively between the two groups but more patients had miscarriages in the EVA group with IUA. CONCLUSIONS: IUAs are a possible complication of USG-MVA. However, USG-MVA is associated with a lower incidence of IUA postoperatively at 6-20 weeks. USG-MVA is a feasible, effective, and safe alternative surgical treatment with less IUA for the management of first-trimester miscarriage. TRIAL REGISTRATION: The study was registered with the Centre for Clinical Research and Biostatics- Clinical Trials Registry (CCRBCTR), which is a partner registry of the WHO Primary Registry-Chinese Clinical Trials Registry (ChiCTR) (Unique Trial Number: ChiCTR1900023198 with the first trial registration date on 16/05/2019).

Incidence of intrauterine adhesion after ultrasound-guided manual vacuum aspiration (USG-MVA) for first-trimester miscarriages: a prospective cohort study.

PURPOSE: Ultrasound-guided manual vacuum aspiration (USG-MVA) is a feasible and effective outpatient treatment to treat early pregnancy loss. METHODS: This was a prospective observational study at a university-affiliated hospital. All women undergoing either a USG-MVA or electric vacuum aspiration (EVA) were invited to return 3-6 months later for follow-up at which women completed a questionnaire to document their post-evacuation menstrual and reproductive history, and underwent a hysteroscopy if they were not pregnant. The severity of intrauterine adhesion (IUA), if present, was graded (Stage I-III) according to the American fertility society classification. RESULTS: A total of 292 women had a hysteroscopy after their initial surgical evacuation, USG-MVA 169(57.9%) versus EVA 123(42.1%). Women undergoing EVA as opposed to a USG-MVA had a 12.9% higher incidence of IUA (24.1% vs. 37.0%, p = 0.042) equivalent to 1.84 times higher risk (95% CI 1.01-3.34; p = 0.048). Women having EVA continued to show an increased but not statistically significant trend towards an increased risk of IUA after adjusting for the type of miscarriage (aOR = 1.3; 95% CI 0.66-2.50; p = 0.46). CONCLUSION: There were no significant differences in their reproductive outcomes and fewer women post-USG-MVA complained of hypomenorrhea. IUA may still occur in women undergoing USG-MVA but it is lower than the rate in women undergoing EVA. Clinical trials registry The trial was registered with the Centre for Clinical Research and Biostatistics - Clinical Trials Registry (CCRBCTR), a partner registry of the WHO Primary Registry-Chinese Clinical Trials Registry (ChiCTR) with a Unique Trial Number: CUHK_CCRB00541 on 22 Dec 2016.

A reappraisal of ovarian stimulation strategies used in assisted reproductive technology.

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.

A point-of-care urine test to predict adverse maternal and neonatal outcomes in Asian women with suspected preeclampsia.

OBJECTIVES: To assess clinical utility of the urine Congo red dot test (CRDT) in predicting composite adverse maternal and neonatal outcomes in women with suspected preeclampsia (PE). METHODS: CRDT result and pregnancy outcomes were prospectively documented in women with new onset or pre-existing hypertension, new or pre-existing proteinuria, PE symptoms and suspected PE-related fetal growth restriction or abnormal Doppler presenting from 20 weeks' gestation between January 2020 and December 2022. Participants and clinicians were blinded to the CRDT result and managed according to internally agreed protocols. Composite maternal outcome was defined as PE, postpartum hemorrhage, intensive care unit admission, and maternal death. Composite neonatal outcome was defined as small for gestational age, preterm birth, 5-min Apgar score < 7, neonatal intensive care unit admission, and neonatal death. RESULTS: Two hundred and forty-four women out of two hundred and fifty-one (97.2%) had a negative CRDT. All seven women with positive CRDT had both adverse maternal and neonatal outcomes, giving positive predictive values (PPV) of 100%. Rates of composite adverse maternal and neonatal outcomes in CDRT negative women were 103/244 [42.2%, 95% confidence interval (CI) 36.2%-48.5%] and 170/244 (69.7%, 95% CI 63.6%-75.1%), respectively. CRDT negative predictive values (NPV) for adverse maternal and neonatal outcomes were, respectively, 141/244 (57.8%, 95% CI 48.6%-68.2%) and 74/244 (30.3%, 95% CI 23.8%-38.1%). CONCLUSION: CRDT had low NPV but high PPV for adverse maternal and neonatal outcomes in women with suspected PE. Its role in clinical management and triage of women with suspected PE is limited as it cannot identify those at low risk of developing adverse outcomes.

Breastfeeding challenges and opportunities during COVID-19 in Hong Kong.

Barriers to sustain breastfeeding could be time and place specific. Here, we summarise new and old challenges to breastfeeding during COVID-19 pandemic in Hong Kong, some of which were obtained from qualitative in-depth interviews with health-care professionals. We document how unnecessary massive mother-baby separations in hospitals and doubts in COVID-19 vaccine safety seriously harm breastfeeding. We also discuss how the trends and increase in acceptance of receiving post-natal care from family doctors, online-antenatal class, work-from-home policy and telemedicine implicate new strategies to protect, promote and support breastfeeding during and after the pandemic. The challenges from the COVID-19 pandemic on breastfeeding have revealed new opportunities to support breastfeeding in Hong Kong and similar settings where exclusive breastfeeding for 6 months is still not the norm.

A point-of care urine test to predict preeclampsia development in Asian women with suspected preeclampsia.

OBJECTIVES: To evaluate the diagnostic performance and clinical utility of the urine Congo red dot test (CRDT) in predicting preeclampsia (PE) within 7 days, 14 days and 28 days of assessment. STUDY DESIGN: A prospective single center double blind non-intervention study conducted from January 2020 to March 2022. Urine congophilia has been proposed as a point-of-care test for the prediction and rapid identification of PE. In our study, urine CRDT and pregnancy outcomes were assessed in women presenting with clinical features of suspected PE after 20 weeks of gestation. RESULTS: Among the 216 women analyzed, 78 (36.1 %) women developed PE, in which only 7 (9.0 %) of them had a positive urine CRDT test. The median (IQR) interval between the initial test and the diagnosis of PE was significantly shorter for women with a positive urine CRDT compared with women with a negative urine CRDT (1 day (0-5 days) vs 8 days (1-19 days), P = 0.027). The negative predictive value of a negative urine CRDT test for PE within 7 days, 14 days and 28 days of assessment were 83.73 % (95 %CI 81.75 %- 85.54 %), 78.92 % (95 % confidence interval [CI] 77.07 %- 80.71 %) and 71.77 % (95 %CI 70.06 %- 73.42 %) respectively. The sensitivity of the urine CRDT in ruling in PE within 7 days, 14 days and 28 days of assessment were 17.07 % (95 %CI 7.15 %- 32.06 %), 13.73 % (95 %CI 5.70 %- 26.26 %) and 10.61 % (95 %CI 4.37 %- 20.64 %), respectively. CONCLUSIONS: Urine CRDT alone has high specificity yet low sensitivity in the short-term prediction of PE in women with suspected PE. Further studies are required to evaluate its clinical utility.

Efficacy, safety and immunogenicity of a human rotavirus vaccine (RIX4414) in Hong Kong children up to three years of age: a randomized, controlled trial.

BACKGROUND: A phase III, double-blind, randomized, controlled trial was conducted in Hong Kong to evaluate the efficacy, safety and immunogenicity of a human rotavirus vaccine, RIX4414 (Rotarix) against severe rotavirus gastroenteritis in children up to three years of age. METHODS: Healthy infants aged 6-12 weeks were enrolled between 08-December-2003 and 31-August-2005 and received two oral doses of either RIX4414 vaccine (N=1513) or placebo (N=1512) given 2 months apart. Vaccine efficacy was assessed from two weeks post-Dose 2 until the children were two and three years of age. Anti-rotavirus IgA seroconversion rate was calculated pre-vaccination and 1-2 months post-Dose 2 using ELISA (cut-off=20 U/mL) for 100 infants. Safety was assessed until the children were two years of age; serious adverse events (SAEs) were recorded throughout the study period. RESULTS: In children aged two and three years of life, vaccine efficacy against severe rotavirus gastroenteritis was 95.6% (95% CI: 73.1%-99.9%) and 96.1% (95% CI: 76.5%-99.9%), respectively. The seroconversion rate 1-2 months after the second dose of RIX4414 was 97.5% (95% CI: 86.8%-99.9%). At least one SAE was recorded in 439 and 477 infants who were administered RIX4414 and placebo, respectively (p-value=0.130). Six intussusception cases were reported (RIX4414=4; placebo=2) and none was assessed to be vaccine-related. CONCLUSION: RIX4414 was efficacious, immunogenic and safe in the prevention of rotavirus gastroenteritis for at least two years post-vaccination in Hong Kong children.

A study on body weight perception and weight control behaviours among adolescents in Hong Kong.

OBJECTIVE: To examine the relationships between body weight perceptions, estimated body mass index, gender, and weight control behaviours. DESIGN: Cross-sectional survey. SETTING: Three secondary schools in Hong Kong. PARTICIPANTS: A total of 1132 secondary school forms 1 and 3 students. MAIN OUTCOME MEASURES: The strength of agreement between perceived weight and estimated body mass index, and the association between perceived weight, estimated body mass index, and weight control behaviours. RESULTS: A total of 14% of students were estimated to be overweight or obese. The agreement between actual (estimated) body mass index and perceived weight was poor in females and fair in males (Kappa 0.137 and 0.225, respectively). In females, there was no evidence of a relationship between body mass index and weight control behaviours. However, there was a relationship between perceived weight and weight control behaviours such that females who perceived themselves as overweight were more likely to exercise, restrict caloric intake, self medicate with diet pills, purge, or use laxatives. In males, there was evidence of a relationship between perceived weight, body mass index, and weight control behaviours. Males who perceived themselves as overweight or were overweight, were more likely to exercise or restrict caloric intake. CONCLUSIONS: Body weight perceptions are not in agreement with actual weight in adolescents. This discrepancy is more marked in females who use a variety of weight control behaviours. These behaviours are motivated by perceived weight rather than actual (estimated) body mass index. Overweight adolescents should be encouraged to adopt appropriate weight control behaviours for their health needs.

Osteonecrosis in children with severe acute respiratory syndrome.

Osteonecrosis is a debilitating bone disease affecting adults who have recovered from severe acute respiratory syndrome in Hong Kong and China, but there are no data on its prevalence in children. We report 5 children with magnetic resonance imaging evidence of osteonecrosis. In view of the high prevalence and asymptomatic presentation of osteonecrosis, we suggest magnetic resonance imaging screening for osteonecrosis in children with severe acute respiratory syndrome.

Severe acute respiratory syndrome in children: experience in a regional hospital in Hong Kong.

OBJECTIVE: To report the clinical, laboratory, and radiologic features of children with severe acute respiratory syndrome (SARS) and to examine the difference between the younger and older age groups. DESIGN: Retrospective descriptive cohort study. SETTING: A regional hospital in Hong Kong. PATIENTS: Children younger than 18 yrs with SARS. RESULTS: Twenty-one children were included, with a mean age of 10.7 +/- 5.1 yrs. Children with SARS presented with fever, nonproductive cough, malaise, chills, headache, myalgia, and loss of appetite. Examination of the chest showed minimal auscultatory findings. Common laboratory findings included lymphopenia, thrombocytopenia, and mild elevations of activated partial thromboplastin time, alanine transaminase, lactic dehydrogenase, and creatine phosphokinase. Bacteriologic and virologic studies were all negative for common pathogens. Unilateral focal opacity was the commonest finding in chest radiography. High-resolution computerized tomography of the thorax was an early diagnostic tool if the chest radiograph was negative. The clinical course was less severe in comparison with adult patients. However, adolescents (age, > or =12 yrs) resembled adults in their clinical features. When compared with the younger age group, the adolescents had significantly higher temperatures, more constitutional upset, and a greater need for steroid treatment. Children younger than 12 yrs seemed less ill but had more coughing. On the whole, the outcome was favorable. CONCLUSION: Severe acute respiratory syndrome affects children, but the course is less severe. Nevertheless, the disease could have a significant psychosocial impact on children because of the potential seriousness of the disease in their adult family members.