Novel Genetic Risk and Metabolic Signatures of Insulin Signaling and Androgenesis in the Anovulation of Polycystic Ovary Syndrome

Funding Information: The authors are grateful to all staff in the PCOSAct group for their effort in the collection of blood samples and clinical dataset which used in current study. Special thanks to Prof. Attila Toth from Institute of Physiological Chemistry, Dresden, Germany for the REC114 antibody. This study was supported by the National key Research and Development Program of China (2019YFC1709500); the National Collaboration Project of Critical Illness by Integrating Chinese Medicine and Western Medicine; the Project of Heilongjiang Province Innovation Team “TouYan;” the Yi-Xun Liu and Xiao-Ke Wu Academician Workstation; the Innovation Team of Reproductive Technique with Integrative Chinese Medicine and Western Medicine in Xuzhou City, China; Heilongjiang University of Chinese Medicine from the National Clinical Trial Base; Heilongjiang Provincial Clinical Research Center for Ovary Diseases; the Research Grant Council (T13-602/21-N, C5045-20EF, and 14122021); and Food and Health Bureau in Hong Kong, China (06171026). Ben Willem J. Mol is supported by a National Health and Medical Research Council (NHMRC) Investigator grant (GNT1176437). Ben Willem J. Mol reports consultancy for ObsEva and Merck and travel support from Merck. Xiaoke Wu, Yongyong Shi, and Chi Chiu Wang developed the research question and designed the study. Xiaoke Wu, Yongyong Shi, Yijuan Cao, and Chi Chiu Wang designed the analysis. Yongyong Shi and Zhiqiang Li contributed to the design of the experiment of whole-exome plus targeted SNP sequencing and the analysis, and interpreted the results. Jingshu Gao, Hui Chang, Duojia Zhang, Jing Cong, Yu Wang, Qi Wu, Xiaoxiao Han, Pui Wah Jacqueline Chung, Yiran Li, and Lin Zeng contributed to the experiment of metabolic profile and immunofluorescent staining and the analysis, and interpreted the results. Astrid Borchert and Hartmut Kuhn provided antibody support and advice. Xu Zheng and Lingxi Chen contributed to create the predictive model with deep machine learning. Jian Li, Qi Wu, Hongli Ma, Xu Zheng, and Lingxi Chen contributed to the analysis of the clinical characteristics and interpreted the results. Jian Li, Hongli Ma, Hui Chang, Jing Cong, and Chi Chiu Wang drafted the manuscript. All authors reviewed and revised the manuscript. Xiaoke Wu is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Xiaoke Wu, Chi Chiu Wang, Yijuan Cao, Jian Li, Zhiqiang Li, Hongli Ma, Jingshu Gao, Hui Chang, Duojia Zhang, Jing Cong, Yu Wang, Qi Wu, Xiaoxiao Han, Pui Wah Jacqueline Chung, Yiran Li, Xu Zheng, Lingxi Chen, Lin Zeng, Astrid Borchert, Hartmut Kuhn, Zijiang Chen, Ernest Hung Yu Ng, Elisabet Stener-Victorin, Heping Zhang, Richard S. Legro, Ben Willem J. Mol, and Yongyong Shi declare that they have no conflict of interest or financial conflicts to disclose. Funding Information: This study was supported by the National key Research and Development Program of China ( 2019YFC1709500 ); the National Collaboration Project of Critical Illness by Integrating Chinese Medicine and Western Medicine ; the Project of Heilongjiang Province Innovation Team “TouYan;” the Yi-Xun Liu and Xiao-Ke Wu Academician Workstation; the Innovation Team of Reproductive Technique with Integrative Chinese Medicine and Western Medicine in Xuzhou City , China; Heilongjiang University of Chinese Medicine from the National Clinical Trial Base ; Heilongjiang Provincial Clinical Research Center for Ovary Diseases ; the Research Grant Council ( T13-602/21-N , C5045-20EF , and 14122021 ); and Food and Health Bureau in Hong Kong, China ( 06171026 ). Publisher Copyright: © 2023Peer reviewedPublisher PD

Clinical effectiveness and safety of time-lapse imaging systems for embryo incubation and selection in in-vitro fertilisation treatment (TILT): a multicentre, three-parallel-group, double-blind, randomised controlled trial.

BackgroundTime-lapse imaging systems for embryo incubation and selection might improve outcomes of in-vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) treatment due to undisturbed embryo culture conditions, improved embryo selection, or both. However, the benefit remains uncertain. We aimed to evaluate the effectiveness of time-lapse imaging systems providing undisturbed culture and embryo selection, and time-lapse imaging systems providing only undisturbed culture, and compared each with standard care without time-lapse imaging.MethodsWe conducted a multicentre, three-parallel-group, double-blind, randomised controlled trial in participants undergoing IVF or ICSI at seven IVF centres in the UK and Hong Kong. Embryologists randomly assigned participants using a web-based system, stratified by clinic in a 1:1:1 ratio to the time-lapse imaging system for undisturbed culture and embryo selection (time-lapse imaging group), time-lapse imaging system for undisturbed culture alone (undisturbed culture group), and standard care without time-lapse imaging (control group). Women were required to be aged 18-42 years and men (ie, their partners) 18 years or older. Couples had to be receiving their first, second, or third IVF or ICSI treatment and could not participate if using donor gametes. Participants and trial staff were masked to group assignment, embryologists were not. The primary outcome was live birth. We performed analyses using the intention-to-treat principle and reported the main analysis in participants with primary outcome data available (full analysis set). The trial is registered on the International Trials Registry (ISRCTN17792989) and is now closed.Findings1575 participants were randomly assigned to treatment groups (525 participants per group) between June 21, 2018, and Sept 30, 2022. The live birth rates were 33·7% (175/520) in the time-lapse imaging group, 36·6% (189/516) in the undisturbed culture group, and 33·0% (172/522) in the standard care group. The adjusted odds ratio was 1·04 (97·5% CI 0·73 to 1·47) for time-lapse imaging arm versus control and 1·20 (0·85 to 1·70) for undisturbed culture versus control. The risk reduction for the absolute difference was 0·7 percentage points (97·5% CI -5·85 to 7·25) between the time-lapse imaging and standard care groups and 3·6 percentage points (-3·02 to 10·22) between the undisturbed culture and standard care groups. 79 serious adverse events unrelated to the trial were reported (n=28 in time-lapse imaging, n=27 in undisturbed culture, and n=24 in standard care).InterpretationIn women undergoing IVF or ICSI treatment, the use of time-lapse imaging systems for embryo culture and selection does not significantly increase the odds of live birth compared with standard care without time-lapse imaging.FundingBarts Charity, Pharmasure Pharmaceuticals, Hong Kong OG Trust Fund, Hong Kong Health and Medical Research Fund, Hong Kong Matching Fund

Towards a global partnership model in interprofessional education for cross-sector problem-solving

Objectives A partnership model in interprofessional education (IPE) is important in promoting a sense of global citizenship while preparing students for cross-sector problem-solving. However, the literature remains scant in providing useful guidance for the development of an IPE programme co-implemented by external partners. In this pioneering study, we describe the processes of forging global partnerships in co-implementing IPE and evaluate the programme in light of the preliminary data available. Methods This study is generally quantitative. We collected data from a total of 747 health and social care students from four higher education institutions. We utilized a descriptive narrative format and a quantitative design to present our experiences of running IPE with external partners and performed independent t-tests and analysis of variance to examine pretest and posttest mean differences in students’ data. Results We identified factors in establishing a cross-institutional IPE programme. These factors include complementarity of expertise, mutual benefits, internet connectivity, interactivity of design, and time difference. We found significant pretest–posttest differences in students’ readiness for interprofessional learning (teamwork and collaboration, positive professional identity, roles, and responsibilities). We also found a significant decrease in students’ social interaction anxiety after the IPE simulation. Conclusions The narrative of our experiences described in this manuscript could be considered by higher education institutions seeking to forge meaningful external partnerships in their effort to establish interprofessional global health education

Uses of FloSeal© in obstetric hemorrhage: Case series and literature review

Objective: FloSeal© has been shown to be an alternative and effective method of hemostasis. The current study examines the various uses of FloSeal© in obstetric hemorrhage and gives an overview of the literature. Case reports: In this retrospective case review, a total of 11 cases with obstetric hemorrhage were reviewed throughout a period of one year. All but one case was successful in using FloSeal© in arresting the bleeding with hysterectomy avoided. FloSeal© can be considered when bleeding occurs locally at the placental bed, bladder base, adhesiolysis site, vaginal tears or at suture holes. Conclusion: FloSeal© was a quick and effective alternative for hemostasis and should be considered when conventional hemostatic techniques fails or is impractical

#86 : Use of Triptorelin Versus Human Chorionic Gonadotropin as Ovulation Trigger

Background and Aims: Gonadotropin releasing hormone agonist (GnRH-a) trigger has been shown to be associated with significantly lower risk of moderate or severe ovarian hyperstimulation syndrome (OHSS) when compared among women at high risk of OHSS. However, trigger failure has been shown to occur in 2% of cycles using GnRH-a as trigger. This study aims to review the use of GnRH-a as ovulation trigger. Method: Retrospective review of records in antagonist cycles from an ART unit in a tertiary hospital from 2017-2021 was performed. Follicles were considered mature when they reach [Formula: see text] 15 mm. Ovulation triggered with urinary human chorionic gonadotropin (uhCG) (5000-10000 IU), recombinant hCG (rhCG) 250 mcg, or triptorelin 0.2 mg when there were [Formula: see text] 3 mature follicles. All embryos obtained from cycles using triptorelin were cryopreserved. Outcome including the number of oocytes retrieved, the follicle to oocyte index, ovarian hyperstimulation syndrome were reviewed. Results: 1378 cycles were included. 1089 cycles had uhCG or rhCG as trigger, while 284 cycles had triptorelin as trigger. Women in the triptorelin group were significantly younger with a lower basal follicle stimulating hormone level and a higher antral follicle count (Table 1). In the triptorelin group, the total number of mature sized follicles, estrogen level at trigger, oocytes retrieved, number of blastocysts were significantly higher compared to the hCG group (Table 2). Follicle to oocyte index was significantly higher in the triptorelin group but the proportion of mature oocytes were similar in both groups. There were no cases of trigger failure and OHSS in the triptorelin group, but 30 cases of OHSS, with18 cases early onset, 12 cases late onset, amongst them 10 cases (1%) were severe OHSS) in the hCG group. Conclusion: GnRH-a trigger is a good candidate as ovulatory trigger in women at risk of OHSS without hampering the laboratory outcome

What We Have Learned from Animal Models to Understand the Etiology and Pathology of Endometrioma-Related Infertility

Endometrioma (OMA) is the most common subtype of endometriosis, in which the endometriotic lesions are implanted in the ovary. Women with OMA are usually associated with infertility, presenting with reduced ovarian reserve, low oocyte quantity and quality, and poor fertility outcomes. However, the underlying pathological mechanisms in OMA-related infertility are still unclear. Due to the limitations and ethical issues of human studies in reproduction, animal models that recapitulate OMA characteristics and its related infertility are critical for mechanistic studies and subsequent drug development, preclinical testing, and clinical trials. This review summarized the investigations of OMA-related infertility based on previous and latest endometrioma models, providing the possible pathogenesis and potential therapeutic targets for further studies

Ultrasound-guided manual vacuum aspiration (USG-MVA) with cervical preparation for early pregnancy loss: A cost-effectiveness analysis.

Background and aimApproximately one in four women will experience a miscarriage in their lifetime. Ultrasound-guided manual vacuum aspiration (USG-MVA) is an ideal outpatient surgical treatment alternative to traditional surgical evacuation. We aimed to examine the cost-effectiveness of US-MVA with cervical preparation for treatment of early pregnancy loss from the perspective of public healthcare provider of Hong Kong.MethodsA decision-analytic model was designed to simulate outcomes in a hypothetical cohort of patients with early pregnancy loss on four interventions: (1) US-MVA, (2) misoprostol, (3) surgical evacuation of uterus by dilation and curettage (surgical evacuation), and (4) expectant care. Model inputs were retrieved from published literature and public data. Model outcome measures were total direct medical cost and disutility-adjusted life-year (DALY). Base-case model results were examined by sensitivity analysis.ResultsThe expected DALYs (0.00141) and total direct medical cost (USD736) of US-MVA were the lowest of all interventions in base-case analysis, and US-MVA was the preferred cost-effective option. One-way sensitivity analysis showed that the misoprostol group became less costly than the US-MVA group if the evacuation rate of misoprostol (base-case value 0.832) exceeded 0.920. In probabilistic sensitivity analysis, At the willingness-to-pay (WTP) threshold of 49630 USD/DALY averted (1x gross domestic product per capita of Hong Kong), the US-MVA was cost-effective in 72.9% of the time.ConclusionsUS-MVA appeared to be cost-saving and effective for treatment of early pregnancy loss from the perspective of public healthcare provider of Hong Kong

#87 : Intrauterine Adhesion in Ultrasound-Guided Manual Vacuum Aspiration (USG-MVA) Versus Electric Vaccum Aspiration (EVA): A Randomized Controlled Trial

Background and Aims: Intrauterine adhesion (IUA) is a possible complication after uterine surgery, especially after sharp curettage for miscarriages as it destroys the endometrial stratum basalis. This study aimed to determine and compare the IUA in women who underwent ultrasound-guided manual vacuum aspiration (USG-MVA) as opposed to traditional surgical evacuation (EVA) for the management of their first-trimester miscarriage. Methods: This was a prospective single-centre, randomised controlled trial conducted in a university-affiliated tertiary hospital. Chinese women aged [Formula: see text]18 years with a delayed miscarriage [Formula: see text]12 weeks of gestation or incomplete miscarriage attending the hospital were randomized to either USG-MVA or EVA for the management of their miscarriage. They were invited to come back for a hysteroscopic assessment for IUA at 6-20 weeks post-surgery to assess the incidence of IUA. Patients were contacted by phone at 6 months to assess their menstrual and reproductive outcomes. Results: 303 patients underwent surgical evacuation, of whom 152 were randomized to the ‘USG-MVA’ and 151 patients to the ‘EVA’. 126 from the USG-MVA group and 125 from the EVA group returned and completed the hysteroscopic assessment. The incidence of the IUA from USG-MVA was 19.0% (n=24/126) and was significantly lower compared to EVA, which was at 32.0% (n=40/125). There was no significant difference in 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

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

Abstract 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