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Introduction: In recent years, the use of frozen embryo transfers (FET) has rapidly increased following the freeze-all strategy due to the advantages of increased maternal safety, improved pregnancy rates, lower ectopic pregnancy rates and better obstetric and neonatal outcomes. Currently, there is still no good scientific evidence to support when to perform FET following a stimulated in vitro fertilisation (IVF) cycle in the freeze-all strategy., Methods/analysis: This will be a randomised controlled trial. A total of 828 women undergoing their first FET following their first stimulated IVF cycle in the freeze-all strategy will be enrolled and randomised into one of the following groups according to a computer-generated randomisation list: (1) the immediate group, in which FET will be performed in the first menstrual cycle following the stimulated IVF cycle; or (2) the delayed group, in which FET will be performed at least in the second menstrual cycle following the stimulated IVF cycle. The primary outcome will be live birth, which is defined as the delivery of any infants at ≥22 gestational weeks with heartbeat and breath., Ethics/dissemination: Ethical approval was granted by the Ethics Committee of Assisted Reproductive Medicine at the Shanghai JiAi Genetics & IVF Institute (JIAI E2019-15). Written informed consent will be obtained from each woman before any study procedure is performed, according to good clinical practice. The results of this trial will be disseminated in a peer-reviewed journal., Trial Registration Number: NCT04371783., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The construction, chemical, aviation, medical, and health care industries have used serious games for safety training. To our knowledge, serious games have not been developed focusing on behavioral change to improve safety through the use of verbal commands and instilling players with heightened awareness of their spatial proximity to other people in their surroundings., Objective: We aimed to develop a theory-driven serious game for improving safety behavior using verbal commands and validate the implementation of the theoretical frameworks used for game development. The game developed, KitchenSpeak, was a first-person character (FPC) game where users respond to in-game prompts to use loud verbal commands when they are approaching another employee's blind spot., Methods: In addition to using the SERES framework in guiding the general game design and development, and the Reflection, Engagement, Choice, Information, Play, Exposition (RECIPE) framework to inform the design of the game mechanics, we also applied gestalt laws of perception for graphic design to guide the design of the game's user interface. We conducted 2 evaluative tests (alpha and beta) to collect end user and stakeholder feedback on the implementation of the theoretical frameworks, as well as to collect relevant information for full-scale implementation and a future validation study., Results: The alpha and beta tests had 8 and 40 participants, respectively. The alpha test results revealed that the theoretical frameworks were adequately applied; however, suggestions were also made to modify and improve the game. The beta test results suggested further improvements for the game design and found no differences in the perception of ease of play between participants with and without previous FPC gaming experience (P=.47; Kruskal-Wallis). Results suggested that the game met its design and theoretical requirements, and it would be easily playable by all players regardless of their previous experience in FPC games., Conclusions: A theory-driven and evidence-based FPC game titled KitchenSpeak was developed to teach the use of kitchen-speak terms in commercial kitchens. Evaluative tests were conducted to validate the implementation of the theoretical frameworks. Our main contributions are creating and validating game-based training to improve behavioral-based safety in the workplace and the incorporation of gestalt laws of perception for graphic design in the game's user interface., (©Chukwudiebube Atagbuzia, Ean H Ng, Ganapathy Natarajan. Originally published in JMIR Formative Research (https://formative.jmir.org), 12.03.2024.)

Molecular markers are increasingly being deployed to accelerate genetic gain in crop plants. The objective of this study was to assess the potential of a mid-density genotyping panel for molecular applications in cowpea breeding. A core set of 2,602 targeted diversity array technology (DArTag) single-nucleotide polymorphisms (SNPs) was designed from an existing 51,128 Cowpea iSelect Consortium Array. The panel's usefulness was assessed using 376 genotypes from different populations of known genetic backgrounds. The panel was informative, with over 78% of SNPs exceeding a minor allele frequency of 0.20. The panel decoded three stratifications in the constituted population, as was expected. Linkage disequilibrium (LD) decay was correctly depicted as slower in a biparental subset than in other populations. A known flower and seed coat color gene region was located on chromosome Vu07, suggesting that the mid-density panel may be used to hypothesize genomic regions underlying target traits in cowpea. Unexpected heterozygosity was detected in some lines and highly among F 1 progenies, divulging the panel's potential application in germplasm purity and hybridity verification. The study unveils the potential of an excellent genomic resource that can be tapped to enhance the development of improved cowpea cultivars., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2024 Patrick Obia Ongom et al.)

Background: Cross-sectional studies have shown that sexual dysfunction and poor quality of life were prevalent among couples undergoing assisted reproduction at specific time points, but nothing is known about how these outcomes change over the course of their intrauterine insemination (IUI) journey., Aim: We investigated the longitudinal changes in sexual function and quality of life of infertile couples undergoing IUI., Methods: Sixty-six infertile couples completed an anonymous questionnaire at 3 time points: after IUI counseling (T1), 1 day before IUI (T2), and 2 weeks after IUI (T3). The questionnaire consisted of demographic data, Female Sexual Function Index (FSFI) or International Index of Erectile Function-5, and Fertility Quality of Life (FertiQoL)., Outcomes: Descriptive statistics, significance testing with the Friedman test, and post hoc analysis with the Wilcoxon signed rank test were used to compare changes in sexual function and quality of life at different time points., Results: Overall, 18 (26.1%), 16 (23.2%), and 12 (17.4%) women and 29 (42.0%), 37 (53.6%), and 31 (44.9%) men were at risk for sexual dysfunction at T1, T2, and T3, respectively. There were significant differences in mean FSFI scores in arousal (3.87, 4.06, 4.10) and orgasm (4.15, 4.24, 4.39) domains at T1, T2, and T3. After post hoc analysis, only the increase in mean orgasm FSFI scores between T1 and T3 was statistically significant. Men's FertiQoL scores remained high during IUI (74.33-75.63 out of 100). Men also scored significantly higher than women on all FertiQoL domains except environment at the 3 time points. Post hoc analysis showed significant improvement in women's FertiQoL domain scores between T1 and T2: mind-body, environment, treatment, and total. Women's FertiQoL score at T2 for the treatment domain was also significantly higher than that at T3., Clinical Implications: Men should not be neglected during IUI as their erectile function got worse in the process, with half of the men being affected. Although women's quality of life showed some improvement during IUI, most of their scores were lower than men's., Strengths and Limitations: The use of psychometrically validated questionnaires and a longitudinal approach are the major strengths; a small sample size and the lack of a dyadic approach are the major limitations., Conclusion: During IUI, women's sexual performance and quality of life improved. The proportion of men having erectile problems was high for this age group, but men's FertiQoL scores remained good and were better than their partners' throughout IUI., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The objective of this prospective study is to compare the prevalence and severity of nausea and vomiting in the first trimester between singleton pregnancies conceived from stimulated in vitro fertilization (IVF) and frozen embryo transfer cycles (FET)., Methods: All women were recruited at 6 weeks gestation and filled in the modified Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) to document whether they had any experience of nausea and vomiting weekly till 12 weeks gestation. The primary outcome was the prevalence of nausea and vomiting and the secondary outcomes included severity of nausea and vomiting and pregnancy outcomes., Results: A total of 360 pregnant women were recruited and 171 were in the stimulated IVF group and 189 in the FET group. The overall return rate was 82.2% (81.8% in the stimulated IVF group and 82.5% in the FET group). Nausea and vomiting were worse in the FET group compared with the IVF group. There were significantly more women who felt nauseated or sick in the FET group (p value = 0.032 for week 11 and p value = 0.046 for week 12); significantly more women with a longer duration of nausea in the FET group (p value = 0.044 for week 7 and p value = 0.030 for week 8); significantly more women with more vomiting in a day in the FET group (p value = 0.042) and significantly more women with retching or dry heaves in the FET group (p value = 0.030 for week 8 and p value = 0.028 for week 11)., Conclusion: Nausea and vomiting were significantly more prevalent and severe in the FET group when compared with the stimulated IVF group., (© 2022. The Author(s).)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters cells via receptor angiotensin-converting enzyme 2 (ACE2) and co-receptor transmembrane serine protease 2 (TMPRSS2). However, patients with SARS-CoV-2 infection receiving ACE1 inhibitors had higher ACE2 expression and were prone to poorer prognostic outcomes. Until now, information on the expression of ACE1, ACE2, and TMPRSS2 in human endometrial tissues, and the effects of ACE inhibitors on embryo implantation are limited. We found human endometria expressed ACE1, ACE2, and TMPRSS2 transcripts and proteins. Lower ACE1, but higher ACE2 transcripts were found at the secretory than in the proliferative endometria. ACE1 proteins were weakly expressed in endometrial epithelial and stromal cells, whereas ACE2 and TMPRSS2 proteins were highly expressed in luminal and glandular epithelial cells. However, ACE1 and TMPRSS4 were highly expressed in receptive human endometrial epithelial (Ishikawa and RL95-2) cells, but not in non-receptive AN3CA and HEC1-B cells. Treatment of human endometrial epithelial cells with ACE1 (Captopril, Enalaprilat, and Zofenopril) or ACE2 (DX600) inhibitors did not significantly alter the expression of ACE1, ACE2 and TMPRSS2 transcripts and spheroid (blastocyst surrogate) attachment onto Ishikawa cells in vitro. Taken together, our data suggest that higher ACE2 expression was found in mid-secretory endometrium and the use of ACE inhibitors did not alter endometrial receptivity for embryo implantation., (Copyright © 2022 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

Couples undergoing assisted reproductive technologies (ART) are prone to sexual dysfunction and lower quality of life (QoL), but whether the incidence of these problems differs with the type of ART is unknown. As such, we conducted this cross-sectional survey to compare the sexual function and QoL of 75 couples undergoing intrauterine insemination (IUI), and 160 couples undergoing in vitro fertilization (IVF). They completed an anonymous questionnaire which included: (i) demographic characteristics; (ii) female sexual function index (FSFI) or (iii) international index of erectile function-5 (IIEF-5); and (iv) fertility QoL questionnaire (FertiQoL). Overall, 22.6% of wives and 39.1% of husbands were at risk for sexual dysfunction, and the risk was similar in IUI and IVF groups. Mean core/treatment/total FertiQoL scores of husbands were higher than wives: 74.98 vs. 68.24/70.02 vs. 65.87/73.52 vs. 67.54 (all p  < 0.001). FertiQoL scores were similar in IUI and IVF groups except wives' treatment FertiQoL score was significantly higher in the IUI group (68.93 vs. 64.44; p  = 0.009). This study confirms that risks for sexual dysfunction were similar in IUI and IVF couples. Wives undergoing IVF had significantly lower treatment FertiQoL score. In both IUI and IVF groups, husbands' QoL was better than wives' QoL.

Current contraceptive methods interfere with folliculogenesis, fertilization, and embryo implantation by physical or hormonal approaches. Although hormonal contraceptive pills are effective in regulating egg formation, they are less effective in preventing embryo implantation. To explore the use of non-hormonal compounds that suppress embryo implantation, we established a high-throughput spheroid-endometrial epithelial cell co-culture assay to screen the Library of Pharmacologically Active Compounds (LOPAC) for compounds that affect trophoblastic spheroid (blastocyst surrogate) attachment onto endometrial epithelial Ishikawa cells. We identified 174 out of 1280 LOPAC that significantly suppressed BeWo spheroid attachment onto endometrial Ishikawa cells. Among the top 20 compounds, we found the one with the lowest cytotoxicity in Ishikawa cells, P11B5, which was later identified as Nemadipine-A. Nemadipine-A at 10 µM also suppressed BeWo spheroid attachment onto endometrial epithelial RL95-2 cells and primary human endometrial epithelial cells (hEECs) isolated from LH +7/8-day endometrial biopsies. Mice at 1.5 days post coitum (dpc) treated with a transcervical injection of 100 µg/kg Nemadipine-A or 500 µg/kg PRI-724 (control, Wnt-inhibitor), but not 10 µg/kg Nemadipine-A, suppressed embryo implantation compared with controls. The transcript expressions of endometrial receptivity markers, integrin αV ( ITGAV ) and mucin 1 ( MUC1 ), but not β-catenin ( CTNNB1 ), were significantly decreased at 2.5 dpc in the uterus of treated mice compared with controls. The reduction of embryo implantation by Nemadipine-A was likely mediated through suppressing endometrial receptivity molecules ITGAV and MUC1 . Nemadipine-A is a potential novel non-hormonal compound for contraception.

Objective: With the surge of confirmed cases of coronavirus disease 2019 (COVID-19) and its associated morbidities and mortalities, continuous companion support during labour was halted in all public hospitals in Hong Kong to prevent the spread of the virus in hospitals. The purpose of this retrospective study was to evaluate the effect of not having continuous companion support during labour on pregnancy and neonatal outcomes during the COVID-19 pandemic period in a regional hospital., Study Design: We retrieved information on women without continuous companion support during the COVID-19 pandemic period from February 1, 2020 to May 15, 2020 and those with continuous companion support within the same period in 2019 in Queen Mary Hospital, Hong Kong. The pregnancy and neonatal outcomes were compared between the two groups., Results: A total of 446 women with continuous companion support in 2019 and 340 women without continuous companion support in 2020 were included in the analysis. The rate of labour augmentation was significantly lower in women with continuous companion support than in those without continuous companion support (3.1% vs. 6.5%, respectively, p = 0.027). Babies born to women with continuous companion support were less likely to have Apgar scores <7 at 1 min than those born to women without continuous companion support (2.5% vs. 5.3%, respectively, p = 0.036). More women with continuous companion support had breastfeeding at the first hour of delivery than those without (86.3% vs. 80.6%, respectively, p = 0.030). There were no differences in other pregnancy and neonatal outcomes. The subgroup analysis with only Chinese women showed that the pregnancy and neonatal outcomes were not significantly different between the two groups., Conclusion: Women without continuous companion support during labour had an increased chance of labour augmentation and babies with an Apgar score <7 at 1 min, and a reduced immediate breastfeeding rate when compared with those with continuous companion support., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Various proteins in the endometrial epithelium are differentially expressed in the receptive phase and play a pivotal role in embryo implantation. The Protein Disulphide Isomerase (PDI) family contains 21 members that function as chaperone proteins through their redox activities. Although total PDIA1 protein expression was high in four common receptive (Ishikawa and RL95-2) and non-receptive (HEC1-B and AN3CA) endometrial epithelial cell lines, significantly higher membrane PDIA1 expression was found in non-receptive AN3CA cells. In Ishikawa cells, oestrogen up-regulated while progesterone down-regulated membrane PDIA1 expression. Moreover, mid-luteal phase hormone treatment down-regulated membrane PDIA1 expression. Furthermore, oestrogen at 10 nM reduced spheroid attachment on Ishikawa cells. Interestingly, inhibition of PDIA1 function by bacitracin or 16F16 increased the spheroid attachment rate onto non-receptive AN3CA cells. Over-expression of PDIA1 in receptive Ishikawa cells reduced the spheroid attachment rate and significantly down-regulated integrin β3 levels, but not integrin αV and E-cadherin. Addition of reducing agent TCEP induced a sulphydryl-rich microenvironment and increased spheroid attachment onto AN3CA cells and human primary endometrial epithelial cells collected at LH+7/8 days. The luminal epithelial cells from human endometrial biopsies had higher PDIA1 protein expression in the proliferative phase than in the secretory phase. Our findings suggest oestrogen and progesterone regulate PDIA1 expression, resulting in the differential expressions of membrane PDIA1 protein to modulate endometrial receptivity. This suggests that membrane PDIA1 expression prior to embryo transfer could be used to predict endometrial receptivity and embryo implantation in women undergoing assisted reproduction treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The CGIAR crop improvement (CI) programs, unlike commercial CI programs, which are mainly geared to profit though meeting farmers' needs, are charged with meeting multiple objectives with target populations that include both farmers and the community at large. We compiled the opinions from >30 experts in the private and public sector on key strategies, methodologies, and activities that could the help CGIAR meet the challenges of providing farmers with improved varieties while simultaneously meeting the goals of: (i) nutrition, health, and food security; (ii) poverty reduction, livelihoods, and jobs; (iii) gender equality, youth, and inclusion; (iv) climate adaptation and mitigation; and (v) environmental health and biodiversity. We review the crop improvement processes starting with crop choice, moving through to breeding objectives, production of potential new varieties, selection, and finally adoption by farmers. The importance of multidisciplinary teams working towards common objectives is stressed as a key factor to success. The role of the distinct disciplines, actors, and their interactions throughout the process from crop choice through to adoption by farmers is discussed and illustrated., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Estrogen and progesterone regulate the expression of endometrial proteins that determine endometrial receptivity for embryo implantation. The protein disulfide isomerase (PDI) family of proteins play a diverse role in regulating protein modification and redox function. Although the role of PDIs in cancer progression has been widely studied, their role in endometrial receptivity is largely unknown. We have focused on the expressions of PDIA1, PDIA2, PDIA3, PDIA4, PDIA5, and PDIA6 isoforms in endometrial epithelium under the influence of estrogen and progesterone and investigated their functional role in regulating endometrial receptivity. We found PDIA1-6 transcripts were expressed in endometrial epithelial Ishikawa, RL95-2, AN3CA, and HEC1-B cell lines. The expression of PDIA1 was low and PDIA5 was high in HEC1-B cells, whereas PDIA2 was high in both AN3CA and HEC1-B cells. In Ishikawa cells, estrogen (10 and 100 nM) upregulated PDIA1 and PDIA6, whereas estrogen (100 nM) downregulated PDIA4 and PDIA5; and progesterone (0.1 and 1 μM) downregulated transcript expressions of PDIA1-6. In human endometrial samples, significantly lowered transcript expressions of PDIA2 and PDIA5 were observed in the secretory phase compared with the proliferative phase, whereas no change was observed in the other studied transcripts throughout the cycle. Inhibition of PDI by PDI antibody (5 and 10 μg/mL) and PDI inhibitor bacitracin (1 and 5 mM) significantly increased the attachment of Jeg-3 spheroids onto AN3CA cells. Taken together, our study suggests a role of PDI in regulating endometrial receptivity and the possibility of using PDI inhibitors to enhance endometrial receptivity., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2021 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

Surfactant replacement therapy (SRT) plays a pivotal role in the management of neonates with respiratory distress syndrome (RDS) because it improves survival and reduces respiratory morbidities. With the increasing use of noninvasive ventilation as the primary mode of respiratory support for preterm infants at delivery, prophylactic surfactant is no longer beneficial. For infants with worsening RDS, early rescue surfactant should be provided. While the strategy to intubate, give surfactant, and extubate (INSURE) has been widely accepted in clinical practice, newer methods of noninvasive surfactant administration, using thin catheter, laryngeal mask airway, or nebulization, are being adopted or investigated. Use of SRT as an adjunct for conditions other than RDS, such as meconium aspiration syndrome, may be effective based on limited evidence., (© Canadian Paediatric Society 2021. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To identify characteristics and outcomes of infants who received multiple doses of surfactant vs those who received one dose or none., Study Design: In this retrospective study, we included neonates of 22-28 weeks' gestation admitted to NICUs in the Canadian Neonatal Network. Patients were divided into three groups: no surfactant, single dose, and multiple doses. The primary outcome was a composite of mortality or any of the major morbidities, including severe neurological injury, bronchopulmonary dysplasia, or ≥stage 3 retinopathy of prematurity., Results: Of 8024 eligible neonates, 2461 (31%) did not receive surfactant, 3545 (44%) received one dose, and 2018 (25%) received >1 dose. Receiving one or more doses of surfactant was associated with significantly higher adjusted odds of mortality or major morbidities in a dose-dependent manner., Conclusions: Receiving one or more doses of surfactant was associated with adverse neonatal outcomes. Receipt of more than one dose may reflect underlying severe lung immaturity.

Objective: Recessive genetic diseases impose physical and psychological impacts to both newborns and parents who may not be aware of being carriers. Expanded carrier screening (ECS) allows screening for multiple genetic conditions at the same time. Whether or not such non-targeted panethnic approach of genetic carrier screening should replace the conventional targeted approach remains controversial. There is limited data on view and acceptance of ECS in general population, as well as the optimal timing of offering ECS to women. This study assesses views and acceptance of ECS in both pregnant women and non-pregnant women seeking fertility counseling or checkup and their reasons for accepting or declining ECS., Materials and Methods: This is a questionnaire survey with ECS information in the form of pamphlets distributed from December 2016 to end of 2018. Women were recruited from the antenatal clinics and the assisted reproductive unit at the Department of Obstetrics and Gynaecology, Queen Mary Hospital and the prepregnancy counseling clinic at the Family Planning Association of Hong Kong., Results: A total of 923 women were recruited: 623 pregnant women and 300 non-pregnant women. There were significantly more non-pregnant women accepting ECS compared to pregnant women (70.7% vs. 61.2%). Eight hundred and sixty-eight (94%) women perceived ECS as at least as effective as or superior to traditional targeted screening. Significantly more pregnant women have heard about ECS compared with non-pregnant women (42.4% vs. 32.3%, P = 0.0197). Majority of women showed lack of understanding about ECS despite reading pamphlets that were given to them prior to filling in the questionnaires. Cost of ECS was a major reason for declining ECS, 28% ( n = 256). Significantly more pregnant women worried about anxiety caused by ECS compared with the non-pregnant group (21.1% vs. 7.4%, P = 0.0006)., Conclusion: Our study demonstrates that expanded carrier screening was perceived as a better screening by most women. Prepregnancy ECS maybe a better approach than ECS during pregnancy, as it allows more reproductive options and may cause less anxiety. Nevertheless, implementation of universal panethnic ECS will need more patient education, ways to reduce anxiety, and consensus on optimal timing in offering ECS., (Copyright © 2020 Cheng, Wong, Chan, Lee, Tang, Ng and Kan.)

Objective: In the present study, we investigated whether varying the task difficulty of the Sentence-Final Word Identification and Recall (SWIR) Test has an effect on the benefit of noise reduction, as well as whether task difficulty predictability affects recall. The relationship between working memory and recall was examined., Design: Task difficulty was manipulated by varying the list length with noise reduction on and off in competing speech and speech-shaped noise. Half of the participants were informed about list length in advance. Working memory capacity was measured using the Reading Span., Study Sample: Thirty-two experienced hearing aid users with moderate sensorineural hearing loss., Results: Task difficulty did not affect the noise reduction benefit and task difficulty predictability did not affect recall. Participants may have employed a different recall strategy when task difficulty was unpredictable and noise reduction off. Reading Span scores positively correlated with the SWIR test. Noise reduction improved recall in competing speech., Conclusions: The SWIR test with varying list length is suitable for detecting the benefit of noise reduction. The correlation with working memory suggests that the SWIR test could be modified to be adaptive to individual cognitive capacity. The results on noise and noise reduction replicate previous findings.

Objective: To identify risk factors for severe neurologic injury (intraventricular hemorrhage grade 3 or greater and/or periventricular leukomalacia) diagnosed by ultrasound scan of the head among infants born at 30 0 -32 6  weeks of gestation and compare different screening strategies., Study Design: This was a retrospective cohort study of infants born at 30 0 -32 6  weeks or >32 6  weeks of gestation with a birth weight <1500 g admitted to neonatal intensive care units in the Canadian Neonatal Network from 2011 to 2016. Stepwise logistic regression analysis was used to identify significant risk factors and calculate aORs and 95% CIs. Risk factor-based screening strategies were compared., Results: The rate of severe neurologic injury was 3.1% among infants screened (285/9221). Significant risk factors included singleton birth (aOR 1.96, 95% CI 1.35-2.85), 5-minute Apgar <7 (aOR 1.81, 95% CI 1.30-2.50), mechanical ventilation on day 1 (aOR 2.65, 95% CI 1.88-3.71), and treatment with vasopressors on day 1 (aOR 3.23, 95% CI 2.19-4.75). Risk categories were low (no risk factor, 1.2%, 25/2137), moderate (singleton with no other risk factor: 1.8%, 68/3678), and high (≥1 risk factor among 5-minute Apgar <7, receipt of vasopressors or mechanical ventilation on day 1: 5.6%, 192/3408). Screening moderate- to high-risk infants identified 91% (260/285) of infants with severe neurologic injury and would require screening fewer infants (1647 infants per year) than screening all infants <33 weeks of gestation (2064 infants screened per year, 93% [265/285] of cases identified)., Conclusions: Risk factor-based ultrasound scan of the head screening among infants born at 30-32 weeks of gestation could help optimize resources better than gestational age based screening., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Polycystic ovary syndrome (PCOS) affects 8-13% of women. The Rotterdam diagnostic criteria include polycystic ovarian morphology (PCOM) on ultrasound, but given recognized challenges, serum anti-Müllerian hormone (AMH) is proposed as an alternative. To inform international PCOS guidelines, a systematic review was completed. Key identified gaps include large international studies in well-defined populations across the lifespan, clustering of AMH with PCOS features, relationships to long-term health outcomes, and improved quality, assay standardization, and sample handling, all needed to determine cut offs. Here we identify research priorities to address these gaps and enhance AMH utility in PCOS. Once issues are addressed, AMH levels could replace more costly and less accessible ultrasound in PCOS diagnosis., (Copyright © 2019. Published by Elsevier Ltd.)

Introduction: The Chinese medicine formulation, tumour-shrinking decoction (TSD, FM1523), which consists of 15 natural medicines, is used for uterine fibroids (UFs) therapy and possesses excellent clinical therapeutic effect., Objective: To develop a sensitive and validated analytical method for the simultaneous quantification of four crucial bioactive compounds including isorhamnetin-3-O-neohesperidoside, curcumin, peimine and tetrahydropalmatine in the principal formulation of this decoction., Methods: An ultra-performance liquid chromatography coupled tandem mass spectrometry (UPLC-MS/MS) with an electrospray ionisation (ESI) source in multiple reaction monitoring (MRM) mode was conducted to investigate these bioactive compounds in the TSD. The chromatographic separation was performed on a C18 column when the flow rate was adjusted at 0.2 mL/min with gradient elution of acetonitrile-water with 0.1% formic acid. Accelerated solvent extraction (ASE) method with higher extraction efficiency was employed for TSD sample pre-treatment., Results: The linearity, limit of detection (LOD) and limit of quantification (LOQ) were determined for this analytical method. The mean recoveries of the compounds were determined between 100.23% and 104.02% with satisfactory relative standard deviation (RSD) in the ranges of 2.65% to 3.81%. The precision was evaluated by intra-day and inter-day tests, which revealed RSD within the ranges of 1.21% to 2.14% and 1.24% to 2.32%, respectively., Conclusion: The bioactive compounds of TSD samples were successfully quantified via UPLC-MS/MS with MRM mode. This study could help to evaluate the pharmacokinetic study of TSD during clinical applications and present a facile strategy for quantifying bioactive compounds in traditional Chinese Medicine decoction., (© 2019 John Wiley & Sons, Ltd.)

Research Question: What is the association between hyperhomocysteinaemia (HHCY), metabolic syndrome, and reproductive outcomes among women with polycystic ovary syndrome (PCOS)., Design: A secondary analysis of PCOSAct with 21 sites in China. A total of 1000 women with PCOS were enrolled; 936 women with baseline homocysteine (HCY) were analysed., Results: Higher HCY was associated with higher body mass index, free testosterone and lower FSH, fasting glucose (P < 0.001; P < 0.001; P = 0.005; P < 0.001) and ovulation rate among all participants (OR 0.59, 95% CI 0.41 to 0.86; OR 0.57, 95% CI 0.39 to 0.83 tertiles 2 and 3 versus tertile 1, respectively). The HHCY group had lower oestradiol and higher free testosterone (P = 0.04; P < 0.001) than the controls. In the metabolic syndrome group, LH, LH-FSH ratio and sex hormone-binding globulin were lowest in the metabolic syndrome group (all P < 0.001). In the HHCY group, ovulation rate decreased and the second or third trimester pregnancy loss rate increased compared with controls (OR 1.678, 95% CI 1.04 to 2.70; OR 0.03, 95% CI 0.00 to 0.42) with treatment adjustment. Compared with the controls, ovulation, conception, pregnancy, second or third trimester pregnancy loss and live birth rates were statistically lower in the metabolic syndrome group after adjusting treatment (OR 1.76, 95% CI 1.15 to 2.70; OR 1.75, 95% CI 1.15 to 2.65; OR 2.09, 95% CI 1.27 to 3.44; OR 0.02, 95% CI 0.00 to 0.33; OR 2.42 95% CI 1.42 to 4.10), and pregnancy, pregnancy loss and live birth rates remained significantly different after adjusting for treatment and sex-hormone factors (OR 1.77, 95% CI 1.05 to 2.99; OR 0.14, 95% CI 0.02 to 0.82; OR 2.02, 95% CI 1.16 to 3.50)., Conclusions: In women with PCOS, HHCY contributes to increased pregnancy loss and reduced ovulation, and metabolic syndrome was related to defects in ovulation, conception, pregnancy, pregnancy loss and live birth, indicating that the two conditions lead to defects at various reproductive stages., (Copyright © 2019. Published by Elsevier Ltd.)

Key Message: The integration of new technologies into public plant breeding programs can make a powerful step change in agricultural productivity when aligned with principles of quantitative and Mendelian genetics. The breeder's equation is the foundational application of quantitative genetics to crop improvement. Guided by the variables that describe response to selection, emerging breeding technologies can make a powerful step change in the effectiveness of public breeding programs. The most promising innovations for increasing the rate of genetic gain without greatly increasing program size appear to be related to reducing breeding cycle time, which is likely to require the implementation of parent selection on non-inbred progeny, rapid generation advance, and genomic selection. These are complex processes and will require breeding organizations to adopt a culture of continuous optimization and improvement. To enable this, research managers will need to consider and proactively manage the, accountability, strategy, and resource allocations of breeding teams. This must be combined with thoughtful management of elite genetic variation and a clear separation between the parental selection process and product development and advancement process. With an abundance of new technologies available, breeding teams need to evaluate carefully the impact of any new technology on selection intensity, selection accuracy, and breeding cycle length relative to its cost of deployment. Finally breeding data management systems need to be well designed to support selection decisions and novel approaches to accelerate breeding cycles need to be routinely evaluated and deployed.

Objective: We have previously shown that the gain provided by prior audiovisual (AV) speech exposure for subsequent auditory (A) sentence identification in noise is relatively larger than that provided by prior A speech exposure. We have called this effect "perceptual doping." Specifically, prior AV speech processing dopes (recalibrates) the phonological and lexical maps in the mental lexicon, which facilitates subsequent phonological and lexical access in the A modality, separately from other learning and priming effects. In this article, we use data from the n200 study and aim to replicate and extend the perceptual doping effect using two different A and two different AV speech tasks and a larger sample than in our previous studies., Design: The participants were 200 hearing aid users with bilateral, symmetrical, mild-to-severe sensorineural hearing loss. There were four speech tasks in the n200 study that were presented in both A and AV modalities (gated consonants, gated vowels, vowel duration discrimination, and sentence identification in noise tasks). The modality order of speech presentation was counterbalanced across participants: half of the participants completed the A modality first and the AV modality second (A1-AV2), and the other half completed the AV modality and then the A modality (AV1-A2). Based on the perceptual doping hypothesis, which assumes that the gain of prior AV exposure will be relatively larger relative to that of prior A exposure for subsequent processing of speech stimuli, we predicted that the mean A scores in the AV1-A2 modality order would be better than the mean A scores in the A1-AV2 modality order. We therefore expected a significant difference in terms of the identification of A speech stimuli between the two modality orders (A1 versus A2). As prior A exposure provides a smaller gain than AV exposure, we also predicted that the difference in AV speech scores between the two modality orders (AV1 versus AV2) may not be statistically significantly different., Results: In the gated consonant and vowel tasks and the vowel duration discrimination task, there were significant differences in A performance of speech stimuli between the two modality orders. The participants' mean A performance was better in the AV1-A2 than in the A1-AV2 modality order (i.e., after AV processing). In terms of mean AV performance, no significant difference was observed between the two orders. In the sentence identification in noise task, a significant difference in the A identification of speech stimuli between the two orders was observed (A1 versus A2). In addition, a significant difference in the AV identification of speech stimuli between the two orders was also observed (AV1 versus AV2). This finding was most likely because of a procedural learning effect due to the greater complexity of the sentence materials or a combination of procedural learning and perceptual learning due to the presentation of sentential materials in noisy conditions., Conclusions: The findings of the present study support the perceptual doping hypothesis, as prior AV relative to A speech exposure resulted in a larger gain for the subsequent processing of speech stimuli. For complex speech stimuli that were presented in degraded listening conditions, a procedural learning effect (or a combination of procedural learning and perceptual learning effects) also facilitated the identification of speech stimuli, irrespective of whether the prior modality was A or AV.

Objective: To determine the effect of paternal age on semen parameters and the live birth rate from in-vitro fertilisation (IVF) treatment., Methods: We performed a retrospective cohort study of couples undergoing a first IVF cycle between 2004 and 2014 in a tertiary assisted reproduction centre in Hong Kong., Results: We analysed 3549 cases. Paternal age ≥40 years was negatively correlated with semen volume, progressive motility, total motility and total normal motile count (P<0.005) and positively correlated with sperm concentration (P<0.001). There was no correlation with sperm count, normal morphology, or total motile count. Subgroup analyses in Chinese men only and in men with normal versus abnormal semen parameters showed the same correlations. Paternal age was positively associated with maternal age (P<0.001) and miscarriage (P=0.006), and negatively associated with ongoing pregnancy and live birth (P<0.001). Logistic regression showed that maternal age, total number of oocytes retrieved, and number of embryos transferred were significant factors which independently predicted the likelihood of live birth from IVF (all P<0.001)., Conclusion: Paternal age was negatively correlated with some semen parameters, which showed a significant decline after age 40 years. However, paternal age is not predictive of the live birth from IVF treatment.

Study Question: What is the intention to have a second child among women attending outpatient gynecology clinics in three major cities in China?, Summary Answer: In total, 69.3% of the participants expressed the intention to have a second child and this was related to infertility status, pronatalist attitudes, and sociodemographic factors., What Is Known Already: In 2016, the new universal two-child policy was introduced in China enabling all Chinese couples to have a second child. A government-led national survey revealed that the majority of women included under the policy would be 35 years old and older and thus would be at higher risk of infertility. Previous studies found that fertility intention differs by infertility status., Study Design Size Duration: A cross-sectional survey was performed to examine the intention of having a second child and its associated factors among infertile and fertile women attending gynecology outpatient clinics in three major cities in China. Clinical nurses approached eligible women in person while waiting for their consultations. Recruitment and data collection were conducted from April to August 2016., Participants/materials Setting Methods: The survey involved four gynecology outpatient clinics in Beijing, Shenzhen, and Hohhot. Married women aged 20-45 years who were seeking outpatient gynecology care for non-malignant problems were invited to participate., Main Results and the Role of Chance: Data from 974 women were included in the analysis. A total of 69.3% of the women expressed the intention to have a second child, and infertile women were more likely to want a second child compared to fertile women (76.6% vs 61.9%, respectively; P < 0.001). Greater ideal parity facilitated the intention for a second child in both groups, while pronatalist attitudes (meaning that they preferred to have their first childbirth at a younger age and attached greater significance to traditional childbearing beliefs), unexplained infertility, presence of a living child and religious affiliation were associated with greater intention among infertile women. In contrast, in the fertile group, older age, full-time work and lower confidence in achieving parity goals diminished the intention for a second child. Although infertile women displayed greater agreement with pronatalist attitudes and desired a higher ideal parity, they had less confidence in achieving their parity goals than their fertile counterparts., Limitations Reasons for Caution: In addition to self-report and self-selection bias, our participants were recruited from urbanized areas and were more educated than the general population. Owing to the extremely busy environment in the clinics, difficulties were encountered in keeping track of the number of women whom the nurses approached, and the response rate was therefore unavailable., Wider Implications of the Findings: With the introduction of the universal two-child policy, there is a need to enhance fertility awareness and to encourage reproductive life planning, as well as to lower the cost of childcare, in order to increase the birth rate in China. Effort is required to make childbearing more compatible with current employment, career and educational development, the burdens of family care (e.g. for elderly parents), social environments and cultural expectations. This is particularly relevant for families who already have a child, as our findings show that their hesitation toward a second child was largely related to difficulties with extra childcare within the woman's current work and family life., Study Funding/competing Interests: This study did not receive any funding. The authors declared no competing interests., Trial Registration Number: Not applicable.

Study Question: Does second-hand smoke (SHS) exposure from husbands have adverse effects on sex hormones, metabolic profiles, clinical phenotypes and fertility outcomes in women with polycystic ovary syndrome (PCOS) undergoing ovulation induction?, Summary Answer: SHS exposure is associated with worsened biochemical hyperandrogenism, higher incidence of metabolic syndrome and reduced conception rates in women with PCOS., What Is Known Already: Smoking in women impairs fecundity at some stages of the reproductive process including folliculogenesis, embryo transport, endometrial angiogenesis and uterine blood flow. Yet little is known about the hazard of SHS exposure in women with PCOS., Study Design, Size, Duration: This study was a secondary analysis of the Polycystic Ovary Syndrome Acupuncture and Clomiphene Trial (PCOSAct), a large randomized controlled trial conducted at 27 hospitals from 2012 to 2015 in mainland China., Participants/materials, Setting, Methods: Out of 1000 women with PCOS, SHS exposure status were available in 500 women, of whom 271 women were non-exposed and 229 exposed to cigarette smoke (170 women ≤10 cigarettes per day as low-SHS exposed and 59 women >10 cigarettes per day as high-SHS exposed). We compared circulating sex steroids, glucose and lipid metabolism, metabolic syndrome and phenotypes, fertility and obstetric outcomes between non-exposed and exposed women., Main Results and the Role of Chance: Women exposed to SHS, compared to non-exposed women, had a higher serum total testosterone (1.7 vs 1.5 nmol/L, P = 0.01), free androgen index (5.7 vs 4.0, P = 0.001) and lower sex hormone binding globulin (30.1 vs 35.6 nmol/L, P = 0.03). Metabolic syndrome, but not other phenotypes, was more frequent in exposed women as compared to non-exposed women (21.8 vs 13.3%, adjusted odds ratio (OR)=1.66; 95% CI, 1.02-2.71, P = 0.04). Ovulation rates between exposed and non-exposed groups were not significantly different (76.9 vs 82.9%, adjusted OR=0.72; 95% CI, 0.45-1.15, P = 0.17). Conception rates were significant lower in the exposed group (26.6 vs 36.9%; adjusted OR=0.61; 95% CI, 0.41-0.91; P = 0.01), while clinical pregnancy and live birth rates showed a similar trend that was not statistically significant. Gestational age, birth weight and other obstetric outcomes were not affected by SHS exposure., Limitations, Reasons for Caution: Data on SHS exposure were missing in 50% of the women. We did not assay serum nicotine or cotinine levels to quantify the SHS exposure status., Wider Implications of the Findings: These data suggest that smoking partners of infertile women with PCOS who seek treatment should be advised to quit smoking., Study Funding/competing Interest(s): Funding was provided by the National Public Welfare Projects for Chinese Medicine (201107005 and 200807002) and the National Clinical Trial Base in Chinese Medicine Special Projects (JDZX2012036 and 2015B009). There are no conflicts of interest., Trial Registration Number: ClinicalTrial.gov number: NCT01573858 and chictr.org.cn number: ChiCTR-TRC-12002081.

Study Question: Do both ulipristal acetate (UPA) and mifepristone inhibit embryo-endometrial attachment at concentrations corresponding to the emergency contraception (EC) dose?, Summary Answer: Both UPA and mifepristone at concentrations corresponding to the EC dose do not have an inhibitory effect on embryo implantation, although mifepristone at a higher concentration appeared to have such an effect., What Is Known Already: Levonorgestrel is commonly used for EC, but it only acts through inhibition of ovulation. UPA and mifepristone have higher efficacy as EC compared to levonorgestrel; while there is some suggestion that mifepristone may interfere with implantation, whether UPA has post-ovulatory action in inhibiting implantation is yet to be confirmed., Study Design, Size, Duration: An in vitro experimental study using trophoblastic spheroids made from JAr cell line as the embryo surrogate, and the Ishikawa cell line and primary human endometrial cells cultured to monolayer as the endometrial surrogate. The primary endometrial cells were collected from nine volunteer women in the mid-luteal phase with consent., Participants/materials, Setting, Methods: The study was conducted in a university gynaecology unit. The JAr and Ishikawa cell lines (or primary endometrial cells) were treated with graded concentrations of UPA (0, 0.04, 0.4 and 4 μM) or mifepristone (0, 0.1, 1 and 10 μM) for 24 h. Embryo-endometrial attachment was studied using an in vitro JAr spheroid-endometrial co-culture model. Expressions of progesterone receptor, β-catenin and glycogen synthase kinase 3 β (GSK-3β) were studied with real-time RT-PCR and Western blotting, respectively., Main Results and the Role of Chance: In the Ishikawa experiments, there was no significant difference in the JAr spheroid attachment rate after treatment with UPA at 0 (93.0%), 0.04 (93.6%), 0.4 (93.4%) and 4 (91.4%) μM concentrations (P > 0.05); the attachment rate was reduced after treatment with mifepristone only at 10 μM (79.8%, P < 0.0001) but not at 0.1 (92.1%) or 1.0 (95.2%) μM concentrations. In the primary endometrial cell experiments, again no significant difference was observed in the JAr spheroid attachment rate after treatment with UPA 4 μM (42.6%) compared to control (46.5%, P > 0.05). Both UPA and mifepristone could significantly up-regulate progesterone receptor expression. There was no significant alteration in expression of β-catenin and GSK-3β after treatment with UPA 4 μM or mifepristone 10 μM (P > 0.05)., Limitations, Reasons for Caution: The co-culture model is only a surrogate which may not fully represent the complicated process of embryo implantation in vivo, although there is no existing perfect model for studying implantation in vitro which fully resembles the latter., Wider Implications of the Findings: The lack of inhibitory effect on embryo implantation by UPA and possibly mifepristone at concentrations corresponding to the EC dose is an important information for contraceptive counseling., Study Funding/competing Interest(s): We had free supply of the UPA compound used in this study from Laboratoire HRA Pharma. This work was supported by a Seed Fund from the Centre of Reproduction, Development and Growth, Faculty of Medicine, The University of Hong Kong, Hong Kong., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com)

Introduction: Preimplantation genetic screening has been proposed to improve the in-vitro fertilisation outcome by screening for aneuploid embryos or blastocysts. This study aimed to report the outcome of 133 cycles of preimplantation genetic diagnosis and screening by array comparative genomic hybridisation., Methods: This study of case series was conducted in a tertiary assisted reproductive centre in Hong Kong. Patients who underwent preimplantation genetic diagnosis for chromosomal abnormalities or preimplantation genetic screening between 1 April 2012 and 30 June 2015 were included. They underwent in-vitro fertilisation and intracytoplasmic sperm injection. An embryo biopsy was performed on day-3 embryos and the blastomere was subject to array comparative genomic hybridisation. Embryos with normal copy numbers were replaced. The ongoing pregnancy rate, implantation rate, and miscarriage rate were studied., Results: During the study period, 133 cycles of preimplantation genetic diagnosis for chromosomal abnormalities or preimplantation genetic screening were initiated in 94 patients. Overall, 112 cycles proceeded to embryo biopsy and 65 cycles had embryo transfer. The ongoing pregnancy rate per transfer cycle after preimplantation genetic screening was 50.0% and that after preimplantation genetic diagnosis was 34.9%. The implantation rates after preimplantation genetic screening and diagnosis were 45.7% and 41.1%, respectively and the miscarriage rates were 8.3% and 28.6%, respectively. There were 26 frozen-thawed embryo transfer cycles, in which vitrified and biopsied genetically transferrable embryos were replaced, resulting in an ongoing pregnancy rate of 36.4% in the screening group and 60.0% in the diagnosis group., Conclusions: The clinical outcomes of preimplantation genetic diagnosis and screening using comparative genomic hybridisation in our unit were comparable to those reported internationally. Genetically transferrable embryos replaced in a natural cycle may improve the ongoing pregnancy rate and implantation rate when compared with transfer in a stimulated cycle.

Background: Our prospective pilot study of acupuncture affecting insulin sensitivity on polycystic ovary syndrome (PCOS) combined with insulin resistance (IR) showed that acupuncture had a significant effect on improving the insulin sensitivity of PCOS. But there is still no randomized controlled trial to determine the effect of acupuncture on the insulin sensitivity in women with PCOS and IR. In this article, we present the protocol of a randomized controlled trial to compare the effect of true acupuncture on the insulin sensitivity of these patients compared with metformin and sham acupuncture. Acupuncture may be an effective therapeutic alternative that is superior to metformin and sham acupuncture in improving the insulin sensitivity of PCOS combined with IR., Methods: This study is a multi-center, controlled, double-blind, and randomized clinical trial aiming to evaluate the effect of acupuncture on the insulin sensitivity in PCOS combined with IR. In total 342 patients diagnosed with PCOS and IR will be enrolled. Participants will be randomized to one of the three groups: (1) true acupuncture + metformin placebo; (2) sham acupuncture + metformin, and (3) sham acupuncture + metformin placebo. Participants and assessors will be blinded. The acupuncture intervention will be given 3 days per week for a total of 48 treatment sessions during 4 months. Metformin (0.5 g per pill) or placebo will be given, three times per day, and for 4 months. Primary outcome measures are changes in homeostasis model assessment of insulin resistance (HOMA-IR) and improvement rate of HOMA-IR by oral glucose tolerance test (OGTT) and insulin releasing test (Ins). Secondary outcome measures are homeostasis model assessment-β (HOMA-β), area under the curve for glucose and insulin, frequency of regular menstrual cycles and ovulation, body composition, metabolic profile, hormonal profile, questionnaires, side effect profile, and expectation and credibility of treatment. Outcome measures are collected at baseline, at the end of treatments, and 3 months after the last acupuncture treatment. On completion of the screening visit, randomization will be conducted using a central randomization system., Discussion: This study will investigate the effects of acupuncture on the insulin sensitivity of PCOS and IR women compared with metformin and sham acupuncture. We will test whether true acupuncture with needles placed in skeletal muscles and stimulated manually and by electrical stimulation is more effective than metformin and sham acupuncture with superficial needle placement with no manual or electrical stimulation in improving the insulin sensitivity in PCOS women with IR., Trial Registration: ClinicalTrials.gov, NCT02491333 ; Chinese Clinical Trial Registry, ChiCTR-ICR-15006639. Registered on 24 June 2015.

Objective: To compare the effectiveness of alternative first line treatment options for women with WHO group II anovulation wishing to conceive., Design: Systematic review and network meta-analysis., Data Sources: Cochrane Central Register of Controlled Trials, Medline, and Embase, up to 11 April 2016., Study Selection: Randomised controlled trials comparing eight ovulation induction treatments in women with WHO group II anovulation: clomiphene, letrozole, metformin, clomiphene and metformin combined, tamoxifen, gonadotropins, laparoscopic ovarian drilling, and placebo or no treatment. Study quality was measured on the basis of the methodology and categories described in the Cochrane Collaboration Handbook. Pregnancy, defined preferably as clinical pregnancy, was the primary outcome; live birth, ovulation, miscarriage, and multiple pregnancy were secondary outcomes., Results: Of 2631 titles and abstracts initially identified, 54 trials reporting on 7173 women were included. All pharmacological treatments were superior to placebo or no intervention in terms of pregnancy and ovulation. Compared with clomiphene alone, both letrozole and the combination of clomiphene and metformin showed higher pregnancy rates (odds ratio 1.69, 95% confidence interval 1.33 to 2.14; 1.71, 1.28 to 2.27; respectively). Letrozole led to higher live birth rates when compared with clomiphene alone (1.67, 1.11 to 2.49). Metformin led to lower multiple pregnancy rates compared with clomiphene alone (0.22, 0.05 to 0.93)., Conclusions: In women with WHO group II anovulation, letrozole and the combination of clomiphene and metformin are superior to clomiphene alone in terms of pregnancy. Compared with clomiphene alone, letrozole is the only treatment showing a significantly higher rate of live birth., Systematic Review Registration: PROSPERO CRD42015027579., Readers' Note: This is the second version of this paper. The original version was corrected following the retraction of two studies and removal of another which were ineligible (references 40, 41, and 75 of the original paper). These studies are not shown in this version. A tracked changes version of the original version is attached as a supplementary file to the correction notice, which explains the issue further., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The aim of the study is to investigate the molecular mechanism behind androgen reduction in porcine granulosa cells (pGCs) with Salvia miltiorrhiza Bunge extract cryptotanshinone. PGCs were isolated from porcine ovaries and identified. Androgen excess model of the pGCs was induced with the MAPK inhibitor PD98059 and then treated with cryptotanshinone. The testosterone level was measured by radioimmunoassay in the culture media. The protein levels of P-ERK1/2, c-Fos, and CYP17 in the cells were measured by western blot. Cryptotanshinone decreased the concentration of testosterone and the protein level of CYP17 and increased the protein levels of P-ERK1/2 and c-Fos in the androgen excess mode. After the c-Fos gene was silenced by infection with c-Fos shRNA lentivirus, we measured the mRNA expression by quantitative RT-PCR and protein level by western blot of P-ERK1/2, c-Fos, and CYP17. This showed that the mRNA expression and protein level of P-ERK1/2 and c-Fos were significantly reduced in the shRNA-c-Fos group compared to the scrambled group, while those of CYP17 were significantly increased. So we concluded that cryptotanshinone can significantly reduce the androgen excess induced by PD98059 in pGCs. The possible molecular mechanism for this activity is regulating the ERK/c-Fos/CYP17 pathway., Competing Interests: The authors declare that they have no competing interests.

Study Question: How do the three new anti-Müllerian hormone (AMH) assay methods, manufactured by Beckman Coulter, Roche and Ansh Labs compare with each other and with the Gen II assay?, Summary Answer: The three new AMH assays are well correlated among themselves and with the Gen II assay, although differences in calibration do exist., What Is Known Already: The Gen II assay has been the mainstay method for AMH measurement in the past few years. Recently, a few new AMH measurement methods have come to the market., Study Design, Size, Duration: This was a prospective assay evaluation performed on 178 human serum samples., Participants/materials, Setting, Methods: AMH concentration was measured in residual serum samples donated by female patients in a reproductive medicine centre. The three new assay methods were tested in parallel and the numerical values obtained were compared among themselves and with those obtained by the Gen II assay. The assay stability upon different sample storage conditions, intra-assay and inter-assay precision, linearity and dilution recovery, and diagnostic performance for polycystic ovary syndrome (PCOS) of the three new AMH assay methods were also compared., Main Results and the Role of Chance: AMH values measured by the Gen II kit and the three new assay methods have good correlations (R > 0.9 for all pairwise correlations). Values measured by the Ansh Labs assay were significantly higher, whereas those by the Roche assay were significantly lower, than those from the Gen II and Beckman-Coulter automated assays (P < 0.05). AMH values were significantly different when measured on the fresh and frozen-thawed serum sample (at -20 o C and -80 o C) for all three new methods (P < 0.05), but the magnitude of difference was very small with the Beckman-Coulter automated assay and Roche assay. The intra-assay coefficients of variation (CVs) were 0.7-2.2%, 0.5-1.4%, and 1.4-5.4% for the Beckman-Counter automated, Roche and Ansh Labs assays, respectively. Their inter-assay CVs were 0.9-2.5%, 0.7-1.9%, and 6.2-13.5%, respectively. All three new assay methods showed acceptable linearity, and provided excellent discrimination of PCOS from controls., Limitations, Reasons for Caution: The precision and dilution linearity experiments involved a small sample size, although these were not the primary outcome measures and have been properly evaluated in previous publications. The study was not designed or powered for determining diagnostic cut-off values., Wider Implications of the Findings: The results demonstrate that the three new AMH assay methods are all valid methods to be adopted in the field of reproduction and are a basis for further work on their clinical application., Study Funding/competing Interests: The authors have no competing interest to declare. The execution of this study was funded by the Department of Obstetrics and Gynaecology, The University of Hong Kong., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Study Question: What is the relationship between decisional conflict, decisional regret and psychological well-being in women following unsuccessful IVF cycles?, Summary Answer: The mediating effect of decisional regret on the relationship between decisional conflict and fertility-related quality of life (FRQOL) has been found to be moderated by the availability (versus absence) of frozen embryos after an unsuccessful IVF cycle., What Is Known Already: Infertility treatment is marked by its open-ended nature. Stresses in treatment decision-making could be aggravated by a culture which honours families through procreation. While studies have investigated treatment-related decision-making among infertile women, little is known about the mental health consequences of decisional conflict and decisional regret following an unsuccessful IVF cycle., Study Design, Size, Duration: A study was conducted over a 3-month period with infertile women who had recently experienced a failed IVF cycle (T 0 ). Decisional conflict when they decided on terminating or continuing treatment (T 1 ) and decisional regret 3 months later (T 2 ) were measured. Participants reported their levels of depression, anxiety and FRQOL at three time points. A total of 151 participants completed all time points (attrition rate: 39%). The average age of participants was 37.2 years, and they had had 1.1 cycles (range: 0-8) on average at the time of study intake. The duration of the study was 2 years., Participants/materials, Setting, Methods: Participants were infertile women who were not pregnant following an IVF cycle recruited from a university-affiliated assisted reproduction centre. Following the notification of a negative pregnancy result, patients were invited to complete measures of FRQOL, depression and anxiety across three time points and decisional conflict and decisional regret at T 1 and T 2 respectively., Main Results and the Role of Chance: Decisional regret partially mediated the effect of decisional conflict on overall and treatment-specific FRQOL (P < 0.05). The mediation by decisional regret was present only among participants who had no remaining frozen embryos after their unsuccessful IVF cycle (P < 0.05)., Limitations, Reason for Caution: Self-selection bias at recruitment remains a concern., Wider Implications of the Findings: Our results show for the first time how mental health implications of decisional conflict may vary among patients with different clinical characteristics (i.e. availability of frozen embryos), despite their common experience of an unsuccessful IVF cycle. Healthcare professionals should be aware of the psychological ramifications of treatment decision-making difficulties, as well as individual differences in adjustment to unsuccessful treatment., Study Funding/competing Interests: The study was funded by the Hong Kong University Grant Council-General Research Fund (HKU740613) and the authors have no conflicts of interest., Trial Registration Number: HKU Clinical Trials Registry (Trial registration number: HKUCTR-1680)., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: There are currently no local data on the sperm retrieval and pregnancy rates in in-vitro fertilisation and testicular sperm extraction cycles, especially with regard to the presence of genetic abnormalities. This study aimed to determine the sperm retrieval and pregnancy rates in infertile couples who underwent in-vitro fertilisation and testicular sperm extraction for non-obstructive azoospermia., Methods: This retrospective case series was conducted at a tertiary assisted reproduction unit in Hong Kong. Men with non-obstructive azoospermia who underwent in-vitro fertilisation and testicular sperm extraction between January 2001 and December 2013 were included. The main outcome measures were sperm retrieval and pregnancy rates., Results: During the study period, 89 men with non-obstructive azoospermia underwent in-vitro fertilisation and testicular sperm extraction. Sperm was successfully retrieved in 40 (44.9%) men. There was no statistically significant difference in the sperm retrieval rate of those with karyotypic abnormalities (2/5, 40.0% vs 28/61, 45.9%; P=1.000) and AZFc microdeletion (3/6, 50.0% vs 28/61, 45.9%; P=1.000) compared with those without. Sperms were successfully retrieved in patients who had mosaic Klinefelter syndrome (2/3, 66.7%) but not in the patient with non-mosaic Klinefelter syndrome. No sperms were found in men with AZFa or AZFb microdeletions. Pregnancy test was positive in 15 (16.9%) patients and the clinical pregnancy rate was 13.5% (12/89) per cycle. The clinical pregnancy rate per transfer was 34.3% (12/35)., Conclusions: The sperm retrieval rate and clinical pregnancy rate per initiated cycle in men undergoing in-vitro fertilisation and testicular sperm extraction in our unit were 44.9% and 13.5%, respectively. No sperms could be retrieved in the presence of AZFa and AZFb microdeletions, but karyotype and AZFc microdeletion abnormalities otherwise did not predict the success of sperm retrieval in couples undergoing in-vitro fertilisation and testicular sperm extraction. Genetic tests are important prior to testicular sperm extraction for patient selection and genetic counselling.

Objective: The aims of the current n200 study were to assess the structural relations between three classes of test variables (i.e. HEARING, COGNITION and aided speech-in-noise OUTCOMES) and to describe the theoretical implications of these relations for the Ease of Language Understanding (ELU) model., Study Sample: Participants were 200 hard-of-hearing hearing-aid users, with a mean age of 60.8 years. Forty-three percent were females and the mean hearing threshold in the better ear was 37.4 dB HL., Design: LEVEL1 factor analyses extracted one factor per test and/or cognitive function based on a priori conceptualizations. The more abstract LEVEL 2 factor analyses were performed separately for the three classes of test variables., Results: The HEARING test variables resulted in two LEVEL 2 factors, which we labelled SENSITIVITY and TEMPORAL FINE STRUCTURE; the COGNITIVE variables in one COGNITION factor only, and OUTCOMES in two factors, NO CONTEXT and CONTEXT. COGNITION predicted the NO CONTEXT factor to a stronger extent than the CONTEXT outcome factor. TEMPORAL FINE STRUCTURE and SENSITIVITY were associated with COGNITION and all three contributed significantly and independently to especially the NO CONTEXT outcome scores (R(2) = 0.40)., Conclusions: All LEVEL 2 factors are important theoretically as well as for clinical assessment.

Introduction: The high prevalence of insulin resistance in women with polycystic ovary syndrome (PCOS) is considered to be one of the major pathophysiological changes in PCOS that leads to anovulatory infertility. We hypothesise that electroacupuncture pretreatment improves insulin sensitivity and leads to a higher ovulation rate and greater chances of live birth after the induction of ovulation. The effect of electroacupuncture pretreatment followed by ovulation induction in women with anovulatory PCOS has not been investigated before, and we present here a randomised controlled trial to test this hypothesis by comparing electroacupuncture pretreatment followed by letrozole versus letrozole alone in anovulatory women with PCOS., Methods/analysis: This is a multicentre, randomised,and controlled trial. A total of 384 patients will be enrolled in this study and will be randomly allocated by a central randomisation system to the treatment group or the control group in a 1:1 ratio. The treatment group will undergo 16 weeks of electroacupuncture pretreatment followed by 4 cycles of letrozole, and the control group will only undergo 4 cycles of letrozole. The primary outcome will be the live birth rate. All statistical analyses will be performed using the SPSS program V.21.0 (SPSS, Chicago, Illinois, USA), and a p value <0.05 will be considered statistically significant., Ethics/dissemination: This study has been approved by the ethics committees of each participating centre. Written consent will be obtained from each patient and her husband before any study procedure is performed. Adverse events will be categorised, and the percentage of patients experiencing adverse events or serious adverse events during the treatment period will be documented. The results of this trial will be disseminated in peer-reviewed journals and presented at international meetings., Trial Registration Number: NCT02491320., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: To study whether a combination of berberine and letrozole results in higher live births than letrozole alone in infertile women with polycystic ovary syndrome (PCOS)., Design: A multicenter randomized double-blinded placebo-controlled trial., Setting: Reproductive and developmental network sites., Patient(s): Eligible women had PCOS as defined by the Rotterdam criteria. We enrolled 644 participants randomized 1:1:1 among letrozole, berberine, and combination groups., Interventions(s): Berberine or berberine placebo were administrated orally at a daily dose of 1.5 g for up to 6 months. Patients received an initial dose of 2.5 mg letrozole or placebo on days 3-7 of the first three treatment cycles. This dose was increased to 5 mg on the last three cycles if not pregnant., Main Outcomes Measure(s): Cumulative live births., Results: The cumulative live births were similar between the letrozole and combination groups after treatment (36% and 34%), and were superior to those in the berberine group (22%). Likely, conception, pregnancy, and ovulation rates were similar between the letrozole and combination groups, and these were significantly higher than in the berberine group. There was one twin birth in the letrozole group, three twin births in the combination group, and none in the berberine group., Conclusion(s): Berberine did not add fecundity in PCOS when used in combination with the new ovulation agent letrozole., Clinical Trial Registration Number: ChiCTR-TRC-09000376 (http://apps.who.int/trialsearch/)., (Copyright © 2016. Published by Elsevier Inc.)

Background: Miscarriage is a common complication of pregnancy occurring in 15-20 % of all clinically recognized pregnancies. Currently, there is still no good scientific evidence to support the routine use of progestogens for the treatment of threatened miscarriage because the existing studies were not large enough to show a significant difference and some of them were not randomized or double-blind., Methods: This is a double-blind, randomized controlled trial. A total of 400 patients presenting with first-trimester threatened miscarriage will be enrolled. They will be randomized to take dydrogesterone 40 mg per os, followed by 10 mg per os three times a day or placebo until twelve completed weeks of gestation or 1 week after the bleeding has stopped, whichever is longer. The primary outcome is the percentage of miscarriage before 20 weeks of gestation., Discussion: We postulate that the dydrogesterone therapy will significantly reduce the risk of miscarriage in women with threatened miscarriage., Trial Registration: This study is registered at ClinicalTrials.gov, NCT02128685 . Registered on 29 April 2014.

In adaptive Speech Reception Threshold (SRT) tests used in the audiological clinic, speech is presented at signal to noise ratios (SNRs) that are lower than those generally encountered in real-life communication situations. At higher, ecologically valid SNRs, however, SRTs are insensitive to changes in hearing aid signal processing that may be of benefit to listeners who are hard of hearing. Previous studies conducted in Swedish using the Sentence-final Word Identification and Recall test (SWIR) have indicated that at such SNRs, the ability to recall spoken words may be a more informative measure. In the present study, a Danish version of SWIR, known as the Sentence-final Word Identification and Recall Test in a New Language (SWIRL) was introduced and evaluated in two experiments. The objective of experiment 1 was to determine if the Swedish results demonstrating benefit from noise reduction signal processing for hearing aid wearers could be replicated in 25 Danish participants with mild to moderate symmetrical sensorineural hearing loss. The objective of experiment 2 was to compare direct-drive and skin-drive transmission in 16 Danish users of bone-anchored hearing aids with conductive hearing loss or mixed sensorineural and conductive hearing loss. In experiment 1, performance on SWIRL improved when hearing aid noise reduction was used, replicating the Swedish results and generalizing them across languages. In experiment 2, performance on SWIRL was better for direct-drive compared with skin-drive transmission conditions. These findings indicate that spoken word recall can be used to identify benefits from hearing aid signal processing at ecologically valid, positive SNRs where SRTs are insensitive.