Access to Workplace Supports is Positively Associated with Exclusive Breastfeeding among Formally Employed Mothers in Kenya.

BACKGROUND: Mothers in low-income settings who work in agricultural employment are challenged to meet breastfeeding (BF) recommendations. Recent legislation in Kenya mandates maternity leave and workplace supports, yet the relation of these benefits with BF practices is poorly understood. OBJECTIVES: We evaluated the associations with workplace-provided BF supports and BF practices among formally employed mothers in Kenya. The availability of supports was hypothesized to be associated with a higher prevalence and greater odds of exclusive breastfeeding (EBF). METHODS: We conducted repeated cross-sectional surveys among formally employed mothers at 1-4 d and 6, 14, and 36 wk (to estimate 24 wk) postpartum in Naivasha, Kenya. We used logistic regression adjusted for maternal age, education, physical burden of work, HIV status, and income to evaluate associations between workplace supports and EBF practices. RESULTS: Among formally employed mothers (n = 564), those who used onsite workplace childcare were more likely to practice EBF than those who used community- or home-based childcare at both 6 wk (95.7% compared with 82.4%, P = 0.030) and 14 wk (60.6% compared with 22.2%, P < 0.001; adjusted OR: 5.11; 95% CI: 2.3, 11.7). Likewise, at 14 wk among mothers who currently used daycare centers, a higher proportion of mothers who visited daycare centers at or near workplaces practiced EBF (70.0%) than of those not visiting daycare centers (34.7%, P = 0.005). EBF prevalence was higher among mothers with access to workplace private lactation spaces than among mothers without such spaces (84.6% compared with 55.6%, P = 0.037), and among mothers who lived in workplace housing than those without onsite housing (adjusted OR: 2.06, 95% CI: 1.25, 3.41). CONCLUSIONS: Formally employed mothers in Kenya who have access to and use workplace-provided BF supports were more likely to practice EBF than mothers who lacked these supports. As the Kenya Health Act is implemented, lactation rooms, onsite housing and daycare, and transportation to visit children can all support BF and EBF among employed mothers.

Alcohol use among people who inject drugs living with HIV in Kenya is associated with needle sharing, more new sex partners, and lower engagement in HIV care.

We assessed the prevalence and correlates of alcohol use among 870 people who inject drugs living with HIV in Kenya, with attention toward (1) sexual and injecting risk behaviors for HIV transmission and (2) HIV care engagement. We defined heavy alcohol use as > 14 drinks/week for men and > 7 drinks/week for women, moderate alcohol use as any lesser but non-zero amount, and any alcohol use as either moderate or heavy use. Approximately 39% of participants reported any alcohol use and 15% heavy use. In multivariate analysis, any alcohol use compared to no use was associated with needle sharing, > 3 new sex partners in the past 3 months, being unaware of HIV status, never enrolling in HIV care, and not being on ART (all p < 0.05). Heavy alcohol use as compared to no use was associated with needle sharing (aOR = 2.72; 95% CI 1.43, 5.13), injection equipment sharing (aOR = 1.80; 95% CI 1.00, 3.16), > 3 new sex partners in the past 3 months (aOR = 1.99; 95% CI 1.12, 3.49), and being unaware of HIV status (aOR = 2.77; 95% CI 1.46, 5.19). There was no association between any measure of alcohol use and unsuppressed viral load. Alcohol use among people who inject drugs living with HIV may carry elevated risk of HIV transmission mediated by sexual and injecting practices and is associated with lower engagement in multiple stages of the HIV care cascade.

Top 10 priorities for future infertility research: an international consensus development study† ‡.

STUDY QUESTION: Can the priorities for future research in infertility be identified? SUMMARY ANSWER: The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care for people with fertility problems were identified. WHAT IS KNOWN ALREADY: Many fundamental questions regarding the prevention, management and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems. STUDY DESIGN, SIZE, DURATION: Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, people with fertility problems and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance. MAIN RESULTS AND THE ROLE OF CHANCE: The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties was entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI and IVF) and ethics, access and organization of care were identified during a consensus development meeting involving 41 participants from 11 countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research and population science. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgment and arbitrary consensus definitions. WIDER IMPLICATIONS OF THE FINDINGS: We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems and others, will help research funding organizations and researchers to develop their future research agenda. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Auckland Medical Research Foundation, Catalyst Fund, Royal Society of New Zealand and Maurice and Phyllis Paykel Trust. G.D.A. reports research sponsorship from Abbott, personal fees from Abbott and LabCorp, a financial interest in Advanced Reproductive Care, committee membership of the FIGO Committee on Reproductive Medicine, International Committee for Monitoring Assisted Reproductive Technologies, International Federation of Fertility Societies and World Endometriosis Research Foundation, and research sponsorship of the International Committee for Monitoring Assisted Reproductive Technologies from Abbott and Ferring. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and editor for the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. A.W.H. reports research sponsorship from the Chief Scientist's Office, Ferring, Medical Research Council, National Institute for Health Research and Wellbeing of Women and consultancy fees from AbbVie, Ferring, Nordic Pharma and Roche Diagnostics. M.L.H. reports grants from Merck, grants from Myovant, grants from Bayer, outside the submitted work and ownership in Embrace Fertility, a private fertility company. N.P.J. reports research sponsorship from AbbVie and Myovant Sciences and consultancy fees from Guerbet, Myovant Sciences, Roche Diagnostics and Vifor Pharma. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from AbbVie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. E.H.Y.N. reports research sponsorship from Merck. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring and retains a financial interest in NexHand. J.S. reports being employed by a National Health Service fertility clinic, consultancy fees from Merck for educational events, sponsorship to attend a fertility conference from Ferring and being a clinical subeditor of Human Fertility. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the present work. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER: N/A.

Developing a core outcome set for future infertility research: an international consensus development study† ‡.

STUDY QUESTION: Can a core outcome set to standardize outcome selection, collection and reporting across future infertility research be developed? SUMMARY ANSWER: A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential treatments for infertility. WHAT IS KNOWN ALREADY: Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret. STUDY DESIGN, SIZE, DURATION: A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries). PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus science methods. MAIN RESULTS AND THE ROLE OF CHANCE: The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition and an arbitrary consensus threshold. WIDER IMPLICATIONS OF THE FINDINGS: Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. The funder had no role in the design and conduct of the study, the collection, management, analysis or interpretation of data, or manuscript preparation. B.W.J.M. is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548). S.B. was supported by University of Auckland Foundation Seelye Travelling Fellowship. S.B. reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.J.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. A.S. reports consultancy fees from Guerbet. E.H.Y.N. reports research sponsorship from Merck. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER: Core Outcome Measures in Effectiveness Trials Initiative: 1023.

Standardizing definitions and reporting guidelines for the infertility core outcome set: an international consensus development study† ‡.

STUDY QUESTION: Can consensus definitions for the core outcome set for infertility be identified in order to recommend a standardized approach to reporting? SUMMARY ANSWER: Consensus definitions for individual core outcomes, contextual statements and a standardized reporting table have been developed. WHAT IS KNOWN ALREADY: Different definitions exist for individual core outcomes for infertility. This variation increases the opportunities for researchers to engage with selective outcome reporting, which undermines secondary research and compromises clinical practice guideline development. STUDY DESIGN, SIZE, DURATION: Potential definitions were identified by a systematic review of definition development initiatives and clinical practice guidelines and by reviewing Cochrane Gynaecology and Fertility Group guidelines. These definitions were discussed in a face-to-face consensus development meeting, which agreed consensus definitions. A standardized approach to reporting was also developed as part of the process. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus development methods. MAIN RESULTS AND THE ROLE OF CHANCE: Forty-four potential definitions were inventoried across four definition development initiatives, including the Harbin Consensus Conference Workshop Group and International Committee for Monitoring Assisted Reproductive Technologies, 12 clinical practice guidelines and Cochrane Gynaecology and Fertility Group guidelines. Twenty-seven participants, from 11 countries, contributed to the consensus development meeting. Consensus definitions were successfully developed for all core outcomes. Specific recommendations were made to improve reporting. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations. There was limited representation from low- and middle-income countries. WIDER IMPLICATIONS OF THE FINDINGS: A minimum data set should assist researchers in populating protocols, case report forms and other data collection tools. The generic reporting table should provide clear guidance to researchers and improve the reporting of their results within journal publications and conference presentations. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials statement, and over 80 specialty journals have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and a financial interest in NexHand. E.H.Y.N. reports research sponsorship from Merck. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER: Core Outcome Measures in Effectiveness Trials Initiative: 1023.

Research priority setting in women's health: a systematic review.

BACKGROUND: Developing a shared agenda is an important step in ensuring future research has the necessary relevance. OBJECTIVE: To characterise research priority setting partnerships (PSPs) relevant to women's health. SEARCH STRATEGY: Included studies were identified by searching MEDLINE and the James Lind Alliance (JLA) database. SELECTION CRITERIA: Priority setting partnerships using formal consensus methods. DATA COLLECTION AND ANALYSIS: Descriptive narrative to describe the study characteristics, methods, and results. MAIN RESULTS: Ten national and two international PSPs were identified. All PSPs used the JLA method to identify research priorities. Nine PSPs had published a protocol. Potential research uncertainties were gathered from guidelines (two studies), Cochrane reviews (five studies), and surveys (12 studies). The number of healthcare professionals (31-287), patients (44-932), and others (33-139) who responded to the survey, and the number of uncertainties submitted (52-4767) varied. All PSPs entered confirmed research uncertainties (39-104) into interim priority setting surveys and healthcare professionals (31-287), patients (44-932), and others (33-139) responded. All PSPs entered a short list of research uncertainties into a consensus development meeting, which enabled healthcare professionals (six to 21), patients (eight to 14), and others (two to 13) to identify research priorities (ten to 15). Four PSPs have published their results. CONCLUSION: Future research priority setting studies should publish a protocol, use formal consensus development methods, and ensure their methods and results are comprehensively reported. TWEETABLE ABSTRACT: Research published in @BJOGtweets highlights future research priorities across women's health, including @FertilityTop10, @jamesmnduffy.

A core outcome set for future endometriosis research: an international consensus development study.

OBJECTIVE: To develop a core outcome set for endometriosis. DESIGN: Consensus development study. SETTING: International. POPULATION: One hundred and sixteen healthcare professionals, 31 researchers and 206 patient representatives. METHODS: Modified Delphi method and modified nominal group technique. RESULTS: The final core outcome set includes three core outcomes for trials evaluating potential treatments for pain and other symptoms associated with endometriosis: overall pain; improvement in the most troublesome symptom; and quality of life. In addition, eight core outcomes for trials evaluating potential treatments for infertility associated with endometriosis were identified: viable intrauterine pregnancy confirmed by ultrasound; pregnancy loss, including ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy; live birth; time to pregnancy leading to live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital abnormalities. Two core outcomes applicable to all trials were also identified: adverse events and patient satisfaction with treatment. CONCLUSIONS: Using robust consensus science methods, healthcare professionals, researchers and women with endometriosis have developed a core outcome set to standardise outcome selection, collection and reporting across future randomised controlled trials and systematic reviews evaluating potential treatments for endometriosis. TWEETABLE ABSTRACT: @coreoutcomes for future #endometriosis research have been developed @jamesmnduffy.

ICSI does not increase the cumulative live birth rate in non-male factor infertility.

STUDY QUESTION: What is the cumulative live birth rate following ICSI cycles compared with IVF cycles for couples with non-male factor infertility? SUMMARY ANSWER: ICSI resulted in a similar cumulative live birth rate compared with IVF for couples with non-male factor infertility. WHAT IS KNOWN ALREADY: The ICSI procedure was developed for couples with male factor infertility. There has been an increased use of ICSI regardless of the cause of infertility. Cycle-based statistics show that there is no difference in pregnancy rates between ICSI and IVF in couples with non-male factor infertility. However, evidence indicates that ICSI is associated with an increased risk of adverse perinatal outcomes. STUDY DESIGN, SIZE, DURATION: A population-based cohort of 14 693 women, who had their first ever stimulated cycle with fertilization performed for at least one oocyte by either IVF or ICSI between July 2009 and June 2014 in Victoria, Australia was evaluated retrospectively. The pregnancy and birth outcomes following IVF or ICSI were recorded for the first oocyte retrieval (fresh stimulated cycle and associated thaw cycles) until 30 June 2016, or until a live birth was achieved, or until all embryos from the first oocyte retrieval had been used. PARTICIPANTS/MATERIALS, SETTING, METHODS: Demographic, treatment characteristics and resulting outcome data were obtained from the Victorian Assisted Reproductive Treatment Authority. Data items in the VARTA dataset were collected from all fertility clinics in Victoria. Women were grouped by whether they had undergone IVF or ICSI. The primary outcome was the cumulative live birth rate, which was defined as live deliveries (at least one live birth) per woman after the first oocyte retrieval. A discrete-time survival model was used to evaluate the cumulative live birth rate following IVF and ICSI. The adjustment was made for year of treatment in which fertilization occurred, the woman's and male partner's age at first stimulated cycle, parity and the number of oocytes retrieved in the first stimulated cycle. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 4993 women undergoing IVF and 8470 women undergoing ICSI had 7980 and 13 092 embryo transfers, resulting in 1848 and 3046 live deliveries, respectively. About one-fifth of the women (19.0% of the IVF group versus 17.9% of the ICSI group) had three or more cycles during the study period. For couples who achieved a live delivery, the median time from oocyte retrieval to live delivery was 8.9 months in both IVF (range: 4.2-66.5) and ICSI group (range: 4.5-71.3) (P = 0.474). Fertilization rate per oocyte retrieval was higher in the IVF than in the ICSI group (59.8 versus 56.2%, P < 0.001). The overall cumulative live birth rate was 37.0% for IVF and 36.0% for ICSI. The overall likelihood of a live birth for women undergoing ICSI was not significantly different to that for women undergoing IVF (adjusted hazard ratio (AHR): 0.99, 95% CI: 0.92-1.06). For couples with a known cause of infertility, non-male factor infertility (female factor only or unexplained infertility) was reported for 64.0% in the IVF group and 36.8% in the ICSI group (P < 0.001). Among couples with non-male factor infertility, ICSI resulted in a similar cumulative live birth rate compared with IVF (AHR: 0.96, 95% CI: 0.85-1.10). LIMITATIONS, REASONS FOR CAUTION: Data were not available on clinic-specific protocols and processes for IVF and ICSI and the potential impact of these technique aspects on clinical outcomes. The reported causes of infertility were based on the treating clinician's classification which may vary between clinicians. WIDER IMPLICATIONS OF THE FINDINGS: This population-based study found ICSI resulted in a lower fertilization rate per oocyte retrieved and a similar cumulative live birth rate compared to conventional IVF. These data suggest that ICSI offers no advantage over conventional IVF in terms of live birth rate for couples with non-male factor infertility. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was received to undertake this study. There is no conflict of interest, except that M.B. is a shareholder in Genea Ltd. TRIAL REGISTRATION NUMBER: N/A.

Non-publication and publication bias in reproductive medicine: a cohort analysis.

STUDY QUESTION: Does publication bias or non-publication exist in fertility trials presented as conference abstracts? SUMMARY ANSWER: This study did not detect any publication bias; however, it did identify a high level of non-publication, with only 49% of abstracts reaching full-text publication four or more years after abstract presentation. WHAT IS KNOWN ALREADY: Systematic reviews of randomized controlled trials (RCTs) are the foundation of evidence based medicine. Non-publication or publication deficit refer to the failure to publish trial results. A publication bias exists when there is any tendency on the parts of the investigators or editors to fail to publish study results on the basis or strength of the study findings. Both present a serious problem for researchers, clinicians and policymakers alike, and ultimately impact on patient care. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study identified 337 fertility RCTs presented as conference abstracts between 2007 and 2010, as captured by an electronic search of the Cochrane Gynaecology and Fertility Database. After excluding ineligible trials and duplicates, 224 abstracts remained. PARTICIPANTS/MATERIALS, SETTING, METHODS: A search for the full-text papers of each abstract was undertaken in Pubmed, MEDLINE, Embase, CINAHL and Google in May 2015 using a probabilistic approach. Trial authors were contacted to query the publication status of abstracts when no full-text was identified. The association between individual variables and the probability of publication, and time to publication, was assessed using logistic regression and Cox regression, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 224 included abstracts, only 110 (49%; 95% CI: 42.6, 55.6) were found to be published as full-text articles. Publication bias was not identified in this cohort; studies with positive results had a similar probability of reaching full-text publication 52/113 (46%; 95% CI: 37.0, 55.3) as studies with non-positive (negative or null) results 58/111 (52%; 95% CI: 17.8, 33.9) (adjusted odds ratio (AOR): 1.02; 95% CI: 0.53, 1.97). Similarly, the time from abstract presentation to full-text publication was similar in studies with positive and non-positive results. Oral presentations were more likely to be published, and to be published sooner, than poster presentations (poster presentation AOR: 0.31; 95% CI: 0.15, 0.61 and adjusted hazard ratio (AHR): 0.57; 95% CI: 0.38, 0.86). Studies that were not registered were less likely to be published and to have delayed publication, than studies which were registered either prospectively or retrospectively (AOR: 0.14; 95% CI: 0.04, 0.44 and AHR: 0.43; 95% CI: 0.25, 0.72). Abstracts which were presented a longer time ago also had a higher probability of reaching full-text publication (P  = 0.01). LIMITATIONS, REASONS FOR CAUTION: Commencing with a cohort of RCTs from ethics committee registers may provide a better picture of the extent of non-publication and publication bias, as not all trials reach the stage of abstract presentation. It is also possible that the search did not identify all published trials, as some may have been published after the follow-up period. WIDER IMPLICATIONS OF THE FINDINGS: This study did not identify any publication bias. However, only half of the abstracts in this cohort have been published as full-text articles, four or more years after their presentation at a conference. This is similar to publication rates reported previously for fertility trials, and is despite increasing awareness of the importance of publishing trial results, and subsequent requirements for all RCTs to be registered prior to trial initiation. A better understanding of the reasons for non-publication should assist in facilitating the prompt full-text publication of RCTs in the future. STUDY FUNDING/COMPETING INTEREST(S): Funding provided from the University of Auckland. All authors declare they have no conflicts of interest in relation to this article. TRIAL REGISTRATION NUMBER: Not applicable.

Endometrial scratching for subfertility: everyone's doing it.

STUDY QUESTION: What proportion of clinicians across Australia, New Zealand and the UK are currently offering or recommending endometrial scratching for subfertility? SUMMARY ANSWER: Eighty-three percent of clinicians responding to this survey are recommending endometrial scratching to women undergoing IVF. WHAT IS KNOWN ALREADY: Endometrial scratching is currently being proposed as a technique to increase the probability of implantation in women undergoing IVF. While trial results provide evidence in favour of this procedure, there remains some uncertainty about both the extent of any beneficial effect and the subgroups of women most likely to benefit. STUDY DESIGN, SIZE, DURATION: Cross-sectional survey with responses from a total of 143 public and private fertility care providers surveyed between August and October 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: An online survey was distributed to all 189 fertility clinics across Australia, New Zealand and the UK. All clinicians, nurses and embryologists were eligible to take part. One hundred and forty-three of the 152 responses received were eligible for inclusion, with multiple responses per clinic in 33 cases. At least one response was received from 68 clinics (36% response rate per clinic). MAIN RESULTS AND THE ROLE OF CHANCE: This survey found that 83% of clinicians commend endometrial scratching prior to IVF. Of these, 92% recommend endometrial scratching to women with recurrent implantation failure (RIF) and 6% recommend it to all women having IVF. Most respondents (73%) agreed that the procedure is beneficial in women with RIF undergoing IVF and disagreed (53%) that the procedure is beneficial for women undergoing their first IVF cycle. The most common timeframe for performing endometrial scratching is the luteal phase of the cycle prior to the IVF cycle. Additionally, only 4% of clinicians recommend endometrial scratching to women undergoing intrauterine insemination or trying to conceive naturally. LIMITATIONS, REASONS FOR CAUTION: Fertility care providers who recommend endometrial scratching may be more likely to respond to the survey and this could exaggerate the use of the procedure reported here. WIDER IMPLICATIONS OF THE FINDINGS: This study was conducted across three countries and may be generalizable to similar settings. While this procedure already appears to be offered by the majority of respondents, the results of further studies in this area may further refine or expand the context in which this procedure is beneficial. STUDY FUNDING/COMPETING INTERESTS: No funding or competing interests. TRIAL REGISTRATION NUMBER: N/A.

Neonatal encephalopathy in New Zealand: Demographics and clinical outcome.

AIM: To establish the incidence of moderate to severe neonatal encephalopathy (NE) in term infants from New Zealand and to document demographic characteristics and neonatal outcomes. METHODS: Cases were reported monthly via the New Zealand Paediatric Surveillance Unit (NZPSU). Data were collected from paediatricians for neonatal items and lead maternity carers for pregnancy and birth details. Term neonatal deaths in the Perinatal and Maternal Mortality Review Committee dataset that were because of hypoxia and/or neonatal deaths from hypoxic ischaemic encephalopathy were added to the cases identified via the NZPSU, if they had not previously been ascertained. RESULTS: For the period January 2010 to December 2012, there were 227 cases, equivalent to a rate of 1.30/1000 term births (95% CI 1.14-1.48). Rates of NE were high in babies of Pacific and Indian mothers but only reached statistical significance for the comparison between Pacific and NZ European. There was also a significant increase in NE rates with increasing deprivation. Resuscitation at birth was initiated for 209 (92.1%) infants with NE. Mechanical ventilation was required, following neonatal unit admission, in 171 (75.3%) infants. Anticonvulsants were used in 157 (69.2%) infants with phenobarbitone (65.6%), phenytoin (14.5%) and benzodiazapines (21.1%), the most common. Cooling was induced in 168 infants (74%) with 145 (86.3%) reported as commenced within a 6-h window. CONCLUSIONS: The rate of NE in New Zealand is consistent with reported international rates. Establishing antecedent factors for NE is an important part of improving care, which may inform strategic efforts to decrease rates of NE.

T cell anergy and activation are associated with suboptimal humoral responses to measles revaccination in HIV-infected children on anti-retroviral therapy in Nairobi, Kenya.

HIV-infected children are less capable of mounting and maintaining protective humoral responses to vaccination against measles compared to HIV-uninfected children. This poses a public health challenge in countries with high HIV burdens. Administration of anti-retroviral therapy (ART) and revaccinating children against measles is one approach to increase measles immunity in HIV-infected children, yet it is not effective in all cases. Immune anergy and activation during HIV infection are factors that could influence responses to measles revaccination. We utilized a flow cytometry-based approach to examine whether T cell anergy and activation were associated with the maintenance of measles-specific immunoglobulin (Ig)G antibodies generated in response to measles revaccination in a cohort of HIV-infected children on ART in Nairobi, Kenya. Children who sustained measles-specific IgG for at least 1 year after revaccination displayed significantly lower programmed cell death 1 (PD-1) surface expression on CD8(+) T cells on a per-cell basis and exhibited less activated CD4(+) T cells compared to those unable to maintain detectable measles-specific antibodies. Children in both groups were similar in age and sex, CD4(+) T cell frequency, duration of ART treatment and HIV viral load at enrolment. These data suggest that aberrant T cell anergy and activation are associated with the impaired ability to sustain an antibody response to measles revaccination in HIV-infected children on ART.

Maternal plasma and breastmilk viral loads are associated with HIV-1-specific cellular immune responses among HIV-1-exposed, uninfected infants in Kenya.

Infants exposed to maternal HIV-1 provide an opportunity to assess correlates of HIV-1-specific interferon (IFN)-γ responses and may be informative in the development of HIV-1 vaccines. HIV-1-infected women with CD4 counts 200-500 cells/mm(3) were randomized to short-course zidovudine/nevirapine (ZDV/NVP) or highly active anti-retroviral therapy (HAART) between 2003 and 2005. Maternal plasma and breastmilk HIV-1 RNA and DNA were quantified during the first 6-12 months postpartum. HIV-1 gag peptide-stimulated enzyme-linked immunospot (ELISPOT) assays were conducted in HIV-1-exposed, uninfected infants (EU), and correlates were determined using regression and generalized estimating equations. Among 47 EU infants, 21 (45%) had ≥1 positive ELISPOT result during follow-up. Infants had a median response magnitude of 177 HIV-1-specific spot-forming units (SFU)/106 peripheral blood mononuclear cells (PBMC) [interquartile range (IQR)=117-287] directed against 2 (IQR = 1-3) gag peptide pools. The prevalence and magnitude of responses did not differ by maternal anti-retroviral (ARV) randomization arm. Maternal plasma HIV-1 RNA levels during pregnancy (P=0.009) and breastmilk HIV-1 DNA levels at 1 month (P=0.02) were associated with a higher magnitude of infant HIV-1-specific ELISPOT responses at 1 month postpartum. During follow-up, concurrent breastmilk HIV-1 RNA and DNA (cell-free virus and cell-associated virus, respectively) each were associated positively with magnitude of infant HIV-1-specific responses (P=0.01). Our data demonstrate the importance of antigenic exposure on the induction of infant HIV-1-specific cellular immune responses in the absence of infection.

Time-lapse in the IVF-lab: how should we assess potential benefit?

Time-lapse imaging of embryos has been widely introduced to fertility laboratories worldwide with the aim of identifying the best quality embryos to transfer that will ultimately improve IVF success rates. In this opinion paper, we explore the lack of evidence of benefit of this novel intervention, analyse the methodological flaws of current studies, offer ideal study designs that assess the various features of time-lapse imaging, and discuss forthcoming studies. In particular, we emphasize the ethical aspects of hastily adopting a costly technology without current high level evidence of improved live birth rates, safety and cost effectiveness.

Risk of ectopic pregnancy lowest with transfer of single frozen blastocyst.

STUDY QUESTION: What type of transferred embryo is associated with a lower rate of ectopic pregnancy? SUMMARY ANSWER: The lowest risk of ectopic pregnancy was associated with the transfer of blastocyst, frozen and single embryo compared with cleavage stage, fresh and multiple embryos. WHAT IS KNOWN ALREADY: Ectopic pregnancy is a recognized complication following assisted reproductive technology (ART) treatment. It has been estimated that the rate of ectopic pregnancy is doubled in pregnancies following ART treatment compared with spontaneous pregnancies. However, it was not clear whether the excess rate of ectopic pregnancy following ART treatment is related to the underlying demographic factors of women undergoing ART treatment, the number of embryos transferred or the developmental stage of the embryo. STUDY DESIGN, SIZE, DURATION: A population-based cohort study of pregnancies following autologous treatment cycles between January 2009 and December 2011 were obtained from the Australian and New Zealand Assisted Reproduction Technology Database (ANZARD). The ANZARD collects ART treatment information and clinical outcomes annually from all fertility centres in Australia and New Zealand. PARTICIPANTS/MATERIALS, SETTING, METHODS: Between 2009 and 2011, a total of 44 102 pregnancies were included in the analysis. The rate of ectopic pregnancy was compared by demographic and ART treatment factors. Generalized linear regression of Poisson distribution was used to estimate the likelihood of ectopic pregnancy. Odds ratios, adjusted odds ratios (AOR) and 95% confidence intervals (CI) were calculated. MAIN RESULTS AND THE ROLE OF CHANCE: The overall rate of ectopic pregnancy was 1.4% for women following ART treatment in Australia and New Zealand. Pregnancies following single embryo transfers had 1.2% ectopic pregnancies, significantly lower than double embryo transfers (1.8%) (P < 0.01). The highest ectopic pregnancy rate was 1.9% for pregnancies from transfers of fresh cleavage embryo, followed by transfers of frozen cleavage embryo (1.7%), transfers of fresh blastocyst (1.3%), and transfers of frozen blastocyst (0.8%). Compared with fresh blastocyst transfer, the likelihood of ectopic pregnancy was 30% higher for fresh cleavage stage embryo transfers (AOR 1.30, 95% CI 1.07-1.59) and was consistent across subfertility groups. Transfer of frozen blastocyst was associated with a significantly decreased risk of ectopic pregnancy (AOR 0.70, 95% CI 0.54-0.91) compared with transfer of fresh blastocyst. LIMITATIONS, REASON FOR CAUTION: A limitation of this population-based study is the lack of information available on clinical- specific protocols and processes for embryo transfer (i.e. embryo quality, cryopreservation protocol, transfer techniques, etc.) and the potential impact on outcomes. WIDER IMPLICATIONS OF THE FINDINGS: The lowest risk of ectopic pregnancy was associated with the transfer of a single frozen blastocyst. This finding adds to the increasing evidence of better perinatal outcomes following frozen embryo transfers. The approach of freezing all embryos in the initiated fresh cycle and transfer of a single frozen blastocyst in the subsequent thaw cycle may improve the overall pregnancy and birth outcomes following ART treatment, in part by reducing the ectopic pregnancy rate. STUDY FUNDING/COMPETING INTERESTS: There is no funding for this study. Authors declared no competing interest related to this study.

In-utero infection with HIV-1 associated with suppressed lymphoproliferative responses at birth.

In-utero exposure to HIV-1 may affect the immune system of the developing child and may induce HIV-1-specific immune responses, even in the absence of HIV-1 infection. We evaluated lymphoproliferative capacity at birth among 40 HIV-1-uninfected infants born to HIV-1-infected mothers and 10 infants who had acquired HIV-1 in utero. Cord blood mononuclear cells were assayed using [(3) H]-thymidine incorporation for proliferation in response to HIV-1 p55-gag and the control stimuli phytohaemagglutinin (PHA), Staphylococcus enterotoxin B (SEB) and allogeneic cells. In response to HIV-1 p55-gag, eight (20%) HIV-1-exposed, uninfected (EU) infants had a stimulation index (SI) ≥ 2 and three (30%) in-utero HIV-1 infected infants had SI ≥2. The frequency and magnitude of responses to HIV-1 p55-gag were low overall, and did not differ statistically between groups. However, proliferative responses to control stimuli were significantly higher in EU infants than in infants infected in utero, with a median SI in response to PHA of 123 [interquartile range (IQR) 77-231] versus 18 (IQR 4-86) between EU and infected infants, respectively (P < 0·001). Among infected infants, gestational maturity was associated with the strength of HIV-1 p55-gag response (P < 0·001); neither maternal nor infant HIV-1 viral load was associated. In summary, EU and HIV-1-infected infants mounted HIV-1-specific lymphoproliferative responses at similar rates (20-30%), and although global immune function was preserved among EU infants, neonatal immune responses were significantly compromised by HIV-1 infection. Such early lymphoproliferative compromise may, in part, explain rapid progression to AIDS and death among HIV-1-infected infants.

Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2.

BACKGROUND: Most persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1. METHODS: We conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, > or = 250 cells per cubic millimeter) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrollment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses. RESULTS: A total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P=0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log(10) copies per milliliter (95% CI, 0.22 to 0.29; P<0.001) and the occurrence of HSV-2-positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P<0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir were observed. CONCLUSIONS: Daily acyclovir therapy did not reduce the risk of transmission of HIV-1, despite a reduction in plasma HIV-1 RNA of 0.25 log(10) copies per milliliter and a 73% reduction in the occurrence of genital ulcers due to HSV-2. (ClinicalTrials.gov number, NCT00194519.)