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ObjectiveEstimate the incidence of placenta accreta and describe risk factors, clinical practice and perinatal outcomes.DesignCase–control study.SettingSites in Australia and New Zealand with at least 50 births per year.ParticipantsCases were women giving birth (≥20 weeks or fetus ≥400 g) who were diagnosed with placenta accreta by antenatal imaging, at operation or by pathology specimens between 2010 and 2012. Controls were two births immediately prior to a case. A total of 295 cases were included and 570 controls.MethodsData were collected using the Australasian Maternity Outcomes Surveillance System.Primary and secondary outcome measuresIncidence, risk factors (eg, prior caesarean section (CS), maternal age) and clinical outcomes of placenta accreta (eg CS, hysterectomy and death).ResultsThe incidence of placenta accreta was 44.2/100 000 women giving birth (95% CI 39.4 to 49.5); however, this may overestimated due to the case definition used. In primiparous women, an increased odds of placenta accreta was observed in older women (adjusted OR (AOR) women≥40 vs Women with placenta accreta were more likely to have a caesarean section (AOR: 4.6, 95% CI 2.7 to 7.6) to be admitted to the intensive care unit (ICU)/high dependency unit (AOR: 46.1, 95% CI 22.3 to 95.4) and to have a hysterectomy (AOR: 209.0, 95% CI 19.9 to 875.0). Babies born to women with placenta accreta were more likely to be preterm, be admitted to neonatal ICU and require resuscitation.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: This review has two objectives. These are: to assess the comparative effectiveness (pregnancy and live birth) and safety (ovarian hyperstimulation syndrome) in women undergoing in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI): 1. of different doses of gonadotropin in women subgrouped by their expected response to stimulation, as defined by at least one ovarian reserve test (ORT) measure (do women with low, moderate or high anticipated response to ovarian stimulation, based on an ORT, benefit from a modified gonadotropin dose?); and 2. of individualisation of gonadotropin dose using ORT, as compared to dose selection without ORT, or to an alternative individualised dosing algorithm using ORT (does using ORT to individualise gonadotropin dose improve IVF/ICSI outcomes, and is there evidence to suggest one algorithm is better than another?).

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.

BACKGROUND: Intentional endometrial injury is being proposed as a technique to improve the probability of pregnancy in women undergoing assisted reproductive technologies (ART) such as in vitro fertilisation (IVF). Endometrial injury is often performed by pipelle biopsy and is a common gynaecological procedure with established safety. However, it causes a moderate degree of discomfort/pain and requires an additional pelvic examination. The effectiveness of this procedure outside of ART, in women or couples attempting to conceive via sexual intercourse or with intrauterine insemination (IUI), remains unclear. OBJECTIVES: To assess the effectiveness and safety of intentional endometrial injury performed in infertile women or couples attempting to conceive through sexual intercourse or intrauterine insemination (IUI). SEARCH METHODS: The Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, LILACS, ISI Web of Knowledge, and clinical trial registries were searched from inception to 21 May 2020, as were conference abstracts and reference lists of relevant reviews and included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated any kind of intentional endometrial injury in women planning to undergo IUI or attempting to conceive spontaneously (with or without ovarian stimulation (OS)) compared to no intervention, a mock intervention, or intentional endometrial injury performed at a different time or to a higher/lower degree. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. Primary outcomes were live birth/ongoing pregnancy and pain experienced during the procedure. Due to high risk of bias associated with many of the studies, primary analyses of all review outcomes were restricted to studies at low risk of bias. Sensitivity analysis including all studies was then performed. MAIN RESULTS: We included 23 RCTs (4035 women). Most of these studies included women with unexplained infertility. Intentional endometrial injury versus either no intervention or a sham procedure The primary analysis was restricted to studies at low risk of bias, which left only one study included. We are uncertain whether endometrial injury has an effect on the probability of live birth, as only one study is included in the analysis and the confidence interval is wide (risk ratio (RR) 1.11, 95% confidence interval (CI) 0.78 to 1.59; 1 RCT, 210 participants). Evidence suggests that if the chance of live birth with no intervention/a sham procedure is assumed to be 34%, then the chance with endometrial injury would be 27% to 55%. When all studies were included in the sensitivity analysis, we were uncertain whether endometrial injury improves live birth/ongoing pregnancy, as the evidence was of very low quality (RR 1.71, 95% CI 1.32 to 2.21; 8 RCTs, 1522 participants; I² = 16%). Evidence suggests that if the chance of live birth/ongoing pregnancy with no intervention/a sham procedure is assumed to be 13%, then the chance with endometrial injury would be 17% to 28%. A narrative synthesis conducted for the other primary outcome of pain during the procedure included studies measuring pain on a zero‐to‐ten visual analogue scale (VAS) or grading pain as mild/moderate/severe, and showed that most often mild to moderate pain was reported (6 RCTs, 911 participants; very low‐quality evidence). Higher versus lower degree of intentional endometrial injury Evidence was insufficient to show whether there is a difference in ongoing pregnancy rates (RR 1.29, 95% CI 0.71 to 2.35; 1 RCT, 332 participants; low‐quality evidence) between hysteroscopy with endometrial injury and hysteroscopy alone. Evidence suggests that if the chance of ongoing pregnancy with hysteroscopy alone is 10%, then the chance with hysteroscopy with endometrial injury would be 7% to 24%. This study did not report the primary outcomes of live birth and pain during the procedure. Timing of intentional endometrial injury Four trials compared endometrial injury performed in the cycle before IUI to that performed in the same cycle as IUI. None of these studies reported the primary outcomes of live birth/ongoing pregnancy and pain during the procedure. One study compared endometrial injury in the early follicular phase (EFP; Day 2 to 4) to endometrial injury in the late follicular phase (LFP; Day 7 to 9), both in the same cycle as IUI. The primary outcome live birth/ongoing pregnancy was not reported, but the study did report the other primary outcome of pain during the procedure assessed by a zero‐to‐ten VAS. The average pain score was 3.67 (standard deviation (SD) 0.7) when endometrial injury was performed in the EFP and 3.84 (SD 0.96) when endometrial injury was performed in the LFP. The mean difference was ‐0.17, suggesting that on average, women undergoing endometrial injury in the EFP scored 0.17 points lower on the VAS as compared to women undergoing endometrial injury in the LFP (95% CI ‐0.48 to 0.14; 1 RCT, 110 participants; very low‐quality evidence). AUTHORS' CONCLUSIONS: Evidence is insufficient to show whether there is a difference in live birth/ongoing pregnancy between endometrial injury and no intervention/a sham procedure in women undergoing IUI or attempting to conceive via sexual intercourse. The pooled results should be interpreted with caution, as the evidence was of low to very low quality due to high risk of bias present in most included studies and an overall low level of precision. Furthermore, studies investigating the effect of timing of endometrial injury did not report the outcome live birth/ongoing pregnancy; therefore no conclusions could be drawn for this outcome. Further well‐conducted RCTs that recruit large numbers of participants and minimise bias are required to confirm or refute these findings. Current evidence is insufficient to support routine use of endometrial injury in women undergoing IUI or attempting to conceive via sexual intercourse.

Objectives To assess the consistency in risk of bias (RoB) judgments across Cochrane reviews for studies appearing in more than one Cochrane review in the field of subfertility. Study Design and Setting We retrieved any study that had been used more than once in systematic reviews present on the Cochrane Database of Systematic Reviews in the area of subfertility. We then retrieved the recorded RoB assessments for these studies and looked at the consistency of judgments made between different authoring teams on the same trials. Results From the 156 bias judgments that were completed by at least two separate groups of authors, 45% of these judgments differed. For the domains of random sequence generation and incomplete outcome data, there was reasonably high level of agreement (71% and 79%, respectively). However, for the domain of blinding, agreement was reached in only 35% of cases. Conclusion This assessment of how consistently the RoB is being applied in Cochrane reviews has shown that, especially in some domains, there are large discrepancies in how RoB is being evaluated. Further work needs to be undertaken to improve the application of this tool.

Objective To systematically review the literature on the association between obesity and endometrial hyperplasia or cancer in premenopausal women. Data Sources We searched the bibliographic databases MEDLINE, EMBASE, PubMed, and CINAHL (inception to May 5, 2015), and checked reference lists of included studies and systematic reviews. Study Eligibility Criteria Studies of more than 50 women with endometrial pathology diagnosed during premenopause that reported on obesity as a risk factor were eligible. Study Appraisal and Synthesis Methods Study identification and data extraction were independently performed by 2 authors. Where possible, data were pooled in a generic inverse variance forest plot. Heterogeneity was reported using the I 2 statistic. Results Nine case-control studies of moderate quality were included. Quantitative analysis of 5 studies showed a dose–response relationship of body mass index and increased risk of endometrial cancer. For studies of women with body mass index of ≥25, the pooled odds ratio was 3.85 (95% confidence interval 2.53–5.84); body mass index of ≥30 was 5.25 (4.00–6.90); and body mass index of ≥40 was 19.79 (11.18–35.03). Conclusion Body mass index is a consistent and leading risk factor for endometrial complex hyperplasia or cancer in premenopausal women. Body mass index should be considered when deciding to assess the endometrium in symptomatic premenopausal women.

ACKNOWLEDGEMENTS We would like to express our appreciation to Dra Abha Maheshwari for her important authorial contribution to the previous version of this review. We also acknowledge the important help provided by the Cochrane Menstrual Disorders and Subfertility Group team, specially by Marian Showell, Trials Search Co-ordinator; by Helen Nagels, Managing Editor; and by Prof. Cindy Farquhar, Co-ordinating Editor. Finally, we would like to express our gratitude to the following investigators, who provided essential information for the preparation of this review: TK Aleyamma, Erin F Wolff, Lukasz Polanski, Nava Dekel, Neeta Singh, Suleyman Guven and Tracy Yeung

The success rate of infertility treatments remains modest. Endometrial injury has been suggested as an intervention to increase the probability of pregnancy in women undergoing assisted reproductive technologies such as in vitro fertilisation (IVF). The majority of studies and systematic reviews have reported that endometrial injury improves the outcomes of IVF, intrauterine insemination and natural conception; however, the size and quality of the studies are poor. The low quality of the available evidence questions the presence of any real beneficial effect, and the applicability of the intervention in different populations remains unclear. The PIP trials are three multi-centre, randomised controlled trials designed to test three separate hypotheses: whether endometrial injury increases the probability of live birth in women or couples 1) who are undergoing autologous embryo transfer as part of an IVF cycle (PIP-IVF), 2) with unexplained infertility who are attempting to conceive naturally (PIP-UE) and 3) with subfertility related to polycystic ovarian syndrome (PCOS) who are on ovulation induction medication and attempting to conceive (PIP-PCOS). Participants will be randomised to either undergo endometrial injury by endometrial pipelle biopsy or to: • no intervention (PIP-IVF), or • a sham procedure (PIP-PCOS and PIP-UE). In PIP-IVF, endometrial injury will be carried out between day three of the cycle prior to the IVF cycle, and day three of the IVF cycle. In PIP-UE and PIP-PCOS, endometrial injury or a sham procedure will be undertaken between days 1–12 of a menstrual cycle or ovulation induction cycle respectively. Participants in PIP-UE and PIP-PCOS will then be followed for three cycles during which time they will attempt to conceive from sexual intercourse. To ensure allocation concealment, randomisation will be carried out using a web-based system or sequentially numbered, opaque, sealed envelopes. The primary outcome is live birth. Secondary outcomes include ongoing pregnancy, clinical pregnancy and miscarriage. The required sample sizes for the PIP studies have been estimated at 840 (PIP-IVF), 350 (PIP-UE) and 280 (PIP-PCOS). Primary analysis will be as per intention-to-treat principles. The PIP trials are designed to address the gaps in the utility of endometrial scratching as a treatment for subfertility in three different populations. If the beneficial effect of this intervention can be confirmed in these settings, endometrial scratching will provide a cost-effective method for helping women and couples to conceive. PIP-IVF ACTRN12614000626662 registered 13/6/2014; PIP-PCOS ACTRN12614000657628 registered 24/6/2014; PIP-UE ACTRN12614000656639 registered 24/6/2014. The trials are ongoing.

Background Dolutegravir (DTG)-based antiretroviral therapy (ART) is highly effective and well-tolerated in adults and is rapidly being adopted globally. We describe the design of the ODYSSEY trial which evaluates the efficacy and safety of DTG-based ART compared with standard-of-care in children and adolescents. The ODYSSEY trial includes nested pharmacokinetic (PK) sub-studies which evaluated pragmatic World Health Organization (WHO) weight-band-based DTG dosing and opened recruitment to children Methods ODYSSEY (Once-daily DTG based ART in Young people vS. Standard thErapY) is an open-label, randomised, non-inferiority, basket trial comparing the efficacy and safety of DTG + 2 nucleos(t) ides (NRTIs) versus standard-of-care (SOC) in HIV-infected children Results Between September 2016 and June 2018, 707 children weighing ≥14 kg were enrolled; including 311 ART-naïve children and 396 children starting second-line. 47% of children were enrolled in Uganda, 21% Zimbabwe, 20% South Africa, 9% Thailand, 4% Europe. 362 (51%) participants were male; median age [range] at enrolment was 12.2 years [2.9–18.0]. 82 (12%) children weighed 14 to Conclusions By employing a basket design, to include ART-naïve and -experienced children, and nested PK sub-studies, the ODYSSEY trial efficiently evaluates multiple scientific questions regarding dosing and effectiveness of DTG-based ART in children. Trial registration NCT, NCT02259127, registered 7th October 2014; EUDRACT, 2014–002632-14, registered 18th June 2014 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002632-14/ES); ISRCTN, ISRCTN91737921, registered 4th October 2014.