Recommendations from the 2024 Australian evidence-based guideline for unexplained infertility: ADAPTE process from the ESHRE evidence-based guideline on unexplained infertility.

INTRODUCTION: The 2024 Australian evidence-based guideline for unexplained infertility provides clinicians with evidence-based recommendations for the optimal diagnostic workup for infertile couples to establish the diagnosis of unexplained infertility and optimal therapeutic approach to treat couples diagnosed with unexplained infertility in the Australian health care setting. The guideline recommendations were adapted for the Australian context from the rigorous, comprehensive European Society of Human Reproduction and Embryology (ESHRE) 2023 Evidence-based guideline: unexplained infertility, using the ADAPTE process and have been approved by the Australian National Health and Medical Research Council. MAIN RECOMMENDATIONS: The guideline includes 40 evidence-based recommendations, 21 practice points and three research recommendations addressing: definition - defining infertility and frequency of intercourse, infertility and age, female and male factor infertility; diagnosis - ovulation, ovarian reserve, tubal factor, uterine factor, laparoscopy, cervical/vaginal factor, male factor, additional testing for systemic conditions; and treatment - expectant management, active treatment, mechanical-surgical procedures, alternative therapeutic approaches, quality of life. CHANGES IN ASSESSMENT AND MANAGEMENT RESULTING FROM THE GUIDELINE: This guideline refines the definition of unexplained infertility and addresses basic diagnostic procedures for infertility assessment not considered in previous guidelines on unexplained infertility. For therapeutic approaches, consideration of evidence quality, efficacy, safety and, in the Australian setting, feasibility, acceptability, cost, implementation and ultimately recommendation strength were integrated across multidisciplinary expertise and consumer perspectives in adapting recommendations to the Australian context by using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework, which had not been used in past guidelines on unexplained infertility to formulate recommendations. The Australian process also included an established data integrity check to ensure evidence could be trusted to guide practice. Practice points were added and expanded to consider the Australian setting. No evidence-based recommendations were underpinned by high quality evidence, with most having low or very low quality evidence. In this context, research recommendations were made including those for the Australian context. The full guideline and technical report are publicly available online and can be accessed at https://www.monash.edu/medicine/mchri/infertility and are supported by extensive translation resources, including the free patient ASKFertility mobile application (https://www.askfertility.org/).

Beyond the numbers: Classifying contributory factors and potentially avoidable adverse events in the gynaecology service of National Women's Health at Auckland District Health Board.

BACKGROUND: Adverse events (AEs) during health care are common and may have long-term consequences for patients. Although there is a tradition of reviewing morbidity and mortality in gynaecology, there is no recommended system for reporting contributory factors and potential avoidability. AIMS: To identify factors that contributed to AEs in the gynaecology service at National Women's Health at Auckland District Health Board and to determine potential avoidability, with the use of a multidisciplinary morbidity review. MATERIALS AND METHODS: Contributory factors from a review of AEs in gynaecology services were identified and classified as organisational and/or management factors, personnel factors and barriers to patients accessing and engaging with care. Potential avoidability of the AE was also considered. A descriptive analysis of the morbidity review of patients who had an AE from 2019 to 2022 was undertaken. RESULTS: One hundred and fifty-three cases of AEs were reviewed and 77 (50.3%) were associated with contributory factors. Of all cases, 45 (29.4%) had organisational factors, 54 (35.3%) had personnel factors and patient factors resulting in barriers to care contributing to 11 (7.2%) cases. Sixty-five cases (42.5%) were classified as potentially avoidable. Of these 65 cases, 38 (58.5%) had organisational factors, 48 (73.8%) had personnel factors and nine (13.9%) had barriers to care. CONCLUSIONS: The AE review process reported 50.3% of AEs had contributory factors that were classified as organisational, personnel and barriers to patients accessing care and that 42.5% of the AEs were potentially avoidable. These reviews can be used for making recommendations that potentially lead to improvements in gynaecology.

A Randomized Trial of Endometrial Scratching before In Vitro Fertilization.

BACKGROUND: Endometrial scratching (with the use of a pipelle biopsy) is a technique proposed to facilitate embryo implantation and increase the probability of pregnancy in women undergoing in vitro fertilization (IVF). METHODS: We conducted a pragmatic, multicenter, open-label, randomized, controlled trial. Eligible women were undergoing IVF (fresh-embryo or frozen-embryo transfer), with no recent exposure to disruptive intrauterine instrumentation (e.g., hysteroscopy). Participants were randomly assigned in a 1:1 ratio to either endometrial scratching (by pipelle biopsy between day 3 of the cycle preceding the embryo-transfer cycle and day 3 of the embryo-transfer cycle) or no intervention. The primary outcome was live birth. RESULTS: A total of 1364 women underwent randomization. The frequency of live birth was 180 of 690 women (26.1%) in the endometrial-scratch group and 176 of 674 women (26.1%) in the control group (adjusted odds ratio, 1.00; 95% confidence interval, 0.78 to 1.27). There were no significant between-group differences in the rates of ongoing pregnancy, clinical pregnancy, multiple pregnancy, ectopic pregnancy, or miscarriage. The median score for pain from endometrial scratching (on a scale of 0 to 10, with higher scores indicating worse pain) was 3.5 (interquartile range, 1.9 to 6.0). CONCLUSIONS: Endometrial scratching did not result in a higher rate of live birth than no intervention among women undergoing IVF. (Funded by the University of Auckland and others; PIP Australian New Zealand Clinical Trials Registry number, ACTRN12614000626662 .).

A randomized trial of endometrial scratching in women with PCOS undergoing ovulation induction cycles.

RESEARCH QUESTION: Does endometrial scratching improve the chance of a live birth in women with polycystic ovary syndrome (PCOS) undergoing ovulation induction and trying to conceive? DESIGN: An international, multicentre, randomized, sham-controlled trial across six fertility clinics in three countries (New Zealand, UK and Brazil). Women with a diagnosis of PCOS who were planning to commence ovulation induction cycles (at least three cycles) in order to conceive were randomly assigned to receive the pipelle (scratch) procedure or a sham (placebo) procedure in the first cycle of ovulation induction. Women kept a diary of ovulation induction and sexual intercourse timing over three consecutive cycles and pregnancies were followed up to live birth. Primary outcome was live birth and secondary outcomes were clinical pregnancy, ongoing pregnancy, multiple pregnancy, adverse pregnancy outcomes, neonatal outcomes, bleeding following procedure and pain score following procedure. RESULTS: A total of 117 women were randomized; 58 to the scratch group and 59 to the sham group. Live birth occurred in 11 (19%) women in the scratch group and 14 (24%) in the sham group (odds ratio 0.76, 95% confidence interval [CI] 0.30-1.92). Secondary outcomes were similar in each group. Significantly higher pain scores were reported in the scratch group (adjusted mean difference 3.2, 95% CI 2.5-3.9) when measured on a visual analogue scale. CONCLUSION: No difference was detected in live birth rate for women with PCOS who received an endometrial scratch when trying to conceive using ovulation induction; however, uncertainty remains due to the small sample size in this study.

Could DNA hydroxymethylation be crucial in influencing steroid hormone signaling in endometrial biology and endometriosis?

Endometriosis affects 10% of reproductive-aged women. It is characterized by the growth of the endometrium, outside the uterus and is associated with infertility and chronic abdominal pain. Lack of noninvasive diagnostic tools and early screening tests results in delayed treatment and subsequently increased disease severity. Endometriosis is a disease associated with a deregulated hormonal response, therefore, understanding the molecular mechanisms that govern this hormonal interplay is of paramount importance. DNA methylation is an epigenetic mark that regulates gene expression and is often associated with genes that code for steroid receptors and enzymes associated with estrogen synthesis and metabolism in endometriosis. DNA hydroxymethylation, which is structurally similar to methylation but functionally different, is a biologically critical mechanism that is also known to regulate gene expression. Ten Eleven Translocation (TET) proteins mediate hydroxymethylation. However, the role of DNA hydroxymethylation or TETs in the endometrium remains relatively unexplored. Currently, the "gold standard" technique used to study methylation patterns is bisulfite genomic sequencing. This technique also detects hydroxymethylation but fails to distinguish between the two, thereby limiting our understanding of these two processes. The presence of TETs in the male and female reproductive tract and its contribution to endometrial cancer makes it an important factor to study in endometriosis. This review summarizes the role of DNA methylation in aberrant steroid hormone signaling and hypothesizes that hydroxymethylation could be a factor influencing hormonal instability seen in endometriosis.

Reporting assisted reproductive technology success rates on Australian and New Zealand fertility clinic websites.

BACKGROUND: Fertility clinics commonly report their success rates online. These can be difficult to interpret as they are influenced by the way the data are presented. To improve transparency, the Reproductive Technology Accreditation Committee (RTAC) has published guidelines to support fertility clinics with their online reporting of success rates. However, it is unclear whether compliance with these guidelines will allow patients to make fair comparisons between clinics. AIMS: To illustrate the variability in patient and treatment populations that contribute to fertility clinic published rates. MATERIALS AND METHODS: Fertility clinics offering in vitro fertilisation treatment in Australia or New Zealand were assessed for compliance with six guidelines adapted from RTAC's code of practice, for reporting success rates in the public domain. All graphs and/or tables reporting clinic success rates were assessed to illustrate the combination of outcome or treatment variables contributing to each dataset. RESULTS: Twenty of the 30 fertility clinic websites reported success rates. Of these only 17 reported live births. The median compliance score with RTAC guidelines was 8/8 (interquartile range: 6-8). Of 41 figures published across all websites, five reported clinical pregnancy rates as their only outcome measure. Thirty-seven figures reported success rates 'per embryo transfer', two figures used 'per egg collection', and no figures described success rates 'per cycle started'. Thirty-two different combinations of reporting variables were observed. CONCLUSIONS: Websites were broadly compliant with RTAC's guidelines. However, considering the variability in patient and treatment groups contributing to success rate data, patients cannot be expected to make an informed decision based on clinics' self-reported outcomes. RTAC guidelines could be improved by providing a clear definition of success, including the appropriate use of denominators.

The use of oil-soluble contrast media for tubal flushing in infertility: A consensus statement from ACCEPT (Australasian CREI Consensus Expert Panel on Trial evidence).

Good evidence that oil-soluble contrast media (OSCM) enhances pregnancy rates when used to assess fallopian tube patency by hysterosalpingogram has prompted rapid clinical uptake by some fertility doctors and imaging specialists in Australia and New Zealand. The ACCEPT group met in July 2019 to develop a consensus document outlining the indications for and safe use of OSCM, to inform and guide clinicians interested in offering procedures using this media to couples with infertility.

Intrauterine insemination with ovarian stimulation versus expectant management for unexplained infertility (TUI): a pragmatic, open-label, randomised, controlled, two-centre trial.

BACKGROUND: Women with unexplained infertility are often offered intrauterine insemination (IUI) with ovarian stimulation as an alternative to in-vitro fertilisation (IVF). However, little evidence exists that IUI is an effective treatment. In 2013, the UK National Institute for Health and Care Excellence recommended that IUI should not be routinely offered for couples with unexplained infertility. METHODS: For this pragmatic, open-label, randomised, controlled, two-centre study, we enrolled women attending two fertility clinics in New Zealand with unexplained infertility and an unfavourable prognosis of natural conception. Participants were randomly assigned (1:1) using a computer-generated randomisation sequence, prepared by an independent statistician, to either three cycles of IUI with ovarian stimulation (with either oral clomifene citrate [50-150 mg, days 2-6] or oral letrozole [2·5-7·5 mg, days 2-6], with choice of ovarian stimulation made by the clinic) or three cycles of expectant management (couples advised to be sexually active around the likely time of ovulation and provided with a diary to record the first day of each menstrual cycle and dates of sexual activity) in blocks of four, six, and ten, without stratification. The participating couple and the clinicians were informed of treatment allocation. The primary outcome was cumulative livebirth rate in the intention-to-treat population. The safety analyses were done in the intention-to-treat population. This study was prospectively registered with the Australian and New Zealand Clinical Trials Register, number ACTRN12612001025820. FINDINGS: Between March 12, 2013, and May 12, 2016, we randomly assigned 101 women to IUI with ovarian stimulation and 100 to expectant management, all of whom were included in the primary efficacy analysis and safety analyses. Women assigned to IUI had a higher cumulative livebirth rate than women assigned to expectant management (31 [31%] livebirths among 101 women vs nine [9%] livebirths among 100 women; risk ratio [RR] 3·41, 95% CI 1·71-6·79; p=0·0003). Of 31 livebirths in the IUI group, 23 resulted from IUI cycles and eight were conceived without assistance before or between IUI cycles. Of nine livebirths in the expectant management group, one patient was pregnant from IUI with ovarian stimulation at study entry and one had received off-protocol treatment (IVF). Two sets of twins were born, both in the IUI group (one from a cancelled cycle for over-response). INTERPRETATION: IUI with ovarian stimulation is a safe and effective treatment for women with unexplained infertility and an unfavourable prognosis for natural conception. FUNDING: Auckland Medical Research Foundation, Evelyn Bond Fund of Auckland District Health Board, Mercia Barnes Trust of Royal Australian and New Zealand College of Obstetricians and Gynaecologists, Maurice and Phyllis Paykel Trust, and The Nurture Foundation for Reproductive Research.

An evaluation of the objective quality and perceived usefulness of maternity clinical practice guidelines at a tertiary maternity unit.

BACKGROUND: Compliance with maternity clinical practice guidelines developed by National Women's Health has been found to be low at audit. OBJECTIVE: To explore the reasons for poor compliance with maternity guidelines by evaluating the quality of a sample of National Women's Health guidelines using a validated instrument and assessing local guideline users' perceptions of and attitudes toward guidelines. DESIGN: Five independent reviewers evaluated the quality of 10 purposively selected guidelines for adherence to the Appraisal of Guidelines Research & Evaluation (AGREE) II instrument standards. A self-administered questionnaire for staff was undertaken regarding views of and barriers to guideline use. RESULTS: None of the guidelines attained a score over 50% for the following domains: stakeholder involvement, rigour of development, applicability, editorial independence. The highest scoring domain was clarity of presentation (mean 69%). All guidelines scored the minimum possible for editorial independence. Survey respondents had positive attitudes toward guidelines, believed that their use could improve quality of care within the service, and felt that encouragement from senior staff members and peers would encourage their use. Accessibility was the most commonly cited of many barriers identified. CONCLUSION: The National Women's Health guidelines evaluated in this study cannot be considered to be high quality, and could be improved by reporting on methodology of the development process. Although poor guideline development may contribute to failure of the local maternity guidelines, it appears that accessibility is a major barrier to their use and implementation.

Gynaecologists and industry: ain't no sunshine.

The field of reproductive medicine is known for its innovations, and where there is innovation there is marketing and engagement with the doctors who are potential prescribers and users of those innovations. Financial connections between drug and device manufacturers with doctors have been extensively debated over the past decade. On one hand, relationships between doctors and industry could be considered synergistic by allowing the development of improved treatments. On the other hand, payment (and other benefits) from industry to doctors may subtly shift the main objective of the collaboration from patients' health to mutual benefits for both doctors and industry. Fertility patients can be considered 'vulnerable' as they face the multiple challenges of seeking to be parents, understanding complex and expensive fertility treatments that are by no means universally successful, and at the same time are under pressure because of their ever-increasing age. They are entitled to receive the most cost-effective treatments. We suggest that specialists in the field of reproductive medicine should be transparent about the receipt of financial benefits, including funding from industry, as it may be influencing both research outcomes and treatments that patients are offered. We also recommend that payments arising from industry-sponsored research should be centralized in institutional funds and not paid directly to researchers. And there should be transparency about the source and the purpose of the payment. Industry sponsorship of medical societies and their educational events should be kept to a minimum and declared quantitatively in societies' websites and scientific programme brochures. Industry sponsorship of scientific meetings should not include the right to host educational symposia or speakers within the programme. All speakers should declare their conflicts of interest (COIs) at their meetings. Guideline groups should require all members to declare their financial COIs before meeting and exclude or limit those members with COI. Governmental authorities should not allow continuing medical education credits to those educational events not complying with the above policies. The crucial role of medical journals as 'gatekeepers' for identifying 'science' must be reaffirmed.

Clinical trial registration in fertility trials - a case for improvement?

STUDY QUESTION: What is the prevalence and source of prospectively and retrospectively registered and unregistered trials in fertility treatments? SUMMARY ANSWER: Trial registration is low and does not appear to be changing over the 5 years studied. WHAT IS KNOWN ALREADY: Trial registration is associated with lower risk of bias than in unregistered trials. STUDY DESIGN, SIZE, DURATION: The Cochrane Gynaecology and Fertility Group's specialised register was searched on 5 November 2015 for randomised controlled trials (RCTs) published from January 2010 to December 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible trials included randomised women or men for fertility treatments, were published in full text, and written in English. Two reviewers independently assessed trial registration status for each trial, by searching the publication, trial registries, and by contacting the original authors. MAIN RESULTS AND ROLE OF CHANCE: Of 693 eligible RCTS, only 44% were registered trials. Of 309 registered trials, 21.7% were prospectively registered, 15.8% were registered within 6 months of first patient enrolment and 62.5% were retrospectively registered trials. Prospective trial registration by country varied from 0% to 100%. The highest frequency of prospective trial registration amongst the top 10 publishing countries was 31% in the Netherlands. LIMITATIONS, REASONS FOR CAUTION: Only English language trials were included in this review. WIDER IMPLICATIONS OF THE FINDINGS: Prospective trial registration is still low. Journals, funders and ethics committees could have a greater role to increase trial registration. STUDY FUNDING/COMPETING INTERESTS: University of Auckland. No competing interests.

Population trends and live birth rates associated with common ART treatment strategies.

STUDY QUESTION: Have ART live birth rates improved in Australia over the last 12 years? SUMMARY ANSWER: There were striking improvements in per-cycle live birth rates observed for frozen/thaw embryo transfers, blastocyst transfer and single embryo transfer (SET), while live birth rates following ICSI were lower than IVF for non-male factor infertility in most years. WHAT IS ALREADY KNOWN: ART and associated techniques have become the predominant treatment of infertility over the past 30 years in most developed countries. However, there are differences in ART laboratory and clinical practices, and success rates worldwide. Australia has one of the highest ART utilization rates and lowest multiple birth rates in the world, thus providing a unique setting to investigate the contribution of common ART strategies in an unrestricted population of patients to ART success rates. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study of 585 065 ART treatment cycles performed in Australia between 2002 and 2013 using the Australian and New Zealand Assisted Reproduction Database (ANZARD). PARTICIPANTS MATERIALS, SETTING, METHOD: An unrestricted population of all women who underwent autologous ART treatment between 2002 and 2013. Visual descriptive analysis was used to assess the trends in ART procedures by the calendar years. Adjusted odds ratios (aORs) of a live birth for four common ART techniques were calculated after controlling for important confounders including female age, infertility diagnosis, stage of the embryo (blastocyst versus cleavage stage), type of embryo (fresh versus thawed), fertilization method (IVF versus ICSI) and number of embryos transferred (SET versus multiple embryos). MAIN RESULTS AND THE ROLE OF CHANCE: The overall live birth rate per embryo transfer increased from 19.2% in 2002 to 23.3% in 2013 (21.9-24.3% for fresh embryo transfers and 14.6-23.3% for frozen/thaw embryo transfers). This occurred concurrently with an increase in SET from 29.7% to 78.9%, and an increase in the average age of women undergoing treatment from 35.0 to 35.9 years. Individuals who had a frozen/thaw embryo transfer cycle in 2002 had 43% (aOR: 0.57, 95% CI: 0.53-0.61) reduced odds of a live birth compared with a fresh embryo transfer cycle. This contrasted with 16% (aOR: 0.84, 95% CI: 0.80-0.98) reduced odds of a live birth from frozen/thaw embryo transfer cycles in 2013. In 2013, the odds of blastocyst transfer resulting in a live birth were more than twice as great as for cleavage stage transfer (aOR 2.01, 95% CI: 1.92-2.11). The adjusted odds of live birth per SET compared with multiple embryo transfer increased significantly over the last 12 years, from a 38% reduced odds of a live birth follow SET in 2002 (aOR: 062, 95% CI: 0.57-0.67) compared to an 8% reduced odds in 2013 (aOR: 0.92, 95% CI: 0.87-0.98). The aOR of a live birth using ICSI compared to IVF in non-male factor patients was lower in most years bringing into question its widespread use. LIMITATION, REASONS FOR CAUTION: This is a retrospective cohort analysis and cannot confirm causality. High-level evidence on the effectiveness of particular ART techniques, particularly ICSI and blastocyst culture, requires prospective randomized controlled trials or detailed statistical analysis using large-scale data that counts for fertilization failure, embryo loss, prognostic factors and cycle characteristics. WIDER IMPLICATION OF THE FINDINGS: The most striking improvements in ART success rates in Australia have been observed for frozen/thaw embryo transfers, blastocyst transfer and SET. Further studies of the role of ICSI in non-male factor infertility and blastocyst transfer success rates that take into account embryo loss are needed. STUDY FUNDING/COMPETING INTERESTS: No funding was received to undertake this study. The authors declare that they do not have competing interests with this study. TRIAL REGISTRATION NUMBER: NA.

Contributory factors and potentially avoidable neonatal encephalopathy associated with perinatal asphyxia.

BACKGROUND: The recently published monograph, Neonatal encephalopathy and neurologic outcome, from the American College of Obstetricians and Gynecologists calls for a root cause analysis to identify components of care that contributed to cases of neonatal encephalopathy to design better practices, surveillance mechanisms, and systems. All cases of infants born in New Zealand with moderate and severe neonatal encephalopathy were reported to the New Zealand Perinatal and Maternal Mortality Review Committee from 2010. A national clinical review of these individual cases has not previously been undertaken. OBJECTIVES: The objective of the study was to undertake a multidisciplinary structured review of all cases of neonatal encephalopathy that arose following the onset of labor in the absence of acute peripartum events in 2010-2011 to determine the frequency of contributory factors, the proportion of potentially avoidable morbidity and mortality and to identify themes for quality improvement. STUDY DESIGN: National identification of, and collection of clinical records on, cases of moderate or severe neonatal encephalopathy occurring after the onset of labor in the absence of an acute peripartum event, excluding those with normal gases and Apgar scores at 1 minute, among all cases of moderate and severe neonatal encephalopathy at term in New Zealand in 2010-2011 was undertaken. Cases were included if they had abnormal gases as defined by any of pH of ≤ 7.2, base excess of ≤ -10, or lactate of ≥ 6 or if there were no cord gases, an Apgar score at 1 minute of ≤ 7. A clinical case review was undertaken by a multidisciplinary team using a structured tool to record contributory factors (organization and/or management, personnel, and barriers to access and/or engagement with care), potentially avoidable morbidity and mortality and to identify themes to guide quality improvement. RESULTS: Eighty-three babies fulfilled the inclusion criteria for the review, 56 moderate (67%) and 27 severe (33%), 21 (25%) of whom were deceased prior to hospital discharge. Eighty-four percent of 64 babies with cord gas results had one of pH of ≤ 7.0, base excess of ≤ -12, or lactate of ≥ 6; and 42% (8 of 19) without cord gases had 5 minute Apgar scores < 5. Excluding 5 babies who died within a day of birth, all but 1 baby were admitted to a neonatal unit within 1 day of birth. Contributory factors were identified in 84% of 83 cases, most commonly personnel factors (76%). Fifty-five percent of cases with morbidity or mortality were considered to be potentially avoidable, and 52% of cases were considered potentially avoidable because of personnel factors. The most frequently identified theme related to the use and interpretation of cardiotocography in labor. CONCLUSION: A multidisciplinary case review of neonatal encephalopathy following apparently uncomplicated labor identified a high rate of potentially avoidable morbidity and mortality and issues amenable to quality improvement such as multidisciplinary training of staff in fetal surveillance in labor.

Obesity and endometrial hyperplasia and cancer in premenopausal women: A systematic review.

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.

Body mass index trumps age in decision for endometrial biopsy: cohort study of symptomatic premenopausal women.

BACKGROUND: Clinical guidelines recommend that women with abnormal uterine bleeding with risk factors have an endometrial biopsy to exclude hyperplasia or cancer. Given the majority of endometrial cancer occurs in postmenopausal women, it has not been widely recognized that obesity is a significant risk factor for endometrial hyperplasia and cancer in young, symptomatic, premenopausal women. OBJECTIVE: We sought to evaluate the effect of body mass index on risk of endometrial hyperplasia or cancer in premenopausal women with abnormal uterine bleeding. STUDY DESIGN: This was a retrospective cohort study in a single large urban secondary women's health service. Participants were 916 premenopausal women referred for abnormal uterine bleeding of any cause and had an endometrial biopsy from 2008 through 2014. The primary outcome was complex endometrial hyperplasia (with or without atypia) or endometrial cancer. RESULTS: Almost 5% of participants had complex endometrial hyperplasia or cancer. After adjusting for clinical and demographic factors, women with a measured body mass index ≥30 kg/m2 were 4 times more likely to develop complex hyperplasia or cancer (95% confidence interval, 1.36-11.74). Other risk factors were nulliparity (adjusted odds ratio, 3.08; 95% confidence interval, 1.43-6.64) and anemia (adjusted odds ratio, 2.23; 95% confidence interval, 1.14-4.35). Age, diabetes, and menstrual history were not significant. CONCLUSION: Obesity is an important risk factor for complex endometrial hyperplasia or cancer in premenopausal women with abnormal uterine bleeding who had an endometrial biopsy in a secondary gynecology service. As over half of women with the outcome in this study were age <45 years, deciding to biopsy primarily based on age, as currently recommended in national guidelines, potentially misses many cases or delays diagnosis. Body mass index should be the first stratification in the decision to perform endometrial biopsy and/or to refer secondary gynecology services.

Validation of local review for the identification of contributory factors and potentially avoidable perinatal deaths.

BACKGROUND: Reporting on perinatal mortality commenced 2006 in New Zealand through the Perinatal and Maternal Mortality Review Committee (PMMRC). Following review of international models, a process was developed for use in local review to identify contributory factors and potentially avoidable perinatal deaths. Local review of 720 perinatal deaths in 2009 found contributory factors in 24% of deaths and 14% to be potentially avoidable. AIMS: To validate the process of local review for identification of contributory factors and potentially avoidable perinatal deaths. MATERIAL AND METHODS: Records of 48 perinatal deaths were reviewed by an independent multidisciplinary panel using the same methodology as local review to determine agreement between local and independent review for identification of contributory factors and potentially avoidable perinatal death. RESULTS: Independent review found contributory factors in 54% of deaths compared to 40% by local review. Independent review identified eight deaths and local review identified one death with contributory factors not identified by the other review. Kappa statistic for agreement for identifying contributory factors was substantial [0.63 (0.42, 0.84)]. Independent review found 42% of deaths potentially avoidable compared to 23% by local review. Independent review identified 10 deaths and local review identified one death not identified by the other review. Kappa statistic for agreement for identifying potentially avoidable deaths was moderate [0.50 (0.26, 0.73)]. CONCLUSIONS: This study provides validation of local review for identification of contributory factors in perinatal death. The higher proportion of potentially avoidable perinatal deaths identified by independent review compared to local review requires further exploration.

An overview of treatments for endometriosis.

CLINICAL QUESTION: What treatments are associated with improved outcomes for women with endometriosis? BOTTOM LINE: The levonorgestrel-releasing intrauterine system (LNG-IUD), gonadotropin-releasing hormone analogues (GnRHa; nafarelin, leuprolide, buserelin, goserelin, triptorelin), laparoscopic ablation, and excision are associated with relief of pain due to endometriosis. Gonadotropin-releasing hormone analogues and laparoscopic ablation or excision are associated with increased clinical pregnancy rates in women with endometriosis. Gonadotropin-releasing hormone analogues, danazol, and depot progestagens are associated with a higher incidence of adverse events.

Improving the reporting of clinical trials of infertility treatments (IMPRINT): modifying the CONSORT statement†‡.

Clinical trials testing infertility treatments often do not report on the major outcomes of interest to patients and clinicians and the public (such as live birth) nor on the harms, including maternal risks during pregnancy and fetal anomalies. This is complicated by the multiple participants in infertility trials which may include a woman (mother), a man (father), and result in a third individual if successful, their offspring (child), who is also the desired outcome of treatment. The primary outcome of interest and many adverse events occur after cessation of infertility treatment and during pregnancy and the puerperium, which create a unique burden of follow-up for clinical trial investigators and participants. In 2013, because of the inconsistencies in trial reporting and the unique aspects of infertility trials not adequately addressed by existing Consolidated Standards of Reporting Trials (CONSORT) statements, we convened a consensus conference in Harbin, China, with the aim of planning modifications to the CONSORT checklist to improve the quality of reporting of clinical trials testing infertility treatment. The consensus group recommended that the preferred primary outcome of all infertility trials is live birth (defined as any delivery of a live infant ≥20 weeks gestations) or cumulative live birth, defined as the live birth per women over a defined time period (or number of treatment cycles). In addition, harms to all participants should be systematically collected and reported, including during the intervention, any resulting pregnancy, and during the neonatal period. Routine information should be collected and reported on both male and female participants in the trial. We propose to track the change in quality that these guidelines may produce in published trials testing infertility treatments. Our ultimate goal is to increase the transparency of benefits and risks of infertility treatments to provide better medical care to affected individuals and couples.