Ultrasound study of natural progression of ovarian endometriomas.

OBJECTIVES: The aim of this study was to determine the natural history of ovarian endometriomas in women who are managed expectantly. METHODS: This was a retrospective cohort study of 83 women with evidence of ovarian endometriomas, who were managed expectantly between April 2007 to May 2022. The study was conducted in the Department of Women's Health, University College London Hospitals and The Gynecology Ultrasound Centre, London, UK. We searched our ultrasound clinic databases to identify women aged 18 years or older with evidence of ovarian endometriomas that were managed expectantly for ≥ 6 months. All women attended for a minimum of two ultrasound scans by a single expert ultrasound operator. In addition to patient demographics, we recorded the number, mean diameter and location of each cyst. The cyst growth rate was expressed as annual change in the mean diameter. RESULTS: 1,922 women attended our gynecology clinic during the study period who were found to have evidence of moderate or severe endometriosis on pelvic ultrasound examination. A total of 83 women had evidence of ovarian endometriomas and were managed expectantly. The median age of women was 39 (range 26 - 51). Each woman had at least two ultrasound scans performed by a single expert operator at a minimum interval of ≥6 months. 50/83 (60%, 95% CI 49-71) women had single cysts and the remainder had multiple cysts. The median number of endometriomas per patient was 1 (range 1 - 5) and the median follow up time was 634 days (range 187 - 2984). 39/83 (47%, 95% CI 36 - 58) women experienced an overall reduction in size of cysts, in 18/83 (22%, 95% CI 13 - 32) the cysts increased in size and in 26/83 (31% 95% CI 22 - 42) women, no meaningful change was observed. The median change in mean diameter of cysts per woman during the study period was -2.7 mm (-57.7 - +39.3), with an annual growth rate of -1.7 mm/year/woman (-24.6 - +42.0). Overall, cysts were smaller at the follow up visit [median diameter 22.3mm (6.7 - 77) vs. 18.5mm (5 - 72) p = 0.009]. We did not identify any clinical characteristics that could reliably predict the chance of endometrioma progression. CONCLUSION: In the majority of women with ultrasound diagnosis of ovarian endometriomas, the cysts do not increase in size significantly over time and they could be managed expectantly. This evidence may help clinicians when counselling asymptomatic or minimally symptomatic women about the options to manage their ovarian endometriomas. This article is protected by copyright. All rights reserved.

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 were 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 judgement, 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. Geoffrey Adamson 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. Hans Evers reports being the Editor Emeritus of Human Reproduction. Andrew Horne 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. Louise Hull reports grants from Merck, grants from Myovant, grants from Bayer, outside the submitted work and ownership in Embrace Fertility, a private fertility company. Neil Johnson reports research sponsorship from Abb-Vie and Myovant Sciences and consultancy fees from Guerbet, Myovant Sciences, Roche Diagnostics, and Vifor Pharma. José Knijnenburg reports research sponsorship from Ferring and Theramex. Richard Legro reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. Ben Mol reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. Ernest Ng reports research sponsorship from Merck. Craig Niederberger 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. Jane Stewart 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. Annika Strandell reports consultancy fees from Guerbet. Jack Wilkinson reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. Andy Vail 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 HFEA for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. Lan Vuong 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: Not applicable.

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 (RCT) 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, Ferility 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. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility group. Hans Evers reports being the Editor Emeritus of Human Reproduction. José Knijnenburg reports research sponsorship from Ferring and Theramex. Richard Legro reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. Ben Mol reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. Craig Niederberger 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. Annika Strandell reports consultancy fees from Guerbet. Ernest Ng reports research sponsorship from Merck. Lan Vuong 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. Hans Evers reports being the Editor Emeritus of Human Reproduction. Richard Legro reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. Ben Mol reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. Craig Niederberger 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. Ernest Ng reports research sponsorship from Merck. Annika Strandell reports consultancy fees from Guerbet. Jack Wilkinson reports being a statistical editor for the Cochrane Gynaecology and Fertility group. Andy Vail 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 HFEA for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. Lan Vuong 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.

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.

Ovarian reserve as a predictor of cumulative live birth.

OBJECTIVES: Develop an up to date prediction model using recent cycle data and key pre-treatment predictor variables to estimate a couple's individualised probability of a cumulative live birth after one cycle of ovarian stimulation and transfer of all frozen embryos, before the first embryo transfer. STUDY DESIGN: This was a retrospective cohort study. To estimate the cumulative live birth rate we only included couples who had used all embryos from their initial stimulation or achieved a live birth. We constructed a logistic regression model using live birth as a dependent variable and age group, duration of infertility, primary vs. secondary infertility, insemination method, cause of infertility, Anti-Mullerian Hormone (AMH), Follicle Stimulating Hormone (FSH) and antral follicle count (AFC) as our independent variables and used a backward elimination method to create the best fitting regression models to predict the probability of a cumulative live birth (p < 0.05 for elimination). RESULTS: There were 516 complete cycles of ovarian stimulation resulting in 357 livebirths giving a cumulative livebirth rate of 69.2 % (95 % CI 66.0-74.0). Women with a live birth had significantly lower median age (34 years [IQR 31-37] vs. 36 years [IQR 33-39], p = 0.01) and FSH (6.7 iu/L [IQR 5.8-7.9] vs. 7.4 iu/L [IQR 6.2-8.6] and a significantly higher median AMH (22.1 pmol/L [IQR 12.1-30.9] vs. 10.5 pmol/L [IQR 7.3-20.7], p = 0.01) and AFC (18 [IQR 12-26] vs. 12 [IQR 9-19], p = 0.01). The backward conditional logistic regression model retained age category, FSH category and AMH category as significant independent predictors. The area under the curve for this model was 0.68 (95 % CI 0.63 - 0.73). CONCLUSION: Our prediction model estimates a couple's individualised probability of achieving a live birth after their first complete cycle of IVF using all known pre-treatment predictors. LIMITATIONS, REASONS FOR CAUTION: The study population were only those eligible for NHS funded IVF treatment which have strict ovarian reserve criteria. Exclusion of those with very low egg reserve is likely to influence the predictive capacity of out model. Furthermore, our model was developed using cycle data from one unit and thus its predictive capacity has not been assessed on an independent cohort of women. We therefore welcome external geographical validation of our model prior to its use in clinical practice.

Who is at risk of endometrial cavity breach at laparoscopic myomectomy?

BACKGROUND: Submucous and large intramural fibroids cause heavy menstrual bleeding and can negatively impact reproductive outcomes. Large submucous and non-cavity distorting fibroids need to be removed laparoscopically. One of the risks of a laparoscopic myomectomy is breaching the endometrial cavity and there have been suggestions that this increases the risk of intrauterine adhesions. The aim of this study was to examine the role of various demographic and pre-operative ultrasound variables at predicting the risk of endometrial cavity breach during laparoscopic myomectomy. METHODS: This was a retrospective study of women who underwent a laparoscopic myomectomy. Women who had more than one fibroid removed and women who did not have pre-operative ultrasound images available were excluded. The size of the fibroid, minimum distance from the endometrial cavity, surface area, intra-cavity surface area, protrusion ratio and extra-cavity size as well as the women's age, parity and pre-operative GnRH analogue use were recorded. The outcome measure was the breach of the endometrial cavity at myomectomy. Univariate analysis was performed to identify variables that are associated with a cavity breach. A logistic regression analysis was used to identify the most significant predictor of a breach. RESULTS: A total of 66 women were included in the study. From these, 10 women sustained a cavity breach. All pre-operative ultrasound variables, i.e. minimum distance of the fibroid from the cavity (p=0.001), protrusion ratio (p=0.001), total surface area (p=0.020), intra-cavity surface area (p=0.001), size (p=0.030) and extra-cavity size (p=0.001) were statistically different between the group that had a cavity breach and the group that did not. In a logistic regression model, protrusion ratio was selected as the best predictor of a breach (OR 1.22; 95% CI 1.10 - 1.37). All breaches occurred in women who were not given GnRH analogue. CONCLUSION: Identifying patients at increased risk of a cavity breach facilitates better individualized pre-operative counselling regarding the risk of a breach and the possibility of intrauterine adhesions. It will also trigger more intra-operative vigilance to minimize the risk of breaching the cavity and, subsequently, the risk of intrauterine adhesions if a breach does occur.

ESHRE/ESGE female genital tract anomalies classification system-the potential impact of discarding arcuate uterus on clinical practice.

STUDY QUESTION: What would be a potential impact of implementing the new ESHRE/European Society of Gynaecological Endoscopy (ESGE) female genital anomalies classification system on the management of women with previous diagnosis of arcuate uteri based on the modified American Society for Reproductive Medicine (ASRM) criteria? SUMMARY ANSWER: A significant number of women with previous diagnosis of arcuate uteri are reclassified as having partial septate uteri according to the new ESHRE/ESGE classification system which may increase the number of remedial surgical procedures. WHAT IS KNOWN ALREADY: The ESHRE/ESGE classification system has defined measurement techniques, reference points and specific cut-offs to facilitate the differentiation between normal and septate uteri. These criteria have been arbitrarily defined and they rely on the measurement of uterine wall thickness and depth of distortion of uterine fundus. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study. We searched our ultrasound clinic database from January 2011 to December 2014 to identify all women diagnosed with arcuate uterus on three-dimensional ultrasound according to the modified ASRM criteria. PARTICIPANTS/MATERIALS, SETTING, METHODS: For each woman, the ultrasound images were stored in our clinical database and they were re-examined according to ESHRE/ESGE specifications. The presence and location of all acquired uterine anomalies, such as fibroids or adenomyosis was noted. We applied the two diagnostic approaches as specified by the ESHRE/ESGE classification: the main option (MO) and the alternative option (AO). We used the Kappa statistic to quantify the agreement between the two approaches. We also compared the number of previous miscarriages in women with normal and partial septate uteri according to the ESHRE/ESGE classification. Non-parametric Mann-Whitney and Kruskal-Wallis tests were used for the analyses and receiver-operating characteristic curves were constructed to assess the predictive values of the calculated uterine distortion indices for the detection of women at risk of suffering multiple pregnancy losses. MAIN RESULTS AND THE ROLE OF CHANCE: We included 270 women diagnosed with arcuate uterus in the study. In all, 77 women (28.5%, 95% confidence interval (CI) 23.1-33.9) had evidence of fibroids or adenomyosis. These abnormalities precluded the application of either proposed ESHRE/ESGE techniques to assess uterine morphology in 25 women (9.3%, 95% CI 5.8-12.7). When using the MO, 138/237 (58.2%, 95% CI 51.9-64.3) women were diagnosed with partial septate uterus compared to 61/230 (26.5%, 95% CI 21.2-32.6) women when using the AO. In 222 women in whom we were able to apply both MO and AO, there was agreement in the diagnosis of septate uterus between the two techniques in 146/222 cases (65.8%, 95% CI 59.3-71.7; Kappa 0.42, 95%CI 0.35-0.5). There was no statistical difference in the proportion of women with history of previous multiple miscarriages between those diagnosed with normal or partial septate uteri using either MO (6.2%, 95% CI 2.9-12.9 vs. 9.5%, 95% CI 5.6-15.6; P = 0.47) or AO (7.2%, 95% CI 4.2-12.1 vs. 11.7%, 95% CI 5.8-22.2; P = 0.29). LIMITATIONS, REASONS FOR CAUTION: This study was retrospective in nature and the definition of arcuate uterus used in the study is not universally accepted. The reproductive history data were collected retrospectively and therefore may be prone to bias. WIDER IMPLICATIONS OF THE FINDINGS: There are methodological weaknesses in the new ESHRE/ESGE classification system which would need to be addressed in future revisions. There was no significant difference in the past reproductive outcomes between women diagnosed with normal and anomalous uteri and the clinicians should exercise caution when offering surgical correction to women diagnosed with partial septate uteri using the new ESHRE/ESGE classification. STUDY FUNDING/COMPETING INTEREST(S): No study funding was received and no competing interests are present. TRIAL REGISTRATION NUMBER: N/A.

Surgical treatment of Cesarean scar ectopic pregnancy: efficacy and safety of ultrasound-guided suction curettage.

OBJECTIVES: To assess the efficacy of ultrasound-guided suction curettage for management of pregnancies implanted into the lower uterine segment Cesarean section scar. METHODS: This was a retrospective study including women diagnosed with Cesarean section scar pregnancy at two large tertiary referral early pregnancy units between 1997 and 2014. Surgical evacuation was offered to selected women presenting in the first trimester ≤ 14 weeks' gestation. All procedures were performed transcervically under ultrasound guidance using suction curettage. A modified Shirodkar cervical suture was used in women who required additional measures to secure hemostasis. RESULTS: A total of 232 women with Cesarean section scar pregnancy were seen at the referral units; 191/232 (82.3%) women were treated surgically. The median intraoperative blood loss was 100 mL (range, 10-3000 mL); 9/191 (4.7% (95% CI, 1.7-7.7%)) women required blood transfusion and, in one (0.5% (95% CI, 0-1.5%)), life-saving hysterectomy had to be performed because of uncontrollable intraoperative bleeding. Of the women who attended for follow-up, 7/116 (6.0% (95% CI, 1.7-10.3%)) required a repeat surgical procedure because of retained products of conception. Multivariable analysis showed that the gestational sac diameter (odds ratio (OR), 1.10 (95% CI, 1.03-1.17)) and pregnancy vascularity on Doppler examination (OR, 3.41 (95% CI, 1.39-8.33)) were significant predictors of heavy intraoperative blood loss (> 1000 mL). CONCLUSIONS: Ultrasound-guided suction curettage is an effective method for the treatment of pregnancies implanted into a lower uterine segment Cesarean section scar and is associated with a low risk of blood transfusion and hysterectomy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Association between ultrasound features of adenomyosis and severity of menstrual pain.

OBJECTIVE: To investigate the association between the ultrasound features of adenomyosis and the severity of menstrual pain. METHODS: This was a prospective observational study set in the general gynecology clinic of a university teaching hospital between January 2009 and January 2010. A total of 718 consecutive premenopausal women aged between 17 and 55 years attended the clinic and underwent structured clinical and transvaginal ultrasound examinations in accordance with the study protocol. Morphological features of adenomyosis on ultrasound scan were recorded systematically. A quantitative assessment of menstrual pain was made by completion of a numerical rating scale (NRS). RESULTS: One hundred and fifty-seven (21.9% (95% CI, 18.8-24.9%)) women were diagnosed with adenomyosis on ultrasound. Multiple linear regression analysis showed that an ultrasound diagnosis of adenomyosis and ultrasound and laparoscopic diagnoses of endometriosis were significantly associated with menstrual pain when measured by an NRS. In addition, there was a statistically significant positive correlation between the severity of menstrual pain and the number of ultrasound features of adenomyosis seen. CONCLUSIONS: Women with ultrasound features of adenomyosis have more severe menstrual pain than do women without these features. The positive correlation between the number of ultrasound features of adenomyosis and the severity of menstrual pain could form the basis of a clinically relevant grading system for adenomyosis. A classification of severity of adenomyosis based on the number of ultrasound features present is a novel concept that should be evaluated prospectively in different populations. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

ß-hCG resolution times during expectant management of tubal ectopic pregnancies.

BACKGROUND: A subset of women with a tubal ectopic pregnancy can be safely managed expectantly. Expectant management involves a degree of disruption with hospital visits to determine serum ß-hCG (ß-human chorionic gonadotrophin) concentration until the pregnancy test becomes negative and expectant management is considered complete. The length of time required for the pregnancy test to become negative and the parameters that influence this interval have not been described. Information on the likely length of follow up would be useful for women considering expectant management of their tubal ectopic pregnancy. METHODS: This was a retrospective study at a tertiary referral center in an inner city London Hospital. We included women who were diagnosed with a tubal ectopic pregnancy by transvaginal ultrasound between March 2009 and March 2014. During the study period 474 women were diagnosed with a tubal ectopic pregnancy and 256 (54 %) of them fulfilled our management criteria for expectant management. A total of 158 (33 %) women had successful expectant management and in those cases we recorded the diameter of the ectopic pregnancy (mm), the maximum serum ß-hCG (IU/L) and levels during follow up until resolution as well as the interval to resolution (days). RESULTS: The median interval from maximum serum ß-hCG concentration to resolution was 18.0 days (IQR 11.0-28.0). The maximum serum ß-hCG concentration and the rate of decline of ß-hCG were independently associated with the length of follow up. Women's age and size of ectopic pregnancy did not have significant effects on the length of follow up. CONCLUSION: Women undergoing expectant management of ectopic pregnancy can be informed that the likely length of follow up is under 3 weeks and that it positively correlates with initial ß-hCG level at the time of diagnosis.

Treatment of endometriosis in women desiring fertility.

Endometriosis is a common condition affecting a significant proportion of women in their reproductive age. Apart from the impact of endometriosis on the quality of life of these patients, it also can have an impact on the potential of these women to have a family. The options for treating women with endometriosis desiring a family include surgery or assisted reproduction techniques. The choice of treatment will depend on the stage of disease and the characteristics of the couple seeking help. We review here the latest evidence on the management of endometriosis in women desiring fertility and describe our current practice.

Prevalence of pelvic adhesions on ultrasound examination in women with a history of Cesarean section.

OBJECTIVES: To investigate the prevalence and location of pelvic adhesions in women with a history of Cesarean section and to identify risk factors for their formation and symptoms associated with their presence. METHODS: This was a prospective observational study of women in whom one or more Cesarean sections had been performed > 12 months previously and who attended for a gynecological ultrasound examination. In all women, both transvaginal and transabdominal scans were performed in order to identify the presence of pelvic adhesions. Medical and surgical history was recorded and a structured questionnaire was used to enquire about any history of pelvic pain and urinary symptoms. RESULTS: A total of 308 women were recruited into the study. On ultrasound examination, 139 (45.1% (95% CI, 39.7-50.7%)) women showed evidence of adhesions within the pelvis. Adhesions in the vesicouterine pouch were the most common and were found in a total of 79 (25.6% (95% CI, 20.7-30.5%)) women. In women with a history of no surgery other than Cesarean section(s) (n = 220), an increasing number of Cesarean sections (odds ratio (OR) 3.4 (95% CI, 2.1-5.5)) and a postoperative wound infection (OR 11.7 (95% CI, 3.5-39.5)) increased the likelihood of adhesions developing in the anterior pelvic compartment. There was a significant association between the presence of anterior compartment adhesions and chronic pelvic pain. Multivariable logistic regression analysis identified anterior abdominal wall adhesions (OR 2.4 (95% CI, 1.0-5.9)) and any adhesions present on ultrasound scan (OR 2.6 (95% CI, 1.2-5.7)) as independent predictors of chronic pelvic pain. CONCLUSIONS: Pelvic adhesions are present in more than a third of women with a history of Cesarean section and they are associated with chronic pelvic pain.

Is adenomyosis associated with menorrhagia?

STUDY QUESTION: Is the presence of adenomyosis associated with menorrhagia? SUMMARY ANSWER: There was no significant association between adenomyosis and menorrhagia, but there was a significant positive correlation between the severity of adenomyosis on ultrasound and the amount of menstrual loss estimated using pictorial blood loss assessment charts. WHAT IS KNOWN ALREADY: There is no consensus in the literature with regards to the association between adenomyosis and menorrhagia. Previous studies have been limited to retrospective studies of highly selected populations which mainly included women who underwent hysterectomy. There are no large prospective studies evaluating the association between adenomyosis and menorrhagia, either in the general population of women or in a general gynaecology clinic setting. STUDY DESIGN, SIZE, DURATION: This was a prospective observational study set in the general gynaecology clinic of a university teaching hospital between January 2009 and January 2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: There were 714 consecutive premenopausal women who attended the clinic and underwent structured clinical and transvaginal ultrasound examination in accordance with the study protocol. Morphological features of adenomyosis were systematically recorded on ultrasound scan. Menorrhagia was determined subjectively by direct questioning and objectively by completion of pictorial blood loss analysis charts. MAIN RESULTS AND THE ROLE OF CHANCE: A diagnosis of adenomyosis was made in 157/714 women [22.0% (95% CI: 19.1-25.2%)]. Multivariable analysis showed significant associations between submucous fibroids [OR 5.60 (95% CI: 2.69-11.6)], any fibroids [OR 1.53 (95% CI: 0.91-2.58)] and endometrial polyps [OR 2.81 (95% CI: 1.15-11.7)] and menorrhagia. There were also significant associations between increasing gravidity and BMI and menorrhagia (P < 0.01). There was no significant association between adenomyosis and menorrhagia in the study population, when adenomyosis was assessed as a binary outcome. When severity of adenomyosis was assessed by counting the number of morphological features of adenomyosis in each woman, we found a significant 22% increase in menstrual loss for each additional feature of adenomyosis [OR 1.21 (95% CI: 1.04-1.40)]. LIMITATIONS, REASONS FOR CAUTION: A classification of severity of adenomyosis based on the number of ultrasound features present is a novel concept that should be prospectively evaluated in different populations. WIDER IMPLICATIONS OF THE FINDINGS: A better understanding of the relationship between adenomyosis and menorrhagia can help improve counselling of women regarding the significance of this common condition and facilitate future studies assessing the effectiveness of different conservative treatments protocols. STUDY FUNDING/COMPETING INTEREST(S): The authors have no competing interests. The study was not supported by an external grant.

Diagnosis of uterine vein thrombosis on transvaginal ultrasound.

Deep venous thrombosis (DVT) is a potentially serious medical disorder, which may result in pulmonary embolism and death. Compression ultrasound is the investigation modality of choice for the diagnosis of DVT of the lower limb. Diagnosis of proximal thrombosis involving the pelvic veins is difficult and is usually made only after the thrombus extends into the veins of the lower limb. We present six cases of incidental uterine vein thrombosis diagnosed by transvaginal ultrasound. Our aim is to describe the technique of the examination of pelvic veins and criteria that could be used to diagnose uterine vein thrombosis. We also highlight difficulties in the management of women diagnosed with asymptomatic uterine vein thrombi as there is little evidence to guide clinicians in choosing between different treatment options.

Visualization of ureters on standard gynecological transvaginal scan: a feasibility study.

OBJECTIVE: To investigate the feasibility of identifying pelvic segments of normal ureters and measuring their size on standard transvaginal ultrasound examination. METHODS: This was a prospective observational study from June to July 2012. All women in the study underwent a transvaginal ultrasound examination performed for various indications either by an expert or by an intermediate-level operator. A standardized assessment of the pelvic organs was performed, recording any congenital or acquired uterine pathology and ovarian abnormalities. Visualization of pelvic segments of both ureters was attempted in all cases. The success in finding the ureters, the time required to identify them and their dimensions at rest and while exhibiting peristalsis were all recorded. RESULTS: A total of 245 consecutive women were included in the study. In all women at least one ureter was successfully identified. Both ureters were seen in 227 women (92.7% (95% CI, 89.4-96.0%)). In 17 (6.9% (95% CI, 3.7-10.1%)) the left ureter was not seen and in one woman (0.4% (95% CI, 0.0-1.2%)) the right ureter could not be visualized (P < 0.001). There were no significant differences in the median time required to visualize the right and left ureters (9.0 (interquartile range (IQR), 6.0-14.0) s vs 8.0 (IQR, 6.0 -14.0) s, respectively; P = 0.9). The median diameter of the right ureter was 1.7 (IQR, 1.4-2.2) mm at rest and 2.9 (IQR, 2.4-3.6) mm during peristalsis. The median diameter of the left ureter was 1.9 (IQR, 1.6-2.3) mm at rest and 2.9 (IQR, 2.4-3.6) mm during peristalsis. CONCLUSION: Pelvic segments of normal ureters can be identified in most women on transvaginal ultrasound examination. Visualization of the ureters could be integrated into the routine pelvic ultrasound examination, particularly in women presenting with pelvic pain or in those with suspected pelvic endometriosis.