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.

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.

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.

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.

Efficacy and safety of a clinical protocol for expectant management of selected women diagnosed with a tubal ectopic pregnancy.

OBJECTIVE: To validate the efficacy and safety of our clinical protocol for expectant management of selected women diagnosed with tubal ectopic pregnancy. METHODS: This was a prospective observational study carried out in the early pregnancy unit of a London inner-city university teaching hospital from 1(st) January 2008 to 31(st) May 2011. All women presenting with suspected early pregnancy complications were assessed clinically and by transvaginal ultrasound. Those with a conclusive ultrasound diagnosis of tubal ectopic pregnancy were selected for either surgical or expectant management. Selection criteria for expectant management were clinical stability with no or minimal abdominal pain, no evidence of significant hemoperitoneum on ultrasound scan, ectopic pregnancy measuring < 30 mm in mean diameter with no evidence of embryonic cardiac activity, serum ß-human chorionic gonadotropin (ß-hCG) < 1500 IU/L and the woman's consent. All women selected for expectant management were followed up as outpatients until the ectopic pregnancy regressed spontaneously (resolution of clinical symptoms, serum ß-hCG < 20 IU/L/negative urine pregnancy test) or surgical intervention was required. We recorded the rate of interventions, complications and length of follow-up. RESULTS: During the study period 339/11 520 (2.9% (95% CI, 2.59-3.21%)) women were diagnosed with tubal ectopic pregnancy. Six women opted to participate in an ongoing randomized controlled trial and were excluded from further analysis. One hundred and sixty-five (49.5% (95% CI, 44.2-55.0%)) of the 333 remaining women met the criteria for expectant management; 146/333 (43.8% (95% CI, 38.5-49.1%)) of them opted for expectant management and 104/333 (31.2% (95% CI, 26.2-36.2%)) of all tubal ectopics resolved without requiring any intervention. All women with failed expectant management were treated by laparoscopic salpingectomy/salpingotomy and none of them required a blood transfusion. CONCLUSION: Our clinical protocol for expectant management of tubal ectopic pregnancies eliminates the need for medical or surgical treatment in more than a third of women diagnosed with tubal ectopic pregnancy with a minimum risk of adverse outcome.

How common is adenomyosis? A prospective study of prevalence using transvaginal ultrasound in a gynaecology clinic.

STUDY QUESTION: What is the prevalence of adenomyosis in a population of women attending a general gynaecological clinic? SUMMARY ANSWER: Adenomyosis was present in 206 of 985 [20.9%; 95% confidence interval (CI): 18.5-23.6%] women included in the study. WHAT IS KNOWN ALREADY: Previous studies of occurrence of adenomyosis have been limited to women who underwent hysterectomy, which is likely to overestimate its prevalence compared with the general population of women. There are no large prospective studies on the prevalence of adenomyosis, 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 985 consecutive 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 with the ultrasound scan to determine its prevalence and factors which may affect its occurrence. MAIN RESULTS AND THE ROLE OF CHANCE: Adenomyosis was present in 206/985 [20.9% (95% CI: 18.5-23.6%)] women included in the study. Multivariate analysis showed that the prevalence of adenomyosis was significantly associated with women's age, gravidity and pelvic endometriosis (P< 0.001). In women who subsequently underwent hysterectomy, there was a good level of agreement between the ultrasound and histological diagnosis of adenomyosis [κ = 0.62 (P = 0.001), 95% CI (0.324, 0.912)]. LIMITATIONS, REASONS FOR CAUTION: Our estimate of prevalence of adenomyosis is likely to be higher than in the general population as we studied symptomatic women attending a gynaecology clinic. WIDER IMPLICATIONS OF THE FINDINGS: Better estimates of the prevalence of adenomyosis can improve our understanding of the burden of the disease, help to identify women at high risk of developing the condition and facilitate the development of preventative strategies and effective treatment. STUDY FUNDING/COMPETING INTEREST(S): The authors have no competing interests to declare. The study was not supported by an external grant.

Inter- and intraobserver variability in three-dimensional ultrasound assessment of the endometrial-myometrial junction and factors affecting its visualization.

OBJECTIVE: To assess the inter- and intraobserver variability of three-dimensional (3D) ultrasound assessment of the endometrial-myometrial junction (EMJ), and to assess demographic and physiological factors that affect the quality of its imaging. METHODS: Women attending our gynecology clinic, who were deemed to have normal uteri on transvaginal ultrasound examination, were enrolled in this prospective study. They underwent 3D volume acquisition of the entire uterus in order to acquire a coronal view of the organ. Visualization of EMJs was classified as optimal, satisfactory or unsatisfactory. In order to assess the intra- and interobserver variabilities of the classification system, the volumes were classified by two independent observers on two separate occasions. The same classification system was then used to evaluate the EMJs of 101 women who were deemed to have normal uteri on transvaginal ultrasound examination. The results were correlated with age, parity, stage of cycle, menopausal status and endometrial thickness in order to assess whether any of these factors affect visualization of the EMJ. RESULTS: A total of 30 uterine volumes were examined in the first analysis. Both the inter- and intraobserver variability were good (kappa values of 0.77 and 0.83). Of the 101 EMJs assessed in the second analysis, 47 were classified as optimal, 42 as satisfactory and 12 as unsatisfactory. Endometrial thickness was positively associated with EMJ visualization and parity was negatively associated with EMJ visualization. CONCLUSIONS: Assessment of EMJ visualization has both good inter- and intraobserver variability in women with normal uteri. Parity and endometrial thickness have contrasting, statistically significant, effects on visualization of the EMJ.

Tumor dissemination after laparoscopic surgery for an unsuspected endometrial stromal tumor.

BACKGROUND: The use of laparoscopic surgery in gynecologic oncology might be complicated by unsuspected side-effects for the patient. Experimental data suggest that the risk of tumor dissemination in the non traumatized peritoneum may be higher after pneumoperitoneum than after laparotomy, and they also show the importance of the surgeon's experience and technique. CASES: We present two cases of uterine endometrial stromal tumors which were laparoscopically excised. In both cases, intraperitoneal tumor seedings were identified shortly after the initial operation. The first patient had a low-grade endometrial stromal sarcoma and succumbed from the disease two years after the initial operation, while the second patient who was diagnosed with endometrial stromal tumor remains disease free two years later. CONCLUSIONS: The laparoscopic excision of an endometrial stromal tumor might result in tumor dissemination into the abdominal cavity. A careful second-look examination of the abdomen or a radical surgical approach is proposed.

Preoperative assessment of submucous fibroids by three-dimensional saline contrast sonohysterography.

OBJECTIVE: Submucous fibroids are a common cause of menstrual disturbance that can be treated by hysteroscopic resection. Preoperative patient selection is critical for the success of surgery and it is usually based on hysteroscopic assessment of fibroid protrusion into the uterine cavity. Three-dimensional saline contrast sonohysterography (3D-SCSH) provides additional information about the size and location of submucous fibroids, but it has not yet been evaluated for its usefulness in preoperative assessment. The aim of this study was to examine the potential value of various demographic and ultrasound variables for the prediction of successful submucous fibroid resection. METHODS: This was a prospective study of symptomatic women diagnosed with submucous fibroids who underwent 3D-SCSH prior to hysteroscopic resection. The women's age and parity and fibroid position, diameter, protrusion ratio, size of the intramural component and distance from the internal cervical os were all recorded. The outcome measure was success of a single hysteroscopic resection in achieving a complete excision of the fibroid. Univariate analysis and multivariate logistic regression analysis using a training set and a testing set were performed to investigate the prediction of successful fibroid resection. RESULTS: A total of 61 women with 67 fibroids were included in the study. There was a statistically significant difference between women who had complete and those who had incomplete resection in the mean protrusion ratio (67.8 (SD 14.5)% vs. 47.0 (SD 17.8)%; P = 0.001), the median maximum fibroid diameter (24.0 (interquartile range (IQR), 19.0-30.5) mm vs. 45.0 (IQR, 28.8-51.3) mm; P = 0.001) and the median size of the intramural component of the fibroid (8.0 (IQR, 4.0-11.5) mm vs. 16.5 (IQR, 12.5-29.3) mm; P = 0.001). Stepwise multivariate logistic regression analysis retained size of intramural component (odds ratio (OR) 0.511), parity (OR 0.002) and fibroid diameter (OR 0.843) as significant independent predictors of a complete fibroid resection. The model had an area under the receiver-operating characteristics curve of 0.975 (SE 0.039) for the training set (n = 39) and 0.864 (SE 0.090) for the testing set (n = 28). CONCLUSION: Submucous fibroid protrusion ratio, fibroid diameter and size of the fibroid's intramural component are significantly associated with the likelihood of successful fibroid resection. A logistic regression model can calculate individual probability of complete resection and may improve preoperative counseling of patients.

Endometrial implantation factors in women with submucous uterine fibroids.

Uterine fibroids are benign tumours, which are associated with subfertility and early pregnancy loss. This study was carried out to examine the effect of submucous fibroids on concentrations of glycodelin, insulin-like growth factor binding protein-1 (IGFBP-1), interleukin-6 (IL-6), interleukin-10 (IL-10), tumour necrosis factor α (TNFα) and osteopontin in uterine flushings. Premenopausal women with a certain diagnosis of submucous fibroid confirmed on three-dimensional saline infusion sonohysterography were recruited into the study. The control group included women without ultrasonic evidence of any uterine or endometrial pathology. All women had uterine flushings performed 7days post LH surge. Enzyme linked immunoassays were performed to analyse glycodelin, IL-6, IL-10, TNFα and osteopontin, whilst immunoradiometric assay was used to analyse IGFBP-1. In 23 women with submucous fibroids, the concentrations of glycodelin and IL-10 in uterine flushings were significantly lower compared with 17 women in the control group (P=0.002; P=0.007, respectively). There were no significant differences between the two groups in concentrations of IGFBP-1, IL-6, TNFα and osteopontin. Women with submucous fibroids had significantly lower concentrations of glycodelin and IL-10 in mid-luteal phase uterine flushings. This finding may explain the association with submucous fibroids and adverse reproductive outcomes. Uterine fibroids are small growths from the muscle of the uterus (womb). Submucous fibroids protrude into the cavity of the womb. We do not know what causes fibroids to form and grow. In most women, fibroids cause no symptoms and they are sometimes detected on routine gynaecological examination. In some women, however, fibroids can cause heavier and longer menstrual periods. Another problem associated with fibroids is bleeding between periods. The effect of fibroids on fertility is not clear, but some doctors believe that they may also cause infertility and early miscarriage. This study tried to see whether presence of submucous fibroids has any effect on various substances produced by the lining of the womb to facilitate development of early pregnancy. Women with a confirmed diagnosis of submucous fibroids were asked to attend the clinic and have the uterine cavity flushed with a special solution 7days after ovulation. The fluid, which was taken back from the womb, was then analysed to measure the amounts of substances that favour pregnancy development. Women with a normal uterine cavity were also asked to have the uterine cavity flushed to act as a comparison. The study showed that the uterine cavities of women with submucous fibroids were producing decreasing amount of substances favourable to early pregnancy development. We speculate that this may explain why some women with submucous fibroids have difficulties falling pregnant. Our findings should be helpful to doctors advising women with submucous fibroids who wish to start a family.

Expectant management of ultrasonically diagnosed ovarian dermoid cysts: is it possible to predict outcome?

OBJECTIVE: The aim of this study was to assess the natural history of ultrasonically diagnosed ovarian dermoid cysts in a large group of women who were managed expectantly, and to assess the factors that were associated with failure of expectant management. METHODS: Our database was searched for dermoid cysts diagnosed on ultrasonography by a single expert operator between 2001 and 2007 in this retrospective study. In women who opted for expectant management, demographic data including age, gravidity and parity were recorded. Indications for scan, site of cysts, dimensions and the outcomes of expectant management were also recorded. RESULTS: Two hundred and eighty-nine women were diagnosed with a total of 323 dermoid cysts by a single expert ultrasound operator. 93/289 (32.2%; 95% CI, 26.8-37.6%) women with 105/323 (32.5%; 95% CI, 27.4-37.6%) ovarian dermoid cysts were managed expectantly for longer than 3 months. The mean age at diagnosis was 33.8 (range, 13-79) years and the median duration of follow up was 12.6 (interquartile range, 7.6-29.3) months. The mean growth rate of dermoid cysts during follow up was 1.67 mm/year. There were no demographic or morphological features that could be used to predict the growth rate of dermoid cysts. After a period of expectant management, 24/93 (25.8%; 95% CI, 16.9-34.7%) women had surgical intervention. The risk of surgical intervention was significantly increased in younger women, those of parity > or = 2 and in women with bilateral cysts or larger-diameter cysts, and reduced in women with a past history of ovarian cyst. CONCLUSIONS: The success rate of expectant management of dermoid cysts is high and this approach should be considered as a viable alternative to surgical management.

The natural history of fibroids.

OBJECTIVES: Fibroids are common, hormone-dependent, benign uterine tumors. They can cause significant morbidity and the symptoms depend largely on their size. The aim of this study was to describe the natural history of fibroids and identify factors that may influence their growth. METHODS: This was a retrospective longitudinal study of premenopausal women who were diagnosed with uterine fibroids on ultrasound examination. All women underwent at least two transvaginal ultrasound scans, which were all performed by a single operator. Fibroids were measured in three perpendicular planes and the mean diameter was calculated. The size and position of every individual fibroid was assessed and recorded on a computerized database. The volume of each fibroid was calculated using the formula for a sphere. RESULTS: A total of 122 women were included in the study. Their median age at the initial examination was 40 (range, 27-45) years. Seventy-two (59.0%) were nulliparous and 74 (60.7%) had multiple fibroids. The median interval between the initial and final examination was 21.5 (range, 8-90) months. The median fibroid volume increased by 35.2% per year. Small fibroids (< 20 mm mean diameter) grew significantly faster than larger fibroids (P = 0.007). The median increase in size was significantly higher in cases of intramural fibroids (53.2 (interquartile range (IQR), 11.2-217)%) than in subserous fibroids (25.1 (IQR, 1.1-87.1)%) and submucous fibroids (22.8 (IQR, - 11.7 to 48.3)%) (P = 0.012). Multivariate analysis retained only fibroid size at presentation as an independent predictor of fibroid growth. CONCLUSION: The growth of fibroids in premenopausal women is influenced by the tumor's size at presentation.

Use of serum progesterone measurements to reduce need for follow-up in women with pregnancies of unknown location.

OBJECTIVE: To assess the efficacy of a progesterone-based algorithm for the management of women with pregnancies of unknown location (PULs) and explore the feasibility of developing a single-visit strategy in those with a low risk of requiring medical intervention. METHODS: All clinically stable women in whom pregnancy could not be identified on ultrasound scan were managed by a pre-defined protocol based on measurement of serum progesterone and beta-human chorionic gonadotropin (beta-hCG). Intervention in the form of surgery or medical treatment with methotrexate was offered to all women with persistent or worsening symptoms and non-declining serum beta-hCG. Decision-tree analysis was used to develop a protocol for the management of women with resolving pregnancies who are at low risk of requiring medical intervention. RESULTS: 1110 women were included in the data analysis: normal intrauterine pregnancy was diagnosed in 248 (22.3%; 95% CI, 19.9-24.8) women. 761 (68.6%; 95% CI, 65.8-71.3) abnormal pregnancies resolved spontaneously on expectant management, while the remaining 101 (9.1%; 95% CI, 7.4-10.8) women with abnormal pregnancies required some form of medical intervention. Intervention rates in patients presenting with initial serum progesterone levels of