Diagnosis of superficial endometriosis on transvaginal ultrasound by visualization of peritoneum of pouch of Douglas.

OBJECTIVE: Around 80% of women with endometriosis have superficial endometriosis (SE) rather than ovarian or deep endometriosis (DE). However, to date, advances in non-invasive, imaging-based diagnosis have been limited to DE or ovarian disease. The objective of this study was to determine whether we can detect SE on transvaginal ultrasound scan (TVS) by assessing the peritoneum of the pouch of Douglas (POD). METHODS: This was a retrospective diagnostic test study following a change in practice to include POD peritoneum assessment for SE during TVS at a tertiary London hospital. Eligible patients underwent TVS by a single clinician trained in endometriosis scanning and a subsequent surgical procedure (laparoscopy) between April 2018 and September 2021. Participants formed a consecutive series. The TVS findings were compared with those of laparoscopy as the gold standard. Comparison of TVS findings with intraoperative findings was performed by calculating the diagnostic test performance measures (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and positive and negative likelihood ratios). RESULTS: The study included a total of 100 patients. We found that 43/100 (43.0%) patients had no endometriosis, 33/100 (33.0%) had SE and 24/100 (24.0%) had DE on laparoscopy. SE was correctly detected on TVS in 17/33 patients, with a sensitivity of 51.5% (95% CI, 33.5-69.2%), specificity of 94.0% (95% CI, 85.4-98.4%), PPV of 81.0% (95% CI, 60.8-92.1%) and NPV of 79.7% (95% CI, 73.4-84.9%). DE was correctly diagnosed in 20/24 cases, including all ovarian cases, with a sensitivity of 83.3% (95% CI, 62.3-95.3%), specificity of 97.4% (95% CI, 90.8-99.7%), PPV of 90.9% (95% CI, 71.6-97.5%) and NPV of 94.9% (95% CI, 88.3-97.8%). The detection of SE on TVS was most accurate in the POD (sensitivity, 50.0%; specificity, 96.4%; PPV, 76.9%; NPV, 88.9%). CONCLUSIONS: This study shows that the detection of SE in the POD is possible using routine TVS. While negative TVS does not reliably confirm the absence of disease or replace diagnostic laparoscopy, positive TVS facilitates non-invasive diagnosis for a much larger group of women than was previously possible. This should help to reduce the time from the onset of symptoms to diagnosis and enable initiation of medical treatment without the risk, cost and delay associated with a surgical diagnosis. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The cost-effectiveness of progesterone in preventing miscarriages in women with early pregnancy bleeding: an economic evaluation based on the PRISM trial.

OBJECTIVES: To assess the cost-effectiveness of progesterone compared with placebo in preventing pregnancy loss in women with early pregnancy vaginal bleeding. DESIGN: Economic evaluation alongside a large multi-centre randomised placebo-controlled trial. SETTING: Forty-eight UK NHS early pregnancy units. POPULATION: Four thousand one hundred and fifty-three women aged 16-39 years with bleeding in early pregnancy and ultrasound evidence of an intrauterine sac. METHODS: An incremental cost-effectiveness analysis was performed from National Health Service (NHS) and NHS and Personal Social Services perspectives. Subgroup analyses were carried out on women with one or more and three or more previous miscarriages. MAIN OUTCOME MEASURES: Cost per additional live birth at ≥34 weeks of gestation. RESULTS: Progesterone intervention led to an effect difference of 0.022 (95% CI -0.004 to 0.050) in the trial. The mean cost per woman in the progesterone group was £76 (95% CI -£559 to £711) more than the mean cost in the placebo group. The incremental cost-effectiveness ratio for progesterone compared with placebo was £3305 per additional live birth. For women with at least one previous miscarriage, progesterone was more effective than placebo with an effect difference of 0.055 (95% CI 0.014-0.096) and this was associated with a cost saving of £322 (95% CI -£1318 to £673). CONCLUSIONS: The results suggest that progesterone is associated with a small positive impact and a small additional cost. Both subgroup analyses were more favourable, especially for women who had one or more previous miscarriages. Given available evidence, progesterone is likely to be a cost-effective intervention, particularly for women with previous miscarriage(s). TWEETABLE ABSTRACT: Progesterone treatment is likely to be cost-effective in women with early pregnancy bleeding and a history of miscarriage.

Embracing diverse worldviews to share planet Earth.

Leading societies toward a more sustainable, equitably shared, and environmentally just future requires elevating and strengthening conversations on the nonmaterial and perhaps unquantifiable values of nonhuman nature to humanity. Debates among conservationists relating to the appropriateness of valuing ecosystems in terms of their human utility have eclipsed the more important and impactful task of expressing conservation concerns in terms that are meaningful to diverse stakeholders. We considered the wide global diversity of perspectives on the biosocial complex-the relationships and interactions between all living species on Earth-and argue that humanity's best chance for effective conservation is to take a pluralistic approach that engages seriously with the worldviews of all stakeholders. Many worldviews-particularly those in indigenous cultures-place a higher value on the spiritual and nonmaterial aspects than what is often represented by the discourse surrounding Western conservation policy. Alternative framings of the biosocial complex that recognize nature's intrinsic value can be powerful motivators for social change and for local-scale conservation efforts. At a national and international level, changing ethical framings of human relationships with nature have started influencing conceptions of human rights relating to the environment and of the rights of nature itself. This change has led to an increased role of the judiciary in promoting environmental sustainability and promoting justice for groups who are most often affected by environmental harms. We hope our essay will motivate the scientific community to change its own perception of what a sound and sustainable relationship between humanity and other species should be and will help citizens become active environmental subjects, connected to the ecosystems around them.

Adopción de Diferentes Cosmovisiones para Compartir el Planeta Tierra Resumen Para poder llevar a las sociedades hacia un futuro sustentable, compartido equitativa y ambientalmente justo se requiere elevar y fortalecer las conversaciones sobre los valores no materiales y probablemente imposibles de cuantificar que la naturaleza no humana tiene para la humanidad. Los debates entre los conservacionistas en relación con lo apropiado que es valorar los ecosistemas en términos de utilidad para los humanos han eclipsado la labor más importante e impactante de expresar los asuntos de conservación en términos que son significativos para diferentes accionistas. Consideramos la amplia diversidad mundial de perspectivas que existen sobre el complejo biosocial - las relaciones e interacciones entre todas las especies vivientes en la Tierra - y argumentamos que la mejor oportunidad que tiene la humanidad para lograr una conservación efectiva es realizar una estrategia pluralística que se comprometa seriamente con las cosmovisiones de todos los accionistas. Muchas cosmovisiones - particularmente aquellas de las culturas indígenas - les otorgan un valor más alto a los aspectos espirituales y no materiales que lo que se suele representar en el discurso que rodea la política de conservación occidental. Los marcos alternativos del complejo biosocial que reconocen el valor intrínseco de la naturaleza pueden ser motivadores poderosos para el cambio social y para los esfuerzos de conservación a escala local. A nivel nacional e internacional, el cambio de los marcos éticos de las relaciones humanas con la naturaleza ha comenzado a influenciar las concepciones de los derechos humanos en relación con el ambiente y los derechos de la naturaleza misma. Este cambio ha resultado en un papel mucho mayor del poder judicial en la promoción de la sustentabilidad ambiental y de la justicia para grupos a los que con frecuencia les afectan los daños ambientales. Esperamos que nuestro ensayo motive a la comunidad científica a cambiar su propia percepción de lo que debe ser una relación sana y sustentable entre la humanidad y otras especies y que ayude a los ciudadanos a volverse sujetos ambientales más activos y conectados con el ecosistema.

Risk of severe ovarian hyperstimulation syndrome in GnRH antagonist versus GnRH agonist protocol: RCT including 1050 first IVF/ICSI cycles.

STUDY QUESTION: Is the risk of severe ovarian hyperstimulation syndrome (OHSS) similar in a short GnRH antagonist and long GnRH agonist protocol in first cycle IVF/ICSI patients less than 40 years of age?. SUMMARY ANSWER: There is an increased risk of severe OHSS in the long GnRH agonist group compared with the short GnRH antagonist protocol. WHAT IS KNOWN ALREADY?: In the most recent Cochrane review, the GnRH antagonist protocol was associated with a similar live birth rate (LBR), a similar on-going pregnancy rate (OPR), and a lower incidence of OHSS (odds ratio (OR) = 0.43 95% confidence interval (CI): 0.33-0.57) compared with the traditional GnRH agonist protocol. Previous trials comparing the two protocols mainly included selected patient populations, a limited number of patients and the applied OHSS criteria differed, making direct comparisons difficult. In two recent large meta-analyses, no significant differences in LBR (OR = 0.86; 95% CI: 0.72-1.02) or in the incidence of severe OHSS were reported, while others found a lower LBR (OR = 0.82; 95% CI: 0.68-0.97) and a reduced risk of severe OHSS using the GnRH antagonist protocol (OR = 0.60; 95% CI: 0.40-0.88). STUDY DESIGN, SIZE, DURATION: Phase IV, dual-centre, open-label, RCT including 1050 women allocated to either short GnRH antagonist or long GnRH agonist protocol in a 1:1 ratio and enrolled over a 5-year period using a web-based concealed randomization code. This is a superiority study designed to detect a difference in severe OHSS, the primary outcome, between the two groups with a power of 80% and stratified for age, assisted reproductive technology (ART) clinic and planned fertilization procedure (IVF/ICSI). The secondary aims were to compare rates of mild and moderate OHSS, positive plasma (p)-hCG, on-going pregnancy and live birth between the two arms. None of the women had undergone previous ART treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS: All infertile women referred for their first IVF/ICSI at two public fertility clinics, less than 40 years of age and with no uterine malformations were asked to participate. A total of 1099 subjects were randomized, including women with poor ovarian reserve, polycystic ovary syndrome and irregular cycles. A total of 49 women withdrew their consent, thus 1050 subjects were allocated to the GnRH antagonist (n = 534) and agonist protocol (n = 516), respectively. In total 1023 women started recombinant human follitropin-ß (rFSH) stimulation, 528 in the GnRH antagonist group and 495 in the GnRH agonist group. All subjects were given a fixed rFSH dose of 150 IU or 225 IU according to age ≤36 years or >36 years, with the option to adjust dose at stimulation day 6. Clinical OHSS parameters were collected at oocyte retrieval, and Days 3 and 14 post-transfer. On-going pregnancy was determined by transvaginal ultrasonography at gestational weeks 7-9. In the intention-to-treat (ITT) analysis for reproductive outcomes, 1050 subjects were included. For the ITT analyses on OHSS 1023 subjects who started gonadotrophin stimulation were included. MAIN RESULTS AND THE ROLE OF CHANCE: The incidence of severe OHSS [5.1% (27/528) versus 8.9% (44/495) (difference in proportion percentage point (Δpp) = -3.8pp; 95% CI: -7.1 to -0.4; P = 0.02)] and moderate OHSS [10.2% (54/528) versus 15.6% (77/495) (Δpp = -5.3pp; 95% CI: -9.6 to -1.0; P = 0.01) ] was significantly lower in the GnRH antagonist group compared with the agonist group, respectively. In the GnRH antagonist and agonist group, respectively, 4.7% (25/528) versus 8.5% (42/495) women were seen by a physician due to OHSS (P = 0.01), and 1.7% (9/528) versus 3.6% (18/495) were admitted to hospital due to OHSS (P = 0.06). No women had ascites-puncture in the GnRH antagonist group versus 2.0% (10/495) in the GnRH agonist group (P < 0.01). LBRs were 22.8% (122/534) versus 23.8% (123/516) (Δpp = -1.0pp; 95% CI: -6.3 to 4.3; P = 0.70) and OPRs were 24.9% (133/528) versus 26.2% (135/516) (Δpp = -1.3pp; 95% CI: -6.7 to 4.2; P = 0.64) per randomized subject in the GnRH antagonist versus agonist group, with a mean number of 1.1 versus 1.2 embryos transferred in the two groups. Pregnancy rates (PR) per randomized subject, per started gonadotrophin stimulation and per embryo transfer were all similar in the two groups. LIMITATIONS, REASONS FOR CAUTION: A possible limitation is the duration of the trial, with new methods, such as 'freeze all' and 'GnRH agonist triggering', being developed during the trial, the new methods were sought avoided, however a total number of 32 women had 'freeze all' and 'GnRH agonist triggering' was performed in three cases. Ultrasonic measurements were performed by different physicians and inter-observer bias may be present. Measures of anti-Mullerian hormone and antral follicle count, to estimate ovarian reserve and thus predict risk of OHSS, were not performed. Finally, the physicians were not blinded to GnRH treatment group after randomization. WIDER IMPLICATIONS OF THE FINDINGS: The short GnRH antagonist protocol should be the protocol of choice for patients undergoing their first ART cycle in females <40 years of age including both low and high responders when an age-dependent initially fixed gonadotrophin dose is used, as an increased risk of severe OHSS and the associated complications is seen in the long GnRH agonist group and as PRs and LBRs are similar in the two groups. Patients at risk of OHSS particularly benefit from the short GnRH antagonist treatment as GnRH agonist triggering can be used. STUDY FUNDING/COMPETING INTERESTS: An unrestricted research grant is funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD). The funders had no influence on the data collection, analyses or conclusions of the study. No conflict of interests to declare. TRIAL REGISTRATION NUMBER: EudraCT #: 2008-005452-24. ClinicalTrial.gov: NCT00756028. Trial registration date: 18 September 2008. Date of first patient's enrolment: 14 January 2009.

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.

Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the International Deep Endometriosis Analysis (IDEA) group.

The IDEA (International Deep Endometriosis Analysis group) statement is a consensus opinion on terms, definitions and measurements that may be used to describe the sonographic features of the different phenotypes of endometriosis. Currently, it is difficult to compare results between published studies because authors use different terms when describing the same structures and anatomical locations. We hope that the terms and definitions suggested herein will be adopted in centers around the world. This would result in consistent use of nomenclature when describing the ultrasound location and extent of endometriosis. We believe that the standardization of terminology will allow meaningful comparisons between future studies in women with an ultrasound diagnosis of endometriosis and should facilitate multicenter research. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Should a detailed ultrasound examination of the complete urinary tract be routinely performed in women with suspected pelvic endometriosis?

STUDY QUESTION: Is there any benefit to including the routine examination by ultrasound of the bladder, ureters and kidneys of women with endometriosis? SUMMARY ANSWER: The benefit of examination of the complete urinary tract of women with suspected endometriosis is that ureteric endometriosis, with or without hydronephrosis, can be detected which facilitates early intervention to prevent nephropathy. WHAT IS ALREADY KNOWN: Women with endometriosis can get ureteric obstruction but there is no clear consensus on the correct diagnostic technique. Ultrasound is accurate at detecting women with bladder endometriosis but ureteric involvement has not been assessed previously. STUDY DESIGN, SIZE, DURATION: This was a prospective observational study, conducted at a teaching hospital over a period of 14 months. A total of 848 women presenting with chronic pelvic pain were included into the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women with chronic pelvic pain underwent a detailed transvaginal and transabdominal pelvic ultrasound examination to investigate possible causes of their symptoms. This included a systematic assessment of the urinary bladder, pelvic sections of the ureters and kidneys. The ultrasound findings were compared with findings at surgery and the results of targeted urological imaging and interventions. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 848 women presenting with chronic pelvic pain were included into the study. 28/848 women (3.3% 95% CI 2.1-4.5) had evidence of urinary tract abnormalities on initial ultrasound scan. Among these 17/848 (2.0% 95% CI 1.06-2.94) had evidence of urinary tract endometriosis, whilst 11/848 (1.3% 95% CI 0.54-2.06) women had other urinary tract abnormalities. Among women with urinary tract endometriosis 11/17 (65%) had evidence of ureteric involvement, 3/17 (18%) had both ureteric and bladder disease and 3/17 (18%) had bladder disease only. 12/17 (59%) women with urinary tract endometriosis also had evidence of hydronephrosis. The diagnosis of ureteral endometriosis had a sensitivity of 12/13 (92%) (95% CI 63.9-99.8), specificity 151/151 100% (95% CI 97.6-100), PPV 100% (95% CI 73.5-100), NPV 99.3% (95% CI 96.3-99.9%) LR- 0.08 (95% CI 0.01-0.39). LIMITATIONS, REASONS FOR CAUTION: The routine examination of the complete urinary tract including the distal ureters is a novel technique that should be evaluated in different populations. WIDER IMPLICATIONS OF THE FINDINGS: Ultrasound is an accurate test to diagnose urinary tract involvement in women with suspected pelvic endometriosis and examination of the complete urinary tract should become an integral part of ultrasound assessment of women with suspected endometriosis.

Mental distress and personality in women undergoing GnRH agonist versus GnRH antagonist protocols for assisted reproductive technology.

STUDY QUESTION: Do mental distress and mood fluctuations in women undergoing GnRH agonist and GnRH antagonist protocols for assisted reproductive technology (ART) differ depending on protocol and the personality trait, neuroticism? SUMMARY ANSWER: ART treatment did not induce elevated levels of mental distress in either GnRH antagonist or agonist protocols but neuroticism was positively associated with increased mental distress, independent of protocols. WHAT IS KNOWN ALREADY: ART treatment may increase mental distress by mechanisms linked to sex hormone fluctuations. General psychological characteristics, such as personality traits indexing negative emotionality, e.g. neuroticism, are likely to affect mental distress during ART treatment. STUDY DESIGN, SIZE, DURATION: A total of 83 women undergoing their first ART cycle were consecutively randomized 1:1 to GnRH antagonist (n = 42) or GnRH agonist (n = 41) protocol. The study population was a subgroup of a larger ongoing Danish clinical randomized trial and was established as an add-on in the period 2010-2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women in the GnRH antagonist protocol received daily injections with recombinant follicle-stimulating hormone, Puregon(®) and subcutaneous injections with GnRH antagonist, Orgalutran(®). Women in the GnRH agonist protocol received nasal administration of the GnRH agonist, Synarela(®) and subcutaneous injections with FSH, Puregon(®). The study design did not allow for a blinding procedure. All women self-reported the Profile of Mood States, the Perceived Stress Scale, the Symptom Checklist-92-Revised, and the Major Depression Inventory questionnaires, at baseline, at ART cycle day 35, on the day of oocyte pick-up, and on the day of hCG testing. Also, a series of Profile of Mood States were reported daily during pharmacological treatment to monitor mood fluctuations. The personality trait Neuroticism was assessed at baseline by the self-reported NEO-PI-R questionnaire. MAIN RESULTS AND THE ROLE OF CHANCE: ART did not induce within- or between-protocol changes in any of the applied measures of mental distress. However, the GnRH antagonist protocol was associated with more pronounced median mood fluctuations during the stimulation phase (antagonist, 11.0 SD, [IQR = 21.1-6.1]; agonist, 8.9 SD, [IQR = 11.3-5.7], P = 0.025). This association became non-significant after applying a Bonferroni-Holm correction. Neuroticism was highly positively associated with increased levels of mental distress throughout treatment independent of protocols (all P-values <0.006), and cross-sectional analysis revealed that women with high or low Neuroticism scores at baseline showed a significant trend towards lower chances of a positive pregnancy test (P-value =0.028). LIMITATIONS, REASONS FOR CAUTION: Information on prognostic factors such as preceding length of infertility, number of retrieved oocytes and number of prior insemination treatments was not accounted for in the analyses. The stratification of protocols by age in the subgroups of women included in this study was suboptimal. Women with prior or current use of antidepressant medication were excluded from our study. WIDER IMPLICATIONS: Our results imply that mental distress emerging during ART treatment is not causally linked to hypogonadism per se or to the choice of protocol. Rather, our data highlight the potential importance of (i) rapid increases in ovarian steroids and (ii) addressing personality traits indexing negative emotionality, i.e. Neuroticism, in women undergoing ART treatment, to optimize both emotional adjustment and, possibly, the chances of obtaining pregnancy. STUDY FUNDING/COMPETING INTERESTS: The Danish Research Council for Independent Research and MSD, Denmark kindly supported the study. The authors declare no competing financial interests. TRIAL REGISTRATION NUMBER: EudraCT - 2008-005452-24.

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.

Kinetic studies of the epimerization of diastereomeric pyrylium salts.

Chiral pyrylium salts are almost unknown in the literature, and none that are epimerizable have been reported prior to our work. Herein, we report two new epimerizable pyryliums and the kinetics of the diastereomeric equilibration of these and one other example. All of these required a careful analysis of the (1)H NMR spectrum to identify the stereoisomers, particularly for one of them. The temporal evolution of the relative isomeric concentrations was determined through acquisition of progressive NMR spectra. The base-catalyzed isomerization kinetics were successfully modeled as sequential, pseudo-first-order reactions that transition through a long-lived intermediate. These results suggest that the pseudobase intermediate is the operative catalyst when epimerizations are initiated with amines with pK(a) 7.4 or greater. Given the bulky nature of the operative acid (pyrylium) and base (pseudobase), the rate of these epimerizations is sensitive to steric bulk in the pyrylium. Thus, the reaction kinetics slow by a factor of 25 when substituents are placed at the ortho versus para position on the pyrylium cyclohexane ring. This is likely due to the difficulty of pseudobase attack at the sterically crowded pyrylium acidic hydrogen position.

Reproducibility of assessment of severity of pelvic endometriosis using transvaginal ultrasound.

OBJECTIVE: To examine the reproducibility of assessment of severity of pelvic endometriosis by transvaginal sonography (TVS). METHODS: This was a prospective observational study conducted from August 2006 to July 2009 in two academic departments of obstetrics and gynecology. Women with clinically suspected or proven pelvic endometriosis were invited to join the study. All patients included underwent TVS performed by two observers and a laparoscopic assessment of pelvic endometriosis. The ultrasound observers were blinded to each other's results. The reproducibility of TVS was examined by evaluation of interobserver agreement for the American Society of Reproductive Medicine (ASRM) score by Bland-Altman analysis and the stage and the diagnosis of deeply infiltrating endometriosis (DIE) by calculation of kappa coefficients. Agreement between the findings on TVS for each observer and those on laparoscopy was also evaluated. RESULTS: Thirty-four patients were recruited to the study, and TVS was performed by two ultrasound observers. Of these patients, one did not undergo laparoscopy and was therefore excluded from the final analysis. No endometriosis was found in 12 (36.4%) patients. One patient (3%) had minimal disease, one (3%) had mild disease, five (15.2%) had moderate disease and 14 (42.4%) had severe disease. Interobserver agreement was very good for disease classification on TVS (Cohen's kappa, 0.931). Agreement between TVS and laparoscopy findings was also very good (Cohen's kappa, 0.955 and 0.966 for the two examiners). For ASRM score on TVS, the interobserver 95% limits of agreement were -16.6 to 12.7, with a mean difference of -1.9 (95% CI, -4.35 to 0.71). CONCLUSION: TVS is a reproducible method for assessment of the severity of pelvic endometriosis and shows good agreement with findings on laparoscopy.

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.

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.

The risk of miscarriage following surgical treatment of heterotopic extrauterine pregnancies.

STUDY QUESTION: What is the risk of loss of a live normally sited (eutopic) pregnancy following surgical treatment of the concomitant extrauterine ectopic pregnancy? SUMMARY ANSWER: In women diagnosed with heterotopic pregnancies, minimally invasive surgery to treat the extrauterine ectopic pregnancy does not increase the risk of miscarriage of the concomitant live eutopic pregnancy. WHAT IS KNOWN ALREADY: Previous studies have indicated that surgical treatment of the concomitant ectopic pregnancy in women with live eutopic pregnancies could be associated with an increased risk of miscarriage. The findings of our study did not confirm that. STUDY DESIGN SIZE DURATION: A retrospective observational case-control study of 52 women diagnosed with live eutopic and concomitant extrauterine pregnancies matched to 156 women with live normally sited singleton pregnancies. The study was carried out in three London early pregnancy units (EPUs) covering a 20-year period between April 2000 and November 2019. PARTICIPANTS/MATERIALS SETTING METHODS: All women attended EPUs because of suspected early pregnancy complications. The diagnosis of heterotopic pregnancy was made on ultrasound scan and women were subsequently offered surgical or expectant management.There were three controls per each case who were randomly selected from our clinical database and were matched for maternal age, mode of conception and gestational age at presentation. MAIN RESULTS AND THE ROLE OF CHANCE: In the study group 49/52 (94%) women had surgery and 3/52 (6%) were managed expectantly. There were 9/52 (17%, 95% CI 8.2-30.3) miscarriages <12 weeks' gestation and 9/49 (18%, 95% CI 8.7-32) miscarriages in those treated surgically. In the control group, there were 28/156 (18%, 95% CI 12.2-24.8) miscarriages <12 weeks' gestation, which was not significantly different from heterotopic pregnancies who were treated surgically [odds ratio (OR) 1.03 95% CI 0.44-2.36]. There was a further second trimester miscarriage in the study group and one in the control group. The live birth rate in the study group was 41/51 (80%, 95% CI 66.9-90.2) and 38/48 (79%, 95% CI 65-89.5) for those who were treated surgically. These results were similar to 127/156 (81%, 95% CI 74.4-87.2) live births in the control group (OR 0.87, 95% CI 0.39-1.94). LIMITATIONS REASONS FOR CAUTION: This study is retrospective, and the number of patients is relatively small, which reflects the rarity of heterotopic pregnancies. Heterotopic pregnancies without a known outcome were excluded from analysis. WIDER IMPLICATIONS OF THE FINDINGS: This study demonstrates that in women diagnosed with heterotopic pregnancies, minimally invasive surgery to treat the extrauterine pregnancy does not increase the risk of miscarriage of the concomitant live eutopic pregnancy. This finding will be helpful to women and their clinicians when discussing the options for treating heterotopic pregnancies. STUDY FUNDING/COMPETING INTERESTS: This work did not receive any funding. None of the authors has any conflict of interest to declare. TRIAL REGISTRATION NUMBER: Research Registry: researchregistry6430.

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.

Recognition of emotion in facial expression by people with Prader-Willi syndrome.

BACKGROUND: People with Prader-Willi syndrome (PWS) may have mild intellectual impairments but less is known about their social cognition. Most parents/carers report that people with PWS do not have normal peer relationships, although some have older or younger friends. Two specific aspects of social cognition are being able to recognise other people's emotion and to then respond appropriately. In a previous study, mothers/carers thought that 26% of children and 23% of adults with PWS would not respond to others' feelings. They also thought that 64% could recognise happiness, sadness, anger and fear and a further 30% could recognise happiness and sadness. However, reports of emotion recognition and response to emotion were partially dissociated. It was therefore decided to test facial emotion recognition directly. METHOD: The participants were 58 people of all ages with PWS. They were shown a total of 20 faces, each depicting one of the six basic emotions and asked to say what they thought that person was feeling. The faces were shown one at a time in random order and each was accompanied by a reminder of the six basic emotions. RESULTS: This cohort of people with PWS correctly identified 55% of the different facial emotions. These included 90% of happy faces, 55% each of sad and surprised faces, 43% of disgusted faces, 40% of angry faces and 37% of fearful faces. Genetic subtype differences were found only in the predictors of recognition scores, not in the scores themselves. Selective impairment was found in fear recognition for those with PWS who had had a depressive illness and in anger recognition for those with PWS who had had a psychotic illness. CONCLUSIONS: The inability to read facial expressions of emotion is a deficit in social cognition apparent in people with PWS. This may be a contributing factor in their difficulties with peer relationships.

OP TRENTON 3: An analysis of primary care presentations to a deployed role 1 in support of a United Nation peacekeeping operation.

OBJECTIVES: Health data of operational relevance from South Sudan are lacking, outdated and non-representative. This study sets out to record and analyse primary healthcare (PHC) presentations to a deployed UK Level 1 Primary Healthcare Centre (L1 PHC) facility in Bentiu, South Sudan, to inform on disease prevalence for UK Military Personnel in a sub-Saharan Operational environment. METHODS: A prospective single-centre cohort study was completed for all PHC presentations to a UK L1 PHC facility while deployed on the United Nations Mission to South Sudan from June 2017 to November 2017. RESULTS: 861 episodes of clinical care were recorded at Bentiu Camp during the 6-month period. 82% were from disease; 18% non-battle injuries and no battle injuries were seen. As per EPINATO2 categorisation, the top three presentations were acute gastrointestinal disease, dermatological disease and routine clinical care. Differences were noted for June-August and September-November, as a proportion of total cases seen. It was noted that gastrointestinal illnesses were three times more likely in the first half of the operation and bites and sting almost twice as likely. CONCLUSIONS: Gastrointestinal disease results in a significant burden on humanitarian operations where an extended Relief-in-Place is a key area of risk. The EPINATO2 reporting tool provides insufficient detail for planning purposes and an improved method of data collection is required. Targeting the diagnosis and management of infectious diseases during predeployment training should prepare L1 PHC for the most common cases encountered. Delivery of targeted Force Health Protection training for all personnel with early deployment of L1 PHC forward could improve support to commanders during the highest risk periods.

The impact of the Covid-19 pandemic on care of women with ectopic pregnancy in a tertiary London hospital.

BACKGROUND: In response to the COVID-19 pandemic, a central London tertiary referral hospital's nurse-led Early Pregnancy & Acute Gynaecology Unit (EPAGU) suspended its walk-in service in favour of a telephone triage system with scheduled appointments. OBJECTIVE: To assess if the pandemic and this adaptation to clinical services had an impact on the presentation, management and complication rate of ectopic pregnancies. MATERIALS AND METHODS: A retrospective review was performed of ectopic pregnancies diagnosed in the EPAGU between 5th of March 2020 - 15th of July 2020 (pandemic) and 5th of March 2019 - 15th of July 2019 (pre-pandemic). MAIN OUTCOME MEASURES: Ultrasound findings, patient demographics, serum hCG concentrations, operative findings and complications. RESULTS: There was a 36% reduction in attendances to the unit during the pandemic. Allowing for this, there was no significant difference in the diagnosis rate between the two periods. There was no significant difference in the gestation at diagnosis, serum hCG concentration or volume of mass at presentation. There was also no significant difference in rate of surgical intervention or complications including rupture of fallopian tube, haemoperitoneum or need for blood transfusion. CONCLUSION: This study suggests this is a safe means of caring for women with ectopic pregnancies which does not limit management options nor lead to higher complication rates. WHAT IS NEW: Other EPAGUs may choose to adopt a telephone triage system with reassurance of its safety.

Optimal nitrogen supply as a key to increased and sustained production of a monoclonal full-size antibody in BY-2 suspension culture.

Plant cell cultures have been used as expression hosts for recombinant proteins for over two decades. The quality of plant cell culture-produced proteins such as full-size monoclonal antibodies has been shown to be excellent in terms of protein folding and binding activity, but the productivity and yield fell short of what was achieved using mammalian cell culture, in which the key to gram-per-liter expression levels was strain selection and medium/process optimization. We carried out an extensive media analysis and optimization for the production of the full-size human anti-HIV antibody 2G12 in N. tabacum cv. BY-2. Nitrogen source and availability was found to be one key factor for the volumetric productivity of plant cell cultures. Increased amounts of nitrate in the culture medium had a dramatic impact on protein yields, resulting in a 10-20-fold increase in product accumulation through a combination of enhanced secretion and higher stability. The results were scalable from shake flasks to stirred-tank bioreactors, where the maximum yield per cultivation volume was 8 mg L(-1) over 7 days. During the stationary phase, antibody levels were 150-fold higher in nitrogen-enriched medium compared to standard medium. The enhanced medium appeared not to affect antibody quality and activity, as determined by Western blots, surface plasmon resonance binding assays and N-glycan analysis.