Development of a single-visit protocol for the management of pregnancy of unknown location following in vitro fertilization: a retrospective study.

STUDY QUESTION: Can women with pregnancy of unknown location (PUL) following in vitro fertilization (IVF) be risk-stratified regarding the subsequent need for medical intervention, based on their demographic characteristics and the results of serum biochemistry at the initial visit? SUMMARY ANSWER: The ratio of serum hCG to number of days from conception (hCG/C) or the initial serum hCG level at ≥5 weeks' gestation could be used to estimate the risk of women presenting with PUL following IVF and needing medical intervention during their follow-up. WHAT IS KNOWN ALREADY: In women with uncertain conception dates presenting with PUL, a single serum hCG measurement cannot be used to predict the final pregnancy outcomes, thus, serial levels are mandatory to establish a correct diagnosis. Serum progesterone levels can help to risk-stratify women at their initial visit but are not accurate in those taking progesterone supplementation, such as women pregnant following IVF. STUDY DESIGN, SIZE, DURATION: This was a retrospective study carried out at two specialist early pregnancy assessment units between May 2008 and January 2021. A total of 224 women met the criteria for inclusion, but 14 women did not complete the follow-up and were excluded from the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: We selected women who had an IVF pregnancy and presented with PUL at ≥5 weeks' gestation. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 30/210 (14.0%, 95% CI 9.9-19.8) women initially diagnosed with PUL required surgical intervention. The hCG/C was significantly higher in the group of women requiring an intervention compared to those who did not (P = 0.003), with an odds ratio of 3.65 (95% CI 1.49-8.89, P = 0.004). A hCG/C <4.0 was associated with a 1.9% risk of intervention, which accounted for 25.7% of the study population. A similar result was obtained by substituting hCG/C <4.0 with an initial hCG level <100 IU/l, which was associated with 2.0% risk of intervention, and accounted for 23.8% of the study population (P > 0.05). LIMITATIONS, REASONS FOR CAUTION: A limitation of our study is that it is retrospective in nature, and as such, we were reliant on existing data. WIDER IMPLICATIONS OF THE FINDINGS: A previous study in women with PUL after spontaneous conception found that a 2% intervention rate was considered low enough to eliminate the need for close follow-up and serial blood tests. Using the same 2% cut-off, a quarter of women with PUL after IVF could also avoid attending for further visits and investigations. STUDY FUNDING/COMPETING INTEREST(S): No external funding was required for this study. No conflicts of interest are required to be declared. TRIAL REGISTRATION NUMBER: N/A.

An age-related nomogram for antral follicle count: an observational study of 3821 women.

RESEARCH QUESTION: What is the relationship between antral follicle count (AFC) and chronological age, and what are the expected values for AFC? DESIGN: This was a retrospective cohort study at a specialist gynaecological ultrasound centre in London, UK. Women presenting to a gynaecology diagnostic unit for investigation of symptoms or routine check-up, and undergoing transvaginal ultrasound (TVUS) examinations, between 1 January 2017 and 22 September 2022 were included in this study. RESULTS: In total, 8821 TVUS records from 7573 patients were analysed. The relationship between AFC and age was estimated to develop an AFC nomogram independent of the stage in the menstrual cycle. AFC corresponding to the 10th, 25th, 50th, 75th and 90th centiles for each patient and age group were calculated. Both nomogram and condition-specific populations displayed a Gaussian relationship between AFC and age. For the nomogram population (scans n = 4256, patients n = 3821), a peak median AFC of 30 was observed between 21-23 years of age. The AFC distribution of the group with previous ovarian cystectomy (scans n = 534, patients n = 443) was found to be significantly different compared with the nomogram population (P < 0.0001). However, the same did not hold true for those on hormonal contraception (scans n = 566, patients n = 534) (P = 0.43). CONCLUSIONS: An AFC nomogram reporting median and interquartile values for AFC by chronological age across the reproductive years was developed. This is a useful tool for providing counselling for those undergoing ovarian reserve assessments, and can be taken any time in the menstrual cycle, including in women on hormonal contraceptives or who have undergone previous ovarian cystectomy.

Ultrasound study of natural progression of ovarian endometrioma.

OBJECTIVE: To determine the natural progression of ovarian endometrioma in women who are managed expectantly. METHODS: This was a retrospective cohort study of 83 women with evidence of ovarian endometrioma who were managed expectantly between April 2007 and 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 endometrioma who were managed expectantly for ≥ 6 months. All women attended for a minimum of two ultrasound scans performed 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: A total of 1922 women who attended our gynecology clinic during the study period were found to have evidence of moderate or severe endometriosis on pelvic ultrasound examination. Of those, 83 women had evidence of ovarian endometrioma and were managed expectantly. The median age of women was 39 (range, 26-51) years at the initial visit. Each woman had at least two ultrasound scans performed by a single expert operator at a minimum interval of ≥ 6 months. Of 83 women diagnosed with endometrioma, 50 (60% (95% CI, 49-71%)) had a single cyst 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 (range, 187-2984) days. A total of 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 in size was observed. The median change in mean cyst diameter per woman during the study period was -2.7 (range, -57.7 to 39.3) mm, with a median annual regression rate of -1.7 (range, -24.6 to 42.0) mm/year/woman. Overall, when compared with the initial visit, cysts were significantly smaller at follow-up (median diameter, 22.3 (range, 6.7-77.0) mm vs 18.5 (range, 5.0-72.0) mm; P = 0.009). We did not identify any clinical characteristics that could reliably predict the chance of endometrioma progression. CONCLUSIONS: In the majority of women with an ultrasound diagnosis of ovarian endometrioma, the cysts do not increase in size significantly over time and they could be managed expectantly. This evidence may help clinicians when counseling asymptomatic or minimally symptomatic women about management of ovarian endometrioma. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Amniotic sac diameter reference interval in early pregnancy between 7 and 10 weeks' gestation.

OBJECTIVE: To establish a normal reference interval for amniotic sac diameter (ASD) between 7 + 0 and 9 + 6 weeks' gestation and its relative size in relation to gestational sac diameter (GSD) and the embryo crown-rump length (CRL). METHODS: This was a prospective, cross-sectional study of consecutive women presenting to the Early Pregnancy Unit, University College Hospital, London, UK, between August 2022 and June 2023. We included live, normally sited, singleton pregnancies with a normal 20-week anomaly scan. We collected 120 cases per gestational week, from 7 + 0 to 9 + 6 weeks' gestation, totaling 360 cases. We performed an inter- and intraobserver variability assessment in the measurement of mean ASD in 30 patients. Regression analyses were used to establish reference intervals for GSD and CRL, ASD and CRL, GSD and ASD, and GSD/ASD ratio and CRL. A fitted regression line was calculated, along with a 90% prediction interval and R2 value. RESULTS: There was good interobserver agreement (mean ± SD difference, 0.007 ± 1.105 mm (95% limits of agreement (LoA), -2.160 to 2.174 mm)) and good intraobserver agreement for Observer A (mean ± SD difference, -0.080 ± 0.741 mm (95% LoA, -1.532 to 1.372 mm)) and Observer B (mean ± SD difference, -0.014 ± 0.919 mm (95% LoA, -1.814 to 1.786 mm)) in the measurement of mean ASD. Regression analyses showed a statistically significant association between each pair of values (P < 0.001 for all). There was a significant quadratic association between mean GSD and CRL (R2 = 56%), mean GSD and ASD (R2 = 60%) and GSD/ASD ratio and CRL (R2 = 68%), and a significant cubic association between mean ASD and CRL (R2 = 90%). The regression equations were used to quantify the values of ASD and GSD/ASD ratios for a range of CRL values and gestational ages. CONCLUSION: Our study has produced comprehensive reference intervals for amniotic sac size in early pregnancy, which could be used in routine clinical practice. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Imaging in gynecological disease (25): clinical and ultrasound characteristics of intramural pregnancy.

OBJECTIVE: To describe the clinical and sonographic characteristics of intramural pregnancy, as well as the available management options and treatment outcomes. METHODS: This was a retrospective single-center study of consecutive patients with a sonographic diagnosis of intramural pregnancy between November 2008 and November 2022. An intramural pregnancy was diagnosed on ultrasound when a pregnancy was implanted within the uterine corpus, above the level of the internal cervical os and separate from the interstitial section of the Fallopian tube, and extended beyond the decidual-myometrial junction. Clinical, ultrasound, relevant surgical and histological information and outcomes were retrieved from each patient's record and analyzed. RESULTS: Eighteen patients were diagnosed with an intramural pregnancy during the study period. Their median age was 35 (range, 28-43) years and the median gestational age at diagnosis was 8 + 1 (range, 5 + 5 to 12 + 0) weeks. Vaginal bleeding with or without abdominal pain was the most common presenting symptom, recorded in eight patients. Nine (50%) patients had a partial and nine (50%) had a complete intramural pregnancy. Embryonic cardiac activity was present in eight (44%) pregnancies. The majority of pregnancies (n = 10 (56%)) were initially managed conservatively, including expectant management in eight (44%) cases, local injection of methotrexate in one (6%) and embryocide in one (6%). Conservative management was successful in nine of the 10 (90%) pregnancies, with a median time to serum human chorionic gonadotropin resolution of 71 (range, 35-143) days. One patient with an ongoing live pregnancy had an emergency hysterectomy for a major vaginal bleed at 20 weeks' gestation. No other patient managed conservatively experienced any significant complication. The remaining eight (44%) patients had primary surgical treatment, comprising transcervical suction curettage in seven (88%) of these cases, while one patient presented with uterine rupture and underwent emergency laparoscopy and repair. CONCLUSIONS: We describe the ultrasound features of partial and complete intramural pregnancy, demonstrating key diagnostic features. Our series suggests that, when intramural pregnancy is diagnosed before 12 weeks' gestation, it can be managed either conservatively or by surgery, with preservation of reproductive function in most women. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Ovarian ectopic pregnancy: clinical characteristics, ultrasound diagnosis and management.

OBJECTIVE: To compare clinical, ultrasound and biochemical characteristics of ovarian ectopic pregnancies (OEP) to tubal ectopic pregnancies (TEP). METHODS: This was a single-center, retrospective, case-control study of women with OEP compared to women with TEP between December 2010 and February 2021. OEP was defined as a pregnancy located completely or partially within the ovarian parenchyma, seen separately to a corpus luteum, where a corpus luteum was within the ipsilateral ovary. We compared demographic features, risk factors, clinical presentation, ultrasound findings and outcomes such as blood loss at surgery, blood transfusion rate, length of hospital stay, follow-up and future pregnancy outcomes of women who conceived. RESULTS: 20 women with OEP were identified and compared to 100 women with TEP. 15/20 (75%) OEPs were diagnosed correctly on the first scan. There was no difference between the groups in terms of maternal age, gestational age, gravidity, parity or risk factors. Compared to TEPs, OEPs were more likely to present with abdominal pain without vaginal bleeding (12/20 (60%) vs 13/100 (13%) (p=<0.01) (OR 10; 95%CI 3.45-29.20)), were more likely to contain an embryo (3/20 (15%) vs 2/100 (2%) (p=0.02) (OR 8.7; 95%CI 1.34-55.65)), have severe hemoperitoneum on ultrasound scan (9/20 (45%) vs 8/100 (8%) (p=<0.01) (OR 9.4; 95%CI 3.01-29.40)) and had higher blood loss at surgery (median 700ml vs 100ml, p=<0.01). All surgically managed OEPs had successful laparoscopic treatment (18 excisions, 1 wedge resection) with preservation of the ovary. Only 1/20 (5%) OEPs required a blood transfusion. CONCLUSIONS: OEPs are more likely than TEPs to contain an embryo and to present with severe hemoperitoneum. In a dedicated early pregnancy setting the majority of OEPs could be detected on ultrasound scan at the initial visit, facilitating optimal minimally invasive surgical management, reducing the risk of blood transfusions and oophorectomy. Our findings can be used as a reference for clinicians who may not otherwise encounter this rare condition. This article is protected by copyright. All rights reserved.

Pelvic pain and venous congestion revisited: examining relationship between chronic pelvic pain and uterine venous size and blood flow.

OBJECTIVE: To investigate the relationship between increased uterine venous plexus diameter and chronic pelvic pain in women attending a gynecology clinic. METHODS: This was a retrospective study of patients attending a tertiary university hospital in London, UK. Women presenting to the gynecology clinic undergoing transvaginal ultrasound examination were recruited into the study. The largest trunk of the uterine venous plexus was measured on each side. Blood flow within the uterine veins was categorized into continuous or interrupted flow and evaluated using color and spectral Doppler ultrasound during normal respiration and on Valsalva maneuver to demonstrate the presence of venous reflux. The largest uterine vein diameter and its blood flow were used for the analysis. The main variables of interest were chronic pelvic pain, uterine vein diameter and type of blood flow. RESULTS: We included 1500 women in the study, of whom 584 (38.9% (95% CI, 36.5-41.5%)) reported chronic pelvic pain. Dysmenorrhea was the most common type of pelvic pain. Age (P < 0.001), menopausal status (P = 0.02), varicose veins (P = 0.01), adenomyosis (P < 0.001) and endometriosis (P < 0.001) were found to be independently associated with the occurrence of pain on multiple logistic regression analysis. There was no difference in uterine vein diameter between women with and those without pain (P = 0.10). Neither uterine vein diameter (P = 0.47) nor type of blood flow (P = 0.07) was significantly associated with the occurrence of pelvic pain on multiple logistic regression. CONCLUSIONS: Our findings show that uterine vein diameter is not associated with pelvic pain. However, we found other important clinical and demographic factors that are associated with chronic pelvic pain. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Natural history of endometriosis in pregnancy: ultrasound study of morphology of deep endometriosis and ovarian endometrioma.

OBJECTIVE: To assess the morphological appearance of deep endometriosis and ovarian endometrioma in pregnancy using pelvic ultrasound examination. METHODS: This was a prospective observational cohort study conducted over 3 years at University College London Hospital, which is a tertiary level referral unit for early pregnancy complications and an accredited endometriosis center. All women who participated provided written consent and were invited for surveillance ultrasound examination at the time of their routine scans in pregnancy. All scans were performed by a single operator to eliminate interobserver variability. The change in size of ovarian endometrioma and nodules was reported as change in their mean diameter. Ovarian endometrioma with irregular thick inner walls, hyperechoic papillary projections and/or high vascularity and hyperechoic nodules with moderate to high vascularity were reported as decidualized. RESULTS: Sixty-five women with a live, normally sited pregnancy and concomitant ultrasound features of deep and/or ovarian endometriosis were included in the study. The median age of the study population was 34 (range, 23-44) years, and the median gestational age at presentation was 7 + 6 (range, 3 + 6 to 18 + 0) weeks. From the cohort, 47/65 (72%) were nulliparous, 48/65 (74%) had a previous diagnosis of endometriosis and 19/65 (29%) conceived via in-vitro fertilization. There were 10/65 (15% (95% CI, 7-24%)) women with ovarian endometrioma alone, 28/65 (43% (95% CI, 31-55%)) with endometriotic nodules alone and the remaining 27/65 (42% (95% CI, 30-54%)) had both. Of the women with ovarian endometrioma who underwent follow-up, 29/34 (85% (95% CI, 73-97%)) experienced cyst regression, 2/34 (6% (95% CI, 0-14%)) experienced cyst growth, and in 3/34 (9% (95% CI, 0.0-18%)) women, cyst size was unchanged. In 10/34 (29% (95% CI, 14-45%)), there was complete resolution of all cysts. Of the women with nodules who underwent follow-up, 43/51 (84% (95% CI, 74-94%)) experienced nodule regression, 2/51 (4% (95% CI, 0-9%)) experienced nodule growth and, in 6/51 (12% (95% CI, 3-21%)) women, nodule size was unchanged. In 4/51 (8% (95% CI, 0-15%)) women, there was complete resolution of all nodules. In 5/37 (14% (95% CI, 3-25%)) women who attended postnatal follow-up, complete resolution of all endometriotic lesions occurred during pregnancy. In 10/34 (29% (95% CI, 14-45%)) women with ovarian endometrioma and 27/51 (53% (95% CI, 39-67%)) women with nodules, a pattern of growth was observed in the first and second trimesters, followed by regression later in pregnancy. Features of decidualization were observed in 17/34 (50% (95% CI, 33-67%)) women with ovarian endometrioma, most commonly in the first trimester, and in 25/51 (49% (95% CI, 35-63%)) women with nodules, most commonly in the second trimester. CONCLUSIONS: For the majority of women, despite features of decidualization being common in the first and second trimesters, ovarian endometrioma and deep nodules regress during pregnancy. Morphological changes of endometriosis in pregnancy are difficult to differentiate from characteristics of malignant lesions. Better understanding of the appearance of endometriosis in pregnancy is vital to minimize intervention and help counsel women regarding their condition. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prevalence of deep and ovarian endometriosis in women attending a general gynecology clinic: prospective cohort study.

OBJECTIVES: To assess using transvaginal ultrasound the prevalence of deep and ovarian endometriosis in premenopausal women attending a general gynecology clinic. We also investigated whether the presence of endometriosis was associated with various demographic factors and other pelvic abnormalities. METHODS: This was a prospective observational cohort study carried out between February 2019 and October 2020. Consecutive premenopausal women who attended our general gynecology clinic underwent pelvic ultrasound examination, performed by a single experienced operator. Pregnant women and those with a history of hysterectomy or oophorectomy were excluded. The primary outcome was the prevalence of deep and/or ovarian endometriosis. Secondary outcomes were the anatomical distribution of endometriotic lesions and the association of endometriosis with demographic characteristics and various pelvic abnormalities, which were analyzed using logistic regression and multivariable analysis. RESULTS: A total of 1026 women were included in the final study sample, of whom 194 (18.9% (95% CI, 16.6-21.4%)) had sonographic evidence of deep and/or ovarian endometriosis. Of the 194 women diagnosed with endometriosis, 106 (54.6% (95% CI, 47.4-61.8%)) were diagnosed with endometriotic nodules only, 26 (13.4% (95% CI, 9.0-19.0%)) with ovarian endometriomas only, and 62 (32.0% (95% CI, 25.5-39.0%)) women had evidence of both. There was a total of 348 endometriotic nodules in 168 women, located most frequently in the retrocervical area (166/348; 47.7% (95% CI, 42.4-53.1%)), uterosacral ligaments (96/348; 27.6% (95% CI, 23.0-32.6%)) and bowel (40/348; 11.5% (95% CI, 8.3-15.3%)). Multivariable analysis found significant positive associations between endometriosis and both adenomyosis (odds ratio (OR), 1.72 (95% CI, 1.10-2.69); P = 0.02) and pelvic adhesions (OR, 25.7 (95% CI, 16.7-39.3); P < 0.001), whilst higher parity (OR, 0.44 (95% CI, 0.24-0.81); P = 0.03) and history of Cesarean section (OR, 0.18 (95% CI, 0.06-0.52); P = 0.002) were associated with a lower occurrence of endometriosis. A total of 75/1026 women (7.3% (95% CI, 5.8-9.1%)) underwent laparoscopy within 6 months of pelvic ultrasound examination. There was very good agreement between ultrasound and surgical findings, with a kappa value of 0.84 (95% CI, 0.69-0.99). CONCLUSIONS: Deep and/or ovarian endometriosis was present in nearly one in five women attending a general gynecology clinic. There were significant positive associations with adenomyosis and pelvic adhesions and negative associations with higher parity and previous Cesarean section. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Reproductive outcome in 326 women with unicornuate uterus.

OBJECTIVES: To study the reproductive outcomes of women with a unicornuate uterus and compare them to those of women with no congenital uterine anomaly. METHODS: This was a single-center, retrospective cohort study. Cases were women aged at least 16 years who were diagnosed with a unicornuate uterus on transvaginal/transrectal ultrasound between January 2008 and September 2021. Controls were women with no congenital uterine anomaly matched 1:1 by age and body mass index. The primary outcome was live-birth rate. Secondary outcomes were pregnancy loss (miscarriage, ectopic pregnancy, termination of pregnancy), preterm delivery, mode of delivery and concomitant gynecological abnormalities (endometriosis, adenomyosis, fibroids). RESULTS: Included in the study were 326 cases and 326 controls. Women with a unicornuate uterus had a significantly lower live-birth rate (184/388 (47.4%) vs 229/396 (57.8%); P = 0.004) and higher rates of overall miscarriage (178/424 (42.0%) vs 155/465 (33.3%); adjusted odds ratio (aOR), 2.21 (95% CI, 1.42-3.42), P < 0.001), ectopic pregnancy (26/424 (6.1%) vs 11/465 (2.4%); aOR, 2.52 (95% CI, 1.22-5.22), P = 0.01), preterm delivery (45/184 (24.5%) vs 17/229 (7.4%); aOR, 3.04 (95% CI, 1.52-5.97), P = 0.001) and Cesarean delivery (116/184 (63.0%) vs 70/229 (30.6%); aOR, 2.54 (95% CI, 1.67-3.88), P < 0.001). Rudimentary-horn pregnancies accounted for 7/26 (26.9%) ectopic pregnancies in the study group. Women with a unicornuate uterus were more likely to have endometriosis (17.5% vs 10.7%; P = 0.018) and adenomyosis (26.7% vs 15.6%; P = 0.001), but were not more likely to have fibroids compared with controls. Women with a functional rudimentary horn were more likely to have pelvic endometriosis compared to those without (odds ratio, 2.4 (95% CI, 1.4-4.1), P = 0.002). CONCLUSIONS: Pregnant women with a unicornuate uterus should be classified as high risk. Removal of a functional rudimentary horn should be discussed with the patient to prevent a rudimentary-horn ectopic pregnancy. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Development of a core outcome set and outcome definitions for studies on uterus-sparing treatments of adenomyosis (COSAR): an international multistakeholder-modified Delphi consensus study.

STUDY QUESTION: What outcomes should be reported in all studies investigating uterus-sparing interventions for treating uterine adenomyosis? SUMMARY ANSWER: We identified 24 specific and 26 generic core outcomes in nine domains. WHAT IS KNOWN ALREADY: Research reporting adenomyosis treatment is not patient-centred and shows wide variation in outcome selection, definition, reporting and measurement of quality. STUDY DESIGN, SIZE, DURATION: An international consensus development process was performed between March and December 2021. Participants in round one were 150 healthcare professionals, 17 researchers and 334 individuals or partners with lived experience of adenomyosis from 48 high-, middle- and low-income countries. There were 291 participants in the second round. PARTICIPANTS/MATERIALS, SETTING, METHODS: Stakeholders included active researchers in the field, healthcare professionals involved in diagnosis and treatment, and people and their partners with lived experience of adenomyosis. The core component of the process was a 2-step modified Delphi electronic survey. The Steering Committee analysed the results and created the final core outcome set (COS) in a semi-structured meeting. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 241 outcomes was identified and distilled into a 'long list' of 71 potential outcomes. The final COS comprises 24 specific and 26 generic core outcomes across nine domains, including pain, uterine bleeding, reproductive outcomes, haematology, urinary system, life impact, delivery of care, adverse events and reporting items, all with definitions provided by the Steering Committee. Nineteen of these outcomes will apply only to certain study types. Although not included in the COS, the Steering Committee recommended that three health economic outcomes should be recorded. LIMITATIONS, REASONS FOR CAUTION: Patients from continents other than Europe were under-represented in this survey. A lack of translation of the survey might have limited the active participation of people in non-English speaking countries. Only 58% of participants returned to round two, but analysis did not indicate attrition bias. There is a significant lack of scientific evidence regarding which symptoms are caused by adenomyosis and when they are related to other co-existent disorders such as endometriosis. As future research provides more clarity, the appropriate review and revision of the COS will be necessary. WIDER IMPLICATIONS OF THE FINDINGS: Implementing this COS in future studies on the treatment of adenomyosis will improve the quality of reporting and aid evidence synthesis. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was received for this work. T.T. received a grant (grant number 2020083) from the South Eastern Norwegian Health Authority during the course of this work. T.T. receives personal fees from General Electrics and Medtronic for lectures on ultrasound. E.R.L. is the chairman of the Norwegian Endometriosis Association. M.G.M. is a consultant for Abbvie Inc and Myovant, receives research funding from AbbVie and is Chair of the Women's Health Research Collaborative. S.-W.G. is a board member of the Asian Society of Endometriosis and Adenomyosis, on the scientific advisory board of the endometriosis foundation of America, previous congress chair for the World Endometriosis Society, for none of which he received personal fees. E.S. received outside of this work grants for two multicentre trials on endometriosis from the National Institute for Health Research UK, the Rosetrees Trust, and the Barts and the London Charity, he is a member of the Medicines and Healthcare Products Regulatory Agency (MHRA), Medicines for Women's Health Expert Advisory Group, he is an ambassador for the World Endometriosis Society, and he received personal fees for lectures from Hologic, Olympus, Medtronic, Johnson & Johnson, Intuitive and Karl Storz. M.H. is member of the British Society for Gynaecological Endoscopy subcommittee. No other conflict of interest was declared. TRIAL REGISTRATION NUMBER: N/A.

Efficacy of transrectal ultrasound in assessing endometrium of postmenopausal women with axial uterus.

OBJECTIVE: To evaluate the acceptance and efficacy of transrectal ultrasound (TRS) in assessing the endometrium in postmenopausal women with an axial uterus. METHODS: This was a prospective cross-sectional study conducted between October 2015 and October 2018 of consecutive postmenopausal women with an axial uterus on transvaginal ultrasound (TVS). Women with a known diagnosis of gynecological malignancy were excluded. TRS was offered immediately after TVS without prior bowel preparation. A single operator determined subjectively whether the endometrium was visualized satisfactorily on TVS and TRS. In women with postmenopausal bleeding (PMB), endometrial thickness (ET) was measured and endometrial morphology was categorized as atrophic, uniformly thickened, benign endometrial polyp or endometrial cancer, based on subjective pattern recognition. All women with PMB and a non-atrophic endometrium underwent outpatient endometrial biopsy, hysteroscopy or hysterectomy. The success rate of TRS in assessing satisfactorily the endometrium was compared with that of TVS. In patients with PMB, ET measurements and subjective diagnosis of endometrial cancer on TVS vs TRS were compared. RESULTS: Of the 1553 women who underwent TVS examination, 103 (6.6%) had an axial uterus, of whom 76 (73.8%) presented with PMB. TRS was accepted by 66/103 (64.1%) women with an axial uterus. TRS assessed satisfactorily a significantly higher proportion of endometria compared with TVS (90.9% vs 62.1%; χ2 = 14.1, P < 0.001). In 50 women with PMB and an axial uterus who underwent both TVS and TRS, TVS failed to visualize the endometrium satisfactorily in 15 (30.0%) women, whilst TRS provided satisfactory images in all cases. Among the 35 women with PMB and a satisfactory endometrial assessment on TVS and TRS, measurements of ET on TRS were significantly lower compared to those on TVS (median difference, -1.2 (interquartile range, -3.0 to -0.4) mm). The overall agreement of TVS and TRS on the presence or absence of endometrial cancer using subjective pattern recognition was 30/35 (85.7%; 95% CI, 74.1-97.3%). While all seven cases of histologically confirmed endometrial cancer were diagnosed correctly on TRS, four were misdiagnosed on TVS as benign polyps or uniformly thickened endometrium. CONCLUSIONS: TRS is an acceptable and effective way to assess the endometrium in postmenopausal women with an axial uterus. Among women presenting additionally with PMB, TRS is associated with a higher proportion of satisfactory endometrial assessments and fewer misdiagnoses of endometrial cancer by subjective pattern recognition compared with TVS. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Prevalence of deep and ovarian endometriosis in early pregnancy: ultrasound diagnostic study.

OBJECTIVE: To assess the prevalence and morphological appearance of deep endometriosis and ovarian endometrioma using pelvic ultrasound examination in women attending for an early pregnancy assessment. METHODS: This was a prospective observational study set within a dedicated early pregnancy unit. The study included 1341 consecutive women who attended for an early pregnancy assessment for reassurance or because of suspected early pregnancy complications. All women underwent a transvaginal scan to assess the location and viability of their pregnancy. In addition, a detailed examination of pelvic organs was carried out to detect the presence of endometriosis and other gynecological abnormalities. Data analysis was performed using logistic regression and multivariable analysis. RESULTS: The prevalence of deep endometriosis and/or ovarian endometrioma in women attending our early pregnancy unit was 4.9% (95% CI, 3.8-6.2%). In 33/66 (50.0% (95% CI, 37.9-62.1%)) women with endometriosis, this was a new diagnosis that was made during their early pregnancy scan. On multivariable analysis, the presence of endometriosis was strongly associated with a history of subfertility (odds ratio (OR), 3.15 (95% CI, 1.63-6.07)) and presence of a congenital uterine anomaly (OR, 5.69 (95% CI, 2.17-14.9)) and uterine fibroids (OR, 2.37 (95% CI, 1.31-4.28)). Morphological changes typical of decidualization were seen in 11/33 (33.3% (95% CI, 17.2-49.4%)) women with ovarian endometrioma and 18/57 (31.6% (95% CI, 19.5-43.7%)) women with deep endometriotic nodules. CONCLUSIONS: Deep endometriosis and ovarian endometrioma were present in a significant proportion of women attending for early pregnancy assessment. The prevalence varied depending on a history of subfertility, and therefore is likely to differ significantly among populations, depending on their characteristics. Ultrasound is a useful tool for the detection of endometriosis in early pregnancy and the identification of women who may benefit from specialist antenatal care. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Reproducibility of assessment of full-dilatation Cesarean section scar in women undergoing second-trimester screening for preterm birth.

OBJECTIVE: To assess the reproducibility of a standardized method of measuring the Cesarean section (CS) scar, CS scar niche and their position relative to the internal os of the uterine cervix by transvaginal ultrasound in pregnant women with a previous full-dilatation CS. METHODS: This was a prospective, single-center reproducibility study on women with a singleton pregnancy and a previous full-dilatation CS who underwent transvaginal ultrasound assessment of cervical length and CS scar characteristics at 14-24 weeks' gestation. The CS scar was identified as a hypoechogenic linear discontinuity of the myometrium at the anterior wall of the lower uterine segment or cervix. The CS scar niche was identified as an indentation at the site of the scar with a depth of at least 2 mm. The CS scar position was evaluated by measuring the distance to the internal cervical os. CS scar niche parameters, including its length, depth, width, and residual and adjacent myometrial thickness, were assessed in the sagittal and transverse planes. Qualitative reproducibility was assessed by agreement regarding visibility of the CS scar and niche. Quantitative reproducibility of CS scar measurements was assessed using three sets of images: (1) real-time two-dimensional (2D) images (real-time acquisition and caliper placement on 2D images by two operators), (2) offline 2D still images (offline caliper placement by two operators on stored 2D images acquired by one operator) and (3) three-dimensional (3D) volume images (volume manipulation and caliper placement on 2D images extracted by two operators). Agreement on CS scar visibility and the presence of a niche was analyzed using kappa coefficients. Intraobserver and interobserver reproducibility of quantitative measurements was assessed using Bland-Altman plots. RESULTS: To achieve the desired statistical power, 72 women were recruited. The CS scar was visualized in > 80% of images. Interobserver agreement for scar visualization and presence of a niche in real-time 2D images was excellent (kappa coefficients of 0.84 and 0.85, respectively). Overall, reproducibility was higher for real-time 2D and offline 2D still images than for 3D volume images. The 95% limits of agreement (LOA) for intraobserver reproducibility were between ± 1.1 and ± 3.6 mm for all sets of images; the 95% LOA for interobserver reproducibility were between ± 2.0 and ± 6.3 mm. Measurement of the distance from the CS scar to the internal cervical os was the most reproducible 2D measurement (intraobserver and interobserver 95% LOA within ± 1.6 and ± 2.7 mm, respectively). Overall, niche measurements were the least reproducible measurements (intraobserver 95% LOA between ± 1.6 and ± 3.6 mm; interobserver 95% LOA between ± 3.1 and ± 6.3 mm). There was no consistent difference between measurements obtained by reacquisition of 2D images (planes obtained twice and caliper placed), caliper placement on 2D stored images or volume manipulation (planes obtained twice and caliper placed). CONCLUSIONS: The CS scar position and scar niche in pregnant women with a previous full-dilatation CS can be assessed in the second trimester of a subsequent pregnancy using either 2D or 3D volume ultrasound imaging with a high level of reproducibility. Overall, the most reproducible CS scar parameter is the distance from the CS scar to the internal cervical os. The method proposed in this study should enable clinicians to assess the CS scar reliably and may help predict pregnancy outcome. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Strengths and limitations of diagnostic tools for endometriosis and relevance in diagnostic test accuracy research.

Endometriosis is a chronic systemic disease that can cause pain, infertility and reduced quality of life. Diagnosing endometriosis remains challenging, which yields diagnostic delays for patients. Research on diagnostic test accuracy in endometriosis can be difficult due to verification bias, as not all patients with endometriosis undergo definitive diagnostic testing. The purpose of this State-of-the-Art Review is to provide a comprehensive update on the strengths and limitations of the diagnostic modalities used in endometriosis and discuss the relevance of diagnostic test accuracy research pertaining to each. We performed a comprehensive literature review of the following methods: clinical assessment including history and physical examination, biomarkers, diagnostic imaging, surgical diagnosis and histopathology. Our review suggests that, although non-invasive diagnostic methods, such as clinical assessment, ultrasound and magnetic resonance imaging, do not yet qualify formally as replacement tests for surgery in diagnosing all subtypes of endometriosis, they are likely to be appropriate for advanced stages of endometriosis. We also demonstrate in our review that all methods have strengths and limitations, leading to our conclusion that there should not be a single gold-standard diagnostic method for endometriosis, but rather, multiple accepted diagnostic methods appropriate for different circumstances. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Consensus on revised definitions of Morphological Uterus Sonographic Assessment (MUSA) features of adenomyosis: results of modified Delphi procedure.

OBJECTIVES: To evaluate whether the Morphological Uterus Sonographic Assessment (MUSA) features of adenomyosis need to be better defined and, if deemed necessary, to reach consensus on the updated definitions. METHODS: A modified Delphi procedure was performed among European gynecologists with expertise in ultrasound diagnosis of adenomyosis. To identify MUSA features that might need revision, 15 two-dimensional (2D) video recordings (four recordings also included three-dimensional (3D) still images) of transvaginal ultrasound (TVS) examinations of the uterus were presented in the first Delphi round (online questionnaire). Experts were asked to confirm or refute the presence of each of the nine MUSA features of adenomyosis (described in the original MUSA consensus statement) in each of the 15 videoclips and to provide comments. In the second Delphi round (online questionnaire), the results of the first round and suggestions for revision of MUSA features were shared with the experts before they were asked to assess a new set of 2D and 3D still images of TVS examinations and to provide feedback on the proposed revisions. A third Delphi round (virtual group meeting) was conducted to discuss and reach final consensus on revised definitions of MUSA features. Consensus was predefined as at least 66.7% agreement between experts. RESULTS: Of 18 invited experts, 16 agreed to participate in the Delphi procedure. Eleven experts completed and four experts partly finished the first round. The experts identified a need for more detailed definitions of some MUSA features. They recommended use of 3D ultrasound to optimize visualization of the junctional zone. Fifteen experts participated in the second round and reached consensus on the presence or absence of ultrasound features of adenomyosis in most of the still images. Consensus was reached for all revised definitions except those for subendometrial lines and buds and interrupted junctional zone. Thirteen experts joined the online meeting, in which they discussed and agreed on final revisions of the MUSA definitions. There was consensus on the need to distinguish between direct features of adenomyosis, i.e. features indicating presence of ectopic endometrial tissue in the myometrium, and indirect features, i.e. features reflecting changes in the myometrium secondary to presence of endometrial tissue in the myometrium. Myometrial cysts, hyperechogenic islands and echogenic subendometrial lines and buds were classified unanimously as direct features of adenomyosis. Globular uterus, asymmetrical myometrial thickening, fan-shaped shadowing, translesional vascularity, irregular junctional zone and interrupted junctional zone were classified as indirect features of adenomyosis. CONCLUSION: Consensus between gynecologists with expertise in ultrasound diagnosis of adenomyosis was achieved regarding revised definitions of the MUSA features of adenomyosis and on the classification of MUSA features as direct or indirect signs of adenomyosis. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Definition and sonographic reporting system for Cesarean scar pregnancy in early gestation: modified Delphi method.

OBJECTIVE: To develop a standardized sonographic evaluation and reporting system for Cesarean scar pregnancy (CSP) in the first trimester, for use by both general gynecology and expert clinics. METHODS: A modified Delphi procedure was carried out, in which 28 international experts in obstetric and gynecological ultrasonography were invited to participate. Extensive experience in the use of ultrasound to evaluate Cesarean section (CS) scars in early pregnancy and/or publications concerning CSP or niche evaluation was required to participate. Relevant items for the detection and evaluation of CSP were determined based on the results of a literature search. Consensus was predefined as a level of agreement of at least 70% for each item, and a minimum of three Delphi rounds were planned (two online questionnaires and one group meeting). RESULTS: Sixteen experts participated in the Delphi study and four Delphi rounds were performed. In total, 58 items were determined to be relevant. We differentiated between basic measurements to be performed in general practice and advanced measurements for expert centers or for research purposes. The panel also formulated advice on indications for referral to an expert clinic. Consensus was reached for all 58 items on the definition, terminology, relevant items for evaluation and reporting of CSP. It was recommended that the first CS scar evaluation to determine the location of the pregnancy should be performed at 6-7 weeks' gestation using transvaginal ultrasound. The use of magnetic resonance imaging was not considered to add value in the diagnosis of CSP. A CSP was defined as a pregnancy with implantation in, or in close contact with, the niche. The experts agreed that a CSP can occur only when a niche is present and not in relation to a healed CS scar. Relevant sonographic items to record included gestational sac (GS) size, vascularity, location in relation to the uterine vessels, thickness of the residual myometrium and location of the pregnancy in relation to the uterine cavity and serosa. According to its location, a CSP can be classified as: (1) CSP in which the largest part of the GS protrudes towards the uterine cavity; (2) CSP in which the largest part of the GS is embedded in the myometrium but does not cross the serosal contour; and (3) CSP in which the GS is partially located beyond the outer contour of the cervix or uterus. The type of CSP may change with advancing gestation. Future studies are needed to validate this reporting system and the value of the different CSP types. CONCLUSION: Consensus was achieved among experts regarding the sonographic evaluation and reporting of CSP in the first trimester. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Women's experiences of early pregnancy assessment unit services: a qualitative investigation.

OBJECTIVE: To explore the experiences of women who had used an Early Pregnancy Assessment Unit (EPAU) service in the UK and make recommendations for their improvement. DESIGN: Qualitative interview study. SETTING: Early Pregnancy Assessment Units in the UK. SAMPLE: A maximum variation sample of women who had consented to be interviewed having attended one of 26 EPAUs involved in the VESPA study in 2018. METHODS: In-depth telephone interviews with 38 women. A thematic framework analysis was conducted, with a focus on how experiences varied according to EPAU service configuration and clinical pathway. MAIN OUTCOME MEASURES: Women's experiences of EPAU services. RESULTS: We found that EPAUs are highly valued, and women's experiences were generally positive. However, women reported a range of issues that negatively affected their experience. These included difficulties accessing the service, insensitive management of the investigation and treatment options of pregnancy loss, poor communication, insufficient information and a lack of support for their psychological health. These issues were not strongly associated with EPAU configuration or clinical pathway. CONCLUSIONS: Recommendations to improve women's experiences include the separation of EPAUs from general maternity services, and we make suggestions on how to remove barriers to access by reviewing opening hours, how to provide sensitive patient management, such as automatically cancelling appointments and scans following pregnancy loss, and how to improve communication, both with women and their partners as well as with other parts of the health service. TWEETABLE ABSTRACT: Early Pregnancy Assessment Units are highly valued by women but aspects of their care experiences, particularly around sensitive management of pregnancy loss, could be improved.

Ultrasound diagnosis of endometrial cancer by subjective pattern recognition in women with postmenopausal bleeding: prospective inter-rater agreement and reliability study.

OBJECTIVES: To assess the inter-rater agreement and reliability of using subjective pattern recognition for diagnosing endometrial cancer (EC) on ultrasound in women with postmenopausal bleeding (PMB). METHODS: This was a prospective cross-sectional study conducted at a gynecological rapid-access clinic, between October 2016 and December 2017, in which consecutive women with PMB and endometrial thickness of ≥ 4.5 mm on transvaginal ultrasound examination were included. Women on hormone replacement therapy or tamoxifen and those with a history of primary gynecological malignancy were excluded. Two raters independently performed ultrasound examinations, blinded to each other's findings, and classified women as having uniformly thickened endometrium, benign endometrial polyp or EC, using subjective pattern recognition. Inter-rater reliability of ultrasound diagnosis was assessed using Cohen's kappa (κ) statistic. All women subsequently underwent either outpatient endometrial biopsy, hysteroscopy or hysterectomy. RESULTS: Forty women were included in the study, with a median age of 61 (interquartile range (IQR), 57-69) years and a median endometrial thickness of 11.0 (IQR, 6.2-20.3) mm. Final histological analysis confirmed 16 (40%) women with EC, 16 (40%) with benign endometrial polyp, four (10%) with atrophic endometrium, three (8%) with proliferative endometrium and one (3%) with endometrial hyperplasia. Inter-rater agreement for the ultrasound diagnoses of uniformly thickened endometrium, benign endometrial polyp and EC was 14/16 (87.5%), 22/30 (73.3%) and 28/34 (82.4%), respectively; inter-rater reliability was good (κ = 0.69; 95% CI, 0.49-0.88). When the ultrasound diagnoses were grouped as either cancer or no cancer, inter-rater agreement was 85% and inter-rater reliability was good (κ = 0.78; 95% CI, 0.61-0.95). Rater A correctly identified 14/16 cases of EC and Rater B identified 15/16. EC was misdiagnosed as benign polyps on ultrasound in two women by Rater A and in one woman by Rater B. The overall accuracies of Rater A and Rater B in differentiating between benign endometrial pathologies and malignancy were 90% and 90%, respectively. CONCLUSIONS: Our results show good inter-rater reliability of subjective pattern recognition in diagnosing uniformly thickened endometrium, benign endometrial polyp and EC on ultrasound in women with PMB. Our findings should facilitate wider use of subjective pattern recognition in routine clinical practice. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Imaging in gynecological disease (21): clinical and ultrasound characteristics of accessory cavitated uterine malformations.

OBJECTIVE: To describe the clinical and ultrasound characteristics of accessory cavitated uterine malformations (ACUMs). METHODS: This was a single-center observational study of consecutive patients diagnosed with an ACUM, who had undergone an ultrasound examination by an experienced ultrasound examiner between January 2013 and May 2019, identified retrospectively from medical records. ACUM was diagnosed when a cavitated lesion with a myometrial mantle and echogenic contents was seen within the anterolateral wall of the myometrium beneath the insertion of the round ligament. In all women, presenting symptoms and clinical history were recorded along with detailed descriptions of the lesions and any concomitant pelvic abnormalities. RESULTS: Twenty patients diagnosed with an ACUM were identified. Median age was 29.2 (interquartile range, 25.0-35.8) years. None of the women was premenarchal or postmenopausal. All of the women reported painful periods or pelvic pain and none of them reported subfertility. Twelve of the ACUMs were in the right anterolateral myometrium and eight were in the left anterolateral myometrium. Both a myometrial mantle and a fluid-filled cavity were considered to be defining features on ultrasound. The fluid contained within the cavity was either echogenic with a ground-glass appearance or hyperechoic. All of the lesions were spherical in shape. The Doppler flow seen in the outer rim was not markedly different from that of the surrounding myometrium, and the content of the cavity was avascular on Doppler examination. The mean outer cavity diameter of the ACUMs was 22.8 (95% CI, 20.9-24.8) mm and the mean internal cavity diameter was 14.1 (95% CI, 12.2-16.1) mm. Four women opted for transvaginal ultrasound-guided alcohol sclerotherapy. Surgical excision was carried out in eight cases, and the diagnosis was confirmed on histopathological examination in all of them. CONCLUSIONS: ACUMs are a uterine abnormality with a distinct ultrasound appearance, which are associated with dysmenorrhea and chronic pelvic pain. Knowledge of their typical appearance on ultrasound could facilitate early detection and treatment. There are several treatment options for ACUM, ranging from simple analgesia to complete excision. Further prospective and longitudinal studies are required to study the prevalence and natural history of this condition. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.