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Objectives To determine anxiety levels of women presenting to Early Pregnancy Assessment Units (EPAU) with abdominal pain and/or vaginal bleeding and assess how these change over time and according to ultrasonographic diagnosis. Methods We undertook a prospective cohort study in a EPAU in a large UK teaching hospital. Women with abdominal pain and/or vaginal bleeding in early pregnancy (less than 12 weeks gestation) presenting for the first time were eligible for inclusion in the study. State anxiety levels were assessed using the standardised short form of Spielberger's state-trait anxiety inventory on three occasions (before, immediately after and 48–72 hours after an ultrasound scan). Scores were correlated with ultrasonographic diagnosis. The diagnosis was either certain or uncertain. Certain diagnoses were either positive i.e. a viable intrauterine pregnancy (IUP), or negative i.e. a non-viable IUP or ectopic pregnancy (EP). Uncertain diagnoses included pregnancies of unknown location (PUL) and uncertain viability (PUV). Statistical analysis involved mixed ANOVAs and the post-hoc Tukey-Kramer test. Results 160 women were included in the study. Anxiety levels decreased over time for women with certain diagnoses (n = 128), even when negative (n = 64), and increased over time for women with uncertain diagnoses (n = 32). Before the ultrasound, anxiety levels were high (21.96 ± 1.11) and there was no significant difference between the five groups. Immediately after the ultrasound, anxiety levels were lower in the viable IUP group (n = 64; 7.75 ± 1.13) than any other group. The difference between the five groups was significant (p

Ultrasound has become an essential tool for the assessment and management of women undergoing assisted reproduction treatment. Ultrasound permits the screening of women prior to treatment and prediction of ovarian reserve and endometrial receptivity, allows for direct monitoring of response to controlled ovarian stimulation, and facilitates oocyte retrieval and embryo transfer. While 3D ultrasound and recently introduced software, such as sonographic automated volume count, have the potential to improve the workflow of fertility units, their use is currently limited in the research setting. This article critically evaluates the available evidence in an attempt to establish the current role of both conventional and advanced ultrasound in the management of women undergoing assisted reproduction treatment.

Objectives To compare two-dimensional (2D) ultrasound imaging with automated three-dimensional (3D) ultrasound imaging for the measurement of antral follicle number and size. Methods Twenty-four subjects aged < 40 years underwent transvaginal ultrasound examination (Voluson E8) in the early follicular phase of the menstrual cycle. A 2D ultrasound scan of both ovaries was performed; each antral follicle was identified and then measured by taking the mean of two diameters. A 3D ultrasound dataset of both ovaries was then acquired and analyzed using Sonography-based Automated Volume Count (SonoAVC™). The time taken to measure the size of all antral follicles in both ovaries was recorded in seconds for each technique. Antral follicle size was recorded to the nearest millimeter and counts for each 1-mm group were obtained. Antral follicle counts were also grouped according to five predefined size categories: 2.0–5.0 mm, 2.0–6.0 mm, 2.0–8.0 mm, 2.0–9.0 mm and 2.0–10.0 mm. Limits of agreement (LOA) and a paired t-test or Wilcoxon signed ranks test were used to analyze the data depending on their distribution. Results When antral follicle numbers were compared for each 1-mm follicle size group, 2D ultrasound imaging recorded more follicles measuring 3.0–3.99 mm (mean ± SD, 4.11 ± 3.70 vs. 2.63 ± 2.31; P = 0.019) and 4.0–4.99 mm (mean ± SD, 4.63 ± 4.86 vs. 2.68 ± 2.89; P = 0.013) than did SonoAVC. LOA were widest with follicles measuring 3.0–3.99 mm (LOA, 6.38 and −3.43) and 4.0–4.99 mm (LOA, 7.99 and −4.09). The antral follicle count in each of the five predefined size categories was significantly lower with SonoAVC than with 2D ultrasound imaging (P < 0.05). SonoAVC took significantly less time to measure the size and record the number of antral follicles than did 2D ultrasound imaging (mean ± SD, 132.05 ± 56.23 s vs. 324.47 ± 162.22 s; P < 0.001). Conclusions Fewer antral follicles are evident overall when SonoAVC is used to analyze 3D ultrasound data. The clinical significance of this remains to be determined but the automated technique is significantly quicker than is making measurements using 2D ultrasound imaging. Copyright © 2010 ISUOG. Published by John Wiley & Sons, Ltd.

Objective To assess the reliability of automated measurements of the total antral follicle count (AFC) made using Sono-Automatic Volume Count (SonoAVC), and to compare these to two-dimensional (2D) and manual three-dimensional (3D) techniques. Methods Fifty-five subjects aged under 40 years who had 3D transvaginal ultrasound examination in the early follicular phase of their menstrual cycle were prospectively recruited. 3D datasets were acquired and subsequently analyzed. The total AFC (2–10 mm antral follicles) was calculated by two observers using three independent methods: 2D real-time equivalent (2D-RTE), 3D manual multiplanar view (3D-MPV), and SonoAVC. For measurements made using SonoAVC, the initial automated count (sAVC-AA) was recorded and postprocessing (sAVC-PP) then applied to identify follicles that had been missed or incorrectly included. Intraclass correlation and limits of agreement were used to evaluate the methods. Results The intra- and interobserver reliability of measurements of total AFC was best with SonoAVC with postprocessing followed by 3D-MPV and 2D-RTE. The initial count calculated by sAVC-AA missed follicles and this was reflected in the significantly lower mean total AFC (6.51 ± 4.79) than that made after postprocessing techniques (sAVC-PP, 18.42 ± 10.53, P < 0.001; 3D-MPV, 19.38 ± 10.85, P < 0.001; and 2D-RTE, 19.26 ± 10.55, P < 0.001). The mean total AFC became more comparable with postprocessing (sAVC-PP) but still remained significantly lower than counts made with 2D-RTE and 3D-MPV (P < 0.05). Conclusion SonoAVC with postprocessing is a reliable method for measuring total AFC. It takes longer to perform, because of the need for postprocessing, and obtains values that are lower than those obtained by the 2D and 3D-MPV techniques. However, the AFC obtained by sAVC-PP is likely to be lower because this method measures and color codes each follicle preventing recounting. Copyright © 2009 ISUOG. Published by John Wiley & Sons, Ltd.

Endometriosis is a common condition, affecting somewhere between 5% and 60% of women of reproductive age and approximately 2 million women in the UK. The exact prevalence is difficult to ascertain and varies according to diagnostic criteria used and the populations studied, varying from 2 to 50% in women without symptoms, 40 to 60% in women with dysmenorrhea, and 20 to 30% in women with subfertility1,2. The etiology is unknown, but the disease is characterized by the objective demonstration of endometrial-like tissue outside the uterus. The condition is seen predominantly in women of reproductive age, and it occurs in all ethnic and social groups. Whilst extrapelvic disease can occur, endometriosis typically affects the pelvic organs and peritoneum. Disease severity is assessed semi-quantitatively at laparoscopy or laparotomy and is scored according to the American Society for Reproductive Medicine3, but is a poor predictor of the patient’s symptoms in many cases. The extent of the disease varies considerably; it may involve small areas of the peritoneum alone, or be associated with significant fibrosis, adhesions and nodular infiltration, in different individuals with the same symptoms1. The ovary may be involved only superficially or can contain a cyst lined with endometrial-like tissue known as an ‘endometrioma’. Endometriotic cysts have always been a controversial entity. There is no consensus as to the pathological processes which define their development or to their management in terms of the timing, type and effects of surgery. Opinion is divided as to whether these cysts arise from progressive invagination of endometriotic deposits on the ovarian cortex4,5, from metaplasia of epithelial inclusions in the ovary5,6 or because of secondary involvement of functional ovarian cysts in the endometriotic process7. The invagination theory is accepted by most, but there is no agreement as to whether the endometrial cells are superficial ovarian implants of endometriosis or they are derived through metaplastic transformation of normal ovarian cortical tissue. The invagination theory is supported by histological studies, which consistently show that these cysts are pseudocysts, with no real plane of cleavage between the endometrialtype stroma and the ovarian cortex, containing an obliterated, mostly endometrial-gland, lining8. The walls of an endometrioma are initially thin, but subsequently become fibrotic and thickened, and can give the cyst an irregular external border. Endometriomata are typically small, with 81% measuring between 30 and 59 mm in diameter9, although they can reach 15–20 cm in diameter. Is an isolated endometrioma a different disease from peritoneal endometriosis? Many women are found to have an endometrioma without evidence of peritoneal disease, and the pathophysiological mechanisms that determine how the disease is expressed remain unclear. Women with peritoneal endometriosis are thought to have reduced fertility, and surgical treatment may improve fecundity in those with minimal to mild disease10. Just how endometriosis affects fertility is unknown, but any effect probably relates to anatomical distortion and immobilization of the pelvic organs through adhesion formation and organ infiltration and/or a change in the peritoneal environment to one that is less favorable for fertilization and embryo implantation. The effect of an isolated endometrioma on fertility is less clear, and there is no definitive evidence that fertility is impaired. However, surgical intervention is often recommended when an endometrioma measures more than 3–4 cm in diameter11 and so, unsurprisingly, endometriomata represent the most frequently reported histological subtype following operative laparoscopy for the excision of ovarian cysts12. Preoperative detection of endometriomata is therefore important, and ultrasound is the investigative tool of choice in most cases. Conventional two-dimensional ultrasound has an established role in the detection of adnexal masses and in their differentiation through pattern recognition of characteristic morphological patterns13. Most studies use transvaginal rather than transabdominal ultrasound, as this approach allows a closer approximation of the probe to the ovary and the use of higher frequencies, which provide better resolution. However, transvaginal

We present a case of Cesarean scar ectopic pregnancy, complicated by the persistence of clinical symptoms despite a rapid and complete biochemical response to a single systemic injection of methotrexate. A 34-year-old woman with three previous Cesarean sections was diagnosed with a Cesarean scar ectopic pregnancy following @ in-vitro fertilization treatment. The diagnosis was suggested by three-dimensional (3D) ultrasound scan and confirmed with magnetic resonance imaging (MRI). Management involved administration of a single systemic injection of methotrexate and follow-up with serial ultrasound assessments and serum beta-human chorionic gonadotropin (β-hCG) measurements. The main challenge was the persistence of clinical symptoms despite adequate medical treatment, as judged by complete resolution of biochemical trophoblastic activity, which resulted in repeated admissions to the hospital. Serial transvaginal ultrasound scans showed an initial increase in the size of the mass, which led to increasing anxiety in the couple. Eventually, 15 weeks after the administration of methotrexate, the couple requested surgical intervention. An uneventful surgical resection of the abnormal area, which showed appearances suggestive of trophoblastic tissue, was undertaken to good effect. In summary, despite a rapid normalization of serum β-hCG following the administration of methotrexate, the patient remained symptomatic and had ultrasound appearances suggestive of incomplete resorption of trophoblast, necessitating surgical intervention. Copyright © 2007 ISUOG. Published by John Wiley & Sons, Ltd.

To quantify the intracycle variation in markers of ovarian reserve measured by antral follicle counts stratified by size using three-dimensional (3D) ultrasound and anti-Müllerian hormone (AMH) in women with normal menstrual cycles.Healthy volunteers with normal menstrual cycles were prospectively recruited. Three-dimensional (3D) ultrasound examination and blood test were performed in early (F1) and mid-follicular (F2) phases and in periovulatory (PO) and luteal (LU) phases of one menstrual cycle. Antral follicles were measured using 'sonography-based automated volume calculation' with post processing (SonoAVC) and ovarian volume was measured using Virtual Organ Computer-aided AnaLysis (VOCAL). Blood serum was processed for hormonal assays including AMH, follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol. Repeated-measures analysis was used to examine the variance in markers of ovarian reserve in different phases of one menstrual cycle.A total of 36 volunteers were included in the final analysis, of whom 34 attended all four visits. Repeated-measures analysis showed a significant variation in total antral follicle count (AFC) (P 0.001). However, on stratifying the antral follicles according to size using SonoAVC, a non-significant variation (P = 0.382) was seen in small AFC (≤ 6.0 mm) and a significant variation (P 0.001) was seen in large AFC (6.0 mm). The ovarian volume showed a significant intracycle variation (P 0.001). A small but significant intracycle variation was noted in AMH (P = 0.041) and a significant variation was seen in levels of serum FSH, LH and estradiol (P 0.05).Small antral follicles (≤ 6.0 mm) measured using 3D ultrasound and AMH show little intracycle variation and perhaps should be evaluated when predicting ovarian reserve independent of menstrual cycle.

OBJECTIVES: Oral contraceptive pills suppress the hypothalomo-pituitary axis which can affect the ultrasound and endocrine markers used to examine ovarian reserve. The objective of this study was to quantify the ultrasound and endocrine markers of functional ovarian reserve in women using a combined oral contraceptive pill (COCP) for more than a year. METHODS: This was a prospective case-control study involving healthy volunteers: 34 women using for more than a year a COCP with hormone-free interval (HFI) were compared to 36 normo-ovulatory age-matched controls who had not used hormonal contraception within the last year. Volunteers using a COCP underwent a 3D ultrasound examination and had a blood sample taken within the first 4 days of active pill ingestion and those in the control group had the scan and blood test in the early follicular phase (days 2-5) of menstrual cycle. The main outcome measure was the difference in antral follicle counts stratified according to size and anti-Mullerian hormone (AMH) follicle-stimulating hormone (FSH) luteinizing hormone (LH) and estradiol (E2) levels. RESULTS: There were no significant differences in the number of small antral follicles measuring 2-6 mm. The COCP group had significantly fewer antral follicles measuring >/= 6 mm (P < 0.001) and had significantly smaller ovaries (P < 0.001) which also had lower vascular indices than the control group (P < 0.05). While serum FSH LH and E2 levels were significantly lower in the COCP group (P < 0.05) there was no significant difference in serum AMH levels between the two groups. CONCLUSIONS: Prolonged use of COCP suppressed pituitary gonadotropins and antral follicle development beyond 6 mm but had no effect on levels of serum AMH and number of small antral follicles. Copyright (c) 2012 ISUOG. Published by John Wiley & Sons Ltd.

Objective To estimate the prevalence of congenital uterine anomalies in subfertile women and to evaluate their influence on early pregnancy following assisted reproduction treatment (ART). Methods We prospectively recruited 1402 subjects undergoing ART over a period of 5 years from 2005 to 2009. Three-dimensional transvaginal sonography was performed in the early follicular phase of the menstrual cycle (days 2–5) and repeated in the late follicular phase (days 10–14) if the shape of the uterine cavity could not be assessed at the first scan. All subjects who conceived following ART were followed up to 12 weeks' gestation. Chi-square test was used to compare the pregnancy rates and miscarriage rates between women shown to have uterine anomalies and those with a normal uterus. Results One thousand three hundred and eighty-five subjects were included for final analysis after excluding 17 subjects in whom a definitive diagnosis could not be made. While 1201 (86.7%) subjects had a normal uterine cavity, uterine anomalies were demonstrated in 184 (13.3%) subjects. Arcuate uteri represented the commonest anomaly (n = 164 (11.8%)) followed by septate (n = 7 (0.5%)), unicornuate (n = 6 (0.4%)), subseptate (n = 5 (0.4%)), bicornuate (n = 1 (0.1%)) and T-shaped uteri (n = 1 (0.1%)). A total of 440 subjects who underwent ART were followed up. The pregnancy rates in women with arcuate uteri (36/66 (54.5%)) and major uterine anomalies (7/10 (70.0%)) were statistically similar (P = 0.09 and P = 0.11, respectively) to that of the matched controls with normal uteri (158/364 (43.4%)). While first-trimester miscarriage rates were similar (P = 0.81) between the control group (20/158 (12.7%)) and women with arcuate uteri (5/36 (13.9%)), women with major uterine anomalies experienced a higher miscarriage rate (3/7 (42.9%); P = 0.05). Conclusions Women who are referred for ART have a high prevalence of congenital uterine anomalies, the most common anomaly being an arcuate uterus. These anomalies are not associated with a reduction in pregnancy rates following ART. However, while the arcuate uterus was not associated with an increase in first-trimester miscarriage, major uterine anomalies seemed to increase the risk of first-trimester miscarriage. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

Objectives: Three-dimensional (3D) ultrasound assisted sonographybased automated volume calculation (SonoAVC) and 2D ultrasound have been described in counting and measuring the size of antral follicles. This study was designed to validate the count and size of antral follicles measured using SonoAVC and 2D against the actual size and number of follicles assessed by dissecting the bovine ovaries. Methods: 3D Ultrasound scan was performed on 22 bovine ovaries. Antral follicles were counted and measured using SonoAVC on multiplanar view and 2D real-time equivalent method on longitudinal and transverse planes of the dataset. All visible antral follicles were dissected manually and measured using a microscope. Ovarian volume calculated using volume displacement (VD) method was compared to Virtual Organ Computer-aided AnaLysis (VOCAL) and 2D method (volume for an ellipsoid). Student’s t test and limits of agreement (LOA) were used to evaluate the methods. Results: The mean ovarian volume calculated by VD was comparable to VOCAL (P = 0.338), but larger than 2D (P 4.0–6.0 mm and > 6.0–10.0 mm showed no significant difference between either methods (P < 0.05), but LOA between MD and SonoAVC were narrower than between MD and 2D. Conclusions: SonoAVC with post-processing underestimates and 2D overestimates the number of antral follicles measuring 4.0 mm or less, but both make comparable counts of follicles measuring more than 4.0 mm when compared with the antral follicles dissected manually. The agreement with SonoAVC with post-processing was more than that with 2D.

This study addresses quantifying the effect of the combined oral contraceptive pill (COCP) on the ultrasonographic and endocrine markers of ovarian reserve.

(endometrial irrigation day) and 12th days after first menstrual day. The 2D power Doppler mid-sagittal uterine images (at peak systolic and end-diastolic vascular filling) were obtained under standard sonographic preset. The endometrial region of interest (ROI) was defined in the images. Mean endometrial color intensity (CI) and endometrial vascular ratio (VR) (color/total pixels in the ROI) were calculated by a special computer program for the systolic and diastolic images. CI and VR systolic-to-diastolic ratios were further calculated (S/D-CI and S/D-VR). Results: S/D-VR decreased significantly from the 5th to the 12th day NSI cycles (1.87 ± 0.54 to 0.69 ± 0.27, correspondingly), p-value < 0.05. Post-irrigation results of S/D-VR were significantly higher in OSI compared to NSI (1.59 ± 0.47 and 0.69 ± 0.27), p-value < 0.05. S/D-CI did not change significantly along the studied days and were similar in NSI and OSI cycles. Conclusions: S/D-VR decreases along the follicular phase in NSI cycles in contrast to the post-irrigation increase in S/D-VR in OSI cycles. Several speculative explanations may be suggested for such endometrial vascular response.

subjects had normal ovarian response with retrieval of 4–15 oocytes in the absence of OHSS. Ovarian vascularity (vascularisation index, VI; flow index, FI; and vascularisation flow index, VFI), total antral follicle count (AFC), and mean ovarian volume (OV) were measured. ANOVA and Kruskal Wallis test were used to compare the groups dependent on the distribution of the data. Multiple logistic regression analysis was used to compare the predictive value of these variables against age and basal FSH for the development of poor response and OHSS. Results: The ovarian VI, FI, and VFI were similar in all three groups (Table 1). Compared to controls, AFC and OV were significantly lower (P < 0.001) in poor responders and significantly higher (P < 0.001) in subjects who developed OHSS. Multiple regression analysis showed the AFC was the only significant (P < 0.001) ultrasound predictor of poor or exaggerated ovarian response and that the 3D ovarian vascular indices offered no additional information.