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Trial design A randomised, parallel-group, double-blind, placebo-controlled multicentre study with health economic and nested qualitative studies to determine if mifepristone (Mifegyne®, Exelgyn, Paris, France) plus misoprostol is superior to misoprostol alone for the resolution of missed miscarriage. Methods Women diagnosed with missed miscarriage in the first 14 weeks of pregnancy were randomly assigned (1 : 1 ratio) to receive 200 mg of oral mifepristone or matched placebo, followed by 800 μg of misoprostol 2 days later. A web-based randomisation system allocated the women to the two groups, with minimisation for age, body mass index, parity, gestational age, amount of bleeding and randomising centre. The primary outcome was failure to pass the gestational sac within 7 days after randomisation. The prespecified key secondary outcome was requirement for surgery to resolve the miscarriage. A within-trial cost-effectiveness study and a nested qualitative study were also conducted. Women who completed the trial protocol were purposively approached to take part in an interview to explore their satisfaction with and the acceptability of medical management of missed miscarriage. Results A total of 711 women, from 28 hospitals in the UK, were randomised to receive either mifepristone plus misoprostol (357 women) or placebo plus misoprostol (354 women). The follow-up rate for the primary outcome was 98% (696 out of 711 women). The risk of failure to pass the gestational sac within 7 days was 17% (59 out of 348 women) in the mifepristone plus misoprostol group, compared with 24% (82 out of 348 women) in the placebo plus misoprostol group (risk ratio 0.73, 95% confidence interval 0.54 to 0.98; p = 0.04). Surgical intervention to resolve the miscarriage was needed in 17% (62 out of 355 women) in the mifepristone plus misoprostol group, compared with 25% (87 out of 353 women) in the placebo plus misoprostol group (risk ratio 0.70, 95% confidence interval 0.52 to 0.94; p = 0.02). There was no evidence of a difference in the incidence of adverse events between the two groups. A total of 42 women, 19 in the mifepristone plus misoprostol group and 23 in the placebo plus misoprostol group, took part in an interview. Women appeared to have a preference for active management of their miscarriage. Overall, when women experienced care that supported their psychological well-being throughout the care pathway, and information was delivered in a skilled and sensitive manner such that women felt informed and in control, they were more likely to express satisfaction with medical management. The use of mifepristone and misoprostol showed an absolute effect difference of 6.6% (95% confidence interval 0.7% to 12.5%). The average cost per woman was lower in the mifepristone plus misoprostol group, with a cost saving of £182 (95% confidence interval £26 to £338). Therefore, the use of mifepristone and misoprostol for the medical management of a missed miscarriage dominated the use of misoprostol alone. Limitations The results from this trial are not generalisable to women diagnosed with incomplete miscarriage and the study does not allow for a comparison with expectant or surgical management of miscarriage. Future work Future work should use existing data to assess and rank the relative clinical effectiveness and safety profiles for all methods of management of miscarriage. Conclusions Our trial showed that pre-treatment with mifepristone followed by misoprostol resulted in a higher rate of resolution of missed miscarriage than misoprostol treatment alone. Women were largely satisfied with medical management of missed miscarriage and would choose it again. The mifepristone and misoprostol intervention was shown to be cost-effective in comparison to misoprostol alone. Trial registration Current Controlled Trials ISRCTN17405024. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 68. See the NIHR Journals Library website for further project information.

Background\ud The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. However, it is unclear whether a combination of mifepristone and misoprostol is more effective than administering misoprostol alone. We investigated whether treatment with mifepristone plus misoprostol would result in a higher rate of completion of missed miscarriage compared with misoprostol alone. \ud \ud Methods\ud MifeMiso was a multicentre, double-blind, placebo-controlled, randomised trial in 28 UK hospitals. Women were eligible for enrolment if they were aged 16 years and older, diagnosed with a missed miscarriage by pelvic ultrasound scan in the first 14 weeks of pregnancy, chose to have medical management of miscarriage, and were willing and able to give informed consent. Participants were randomly assigned (1:1) to a single dose of oral mifepristone 200 mg or an oral placebo tablet, both followed by a single dose of vaginal, oral, or sublingual misoprostol 800 μg 2 days later. Randomisation was managed via a secure web-based randomisation program, with minimisation to balance study group assignments according to maternal age (

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

OBJECTIVES To assess how nausea and vomiting in pregnancy (NVP) and hyperemesis gravidarum (HG) are managed and treated across primary and secondary care. DESIGN Population-based pregnancy cohort. SETTING Medical records (CPRD-GOLD) from England. POPULATION 417 028 pregnancies during 1998-2014. METHODS Proportions of pregnancies with recorded NVP/HG diagnoses, primary care treatment, and hospital admissions were calculated. Multinomial logistic regression was employed to estimate adjusted relative risk ratios (aRRRs) with 99% confidence intervals (CIs) for the association between NVP/HG management paths and maternal characteristics. MAIN OUTCOME MEASURES NVP/HG diagnoses, treatments, and hospital admissions. RESULTS Overall prevalence of clinically recorded NVP/HG was 9.1%: 2.1% had hospital admissions, 3.4% were treated with antiemetics in primary care only, and 3.6% had only recorded diagnoses. Hospital admissions and antiemetic prescribing increased continuously during 1998-2013 (trend P

The aim of this study was to determine whether serum concentrations of Ang-1, Ang-2, Flt-1, IL-15 and/or TRAIL can be used to predict outcome in women with pregnancies of uncertain viability (PUVs). Women presenting to the Early Pregnancy Unit at the Queen’s Medical Centre in Nottingham between 17.06.14 and 01.09.15 were prospectively recruited. Serum concentrations of Ang-1, Ang-2, Flt-1, IL-15 and TRAIL were measured in women with PUVs. Women were followed-up according to departmental protocols until viability was determined. Biomarker concentrations were correlated with pregnancy outcome. Ninety-four PUVs were studied, of which 61 (64.9%) were subsequently proven to be viable. There were statistically significant (p

The combined oral contraceptive (COC) pill has been used in patients undergoing IVF treatment to schedule the treatment cycle, to improve the ovarian response in poor responders and, somewhat paradoxically therefore, to also reduce the incidence of ovarian hyperstimulation syndrome in women with polycystic ovarian disease. Most of the evidence is based on its pretreatment use in conjunction with gonadotrophin-releasing hormone agonist protocols used during IVF. Pretreatment with the COC might reduce the formation of functional ovarian cysts during the initial phase of pituitary suppression and allow a more homogenous follicle population to develop during controlled ovarian stimulation. While the requirement for gonadotrophins may increase with the pretreatment use of the COC and the clinical pregnancy rates reduce, live birth rates do not appear to be affected. This report revisits the current evidence on the role of the COC in patients undergoing IVF treatment and its potential role in assisted reproduct...

Objective To evaluate the relationship between serum anti-Mullerian hormone (AMH) and antral follicle size, and to ascertain which cohort of antral follicles is most predictive of the response to controlled ovarian stimulation during assisted reproduction treatment (ART). Design Prospective study. Setting University-based Assisted Conception Unit. Patient(s) One hundred thirteen women undergoing first cycle of ART. Intervention(s) Transvaginal 3D-ultrasound assessment and venipuncture in the early-follicular phase of the menstrual cycle. Main Outcome Measure(s) Serum AMH levels, number of mature oocytes retrieved and poor ovarian response. Result(s) The antral follicle cohorts measuring 2 to 3 mm, >3 to 4 mm, >4 to 5 mm, and >5 to 6 mm were most significantly correlated with AMH ( r = .30, .27, .30, and .41, respectively) and the number of mature oocytes retrieved ( r = .28, .23, .29, and .34, respectively). Although these follicle cohorts of 2-6 mm were significant predictors of the number of mature oocytes retrieved on regression analysis, their discriminative ability (area under the curve [AUC]: 0.829) for the prediction of poor ovarian response was similar to total counts made using cohorts of 2 to 4 mm, 2 to 5 mm, 2 to 8 mm, and 2 to 10 mm (AUCs: 0.794, 0.812, 0.852, and 0.826, respectively). Conclusion(s) The number of antral follicles measuring 2 to 6 mm is most reflective of the quantitative ovarian reserve. However, the ability of this group of antral follicles to predict poor ovarian response appears similar to that of the follicular cohorts of 2 to 4 mm, 2 to 5 mm, 2 to 8 mm, and 2 to 10 mm.

Objective To evaluate the effect of a new automated technique of follicle measurement (Sono automated volume calculation [SonoAVC]) on the timing of oocyte maturation and subsequent oocyte retrieval. Design Prospective randomized controlled trial. Setting University-based Assisted Conception Unit. Patient(s) Seventy-two women undergoing their first cycle of assisted reproduction treatment. Intervention(s) The timing of final follicle maturation and oocyte retrieval based on follicle tracking with use of either conventional two-dimensional (2D) ultrasound or SonoAVC. Main Outcome Measure(s) The number of mature oocytes retrieved and clinical pregnancy rate. Result(s) The number of the mature oocytes collected (10.70 ± 6.08 vs. 11.43 ± 6.17), the number of fertilized oocytes (7.27 ± 4.78 vs. 7.97 ± 5.25), and the clinical pregnancy rates (42% vs. 43%) were similar with both 2D ultrasound and SonoAVC methods. Conclusion(s) Automated follicle tracking using SonoAVC identifies a comparable number of follicles to real-time 2D ultrasound in this preliminary study. Timing final follicle maturation and egg retrieval on the basis of these automated measures does not appear to improve the clinical outcome of assisted reproduction treatment.

The purpose of this study was to evaluate tissue damage caused by the PlasmaJetTM coagulator in the uterus, ovary, and fallopian tube at different power settings in vitro and then to examine the damage caused in vivo. In vitro evaluation included prospective recruitment of six subjects undergoing hysterectomy with or without salpingo-oophorectomy. Tissue damage was evaluated histologically for power levels at 10%, 15%, and 20%, and for duration of 2 and 5 s at a clinically acceptable distance of 0.5 to 1 cm between the tip of probe and tissue. In vivo evaluation included 15 subjects undergoing hysterectomy with or without salpingo-oophorectomy. The most suitable power setting and duration of diathermy was decided from in vitro examination and applied on in vivo setting. Tissue damage was evaluated histologically. There was no significant difference seen in the depth and width of tissue damage in the in vitro specimens at different low power levels and duration of diathermy (P > 0.05). A setting of 20% power and duration of 5 s of diathermy was used therefore for in vivo setting. Mean ± SD depth (millimetres) of tissue damage in uterus, ovary, and fallopian tube were 0.63 ± 0.19, 0.61 ± 0.14, and 0.63 ± 0.18, respectively. Mean ± SD width (millimetres) of tissue damage in uterus, ovary, and fallopian tube were 4.66 ± 0.05, 4.05 ± 0.61, and 4.51 ± 0.77, respectively. Irrespective of tissue type, the average depth and width of tissue damage with application of PlasmajetTM coagulator for 5 s at low power is 0.62 and 4.24 mm, respectively. It therefore appears to be a safe method of coagulation in vitro and in vivo at 20% power on gynaecological tissues.

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.

Sono-automatic volume calculation (SonoAVC) automatically identifies and measures the dimensions of hypoechogenic areas within datasets acquired using three-dimensional ultrasound. The objective of this study was to evaluate the predictive value of automated antral follicle counts according to their relative sizes in women undergoing assisted reproduction treatment (ART).A total of 156 subjects agedor =40 years with a baseline FSHor =15 IU that undergo their first cycle of ART were prospectively recruited. SonoAVC was used to measure the datasets and record the number of antral follicles measuringor =9 mm in diameter. These follicles were then grouped into subsets according to their relative sizes:or =2.0, 2.1-4.0, 4.1-6.0, 6.1-8.0 and 8.1-9.0 mm. The primary outcome was viable pregnancy confirmed on ultrasound 5 weeks following embryo transfer.A total of 142 subjects were included for analysis of primary end-point. Those subjects who conceived had significantly more antral follicles measuringor =2 (P = 0.041) and 2.1-4.0 mm (P0.001) than those who had unsuccessful treatment. There were no significant differences between the groups in the number of antral follicles measuring 4.1-6.0 (P = 0.191), 6.1-8.0 (P = 0.203) and 8.1-9.0 mm (P = 0.601). Multiple logistic regression showed that antral follicles measuring 2.1-4.0 mm were an independent predictor of pregnancy [Exp(B) = 1.234, 95% CI = 1.092-1.491; P = 0.004; AUC = 0.693].SonoAVC provides automated measures of antral follicle number and size. Using this technique, the number of antral follicles measuring 2.1-4.0 mm in diameter is an independent, significant predictor of pregnancy following in vitro fertilization treatment.

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.

The management of subfertility involves a detailed assessment of the couple to identify factors that may affect or predict the outcome of treatment. Three-dimensional imaging is one of the recent advances in the field of ultrasound which has several obvious benefits that relate to an improved spatial orientation and the demonstration of additional image planes such as the coronal plane. Many clinicians remain unconvinced by its reputed advantages and three-dimensional ultrasound is not without disadvantages. These mainly relate to the cost involved and training requirements. Threedimensional ultrasound imaging is still at a relatively early stage in terms of its role as a day-to-day imaging modality in gynecology and reproductive medicine. Other than its application in the assessment and differentiation of uterine anomalies there is little evidence that three-dimensional ultrasound results in clinically-relevant benefit or negates the need for further investigation. Future work should ensure that three-dimensional ultrasound is compared to conventional imaging in randomized trials where the observer is blinded to the outcome such that its role in reproductive medicine can be truly evaluated in an evidence-based manner.

Objective To survey the preferences and variations in the current use of first- and second-generation endometrial ablative techniques for menorrhagia among the consultant gynecologists in the United Kingdom, given the call for further studies to systematically compare the clinical effectiveness of the various endometrial ablation techniques. Design Postal questionnaire survey. Population One thousand, four hundred sixty consultant gynecologists in the United Kingdom. Main Outcome Measure(s) Preferred endometrial ablation/resection method and variations in the current practices. Result(s) Six hundred ten (41%) consultants responded. Of these, 449 (73%) performed endometrial ablation/resection. Thermal balloon ablation (32.1%) was the preferred method, followed by microwave endometrial ablation (29.8%), transcervical resection of the endometrial alone or combined with roller ball diathermy (18.5%), Novasure (9.8%), hydrotherm ablation (6.9%), roller ball (2%), and laser (0.9%). Patient response to treatment was assessed using clinical history (64.3%), menstrual calendar (7.6%), clinical history and menstrual calendar (21.3%), questionnaires (5.8%), and pictorial blood loss assessment charts (0.4%). A total of 52.2% used gonadotrophin releasing hormone analogues preoperatively. Variations in techniques for transcervical resection of the endometrial included methods used to treat the uterine fundus and cornuae, fluid management, and operating pressures. Conclusion(s) Second-generation endometrial ablation devices were preferred to first-generation devices for the management of menorrhagia. Thermal balloon ablation was the most preferred method. However, variations in surgical practices will make assessment of clinical efficacy a challenge.

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.

A prospective study of 125 patients diagnosed with first trimester miscarriage was carried out in order to compare management outcomes and patient satisfaction. Miscarriage managed medically and surgically was compared. A comfort score between 1 and 5 (1 very uncomfortable, 5 no discomfort) was given by each patient during, where appropriate, and following the intervention; rates of success (determined by negative scan/absence of re-presentation) and whether the patient required subsequent admission to hospital/delayed stay (deemed as >24 h) were also recorded. Manual vacuum aspiration (MVA) compared favourably vs other procedures with a mean comfort score during procedure of 2.61 vs 3.9 in medical management and a mean comfort score post procedure of 3.95 vs 4.0 for MMM and 3.81 for surgical management. Similarly, MVA demonstrated a lower failure rate (2.5%) vs MMM (68%) and SMM (10%) and none required admission or a delayed stay vs MMM (4%) and SMM (10%).

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.

The PlasmaJet (PJ) coagulator uses neutral pure argon plasma to achieve coagulation. Helica thermal coagulator (HTC) achieves coagulation with helium gas. HTC is currently used in the treatment of mild to moderate endometriosis.The objective of this study was to compare the tissue damage caused by PJ to the HTC in the uterus, ovary and fallopian tube. Our hypothesis was that PJ is a safe technology to use and the tissue damage caused is comparable to HTC.Fifteen subjects undergoing hysterectomy with or without salpingo-oophorectomy were prospectively recruited for in vivo assessment of the two instruments. Both instruments were used on a small area of uterus, ovary and fallopian tube following the ligation of uterine artery pedicle. PJ was used at a power setting of 20 % for duration of 5 s at a clinically acceptable distance of 0.5 to 1 cm from the tissue surface. HTC was used at a widely accepted low power setting in the treatment of endometriosis for a similar duration and distance. Tissue damage was evaluated histologically. ANOVA was used to compare the mean differences.Data were normally distributed. Five subjects had a subtotal hysterectomy and 10 had hysterectomy with salpingo-oophorectomy. A total of 15 uteri, 10 ovaries and 10 fallopian tubes were histologically analysed for the tissue effect of PJ and HTC. There was no significant difference in the mean ± SD depth of tissue damage seen between PJ and HTC in the uterus (0.63 ± 0.19 vs. 0.68 ± 0.18; P = 0.481), ovary (0.61 ± 0.14 vs. 0.67 ± 0.15; P = 0.420) and fallopian tube (0.63 ± 0.18 vs. 0.60 ± 0.13; P = 0.688). A significantly lesser lateral spread of tissue damage (width) was seen with PJ than HTC in all three tissue types (uterus: 4.66 ± 0.91 vs. 7.67 ± 1.21, P0.001; ovary: 4.05 ± 0.61 vs. 5.90 ± 0.95, P0.001; fallopian tube: 4.50 ± 0.77 vs. 6.00 ± 1.28, P = 0.034).The depth of tissue damage caused by PJ at 20 % power is comparable to that with HTC on gynaecological tissues. The lateral spread (width of tissue damage) is however lesser with PJ than with HTC.

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.

This study tested the hypothesis that the automated assessment of a stimulated ovary, using 3D ultrasound and sono-AVC (automatic volume calculation), provides quicker analysis of follicular number and size than conventional 2D ultrasound, without any loss in measurement validity. Transvaginal ultrasound was performed on day 10 of stimulation in 89 prospectively recruited subjects undergoing IVF treatment. The number and mean diameter of follicles present in both ovaries was measured manually using 2D ultrasound. 3D data were then acquired and analysed using sono-AVC. Outcome measures included the number of follicles with a mean diameter >9 mm, >13 mm and >17 mm. The time taken for measurements and data acquisition was recorded. The two methods were compared using a paired t-test or the Wilcoxon signed rank test. Complete data were available for 82 subjects. There was no significant difference in the number of follicles with mean diameters >9 mm, >13 mm and >17 mm measured by either method. The total time taken for follicular measurements was significantly less (P < 0.01) for the automated 3D method (180.5 +/- 63.6 versus 236.1 +/- 57.1 s) which was associated with significantly less exposure to ultrasound (39.0 +/- 6.0 versus 236.10 +/- 57.1 s; P < 0.001). Automated 3D follicular measurements using sono-AVC provide a comparable but quicker assessment of follicle number and size.

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.