Mifepristone and misoprostol versus placebo and misoprostol for resolution of miscarriage in women diagnosed with missed miscarriage: the MifeMiso RCT.

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.

Miscarriage is a common complication of pregnancy, affecting approximately one in four women. Sometimes, medical treatment (i.e. tablets) may be offered to start or speed up the miscarriage process in order for the womb to empty itself. A drug called misoprostol (a tablet that makes the womb contract) is currently recommended for this treatment. However, the addition of another drug called mifepristone [a tablet that reduces pregnancy hormones (Mifegyne^®, Exelgyn, Paris, France)] might help the miscarriage to resolve more quickly. Therefore, we carried out the MifeMiso trial to test if mifepristone plus misoprostol is more effective than misoprostol alone in resolving miscarriage within 7 days. Women were randomly allocated by a computer to receive either mifepristone or placebo, followed by misoprostol 2 days later. Neither the women nor their health-care professionals knew which treatment they received. Some women also talked to the researchers about their experiences of taking part in the study. In total, 711 women were randomised to receive either mifepristone plus misoprostol or placebo plus misoprostol. Overall, 83% of women who received mifepristone plus misoprostol had miscarriage resolution within 7 days, compared with 76% of the women who received a placebo plus misoprostol. Surgery was required less often in women who received mifepristone plus misoprostol: 17% of women who received it required surgery, compared with 25% of women who received the placebo. Treatment with mifepristone did not appear to have any negative effects. Treatment with mifepristone plus misoprostol was more cost-effective than misoprostol alone, with an average saving of £182 per woman. Having taken part in the study, most women would choose medical management again and would recommend it to someone they knew who was experiencing a miscarriage.

Mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage (MifeMiso): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: 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. METHODS: 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 (<30 years vs ≥30 years), body-mass index (<35 kg/m2vs ≥35 kg/m2), previous parity (nulliparous women vs parous women), gestational age (<70 days vs ≥70 days), amount of bleeding (Pictorial Blood Assessment Chart score; ≤2 vs ≥3), and randomising centre. Participants, clinicians, pharmacists, trial nurses, and midwives were masked to study group assignment throughout the trial. The primary outcome was failure to spontaneously pass the gestational sac within 7 days after random assignment. Primary analyses were done according to intention-to-treat principles. The trial is registered with the ISRCTN registry, ISRCTN17405024. FINDINGS: Between Oct 3, 2017, and July 22, 2019, 2595 women were identified as being eligible for the MifeMiso trial. 711 women were randomly assigned to receive either mifepristone and misoprostol (357 women) or placebo and misoprostol (354 women). 696 (98%) of 711 women had available data for the primary outcome. 59 (17%) of 348 women in the mifepristone plus misoprostol group did not pass the gestational sac spontaneously within 7 days versus 82 (24%) of 348 women in the placebo plus misoprostol group (risk ratio [RR] 0·73, 95% CI 0·54-0·99; p=0·043). 62 (17%) of 355 women in the mifepristone plus misoprostol group required surgical intervention to complete the miscarriage versus 87 (25%) of 353 women in the placebo plus misoprostol group (0·71, 0·53-0·95; p=0·021). We found no difference in incidence of adverse events between the study groups. INTERPRETATION: Treatment with mifepristone plus misoprostol was more effective than misoprostol alone in the management of missed miscarriage. Women with missed miscarriage should be offered mifepristone pretreatment before misoprostol to increase the chance of successful miscarriage management, while reducing the need for miscarriage surgery. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Progesterone to prevent miscarriage in women with early pregnancy bleeding: the PRISM RCT.

BACKGROUND: Progesterone is essential for a healthy pregnancy. Several small trials have suggested that progesterone therapy may rescue a pregnancy in women with early pregnancy bleeding, which is a symptom that is strongly associated with miscarriage. OBJECTIVES: (1) To assess the effects of vaginal micronised progesterone in women with vaginal bleeding in the first 12 weeks of pregnancy. (2) To evaluate the cost-effectiveness of progesterone in women with early pregnancy bleeding. DESIGN: A multicentre, double-blind, placebo-controlled, randomised trial of progesterone in women with early pregnancy vaginal bleeding. SETTING: A total of 48 hospitals in the UK. PARTICIPANTS: Women aged 16-39 years with early pregnancy bleeding. INTERVENTIONS: Women aged 16-39 years were randomly assigned to receive twice-daily vaginal suppositories containing either 400 mg of progesterone or a matched placebo from presentation to 16 weeks of gestation. MAIN OUTCOME MEASURES: The primary outcome was live birth at ≥ 34 weeks. In addition, a within-trial cost-effectiveness analysis was conducted from an NHS and NHS/Personal Social Services perspective. RESULTS: A total of 4153 women from 48 hospitals in the UK received either progesterone (n = 2079) or placebo (n = 2074). The follow-up rate for the primary outcome was 97.2% (4038 out of 4153 participants). The live birth rate was 75% (1513 out of 2025 participants) in the progesterone group and 72% (1459 out of 2013 participants) in the placebo group (relative rate 1.03, 95% confidence interval 1.00 to 1.07; p = 0.08). A significant subgroup effect (interaction test p = 0.007) was identified for prespecified subgroups by the number of previous miscarriages: none (74% in the progesterone group vs. 75% in the placebo group; relative rate 0.99, 95% confidence interval 0.95 to 1.04; p = 0.72); one or two (76% in the progesterone group vs. 72% in the placebo group; relative rate 1.05, 95% confidence interval 1.00 to 1.12; p = 0.07); and three or more (72% in the progesterone group vs. 57% in the placebo group; relative rate 1.28, 95% confidence interval 1.08 to 1.51; p = 0.004). A significant post hoc subgroup effect (interaction test p = 0.01) was identified in the subgroup of participants with early pregnancy bleeding and any number of previous miscarriage(s) (75% in the progesterone group vs. 70% in the placebo group; relative rate 1.09, 95% confidence interval 1.03 to 1.15; p = 0.003). There were no significant differences in the rate of adverse events between the groups. The results of the health economics analysis show that progesterone was more costly than placebo (£7655 vs. £7572), with a mean cost difference of £83 (adjusted mean difference £76, 95% confidence interval -£559 to £711) between the two arms. Thus, the incremental cost-effectiveness ratio of progesterone compared with placebo was estimated as £3305 per additional live birth at ≥ 34 weeks of gestation. CONCLUSIONS: Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with threatened miscarriage overall, but an important subgroup effect was identified. A conclusion on the cost-effectiveness of the PRISM trial would depend on the amount that society is willing to pay to increase the chances of an additional live birth at ≥ 34 weeks. For future work, we plan to conduct an individual participant data meta-analysis using all existing data sets. TRIAL REGISTRATION: Current Controlled Trials ISRCTN14163439, EudraCT 2014-002348-42 and Integrated Research Application System (IRAS) 158326. 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. 24, No. 33. See the NIHR Journals Library website for further project information.

Miscarriage is a common complication of pregnancy that affects one in five pregnancies. Several small studies have suggested that progesterone, a hormone essential for maintaining a pregnancy, may reduce the risk of miscarriage in women presenting with early pregnancy bleeding. This research was undertaken to test whether or not progesterone given to pregnant women with early pregnancy bleeding would increase the number of live births when compared with placebo (dummy treatment). The women participating in the study had an equal chance of receiving progesterone or placebo, as determined by a computer; one group received progesterone (400 mg twice daily as vaginal pessaries) and the other group received placebo with an identical appearance. Treatment began when women presented with vaginal bleeding, were < 12 weeks of gestation and were found to have at least a pregnancy sac on an ultrasound scan. Treatment was stopped at 16 weeks of gestation, or earlier if the pregnancy ended before 16 weeks. Neither the participants nor their health-care professionals knew which treatment was being received. In total, 23,775 women were screened and 4153 women were randomised to receive either progesterone or placebo pessaries. Altogether, 2972 participants had a live birth after at least 34 weeks of gestation. Overall, the live birth rate in the progesterone group was 75% (1513 out of 2025 participants), compared with 72% (1459 out of 2013 participants) in the placebo group. Although the live birth rate was 3% higher in the progesterone group than in the placebo group, there was statistical uncertainty about this finding. However, it was observed that women with a history of one or more previous miscarriages and vaginal bleeding in their current pregnancy may benefit from progesterone. For women with no previous miscarriages, our analysis showed that the live birth rate was 74% (824 out of 1111 participants) in the progesterone group compared with 75% (840 out of 1127 participants) in the placebo group. For women with one or more previous miscarriages, the live birth rate was 75% (689 out of 914 participants) in the progesterone group compared with 70% (619 out of 886 participants) in the placebo group. The potential benefit appeared to be most strong for women with three or more previous miscarriages, who had a live birth rate of 72% (98 out of 137 participants) in the progesterone group compared with 57% (85 out of 148 participants) in the placebo group. Treatment with progesterone did not appear to have any negative effects.

A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy.

BACKGROUND: Bleeding in early pregnancy is strongly associated with pregnancy loss. Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone therapy may improve pregnancy outcomes in women who have bleeding in early pregnancy. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate progesterone, as compared with placebo, in women with vaginal bleeding in early pregnancy. Women were randomly assigned to receive vaginal suppositories containing either 400 mg of progesterone or matching placebo twice daily, from the time at which they presented with bleeding through 16 weeks of gestation. The primary outcome was the birth of a live-born baby after at least 34 weeks of gestation. The primary analysis was performed in all participants for whom data on the primary outcome were available. A sensitivity analysis of the primary outcome that included all the participants was performed with the use of multiple imputation to account for missing data. RESULTS: A total of 4153 women, recruited at 48 hospitals in the United Kingdom, were randomly assigned to receive progesterone (2079 women) or placebo (2074 women). The percentage of women with available data for the primary outcome was 97% (4038 of 4153 women). The incidence of live births after at least 34 weeks of gestation was 75% (1513 of 2025 women) in the progesterone group and 72% (1459 of 2013 women) in the placebo group (relative rate, 1.03; 95% confidence interval [CI], 1.00 to 1.07; P = 0.08). The sensitivity analysis, in which missing primary outcome data were imputed, resulted in a similar finding (relative rate, 1.03; 95% CI, 1.00 to 1.07; P = 0.08). The incidence of adverse events did not differ significantly between the groups. CONCLUSIONS: Among women with bleeding in early pregnancy, progesterone therapy administered during the first trimester did not result in a significantly higher incidence of live births than placebo. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment program; PRISM Current Controlled Trials number, ISRCTN14163439.).

Assessment of discharge treatment prescribed to women admitted to hospital for hyperemesis gravidarum.

AIMS: Prescribing drug treatment for the management of hyperemesis gravidarum (HG), the most severe form of nausea and vomiting in pregnancy, remains controversial. Since most manufacturers do not recommend prescribing antiemetics during pregnancy, little is known regarding which treatments are most prevalent among pregnant patients. Here, we report for the first time, evidence of actual treatments prescribed in English hospitals. METHODS: A retrospective pregnancy cohort was constructed using anonymised electronic records in the Nottingham University Hospitals Trust system for all women who delivered between January 2010 and February 2015. For women admitted to hospital for HG, medications prescribed on discharge were described and variation by maternal characteristics was assessed. Compliance with local and national HG treatment guidelines was evaluated. RESULTS: Of 33 567 pregnancies (among 30 439 women), the prevalence of HG was 1.7%. Among 530 HG admissions with records of discharge drugs, cyclizine was the most frequently prescribed (almost 73% of admissions). Prochlorperazine and metoclopramide were prescribed mainly in combination with other drugs; however, ondansetron was more common than metoclopramide at discharge from first and subsequent admissions. Steroids were only prescribed following readmissions. Thiamine was most frequently prescribed following readmission while high dose of folic acid was prescribed equally after first or subsequent admissions. Prescribing showed little variation by maternal age, ethnicity, weight, socioeconomic deprivation, or comorbidities. CONCLUSION: Evidence that management of HG in terms of discharge medications mainly followed local and national recommendations provides reassurance within the health professional community. Wider documentation of drugs prescribed to women with HG is required to enable full assessment of whether optimal drug management is being achieved.

Serum concentrations of Ang-2 and Flt-1 may be predictive of pregnancy outcome in women with pregnancies of uncertain viability: a phase I exploratory prognostic factor study.

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 < .01), linear (p-valuetrend <.01) associations between Ang-2 and Flt-1 concentrations and pregnancy viability such that women with lower concentrations were significantly more likely to have viable pregnancies than women with higher concentrations. In conclusion, Ang-2 and Flt-1 may be useful in predicting outcome in women with PUVs. Impact statement What is already known on this subject: Predicting outcome in women with pregnancies of uncertain viability (PUVs) is challenging. There is currently no accurate and reliable method. All PUVs need to be followed-up until a definitive diagnosis of either a viable or non-viable pregnancy can be made. This takes time, utilises limited resources and generates significant anxiety. Recent studies have demonstrated serum concentrations of Ang-1, Ang-2, Flt-1, IL-15 and TRAIL in viable pregnancies are significantly different to those in non-viable or ectopic pregnancies. What the results of this study add: The results from this prospective study of 94 women with PUVs suggest that serum concentrations of Ang-2 and Flt-1 may be able to predict pregnancy viability in cases of uncertainty. Women with PUVs and low concentrations of Ang-2 or Flt-1 are significantly more likely to have viable pregnancies than women with high concentrations. What the implications are of these findings for clinical practice and/or further research: Evidence from multiple studies is necessary to appreciate the discriminating ability of these prognostic factors. Rapid clinical adoption in the absence of such evidence may lead to wasted resources. If our findings are confirmed, however, these biomarkers, either alone or as part of a prognostic model, may be capable of accurately predicting pregnancy outcome in cases of uncertainty. This would reduce the strain on limited resources and alleviate anxiety for women.

Evaluating the impact of the reconfiguration of gynaecology services at a University Hospital NHS trust in the United Kingdom.

BACKGROUND: The project aim was to investigate the impact of reconfiguring gynaecology services on the key performance indicators of a University Hospital NHS Trust in the UK. The reconfiguration involved the centralisation of elective gynaecology on one hospital site and emergency gynaecology on the other. METHODS: Data measuring outcomes of the Trust's performance indicators (clinical outcomes, patient experience, staff satisfaction, teaching/training, research/development and value for money) were collected. Two time periods, 12 months before and after the reconfiguration in March 2011, were compared for all outcome measures except patient experience. Retrospective data from the hospitals audit department on clinical activity/outcomes and emergency gynaecology patient's feedback questionnaires were analysed. Staff satisfaction, teaching/training and research/development were measured through an online survey of gynaecology consultants. RESULTS: Post reconfiguration, the total number of admissions reduced by 6% (6,867 vs 6,446). There was a 14% increase in elective theatre sessions available (902.29 vs 1030.57) and an 84% increase in elective theatre sessions cancelled (44.43 vs 81.71). However, the average number of elective operations performed during each theatre session remained similar (2.63 vs 2.5). There was a significant increase in medical devices related clinical incidents (2 vs 11). With patient experience, there was a significant reduction in patient's overall length of stay on the emergency gynaecology ward and waiting times for investigations. For staff satisfaction, Consultants were significantly more dissatisfied with workload (3.45 vs 2.85) and standards of care (3.75 vs 2.93). With research and development, consultants remained dissatisfied with time/funding/opportunities for research. No significant impact on undergraduate/postgraduate teaching was found. No financial data on gynaecology was provided for the assessment of value for money. CONCLUSIONS: Reconfiguration of gynaecology services at this Trust may have resulted in a reduction in gynaecological activity and increased cancellation of elective operations but did not significantly reduce the number of elective operations performed. Although consultants expressed increased dissatisfaction with standards of clinical care, clinical incident reports did not significantly increase apart from medical devices incidents. Patient experience of emergency gynaecology services was improved. This manuscript provides a framework for similar exercises evaluating the impact of service redesign in the NHS.

Comparison of tissue effects quantified histologically between PlasmaJet coagulator and Helica thermal coagulator.

INTRODUCTION: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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, P < 0.001; ovary: 4.05 ± 0.61 vs. 5.90 ± 0.95, P < 0.001; fallopian tube: 4.50 ± 0.77 vs. 6.00 ± 1.28, P = 0.034). CONCLUSION: 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.

The interovarian variation in three-dimensional ultrasound markers of ovarian reserve in women undergoing baseline investigation for subfertility.

OBJECTIVE: To evaluate differences in the three-dimensional (3D) ultrasound markers of ovarian reserve between the ovaries within an individual undergoing investigation for subfertility. DESIGN: Prospective observational study. SETTING: University-based assisted conception unit. PATIENT(S): Two hundred seventy women undergoing baseline early follicular phase ultrasound as an investigation for subfertility. INTERVENTION(S): Three-dimensional ultrasound scan in early follicular phase between days 2 and 5 of the menstrual cycle. MAIN OUTCOME MEASURE(S): Variations in 3D ultrasound markers of ovarian reserve between the two ovaries within same individual. RESULT(S): Two hundred fifteen subjects were analyzed for ovarian volume and antral follicle count, and 205 subjects for 3D power Doppler indices. Significant differences were noted (median, range) in the number of antral follicles measuring >6.0 mm and ovarian volume. Significant correlation was noted between the two ovaries in antral follicles measuring 6.0 mm or less, ovarian volume, and 3D power Doppler indices. On stratifying the antral follicles according to size using sonography-based automated volume calculation with postprocessing, maximum variation was seen in follicles measuring more than 6.0 mm as measured using limits of agreement. CONCLUSION(S): There are significant differences in the antral follicles measuring >6.0 mm and ovarian volume, as measured using 3D ultrasound, that require consideration when comparing the two ovaries within an individual.

The cohort of antral follicles measuring 2-6 mm reflects the quantitative status of ovarian reserve as assessed by serum levels of anti-Müllerian hormone and response to controlled ovarian stimulation.

OBJECTIVE: To evaluate the relationship between serum anti-Müllerian 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.

Timing of oocyte maturation and egg collection during controlled ovarian stimulation: a randomized controlled trial evaluating manual and automated measurements of follicle diameter.

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.

A survey of preferences and practices of endometrial ablation/resection for menorrhagia in the United Kingdom.

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.