Reproductive Implications and Management of Congenital Uterine Anomalies: Scientific Impact Paper No. 62 November 2019.

Congenital uterine anomalies (CUAs) are malformations of the womb that develop during fetal life. When a baby girl is in her mother's womb, her womb develops as two separate halves from two tubular structures called 'müllerian ducts', which fuse together before she is born. Abnormalities that occur during the baby's development can be variable from complete absence of a womb through to more subtle anomalies, which are classified into specific categories. While conventional ultrasound is good in screening for CUAs, 3D ultrasound is used to confirm a diagnosis. If a complex womb abnormality is suspected, MRI scanning may also be used, with a combination of laparoscopy in which a camera is inserted into the cavity of the abdomen, and hysteroscopy, when the camera is placed in the womb cavity. As there can be a link between CUAs and abnormalities of the kidney and bladder, scans of these organs are also usually requested. Although CUAs are present at birth, adult women typically do not have any symptoms, although some may experience painful periods. Most cases of CUA do not cause a woman to have difficulty in becoming pregnant and the outcome of pregnancy is good. However, these womb anomalies are often discovered during investigations for infertility or miscarriage. Moreover, depending upon the type and severity of CUA, there may be increased risk of first and second trimester miscarriages, preterm birth, poor growth of the baby in the mother's womb (fetal growth restriction), pre-eclampsia and difficult positioning of the baby for birth (fetal malpresentation). Surgical treatment is only recommended to a woman who has had recurrent miscarriages and has a septate uterus, i.e., the womb cavity is divided by a partition. In this case, surgery may improve her chances for a successful pregnancy, although the risks of surgery, especially scarring of the womb should be considered. However, further evidence from randomised controlled trials are required to provide conclusive evidence-based recommendations for surgical treatment for septate uterus. Surgical treatment for other types of CUAs is not usually recommended as the risks outweigh potential benefits, and evidence for any benefits is lacking. Women with CUAs may be at an increased risk of preterm birth even after surgical treatment for a septate uterus. These women, if suspected to be at an increased risk of preterm birth based on the severity of CUA, should be followed up using an appropriate protocol for preterm birth as outlined in UK Preterm Birth Clinical Network Guidance.1 >.

Liabilities and penalties under Mental Healthcare Act 2017.

INTRODUCTION: Mental Healthcare Act (MHCA) 2017 is an act passed to regulate and provide mental health care and services. The act considers psychiatrists as one of the main mental health providers. Liabilities are prescribed under various chapters of MHCA 2017. It is imperative for practitioners to be completely aware of and follow the rules as per MHCA 2017, now that the rules are already framed. MATERIALS AND METHODS: A thorough review of MHCA 2017, Central Mental Health Rules, and State Mental Health Rules 2018 was done. In addition, related scientific articles were accessed in PubMed and Google Scholar using keywords such as mental health legislation, law, and mental health. Relevant articles were reviewed to arrive at suggestions. OBSERVATIONS: Important liabilities are around the domains of registration of professionals and institutions, maintenance of records, promoting the rights of the persons with mental illness during treatment, and following the provisions of MHCA 2017 during admission and discharge. Punishment for contravention of provisions of the Act or rules or regulations made thereunder is clear and stringent and may vary from fine to imprisonment. SUGGESTIONS: Mental Health Professionals should understand the provisions of MHCA 2017 along with the rules and regulations made under this act. Please maintain basic medical records of all outpatients and inpatients and basic report of psychological assessments and release it upon request by the patient or nominated representative.

Effect of ethnicity on live birth rates after in vitro fertilisation/intracytoplasmic sperm injection treatment: analysis of UK national database.

OBJECTIVE: To evaluate the effect of ethnicity of women on the outcome of in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatment. DESIGN: Observational cohort study. SETTING: UK National Database. POPULATION: Data from 2000 to 2010 involving 38 709 women undergoing their first IVF/ICSI cycle were analysed. METHODS: Anonymous data were obtained from the Human Fertilization and Embryology Authority (HFEA), the statutory regulator of IVF and ICSI treatment in the UK. Data analysis was performed by regression analysis with adjustment for age, cause and type of infertility and treatment type (IVF or ICSI) to express results as odds ratio (OR) and 95% confidence intervals (95% CI). METHODS: Live birth rate per cycle of IVF or ICSI treatment. RESULTS: While white Irish (OR 0.73; 95% CI 0.60-0.90), Indian (0.85; 0.75-0.97), Bangladeshi (0.53: 0.33-0.85), Pakistani (0.68; 0.58-0.80), Black African (0.60; 0.51-0.72), and other non-Caucasian Asian (0.86; 0.73-0.99) had a significantly lower odds of live birth rates per fresh IVF/ICSI cycle than White British women, ethnic groups of White European (1.04; 0.96-1.13), Chinese (1.12; 0.77-1.64), Black Caribbean (0.76; 0.51-1.13), Middle Eastern (0.73; 0.51-1.04), Mediterranean European (1.18; 0.83-1.70) and Mixed race population (0.94; 0.73-1.19) had live birth rates that did not differ significantly. The cumulative live birth rates showed similar patterns across different ethnic groups. CONCLUSION: Ethnicity is a major determinant of IVF/ICSI treatment outcome as indicated by significantly lower live birth rates in some of the ethnic minority groups compared with white British women. TWEETABLE ABSTRACT: Ethnicity affects IVF outcome with lower live birth rates in some ethnic groups more than in white British.

The evolving role of saline infusion sonography (SIS) in infertility.

Saline infusion sonography (SIS) has become a valuable diagnostic modality in gynaecology over the last three decades. SIS is now commonly employed for detailed evaluation of the uterine cavity as part of pre-treatment assessment in infertile women. The objective of this paper is review the scientific literature on SIS in infertility. Medline, Ovid and Cochrane databases were searched for relevant articles. The indications, technical aspects and the potential advantages of SIS are discussed. The efficacy and sensitivity of SIS are compared to hysteroscopy in the evaluation of uterine polyps, fibroids, intrauterine adhesions and uterine anomalies. Increasing evidence suggests the use of SIS prior to an in-vitro fertilization (IVF) cycle as it has increased sensitivity in the detection of intrauterine pathology. SIS is cost-effective and results in better patient satisfaction scores than hysteroscopy.

Diagnostic accuracy of saline infusion sonography in the evaluation of uterine cavity abnormalities prior to assisted reproductive techniques: a systematic review and meta-analyses.

BACKGROUND: The diagnostic accuracy of a 2-D transvaginal scan, which is commonly employed to evaluate the regularity and shape of the uterine cavity in subfertile women, is relatively poor compared with other diagnostic modalities like saline infusion sonography (SIS) or hysteroscopy. SIS is a minimally invasive, cost-effective and acceptable diagnostic modality. Therefore the aim of this systematic review was to assess the diagnostic accuracy of SIS in the evaluation of the uterine cavity in subfertile women. METHODS: A systematic review was conducted of diagnostic studies that compared SIS with hysteroscopy. Twenty relevant studies (including 1645 procedures) were identified and a subsequent meta-analysis was performed. Electronic databases were searched for relevant studies and references of relevant studies were cross checked. Validity was assessed and data were extracted independently by two authors. Heterogeneity was examined, studies were plotted in an ROC area and data were pooled. The main outcome measure was the diagnostic accuracy of saline infusion sonography. The pooled sensitivity, specificity, likelihood ratios and the post-test probabilities of saline infusion sonography on the prediction of uterine cavity abnormalities were calculated. RESULTS: The pooled sensitivity of SIS in the detection of all intrauterine abnormalities was 0.88 (95% confidence interval (CI): 0.85-0.90). The pooled specificity was 0.94 (95% CI 0.93-0.96). The positive and negative likelihood ratios were 20.93 (95% CI: 9.06-48.34) and 0.15 (95% CI: 0.10-0.22), respectively. SIS had good accuracy in the detection of all intrauterine abnormalities (area under the summary receiver operating curve (sROC) = 0.97 ± 0.01). SIS also had a high pooled sensitivity and specificity in the detection of congenital uterine anomalies, 0.85 (95% CI: 0.79-0.90) and 1.00 (95% CI 0.99-1.00), respectively. However the limitations of the review include the heterogeneity amongst the included studies. CONCLUSIONS: SIS is a highly sensitive investigative modality and comparable to the gold standard tool, hysteroscopy in the detection of intrauterine abnormalities in subfertile women. SIS is a highly sensitive and specific test in the diagnosis of uterine polyps, submucous myomas, uterine anomalies and intrauterine adhesions and can be used as a screening tool for subfertile patients prior to IVF treatment.

Effect of ethnicity on live birth rates after in vitro fertilisation or intracytoplasmic sperm injection treatment.

OBJECTIVE: To assess the relationship between the ethnicity of women and the clinical success of in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatment. DESIGN: Observational cohort study. SETTING: Nottingham University Research and Treatment Unit in Reproduction (NURTURE), UK. SAMPLE: A total of 1517 women, of which 1291 were white Europeans and 226 belonged to an ethnic minority group. All the women were undergoing their first cycle of assisted reproductive technology (ART) between 2006 and 2011. METHODS: All of the women underwent their first cycle of ART between 2006 and 2011. MAIN OUTCOME MEASURES: Live birth rates following IVF or ICSI treatment. RESULTS: Although pre-treatment ovarian reserve variables [mean age, basal follicle stimulating hormone (FSH), and total antral follicle count] were significantly favourable in the ethnic group, the live birth rates were significantly lower in this group (35%) compared with the white European group (43.8%) (relative risk 0.8; 95% CI 0.66-0.97). On logistic regression analysis, ethnicity was an independent predictor of live birth rate (OR 0.688; 95% CI 0.513-0.924). After controlling for the other independent variables (age and FSH), the significant association between ethnicity and live birth rate remained strong (OR 0.591; 95% CI 0.425-0.822) on multivariate logistic regression analysis. CONCLUSIONS: Live birth rates following IVF or ICSI treatment were significantly lower in the ethnic minority group compared with white European women, which suggests that ethnicity is a major determinant of live birth following IVF treatment.

Effects of dehydroepiandrosterone on in vivo ovine follicular development.

STUDY QUESTION: What are the effects of exposure of ovarian tissue to dehydroepiandrosterone (DHEA) supplementation in vivo? SUMMARY ANSWER: DHEA exposure stimulates initiation of primordial follicles and development of gonadotrophin-responsive preantral/early antral follicles possibly mediated through promoting granulosa cell proliferation and enhancing anti-Mullerian hormone (AMH) expression. WHAT IS KNOWN ALREADY?: Ovarian ageing is a cause of subfertility and is associated with poor outcomes of IVF treatment and premature menopause. A few clinical studies have shown that DHEA can improve ovarian response and increase the chances of pregnancy after IVF treatment in women with a diminished ovarian reserve (DOR) suggesting DHEA may help to overcome the effect of ovarian ageing. However, there are no data about how DHEA acts on ovarian folliculogenesis. STUDY DESIGN, SIZE AND DURATION: A cortical autograft experimental model was conducted in six female sheep aged at least 24 months. The period of DHEA treatment in the animals lasted for 10 weeks. PARTICIPANTS/MATERIALS, SETTING, METHODS: All the animals were subjected to unilateral oophorectomy. Half of the ovary was fixed for histological analysis as a time-zero control. The remaining tissue was used to isolate patches of ovarian cortex which were autografted back onto the ovarian pedicle. The grafting procedure eradicated all growing follicles and synchronized early follicular development. After a 10-week treatment period with DHEA implants, the ewes were sacrificed and the graft and remaining ovary were harvested. Histological and immunohistochemistry (IHC) findings, accompanied with serum hormonal profiles were compared to determine the effect on the follicle population. MAIN RESULTS AND THE ROLE OF CHANCE: Higher proportions of the follicle population in the remaining ovary were observed to be in the antral stage after DHEA treatment. The observation coincided with an increase in the rate of primordial follicle initiation and preantral follicle development in cortical grafts and the remaining ovarian tissue, respectively. The IHC results indicated that DHEA increased the expression of both the proliferation marker (KI-67) in granulosa cells and the follicular AMH expression at the preantral and early antral follicle stages. LIMITATIONS, REASONS FOR CAUTION: The experimental design compared follicle populations before and after DHEA treatment within individual animals to allow changes over time to be detected against a background of high inter-animal variation. However, since no controls without DHEA were included, we cannot say what would have happened over time in its absence, and it is possible that other factors may have resulted in the changes in follicle development observed during the experiment. WIDER IMPLICATIONS OF THE FINDING: Our data supports the idea that DHEA might be a useful therapy to delay the effects of ovarian ageing. Therefore, it may have a role as an adjunct during IVF to improve ovarian response in women with DOR and as a treatment for premature ovarian insufficiency. STUDY FUNDING/COMPETING INTEREST(S): The research received finance support from the University of Nottingham. The authors declare no conflict of interest in this study.

Scrotal cooling and its benefits to male fertility: a systematic review.

The aim of this study was to systematically review the evidence for the impact of scrotal cooling on spermatogenesis. EMBASE (1980-2010) and MEDLINE (1950-Sept. 2010) databases were searched using the terms 'male infertility or subfertility or fertility', combined with a separate search of 'scrotal cooling', without any limits or restrictions. A total of eight articles met the criteria for inclusion in the study. There was insufficient evidence to draw any firm conclusions about the impact of scrotal cooling on male fertility. A positive trend of improved male fertility was however observed. There is therefore a need for well designed randomised controlled trials.

Which follicles make the most anti-Mullerian hormone in humans? Evidence for an abrupt decline in AMH production at the time of follicle selection.

Anti-Müllerian hormone (AMH) is exclusively produced by granulosa cells (GC) of the developing pre-antral and antral follicles, and AMH is increasingly used to assess ovarian function. It is unclear which size follicles make the most AMH (total content) and are the main contributors to circulating AMH concentrations. To determine AMH gene expression in GC (q-RT-PCR) and follicular AMH production (Elisa and RIA) in relation to follicular development, 87 follicles (3-13 mm diameter) including both GC and the corresponding follicular fluid (FF) were collected in connection with fertility preservation of human ovaries. Further, follicle number and diameter, graded in 1 mm increments, were determined by 3D ultrasound in 113 women in their natural menstrual cycle to determine follicle number and diameter in relation to circulating AMH levels. This study demonstrates for the first time a positive association between AMH gene expression in human and both total follicular fluid AMH (P < 0.02) and follicular fluid AMH concentration (P < 0.01). AMH gene expression and total AMH protein increased until a follicular diameter of 8 mm, after which a sharp decline occurred. In vivo modelling confirmed that 5-8 mm follicles make the greatest contribution to serum AMH, estimated for the first time in human to be 60% of the circulating concentration. Significant positive associations between gene expression of AMH and FSHR, AR and AMHR2 expression (P < 0.00001 for all three) and significant negative association between follicular fluid AMH concentration and CYP19a1 expression were found (P < 0.0001). Both AMH gene expression (P < 0.02) and follicular fluid concentration of AMH (P < 0.00001) correlated negatively with estradiol concentration.

Reproductive outcomes in women with congenital uterine anomalies: a systematic review.

OBJECTIVE: Congenital uterine anomalies are common but their effect on reproductive outcome is unclear. We conducted a systematic review to evaluate the association between different types of congenital uterine anomaly and various reproductive outcomes. METHODS: Searches were performed using MEDLINE, EMBASE, the Cochrane Library and Web of Science. The Newcastle-Ottawa Quality Assessment Scale was used for quality assessment. Uterine defects were grouped into arcuate uteri, canalization defects (septate and subseptate uteri) and unification defects (unicornuate, bicornuate and didelphys uteri). Pooled risk ratios (RR) with 95% confidence intervals (CI) were computed using random effects models. RESULTS: We identified nine studies comprising 3805 women. Meta-analysis showed that arcuate uteri were associated with increased rates of second-trimester miscarriage (RR, 2.39; 95% CI, 1.33-4.27, P = 0.003) and fetal malpresentation at delivery (RR, 2.53; 95% CI, 1.54-4.18; P < 0.001). Canalization defects were associated with reduced clinical pregnancy rates (RR, 0.86; 95% CI, 0.77-0.96; P = 0.009) and increased rates of first-trimester miscarriage (RR, 2.89; 95% CI; 2.02-4.14; P < 0.001), preterm birth (RR, 2.14; 95% CI, 1.48-3.11; P < 0.001) and fetal malpresentation (RR, 6.24; 95% CI, 4.05-9.62; P < 0.001). Unification defects were associated with increased rates of preterm birth (RR, 2.97; 95% CI, 2.08-4.23; P < 0.001) and fetal malpresentation (RR, 3.87; 95% CI, 2.42-6.18; P < 0.001). CONCLUSIONS: Canalization defects reduce fertility and increase rates of miscarriage and preterm delivery. None of the unification defects reduces fertility but some are associated with miscarriage and preterm delivery. Arcuate uteri are specifically associated with second-trimester miscarriage. All uterine anomalies increase the chance of fetal malpresentation at delivery.

The prevalence of congenital uterine anomalies in unselected and high-risk populations: a systematic review.

BACKGROUND: The prevalence of congenital uterine anomalies in high-risk women is unclear, as several different diagnostic approaches have been applied to different groups of patients. This review aims to evaluate the prevalence of such anomalies in unselected populations and in women with infertility, including those undergoing IVF treatment, women with a history of miscarriage, women with infertility and recurrent miscarriage combined, and women with a history of preterm delivery. METHODS: Searches of MEDLINE, EMBASE, Web of Science and the Cochrane register were performed. Study selection and data extraction were conducted independently by two reviewers. Studies were grouped into those that used 'optimal' and 'suboptimal' tests for uterine anomalies. Meta-analyses were performed to establish the prevalence of uterine anomalies and their subtypes within the various populations. RESULTS: We identified 94 observational studies comprising 89 861 women. The prevalence of uterine anomalies diagnosed by optimal tests was 5.5% [95% confidence interval (CI), 3.5-8.5] in the unselected population, 8.0% (95% CI, 5.3-12) in infertile women, 13.3% (95% CI, 8.9-20.0) in those with a history of miscarriage and 24.5% (95% CI, 18.3-32.8) in those with miscarriage and infertility. Arcuate uterus is most common in the unselected population (3.9%; 95% CI, 2.1-7.1), and its prevalence is not increased in high-risk groups. In contrast, septate uterus is the most common anomaly in high-risk populations. CONCLUSIONS: Women with a history of miscarriage or miscarriage and infertility have higher prevalence of congenital uterine anomalies compared with the unselected population.

Prevalence of uterine anomalies and their impact on early pregnancy in women conceiving after assisted reproduction treatment.

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.

A randomised controlled trial of 300 versus 225 IU recombinant FSH for ovarian stimulation in predicted normal responders by antral follicle count.

OBJECTIVE: To test the hypothesis that among women predicted to have a normal ovarian response, ovarian stimulation using 300 IU follicle-stimulating hormone (FSH) results in the retrieval of more mature oocytes than 225 IU during in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) treatment. DESIGN: Prospective randomised controlled study. SETTING: University-based assisted conception unit. POPULATION: A cohort of 131 women predicted to have a normal ovarian response to gonadotrophin stimulation, based on antral follicle count. METHODS: Subjects undergoing their first cycle of IVF/ICSI were randomised to receive a fixed daily dose of 300 (experimental arm) or 225 IU (control arm) of recombinant FSH (Gonal-F). MAIN OUTCOME MEASURES: Number of mature oocytes retrieved and live birth rates. RESULTS: The number (mean +/- standard deviation) of mature oocytes retrieved (8.2 +/- 5.0 versus 9.0 +/- 4.8, for 300 and 225 IU, respectively; P = 0.34) was similar in each group. There were no differences between the 300- and 225 IU arms in live birth rates (31 versus 41%, respectively; P = 0.25), cycle cancellations resulting from insufficient ovarian response (0 versus 6.1%, respectively; P = 0.12), and prevalence of moderate (3.1 versus 3.0, respectively; P = 1.0) and severe (0 versus 1.5%, respectively; P = 1.0) ovarian hyperstimulation syndrome. CONCLUSIONS: The use of a higher daily dose of 300 IU of recombinant FSH for ovarian stimulation does not improve the number of mature oocytes retrieved, or live birth rates, among women with a predicted normal response during conventional IVF/ICSI.

The predictive value of the automated quantification of the number and size of small antral follicles in women undergoing ART.

BACKGROUND: 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). METHODS: A total of 156 subjects aged < or =40 years with a baseline FSH < or =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 measuring < or =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. RESULTS: A total of 142 subjects were included for analysis of primary end-point. Those subjects who conceived had significantly more antral follicles measuring < or =2 (P = 0.041) and 2.1-4.0 mm (P < 0.001) 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]. CONCLUSION: 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.

Automated follicle tracking improves measurement reliability in patients undergoing ovarian stimulation.

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.

Can quantitative three-dimensional power Doppler angiography be used to predict ovarian hyperstimulation syndrome?

OBJECTIVE: To test the hypothesis that ovarian vascularity is increased in women developing ovarian hyperstimulation syndrome (OHSS) and to assess its value as a predictor of OHSS during in-vitro fertilization (IVF). METHODS: 118 subjects undergoing their first cycle of IVF had a three-dimensional (3D) transvaginal ultrasound scan in the early follicular phase of the menstrual cycle preceding IVF treatment. 18 of them developed moderate or severe OHSS and 100 subjects had normal ovarian response. Antral follicle count, ovarian volume, and ovarian vascularity (vascularization index (VI), flow index (FI) and vascularization flow index (VFI)) were compared between OHSS and control groups. Multiple regression analysis was used to assess the predictive value of these variables against age, body mass index and basal follicle-stimulating hormone level for the development of OHSS. RESULTS: The ovarian blood flow indices VI (11.1 +/- 11.6 vs. 8.6 +/- 7.3%; P = 0.23), FI (38.0 +/- 4.8 vs. 38.0 +/- 5.5; P = 0.95) and VFI (4.2 +/- 3.3 vs. 3.5 +/- 3.1; P = 0.40) were similar in the OHSS group and the normal responders. While antral follicle count was significantly higher in women developing OHSS (33.0 +/- 15.1) than in the control group (19.2 +/- 9.9, P < 0.001), ovarian volume did not differ between the two groups (10.6 +/- 3.8 vs. 8.9 +/- 4.8 cm(3), respectively, P = 0.11). On multiple regression analysis, antral follicle count was the only significant predictor of OHSS (P < 0.01). CONCLUSIONS: Women developing OHSS during IVF do not demonstrate an increased ovarian blood flow as measured by 3D ultrasound but do have a significantly higher antral follicle count, which is the only significant predictor of OHSS.

Changes in myometrial 'perfusion' during normal labor as visualized by three-dimensional power Doppler angiography.

OBJECTIVES: Myometrial contractions are one of the most important aspects of effective labor. For cells within the myometrium to work efficiently they need to be well oxygenated and this requires an adequate blood supply. This study used quantitative three-dimensional (3D) power Doppler angiography to calculate the percentage change in myometrial blood flow during a relaxation-contraction-relaxation cycle of active labor. METHODS: Transabdominal 3D power Doppler ultrasound imaging was used to acquire volumetric data during the first stage of spontaneous labor in 20 term, nulliparous women. 3D datasets were acquired during a single cycle of uterine relaxation, contraction and subsequent relaxation for each subject. The resultant datasets were analyzed independently by two investigators on two occasions using Virtual Organ Computer-aided AnaLysis to define a volume of interest within the myometrium; the power Doppler signal within this volume was quantified to provide 3D indices of vascularity: vascularization index (VI), flow index (FI) and vascularization flow index (VFI). The percentage change in these indices, during a uterine contraction, was calculated from the baseline value during the initial uterine relaxation phase (taken as a maximum of 100%). RESULTS: Myometrial blood flow fell significantly during the uterine contraction and returned during the subsequent relaxation phase of the cycle (P < 0.001 for VI and VFI, P = 0.002 for FI). From the initial baseline relaxation value, VI dropped to 43.9%, FI to 85.5% and VFI to 40.8% during uterine contraction, and returned to 86.7%, 98.1% and 89.1%, respectively, during the subsequent relaxation. The intraclass correlation coefficients in blood flow measurements of 0.982-0.999 between the two investigators were indicative of good interobserver reliability. CONCLUSIONS: This study confirms that myometrial perfusion, as measured by quantitative 3D power Doppler angiography, significantly falls during uterine contractions, returns during the subsequent relaxation phase, and can be quantified reliably from stored datasets. Further work is now required to establish clinical applicability for this non-invasive investigation.

Intraobserver and interobserver reliability of automated antral follicle counts made using three-dimensional ultrasound and SonoAVC.

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.

Effect of pituitary desensitization on the early growing follicular cohort estimated using anti-Mullerian hormone.

BACKGROUND: This study evaluated the effect of pituitary desensitization on the early growing follicle population through assessment of serum anti-Mullerian hormone (AMH) concentration. Other markers of ovarian reserve, basal follicular stimulating hormone (FSH), luteinizing hormone (LH), estradiol, inhibin-B and three-dimensional ultrasound ovarian parameters were also assessed for comparison. METHODS: One hundred and two subjects aged <40 years with FSH levels <12 IU/l underwent venepuncture and transvaginal ultrasound in the early follicular phase of the menstrual cycle and after 14 days of down-regulation using gonadotrophin releasing hormone (GnRH) agonists. Serum levels of AMH and other markers of ovarian reserve measured during the early follicular phase were compared with those measured following down-regulation. RESULTS: While AMH levels increased significantly by approximately 32% (P < 0.01), there was a significant decline of approximately 40-50% (P < 0.01) in the levels of inhibin-B, FSH, LH and estradiol. Down-regulation treatment was also associated with a decrease (P < 0.01) in mean ovarian volume and in ovarian blood flow, but no difference was seen in the antral follicle count. CONCLUSIONS: Pituitary desensitization results in a significant increase in AMH levels, which implies that either the secretion of AMH by early growing follicles is enhanced or that the size of this follicle cohort is increased. The number of antral follicles visualized on ultrasound in the early follicular phase and at down-regulation appears unchanged, suggesting that any effect is restricted to the smaller selectable follicles. Our results may explain the enhanced ovarian response to conventional controlled ovarian stimulation and higher pregnancy rates when pretreatment with GnRH-agonists is employed.