A clinically useful simplified blastocyst grading system.

The aim of this study was to investigate whether a new simplified blastocyst grading system (A: fully expanded, clear inner cell mass, cohesive trophectoderm; B: not yet expanded, clear inner cell mass, cohesive trophectoderm; C: small inner cell mass ± irregular trophectoderm ± excluded/degenerate cells) was clinically useful. All day-5 single embryo transfers between 15 June 2009 and 29 June 2012 were reviewed. Implantation, clinical pregnancy and live birth rates were related to embryo quality. Five embryologists were asked to grade and decide the clinical fate of 80 images of day-5 embryos on two occasions 4-6 weeks apart. Implantation, clinical pregnancy and live birth rates decreased with deteriorating embryo quality. A highly significant (P < 0.01) difference was observed between the groups. Inter-observer agreement was substantial for grade allocation (K = 0.63) and clinical decision-making (K = 0.66). Intra-observer agreement ranged from substantial (K = 0.71) to almost perfect (K = 0.88) for grade allocation, and was almost perfect for clinical fate determination (K ≥ 0.84). This grading system is quick and easy to use, effectively predicts IVF outcome and has levels of agreement similar to, if not better than, those associated with more complex grading systems.

Aspirin and heparin as adjuvants during IVF do not improve live birth rates in unexplained implantation failure.

This study tested the hypothesis that using aspirin and/or heparin as adjuvants in IVF improves the treatment outcome. This retrospective cohort-control study recruited 234 consecutive subjects aged ≤ 44 years who had previously had one or more unsuccessful IVF cycle. All underwent IVF using conventional protocols. The study group received aspirin and/or heparin post embryo transfer until the day of pregnancy test or until 12 weeks of pregnancy. The control group did not receive adjuvant treatment. The outcome measures were live birth, clinical pregnancy and miscarriage rates. The outcomes were compared by chi-squared test and relative-risk analysis. Analysis was performed in 206 subjects. There was no statistically significant difference in the live birth rate (35.0%, 36/103 versus 47.6%, 49/103), clinical pregnancy rate (40.8%, 42/103 versus 53.4%, 55/103) and miscarriage rate (14.3%, 6/42 versus 10.9%, 6/55) between the study group and the control group. The data in this study show that low-dose aspirin and/or heparin as adjuvant therapies during IVF do not improve live birth rates in an unselected group of subfertile women who have previously had one or more unexplained implantation failure following IVF.

Qualifying the difficulty of embryo transfer with a visual analogue scale and assessing its impact on IVF outcomes.

The aim of this study was to determine whether a continuous visual analogue scale (VAS) is a reliable tool to grade embryo transfer (ET) difficulty when assessing IVF outcomes. No standardized grading system exists for reporting ET 'difficulty' which is typically recorded in descriptive terms. Clinicians performing 188 fresh single ETs between November 2014 and May 2016 also recorded a VAS score (0-100). Embryo transfers were stratified into three levels of ET 'difficulty': (A) 'easy' - no resistance; (B) 'medium' - resistance overcome by advancing the catheter's outer sheath; and (C) 'difficult' - a malleable stylet was required to overcome resistance; and these compared to the VAS scores. Clinical pregnancy and live birth rates were the primary outcomes. VAS scores were categorized into four incremental groupings according to the 25th, 50th and 75th percentiles (Groups 1-4) for analysis. No significant relationship (p > 0.05) was seen in clinical pregnancy or live birth rates in either the standard difficulty or the VAS groupings. The median VAS scores in Groups A-C increased as difficulty increased, but the interquartile ranges overlap with wide clinician variation, suggesting the VAS is not itself a reliable enough tool to record ET difficulty in isolation.

Peripartum group A streptococcal sepsis: a case report.

BACKGROUND: Infections of the upper respiratory tract and skin are commonly attributed to group A Streptococcus (GAS). The organism can be found in the female genital tract and can cause peripartum sepsis in rare cases. CASE: A case of GAS peripartum sepsis did not respond to conservative measures despite early initiation of intravenous antibiotics. Radical surgical intervention improved the condition. CONCLUSION: A GAS uterine infection should be suspected at an early stage in cases of puerperal pyrexis that do not respond to broad-spectrum antibiotics.

Temporal validation of a simplified blastocyst grading system.

We have recently established the clinical effectiveness and credibility of a simplified blastocyst grading system by demonstrating its prognostic potential and the inter- and intra-observer variability associated with it. To be considered clinically useful, however, the grading system also needs to be accurate (i.e. well calibrated with good discriminative ability). This study prospectively evaluates the performance of the grading system on subsequent patients from the same IVF unit in an attempt to temporally validate the model. All day 5 single embryo transfers between 1st July 2012 and 30th June 2014 were included in the study. The observed implantation, clinical pregnancy and live birth rates according to grade of embryo transferred were compared to the expected rates as predicted by the development data set and the statistical significance of any differences between the two were calculated using the Chi-square test. A total of 435 single embryo transfers were included. For each grade of embryo transferred, there was generally no significant difference between the observed and expected frequencies of implantation, clinical pregnancy and live birth suggesting that the simplified blastocyst grading system is accurate and temporal validation has been satisfactorily demonstrated. It is now necessary to externally validate the grading system to prove generality before further dissemination.

Prediction of in vitro fertilization outcome at different antral follicle count thresholds in a prospective cohort of 1,012 women.

OBJECTIVE: To estimate the probability of live birth, adverse treatment outcome, and extremes of ovarian response at different antral follicle count (AFC) cutoff levels in a large prospective cohort of women undergoing IVF treatment. DESIGN: Prospective study. SETTING: University-based assisted conception unit. PATIENT(S): A total of 1,012 consecutive subjects of all ages undergoing their first cycle of assisted reproductive techniques. INTERVENTION(S): Transvaginal three-dimensional ultrasound assessment and venipuncture in the early follicular phase of the menstrual cycle. MAIN OUTCOME MEASURE(S): Live birth rate, poor ovarian response, and ovarian hyperstimulation syndrome (OHSS). RESULT(S): Analysis was performed in 1,012 subjects. Both age (r = 0.88) and AFC (r = 0.92) thresholds show significant linear relationship with the probability of live birth, but AFC demonstrates a stronger correlation. At AFC quartiles of 3-10, 11-15, 16-22, and ≥23, the mean live birth rates were 23%, 34%, 39%, and 44%, respectively. No live birth was observed in women with AFC <4. Antral follicle count was predictive of ovarian response, with a 67% likelihood of poor ovarian response for AFC ≤4. Although the risk of moderate or severe OHSS is 2.2% with AFC of ≤24, the risk increases to 8.6% at AFC of ≥24. The risk of OHSS increases further to 11% if there are signs and symptoms of polycystic ovary syndrome. CONCLUSION(S): Although age and AFC are significantly correlated with live birth, AFC demonstrates a stronger correlation. Antral follicle count thresholds are useful to predict live birth rates and risks of poor ovarian response and OHSS during IVF treatment.

Sperm donor recruitment within an NHS fertility service since the removal of anonymity.

The marked decline in the number of sperm donors recruited in the UK has been largely attributed to changes in regulations and in particular those related to the removal of anonymity. After a 5-year period of inactivity, the sperm donor bank in Nottingham was provided with limited resources to try and recruit donors who were willing to be identified on the HFEA register. Marketing was sporadic and at first low cost and the enquiry rate only increased significantly when the centre's website became operational and higher cost advertising was used. Over a 4-year period, a total of 151 enquiries gave rise to 14 useable donors at a cost of approximately £5,500 each. Donor sperm was generally of high quality having been density gradient prepared prior to cryopreservation and provided an overall ongoing pregnancy rate of 21.6% and 45.6% by IUI and IVF, respectively. The overall exercise demonstrated that identifiable donors were coming forward but in lower numbers compared to those observed before 2005. At current treatment prices, centres should be aware that recouping the costs of donor recruitment and processing may be difficult and that the cost of both donor sperm and donor insemination are likely to rise significantly.

A prospective, comparative analysis of anti-Müllerian hormone, inhibin-B, and three-dimensional ultrasound determinants of ovarian reserve in the prediction of poor response to controlled ovarian stimulation.

OBJECTIVE: To compare three-dimensional ultrasound parameters, antral follicle count (AFC), ovarian volume, and ovarian vascularity indices with anti-Müllerian hormone (AMH) and other conventional endocrine markers for the prediction of poor response to controlled ovarian hyperstimulation (COH) during assisted reproduction treatment (ART). DESIGN: Prospective study. SETTING: University-based assisted conception unit. PATIENT(S): One hundred thirty-five women undergoing the first cycle of ART. INTERVENTION(S): Transvaginal three-dimensional ultrasound assessment and venipuncture in the early follicular phase of the menstrual cycle immediately before ART. MAIN OUTCOME MEASURE(S): Poor ovarian response and nonconception. RESULT(S): Antral follicle count (Exp(B): 0.65) and AMH (Exp(B): 0.13) were the most significant predictors of poor ovarian response on multiple regression analysis and their predictive accuracy was similar, with an area under the curve (AUC) of 0.935 and 0.905, respectively. The AFC and AMH, as a combined test, did not significantly improve the level of prediction (AUC = 0.946). The sensitivity and specificity for prediction of poor ovarian response were 93% and 88% for AFC and 100% and 73% for AMH at an optimum cutoff values of < or =10 and < or =0.99 ng/mL, respectively. Age (Exp(B): 1.191) was the only significant predictor of nonconception, although its predictive accuracy was also low (AUC = 0.674). CONCLUSION(S): The AFC and AMH are the most significant predictors of poor response to ovarian stimulation during ART. The AMH and AFC, either alone or in combination, demonstrate a similar predictive power but are not predictive of nonconception, which is dependent on the woman's age.

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.

Validation of a novel computer-assisted sperm analysis (CASA) system using multitarget-tracking algorithms.

OBJECTIVE: To determine the accuracy and precision of a novel computer-assisted sperm analysis (CASA) system by comparison with existing recommended manual methods. DESIGN: Prospective study using comparative measurements of sperm concentration and motility on latex beads and immotile and motile sperm. SETTING: Tertiary referral fertility center with strong academic links. PATIENT(S): Sperm donors and male partners of couples attending for fertility investigations. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Achievement of Accubead target value for high and low concentration suspensions. Repeatability as demonstrated by coefficients of variation and intraclass correlation coefficients. Correlation and limits of agreement between CASA and manual methods. RESULT(S): The CASA measurements of latex beads and sperm concentrations demonstrated a high level of accuracy and repeatability. Repeated Accubead measurements attained the required target value (mean difference from target of 2.61% and 3.71% for high- and low-concentration suspensions, respectively) and were highly reproducible. Limits of agreement analysis suggested that manual and CASA counts compared directly could be deemed to be interchangeable. Manual and CASA motility measurements were highly correlated for grades a, b, and d but could not be deemed to be interchangeable, and manual motility estimates were consistently higher for motile sperm. CONCLUSION(S): The novel CASA system was able to provide semen quality measurements for sperm concentration and motility measurements which were at least as reliable as current manual methods.

The three-dimensional ultrasonographic ovarian vascularity of women developing poor ovarian response during assisted reproduction treatment and its predictive value.

OBJECTIVE: To test the hypothesis that ovarian vascularity is decreased in women who demonstrate poor ovarian response to controlled ovarian stimulation as part of assisted reproduction treatment. DESIGN: Prospective study. SETTING: University-based Assisted Conception Unit. PATIENT(S): One hundred forty-one women undergoing their first cycle of assisted reproduction treatment (ART). INTERVENTION(S): Transvaginal 3D ultrasound assessment and venepuncture in the early follicular phase of the menstrual cycle immediately before ART. MAIN OUTCOME MEASURE(S): Ovarian vascularity indices (VI, FI, and VFI), ovarian volume (OV), and antral follicle count (AFC). RESULTS: The ovarian VI (7.5 +/- 5.3 vs. 8.6 +/- 7.3), FI (38.9 +/- 6.9 vs. 38.0 +/- 5.5), and VFI (3.2 +/- 2.6 vs. 3.5 +/- 3.1) were similar in both poor and normal responders. AFC and OV were significantly lower in women who developed poor response (9 +/- 3.3 and 6.3 +/- 3.5 cm(3), respectively) than in normal responders (19.2 +/- 9.9 and 8.9 +/- 4.8 cm(3), respectively). Antral follicle count and basal FSH were the only significant predictors of poor ovarian response on multiple regression analysis. CONCLUSION(S): Ovarian blood flow, as measured by 3D ultrasound, is not decreased in women who demonstrate a poor response to ovarian stimulation and is not predictive of poor response during IVF treatment. The AFC is the single best predictor of poor ovarian response.

Establishing the intercycle variability of three-dimensional ultrasonographic predictors of ovarian reserve.

OBJECTIVE: To estimate the intercycle variability of antral follicle counts (AFCs) and ovarian volume, as measured by using three-dimensional ultrasound, and to compare these to the variation in basal FSH levels. DESIGN: Prospective study. SETTING: University-based assisted conception unit. PATIENT(S): One hundred women undergoing two cycles of assisted reproductive technology. INTERVENTION(S): Transvaginal three-dimensional ultrasound assessment and venepuncture in the early follicular phase of the menstrual cycle, immediately before assisted reproductive technology. MAIN OUTCOME MEASURE(S): Intercycle variability of AFC, ovarian volume, and basal FSH. RESULT(S): The limits of agreement between cycles were +4.03 and -3.71 for AFC, +2.67 and -3.03 cm(3) for ovarian volume, and +4.36 and -4.52 IU/L for FSH levels. The AFC showed the least degree of variation, with a range of 0.48 times its own mean, in contrast to corresponding values of 0.73 and 1.29 for ovarian volume and basal FSH levels, respectively. The intraobserver variability for AFC and ovarian volume and the intraassay variability for FSH were 0.37, 0.17, and 0.42 times the mean of those respective variables. CONCLUSION(S): The AFC demonstrates a lower intercycle variability than do ovarian volume and basal FSH level. The observed intercycle variability of the AFC may primarily be caused by observer variability, and the true biological variation may be minimal.