Comparison of antimüllerian hormone levels and antral follicle count as predictor of ovarian response to controlled ovarian stimulation in good-prognosis patients at individual fertility clinics in two multicenter trials

Objective To compare antimüllerian hormone (AMH) and antral follicle count (AFC) as predictors of ovarian response to controlled ovarian stimulation at individual fertility clinics. Design Retrospective analysis of individual study center data in two multicenter trials. Centers that provided >10 patients were included in the analysis. Setting A total of 19 (n = 519 patients) and 18 study centers (n = 686 patients) participating in a long GnRH agonist trial (MERIT) and a GnRH antagonist trial (MEGASET), respectively. Patient(s) Infertile women of good prognosis. Intervention(s) Long GnRH agonist or GnRH antagonist cycles. Main Outcome Measure(s) Correlation between AMH and AFC, and oocyte yield by each study center for each trial. Results(s) Antimüllerian hormone was more strongly correlated with oocyte yield than AFC: r = 0.56 vs. r = 0.28 in the GnRH agonist cohort, and r = 0.55 vs. r = 0.33 in the GnRH antagonist cohort. The correlation was numerically higher for AMH than for AFC at a significantly higher proportion of study centers: 17 (89%) and 15 (83%) centers in the long GnRH agonist and GnRH antagonist trial, respectively. Assessment of the relative capacity of AMH and AFC for predicting oocyte yield demonstrated that AMH dominated the model: AMH, R2 = 0.29 and 0.23; AFC: R2 = 0.07 and 0.07; AMH + AFC: R2 = 0.30 and 0.23 for long GnRH agonist and GnRH antagonist trials, respectively. Conclusions(s) Antimüllerian hormone was a stronger predictor of ovarian response to gonadotropin therapy than AFC at the study center level in both randomized trials utilizing GnRH agonist and GnRH antagonist protocols. Antral follicle count provided no added predictive value beyond AMH.</p

Follicular and endocrine dose responses according to anti-Müllerian hormone levels in IVF patients treated with a novel human recombinant FSH (FE 999049)

Objective: To study the association between serum anti-Mullerian hormone (AMH) levels and follicular development and endocrine responses induced by increasing doses (5.2-12.1 mu g/day) of a novel recombinant human FSH (rhFSH, FE 999049) in patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in a GnRH antagonist protocol. Design: Secondary analysis of a randomized controlled trial with stratified randomization according to AMH (lower stratum: 5.0-14.9 pmol/l; higher stratum: 15.0-44.9 pmol/l). Patients: Infertile women of good prognosis (n = 265). Measurements: Follicular development and endocrine parameters during controlled ovarian stimulation (COS) with rhFSH. Results: Serum FSH levels increased with increasing rhFSH doses and steady-state levels for each dose were similar in both AMH strata. In the whole study population, significant (P = 12 mm, and serum levels of oestradiol, inhibin B, inhibin A and progesterone at end of stimulation. In comparison with the higher AMH stratum, patients in the lower AMH stratum had significantly different slopes of the dose-response curves for these hormones, and no clear dose-related increase was observed for the number of follicles in these patients. Conclusions: Dose-response relationships between rhFSH and follicular development and endocrine parameters are significantly different for IVF/ICSI patients with lower and higher serum AMH levels at start of COS

Individualized versus conventional ovarian stimulation for in vitro fertilization:a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial

Objective: To compare the efficacy and safety of follitropin delta, a new human recombinant FSH with individualized dosing based on serum antimüllerian hormone (AMH) and body weight, with conventional follitropin alfa dosing for ovarian stimulation in women undergoing IVF. Design: Randomized, multicenter, assessor-blinded, noninferiority trial (ESTHER-1). Setting: Reproductive medicine clinics. Patient(s): A total of 1,329 women (aged 18–40 years). Intervention(s): Follitropin delta (AMH &lt;15 pmol/L: 12 μg/d; AMH ≥15 pmol/L: 0.10–0.19 μg/kg/d; maximum 12 μg/d), or follitropin alfa (150 IU/d for 5 days, potential subsequent dose adjustments; maximum 450 IU/d). Main Outcomes Measure(s): Ongoing pregnancy and ongoing implantation rates; noninferiority margins −8.0%. Result(s): Ongoing pregnancy (30.7% vs. 31.6%; difference −0.9% [95% confidence interval (CI) −5.9% to 4.1%]), ongoing implantation (35.2% vs. 35.8%; −0.6% [95% CI −6.1% to 4.8%]), and live birth (29.8% vs. 30.7%; −0.9% [95% CI −5.8% to 4.0%]) rates were similar for individualized follitropin delta and conventional follitropin alfa. Individualized follitropin delta resulted in more women with target response (8–14 oocytes) (43.3% vs. 38.4%), fewer poor responses (fewer than four oocytes in patients with AMH &lt;15 pmol/L) (11.8% vs. 17.9%), fewer excessive responses (≥15 or ≥20 oocytes in patients with AMH ≥15 pmol/L) (27.9% vs. 35.1% and 10.1% vs. 15.6%, respectively), and fewer measures taken to prevent ovarian hyperstimulation syndrome (2.3% vs. 4.5%), despite similar oocyte yield (10.0 ± 5.6 vs. 10.4 ± 6.5) and similar blastocyst numbers (3.3 ± 2.8 vs. 3.5 ± 3.2), and less gonadotropin use (90.0 ± 25.3 vs. 103.7 ± 33.6 μg). Conclusion(s): Optimizing ovarian response in IVF by individualized dosing according to pretreatment patient characteristics results in similar efficacy and improved safety compared with conventional ovarian stimulation

Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial

Objective To compare the efficacy and safety of follitropin delta, a new human recombinant FSH with individualized dosing based on serum antimüllerian hormone (AMH) and body weight, with conventional follitropin alfa dosing for ovarian stimulation in women undergoing IVF. Design Randomized, multicenter, assessor-blinded, noninferiority trial (ESTHER-1). Setting Reproductive medicine clinics. Patient(s) A total of 1,329 women (aged 18â40Â&nbsp;years). Intervention(s) Follitropin delta (AMH &lt;15 pmol/L: 12Â&nbsp;μg/d; AMH â¥15 pmol/L: 0.10â0.19Â&nbsp;μg/kg/d; maximum 12Â&nbsp;μg/d), or follitropin alfa (150 IU/d for 5Â&nbsp;days, potential subsequent dose adjustments; maximum 450 IU/d). Main Outcomes Measure(s) Ongoing pregnancy and ongoing implantation rates; noninferiority margins â8.0%. Result(s) Ongoing pregnancy (30.7% vs. 31.6%; difference â0.9% [95% confidence interval (CI) â5.9% to 4.1%]), ongoing implantation (35.2% vs. 35.8%; â0.6% [95% CI â6.1% to 4.8%]), and live birth (29.8% vs. 30.7%; â0.9% [95% CI â5.8% to 4.0%]) rates were similar for individualized follitropin delta and conventional follitropin alfa. Individualized follitropin delta resulted in more women with target response (8â14 oocytes) (43.3% vs. 38.4%), fewer poor responses (fewer than four oocytes in patients with AMH &lt;15 pmol/L) (11.8% vs. 17.9%), fewer excessive responses (â¥15 or â¥20 oocytes in patients with AMH â¥15 pmol/L) (27.9% vs. 35.1% and 10.1% vs. 15.6%, respectively), and fewer measures taken to prevent ovarian hyperstimulation syndrome (2.3% vs. 4.5%), despite similar oocyte yield (10.0 ± 5.6 vs. 10.4 ± 6.5) and similar blastocyst numbers (3.3 ± 2.8 vs. 3.5 ± 3.2), and less gonadotropin use (90.0 ± 25.3 vs. 103.7 ± 33.6Â&nbsp;μg). Conclusion(s) Optimizing ovarian response in IVF by individualized dosing according to pretreatment patient characteristics results in similar efficacy and improved safety compared with conventional ovarian stimulation. Clinical Trial Registration Number NCT01956110

In Vitro Biofilm Formation of Commensal and Pathogenic Escherichia coli Strains: Impact of Environmental and Genetic Factors

Our understanding of Escherichia coli biofilm formation in vitro is based on studies of laboratory K-12 strains grown in standard media. However, pathogenic E. coli isolates differ substantially in their genetic repertoire from E. coli K-12 and are subject to heterogeneous environmental conditions. In this study, in vitro biofilm formation of 331 nondomesticated E. coli strains isolated from healthy (n = 105) and diarrhea-afflicted children (n = 68), bacteremia patients (n = 90), and male patients with urinary tract infections (n = 68) was monitored using a variety of growth conditions and compared to in vitro biofilm formation of prototypic pathogenic and laboratory strains. Our results revealed remarkable variation among the capacities of diverse E. coli isolates to form biofilms in vitro. Notably, we could not identify an association of increased biofilm formation in vitro with a specific strain collection that represented pathogenic E. coli strains. Instead, analysis of biofilm data revealed a significant dependence on growth medium composition (P < 0.05). Poor correlation between biofilm formation in the various media suggests that diverse E. coli isolates respond very differently to changing environmental conditions. The data demonstrate that prevalence and expression of three factors known to strongly promote biofilm formation in E. coli K-12 (F-like conjugative pili, aggregative adherence fimbriae, and curli) cannot adequately account for the increased biofilm formation of nondomesticated E. coli isolates in vitro. This study highlights the complexity of genetic and environmental effectors of the biofilm phenotype within the species E. coli