Martin Imhof

BRCA1/2 mutations associated with progression-free survival in ovarian cancer patients in the AGO-OVAR 16 study

OBJECTIVE AGO-OVAR 16 demonstrated that pazopanib maintenance therapy significantly increased progression-free survival (PFS) in patients with ovarian cancer whose disease had not progressed after first-line therapy. In a sub-study, we evaluated the effect of clinically important germline BRCA1 and BRCA2 mutations on PFS. METHODS Of 940 AGO-OVAR 16 participants, 664 had BRCA1/2 exon sequencing data (pazopanib, n=335; placebo, n=329). A Cox model was used to test the association between genetic variants and PFS. RESULTS Ninety-seven of 664 patients (15%) carried clinically important BRCA1/2 mutations (BRCA1/2 carriers: pazopanib 14%, placebo 16%). Median PFS was longer in BRCA1/2 mutation carriers than in BRCA1/2 non-carriers in the placebo arm (30.3 vs 14.1 months, hazard ratio, 0.48; 95% confidence interval [CI]: 0.29-0.78; P=0.0031); a similar non-significant trend was noted with pazopanib (30.2 vs 17.7 months, hazard ratio, 0.64; 95% CI: 0.40-1.03; P=0.069). Among BRCA1/2 non-carriers, PFS was longer for pazopanib-treated patients than placebo-treated patients (17.7 vs 14.1 months, hazard ratio, 0.77; 95% CI: 0.62-0.97; P=0.024). Among BRCA1/2 carriers, there was no significant PFS difference between treatments, although numbers were small (pazopanib, 46; placebo, 51), resulting in a wide CI (hazard ratio, 1.36; 95% CI: 0.66-2.82). CONCLUSIONS Patients with clinically important BRCA1/2 mutations had better prognosis. BRCA1/2 mutation status might be added as strata in future trials in primary ovarian cancer.

Clinical outcome monitoring in a reproductive surgery unit: a prospective cohort study in 796 patients

OBJECTIVE To systematically monitor the frequency and risk factors of adverse events (AEs) in a reproductive surgery endoscopy unit. DESIGN Prospective cohort study. SETTING Academic research institution. PATIENT(S) All consecutive surgical patients of a reproductive surgery unit from December 2005 to March 2007. INTERVENTION(S) Monitoring for predefined AEs by trained observers. MAIN OUTCOME MEASURE(S) Number of preventable and not preventable AEs, medical errors, and system problems. Univariate analysis and multivariate logistic regression were used to identify risk factors of AEs. RESULT(S) Seven hundred ninety-six women were included. We identified 60 AEs in 45 patients (risk 6%; 95% confidence interval [CI] 1%-11%). Adverse events were postoperative fever (n = 1), wound breakdown (n = 1), intraoperative or postoperative administration of packed erythrocytes (n = 6), surgical revision (n = 7), unplanned readmission (n = 5), transfer to intensive care unit (n = 1), conversion (n = 8), intraoperative organ injury (n = 9), blood loss >500 mL (n = 3), surgery canceled (n = 15), and other AEs (n = 4). Six patients (risk 0.8%; 95% CI 0-2%) had multiple AEs. One (0.01%) and 11 (1.4%) AEs were deemed due to medical errors and system problems, respectively. Twelve and 48 AEs were deemed preventable and not preventable, respectively. In a univariate and multivariate analysis, only duration of surgery (odds ratio 3.78; 95% CI 1.95-7.33) was significantly associated with having an AE. CONCLUSION(S) Clinical outcome monitoring is a useful tool for assessing the outcome quality of reproductive surgery by identifying potentially preventable AEs and associated risk factors.

The Impact of a Standardized Oral Multinutrient Supplementation on Embryo Quality in in vitro Fertilization/Intracytoplasmic Sperm Injection: A Prospective Randomized Trial.

The role of micronutrients in fertility has recently gained increased attention. We aimed to test the impact of a standardized, multinutrient supplementation on outcomes after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in a pilot study. One hundred women undergoing IVF/ICSI were prospectively included and randomized to receive either a multinutrient supplementation named PROfertil® female that included folic acid, selenium, vitamin E, catechins, glycyrrhizin, diosgenin, damiana and omega-3-fatty acids (study group; n = 50), or 400 µg folic acid (control group; n = 50). Outcome parameters were embryo quality on day 3 after oocyte retrieval (good quality vs. poor quality) and the clinical pregnancy rate. In an intention-to-treat analyses, a higher rate of women with at least one good quality embryo (with at least 6 cells and a fragmentation rate <20%) were found for the study (29/50, 58.0%) compared to the control group (18/50, 36.0%; p = 0.045 in chi-square test; relative risk 1.611, 95% CI 1.009-2.597). In conclusion, a multinutrient supplementation that includes folic acid, selenium, vitamin E, catechins, glycyrrhizin, diosgenin, damiana and omega-3-fatty acids seems beneficial in terms of embryo quality.

‘Ovarian Tissue Banking’ – erste Ergebnisse

Chemotherapie und Strahlentherapie bewirken bei jungen Frauen mit onkologischen Erkrankungen oft eine starke Reduktion der ovarialen Funktion mit menopausalen Beschwerden und Infertilität. Die teilweise oder vollständige Erhaltung des Ovars könnte nach Reimplantation die Hormonproduktion wiederherstellen und eine natürliche Empfängnis ermöglichen. Gewebescheiben von Ovarien konnten bereits erfolgreich reimplantiert werden, waren aber nur von kurzer Lebensdauer. Die Retransplantation kryopräservierter ganzer Ovarien wird nach Vorversuchen an Schweinen zurzeit bei Schafen durchgeführt. Hormonproduktion und Schwangerschaft sollen die ovariale Funktion beweisen.