Early detection of pregnancy after IVF and embryo transfer with hyperglycosylated HCG versus Elecsys HCG+ß assay.

RESEARCH QUESTION: Is measurement of hyperglycosylated HCG (hHCG) superior to beta-HCG (HCG+ß) for early pregnancy detection after IVF and embryo transfer? DESIGN: Blood samples were collected on day 4 (+1), 7 (+1) and 11 (+2) after embryo transfer from women aged 18-45 years undergoing first or second fresh or frozen IVF embryo transfer cycles. Biochemical pregnancy was assessed on-site by HCG determination on day 11; clinical pregnancy was assessed by ultrasound on day 21 (+4/-3). Serum hHCG (immunochemiluminometric assay) and HCG+ß (Elecsys® HCG+ß assay) concentrations were measured. Performance of hHCG and HCG+ß for predicting pregnancy was evaluated and cut-offs selected. RESULTS: In total, 155 women were enrolled and underwent IVF and embryo transfer. Area under the curve (AUC) (95% CI) on day 4 was not significantly different for hHCG (AUC 0.88; 95% CI 0.83 to 0.94) and HCG+ß (AUC 0.90; 95% CI 0.84 to 0.95), as was predictive performance on day 7 and 11, with higher AUC estimates compared with day 4. Applying cut-offs derived according to Youden's index on day 4 (hHCG, 100 pg/ml; HCG+ß, 1.30 mIU/ml), both biomarkers demonstrated high negative predictive values for ruling out pregnancy (hHCG, 83.8%; HCG+ß, 82.8%) and high positive predictive values for ruling in pregnancy (hHCG, 89.0%; HCG+ß, 84.9%) on day 21. Diagnostic performance improved from day 4 to day 11. CONCLUSIONS: Predictive performance for early pregnancy post-IVF embryo transfer of day-5 blastocysts was not significantly different for hHCG and HCG+ß; hHCG superiority over HCG+ß was not shown.

Efficacy and safety profile of boceprevir- or telaprevir-based triple therapy or dual peginterferon alfa-2a or alfa-2b plus ribavirin therapy in chronic hepatitis C: the real-world PegBase observational study.

BACKGROUND: The aim of the study was to determine the efficacy and safety of triple therapy with a first-generation protease inhibitor (PI; boceprevir, telaprevir) plus peginterferon alfa-2a or -2b plus ribavirin, and dual therapy (peginterferon alfa-2a or -2b plus ribavirin) in patients with chronic hepatitis C (CHC) in routine clinical practice. METHODS: PegBase was an international, prospective, observational study in which 4441 patients with CHC were enrolled in 27 countries. This analysis focuses on results in 4100 treatment-naïve and previously treated patients treated with PI-based triple therapy or dual therapy, according to the discretion of the investigator and local standards of practice. The primary efficacy outcome was sustained virological response after 12-week follow up (SVR12). RESULTS: SVR12 rates in treatment-naïve genotype (G) 1 patients were 56.6% and 62.9% for recipients of boceprevir plus peginterferon alfa-2a/ribavirin and boceprevir plus peginterferon alfa-2b/ribavirin, respectively, and 65.3% and 58.6% for recipients of telaprevir plus peginterferon alfa-2a/ribavirin and telaprevir plus peginterferon alfa-2b/ribavirin, respectively. In previously treated patients assigned to these four regimens, SVR12 rates were 43.6%, 48.3%, 60.3% and 56.1%, respectively. Among treatment-naïve patients assigned to peginterferon alfa-2a/ribavirin and peginterferon alfa-2b/ribavirin, respectively, SVR12 rates were 49.2% and 41.9% in G1 patients, 75.7% and 83.3% in G2 patients, 65.9% and 65.9% in G3 patients, and 49.7%, and 51.1% in G4 patients. The safety and tolerability of dual and triple therapy were consistent with previous reports. CONCLUSION: The efficacy and safety of first-generation PI-based triple-therapy and dual-therapy regimens in this real-world cohort were broadly comparable to those of previous studies.

Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.