Background:
The relative cardiovascular safety of gonadotropin-releasing hormone (GnRH) antagonists compared with GnRH agonists in men with prostate cancer and known atherosclerotic cardiovascular disease (ASCVD) remains controversial.
Methods:
In this international, multicenter, prospective, randomized, open-label trial, men with prostate cancer and concomitant ASCVD were randomized 1:1 to receive the GnRH antagonist degarelix or the GnRH agonist leuprolide for 12 months. The primary outcome was the time to first adjudicated major adverse cardiovascular event (MACE) (composite of death, myocardial infarction, or stroke) through 12 months.
Results:
Due to slower than projected enrollment and fewer than projected primary outcome events, enrollment was stopped before the 900 planned participants were accrued. From 3 May 2016 to 16 April 2020, a total of 545 patients from 113 sites across 12 countries were randomized. Baseline characteristics were balanced between study groups. The median age was 73 years, 49.8% had localized prostate cancer; 26.3% had locally advanced disease and 20.4% had metastatic disease. MACE occurred in 15 (5.5%) patients assigned to degarelix and 11 (4.1%) assigned to leuprolide (hazard ratio [HR] 1.28, 95% confidence interval [CI] 0.59-2.79; p=0.53).
Conclusions:
PRONOUNCE is the first, international, randomized clinical trial to prospectively compare the cardiovascular safety of a GnRH antagonist and a GnRH agonist in patients with prostate cancer. The study was terminated prematurely due to smaller than planned number of participants and events and no difference in MACE at 1 year between patients assigned to degarelix or leuprolide was observed. The relative cardiovascular safety of GnRH antagonists and agonists remains unresolved.
Clinical Trial Registration:
URL: https://clinicaltrials.gov Unique Identifier: NCT02663908
Stimulation with HP-HMG is associated with ovulation rates at least as good as a rFSH in anovulatory WHO Group II women. LH activity modifies follicular development so that fewer intermediate-sized follicles develop. This could have a positive impact on the safety of ovulation induction protocols.
Objective To assess the influence of body weight on the outcome of ovulation induction in women with World Health Organization (WHO) group II anovulatory infertility.Design The combined results of two studies in which either a highly purified urinary follicle-stimulating hormone or highly purified urinary menotrophin were compared with recombinant follicle-stimulating hormone.Setting Thirty-six fertility clinics.Population A total of 335 women with WHO group II anovulatory infertility failing to ovulate or conceive on clomifene citrate.Methods Ovarian stimulation using a low-dose step-up protocol.Main outcome measures The effects of body weight on ovarian response, ovulation rate and pregnancy rate after one treatment cycle.Results With increasing body mass index (BMI), a higher threshold dose of gonadotrophins was required and there were more days of stimulation; yet, despite a greater concentration of antral follicles, there were fewer intermediate and large follicles. There was no difference in the rates of ovulation and clinical pregnancy in relation to body weight.Conclusions Body weight affects gonadotrophin requirements but not overall outcome of ovulation induction in women with anovulatory polycystic ovary syndrome and a BMI of less than 35 kg/m 2 .
Embryo quality can be determined with a good degree of interobserver agreement independently of the method of evaluation. Embryologists classify embryos with excellent intraobserver reproducibility.
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