Serum concentrations of HE4 change little during in vitro fertilization

Objective. Human epididymal secretory protein 4 (HE4) is a biomarker for ovarian cancer. The effect of follicle stimulating hormone (FSH) stimulation during in vitro fertilization (IVF) on HE4 was evaluated to determine whether substantial hormonal stimulation of the ovaries affects the serum levels of this marker. Findings were compared with serum concentrations of cancer antigen 125 (CA125), currently the most commonly used marker for ovarian cancer. Design. Prospective cohort study. Setting. University hospital infertility clinic. Population. Infertility patients undergoing IVF treatment. Methods. We determined the serum concentration of HE4 and CA125 in serial blood samples in 20 women treated with IVF. Samples were taken following gonadotrophin-releasing hormone agonist suppression, two to three times during FSH stimulation, at ovum pick-up and 2 weeks following embryo transfer at the time of the pregnancy test. Ovarian follicles were counted and serum estradiol concentrations measured throughout treatment. Main outcome measures. Serum HE4, CA125 and estradiol concentrations. Results. Serum HE4 levels did not increase significantly during the FSH stimulation. The majority of values remained below the normal reference range (<70 PM) throughout the treatment. Serum CA125 concentration also remained low during stimulation. Serum estradiol concentration reflected the severity of ovarian stimulation during IVF, increasing 3.9-fold with stimulation. Conclusions. Serum HE4 concentrations respond little if at all to supraphysiological ovarian stimulation, suggesting that the amount of circulating HE4 in women with normal ovaries is independent of gonadotropin stimulation. Hormonal stimulation of the ovaries is unlikely to affect the differential diagnosis of ovarian tumors with HE4.