Changes in estrone and estradiol levels during follicle development: a retrospective large-scale study

BACKGROUND The improved reagent for measuring estradiol (E2), the ST AIA-PACK iE2 reagent, has a higher specificity for the measurement of E2 levels than the original ST AIA-PACK E2 reagent, because of its lower cross-reactivity with estrone (E1). As we had E2 data obtained with either of the reagents, we analyzed changes in E1 and E2 levels during follicle development. METHODS The study included 14371 serum hormone measurements from 4412 patients who underwent oocyte retrieval or frozen/thawed embryo transfer in natural cycle in vitro fertilization in Shinbashi YUME clinic, Tokyo, between June 2011 and May 2014. The age of the patients ranged from 24 to 48 year (mean and standard deviation, 39.8 ± 4.0 year). Patients were categorized into three age groups (<38 year, 38-40 year, and >40 year) and into 10 groups of largest follicle diameter from 11 to 20 mm, with 1-mm intervals. Serum E2 levels were measured in the follicular phase with either the ST AIA-PACK E2 reagent or the ST AIA-PACK iE2 reagent, and the data were compared. Also, for 26 randomly selected samples, E2 was measured using both reagents, together with E1 and E3, and the E1/E2 ratios were compared. RESULTS E2 concentrations measured with the ST AIA-PACK iE2 reagent were significantly lower than those measured with the ST AIA-PACK E2 reagent in the largest follicle diameter category of 11-17 mm in the <38 year group, in the largest follicle diameter category of 11-18 mm in the 38-40 year group, and in the largest follicle diameter category of 11-15 mm in the >40 year group. The serum E1/E2 ratio in the 26 samples was 3.4 ± 1.1 and 0.7 ± 0.1 in the early follicular phase and in the ovulatory phase, respectively. CONCLUSIONS The difference between the E2 concentrations measured with the ST AIA-PACK E2 reagent and the ST AIA-PACK iE2 reagent tended to decrease as the follicle diameter increased, particularly in the older patients, which suggests E1 secretion is more abundant in the early follicular phase and in younger patients than in the ovulatory phase and in older patients.