A Novel Fertility Indicator Equation Using Estradiol Levels for Assessment of Phase of the Menstrual Cycle

Background and Objectives: Urinary hormone home monitoring assays are now available for fertility awareness methods (FAMs) of family planning, but lack sensitivity and precision in establishing the start of the fertile phase. We hypothesized that with a suitable algorithm, daily serum or blood estradiol (E2) levels could serve as a better analyte to determine the phase of the ovulatory cycle and the fertile start day (FSD). Materials and Methods: Published day-specific serum E2 levels, indexed to the serum luteinizing hormone (LH) peak, were analyzed from three independent laboratories for a threshold for a FSD. A fertility indicator quation (FIE) was discovered and tested with these data and a FSD was determined using the mean or median and variance ranges of the day-specific E2 data. Results: The considerable variance of day-specific serum E2 levels made an absolute serum E2 indicator for phase of cycle problematic. However, a FIE was discovered which maps the day-specific E2 levels of the ovulatory cycle enabling the fertile phase and transition to the luteal phase to be signaled. In this equation, FIE(D) is the value of FIE on day, D, of the cycle and has both a magnitude and sign. The magnitude of FIE(D) is the product of the normalized change in day-specific E2 levels over two consecutive intervals, (D-2, D-1) and (D-1, D), multiplied by 100, and is formulated as: (E2 (on D-1) - E2 (on D-2))/E2 (on D-2) × (E2(on D) - E2 (on D-1))/E2 (on D-1) × 100. The sign of FIE(D) is either + or - or ind (indeterminate) and is assigned on the basis of the direction of this product. Using a FIE threshold of ≥2.5 as the start of the fertile phase, the FSDs were Day -5 or Day -6, with FSD Day -4 for an outlier set of E2 levels. The maximum FIE value ranged 9.5-27.8 and occurred most often on Day -2. An inflection point with a large change in FIE magnitude and change in sign from + to - always occurred at Day 0 for all sets of day-specific E2 data signaling transition to the luteal phase. Conclusions: The fertility indicator equation, a product of two sequential normalized changes in serum E2 levels with a sign indicating confidence in direction of change, is powerful in identifying the fertile phase and subsequent transition to the postovulatory phase and may serve as a useful algorithm for FAMs of family planning.