The radiosensitivity of the human oocyte.

BACKGROUND We determined the best model available for natural follicle decline in healthy women and used this to calculate the radiosensitivity of the human oocyte. METHODS Ovarian failure was diagnosed in six patients with a median age of 13.2 years (range 12.5-16.0) who were treated with total body irradiation (14.4 Gy) at 11.5 years of age (4.9-15.1). We previously estimated the dose of radiation required to destroy 50% of the oocytes (LD(50)) to be <4 Gy. This estimate is an oversimplification, because decay represents an instantaneous rate of temporal change based upon the remaining population pool, expressed as a differential equation: dy/dx = -y[0.0595 + 3716/(11780 + y)], with initial value y(0) = 701 200. RESULTS Solving the differential equation, we have estimated the number of follicles left after irradiation given as sol(51 - s + r), where r equals age at treatment, s equals age at diagnosis of ovarian failure, and 51 years is the average age of menopause. The surviving fraction of oocytes as a percentage is 100 times this value divided by sol(r). The mean surviving fraction for the six cases is 0.66%. We obtain a function, g(z), which decreases in value from 100% at zero dosage to mean value at dosage z = 14.4 Gy. We have g(z) = 10(mx+c), where c = log(10)100 = 2, and m = [log(10)(0.66) - c]/14.4. Solving g(z) = 50 gives an LD(50) of 1.99. CONCLUSIONS Based on new data and a revised mathematical model of natural oocyte decline, we have determined the surviving fraction of oocytes following irradiation and estimate the LD(50) of the human oocyte to be <2 Gy.