Human Reproduction, Vol. 18, No. 1, 117-121,
January 2003
© 2003 European Society of Human Reproduction and Embryology
The radiosensitivity of the human oocyte
1 Section of Child Life and Health, Department of Reproductive and Developmental Sciences, University of Edinburgh and 2 School of Computer Science, University of St Andrews, UK 3 To whom correspondence should be addressed at: Department of Haematology/Oncology, Royal Hospital for Sick Children, 17 Millerfield Place, Edinburgh EH9 1LW, UK. e-mail: hamish.wallace{at}luht.scot.nhs.uk
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 (LD50) 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) = 10mx+c, where c = log10100 = 2, and m = [log10(0.66) – c]/14.4. Solving g(z) = 50 gives an LD50 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 LD50 of the human oocyte to be <2 Gy.
Key words: fertility/human oocyte/ovarian failure/radiotherapy
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