The radiosensitivity of the human oocyte

By Dr. Michael Opsahl on April 6, 2011 in FertilityPreservation

This study advances the authors long interest in the subject of fertility estimation after radiation therapy. Fertility preservation matters when we think about successful cancer treatment and more recently, for normal women who are not ready for pregnancy at an older maternal age.

The authors use the best available mathematical models of oocyte depletion in the natural state to derive the LD50 (dose of radiation that depletes 50% of the oocytes in the ovary) from radiation therapy. They used patients from their practice who received childhood radiation and then became menopausal.

Oocyte decay represents an instantaneous rate of temporal change based upon the remaining number of oocytes, expressed as a differential equation: dy/dx = ±y[0.0595 + 3716/(11780 + y)], with initial value y(0) = 701,200 oocytes. A dry fact but useful to know that it exists help with counseling patients and family.

The following graph plots the natural loss off oocytes in the top solid curve to that of a patient who received radiation to demonstrate the depletion of eggs.

Figure 1. The Faddy±Gosden model. The solution of the Faddy±Gosden equation enables the size of the oocyte pool to be determined for any given age from birth to menopause, at an estimated age of 51 years. The calculation of an estimated surviving fraction for case 5 in Table I is shown: ovarian failure occurred at age 13 years in case 5. By applying the Faddy±Gosden model, we can determine the size of the surviving fraction following radiotherapy at age 10.5 years to be 0.56%.

The next graph demonstrates the calculation to determine the LD50.

Figure 2. Dose±response relationships for the human oocyte. The mean surviving fraction of oocytes for each patient has been calculated and plotted against the dose of radiation received: (i) for the six patients who received 14.4 Gy, and (ii) for the 18 patients who received 30 Gy. These lines represent the estimated (fractionated) dose±response relationship for the human oocyte. The LD50 is given by the dose required to leave a surviving fraction of 50%. Our revised LD50 of <2 Gy is taken from the relationship obtained by data from the cohort of six patients.

The authors therefore maintain that the most accurate estimate (LD50 <2 Gy) is calculated from applying the Faddy±Gosden solution to the second cohort, who were treated at an older age [median 11.5 (range 4.9±15.1) versus 4 (1±13) years] and with a lower total radiation dose.