Читать книгу Assisted Reproduction Techniques - Группа авторов - Страница 165

The human ovary has a nonrenewable pool of primordial follicles which reaches a maximum of around 7 million at 5–6 months’ gestational age, declining at an exponential rate thereafter. On average, the number of follicles remaining at birth is 2 million, falling to 300,000 by menarche. Thereafter, the rate of decline follows a bi‐exponential pattern, with acceleration after the age of 37 years when numbers reach approximately 25,000. As only 400 or so follicles are ultimately released as mature oocytes during the reproductive lifespan, the overwhelming majority of follicles are lost through the process of atresia and apoptosis. Menopause occurs when the number of remaining follicles reaches approximately 1000 [2].

Ionizing radiation can cause direct DNA damage to ovarian follicles, leading to follicular atrophy and decreased ovarian follicular reserve. This can hasten the natural decline of follicular numbers, leading to impaired ovarian hormone production and early menopause. Factors that are determinants of ovarian failure include radiation dosage, age at the time of radiation exposure and extent of radiation field treatment.

The human oocyte is generally extremely sensitive to radiation therapy. A mathematical model suggests that the dose required to destroy 50% of immature oocytes (LD₅₀) is less than 2 Gy [4]. The effective sterilizing dose (ESD) of fractionated RT at which ovarian failure occurs immediately in 97.5% of patients was found to decrease with increasing age at treatment. The estimated ESD at birth was 20.3 Gy; at 10 years, 18.4 Gy; at 20 years, 16.5 Gy; and at 30 years, 14.3 Gy. However, there is wide individual variability in ovarian follicular reserve at time of treatment, which can explain differences in onset of premature ovarian failure between patients at similar ages [5].

A study assessing ovarian function in 100 female cancer survivors treated with chemotherapy and/or RT identified from the Childhood Cancer Registry found 17 patients had premature ovarian failure, required hormone replacement therapy and were found to have follicle depleted or undetectable ovaries [6]. A total of 70 patients with spontaneous menses had reduced ovarian volumes per ovary than controls (4.8 cm³ vs. 6.8 cm³; P <0.001) and fewer antral follicles per ovary (7.5 vs. 11; P <0.001). In addition, follicle number was inversely associated with ovarian irradiation, alkylating chemotherapy, older age at diagnosis and longer follow up. These results demonstrate that survivors with spontaneous menstrual cycles may have diminished ovarian reserve [6].

Use of higher energy photons may reduce side scatter when ovaries are outside the primary field, and external shielding can be considered to reduce external scatter from the linear accelerator. Novel radiation techniques, including IMRT and proton RT, may spare the ovaries from significant radiation and reduce potential adverse effects on fertility [2].