Ultrastructure of human ovarian primordial follicles after combination chemotherapy for Hodgkin's disease

Ovarian damage, with consequent permanent infertility, is one of the more common side-effects which occurs during chemotherapeutic treatment of patients affected by Hodgkin's disease. This damage is morphologically represented by a marked loss of primordial and primary follicles. The administration of contraceptive drugs before starting chemotherapy enhances survival of a greater number of ovarian follicles, as revealed by morphometric analyses, nevertheless, total ovarian protection is not assured. This study evaluated the number and the morphology of ovarian follicles, by means of transmission electron microscopy, in patients with Hodgkin's disease treated with multi-drug chemotherapeutic protocols following the administration of medroxyprogesterone acetate. Ovarian biopsies were performed prior to any pharmacological treatment, after medroxyprogesterone therapy, and after this therapy plus chemotherapy. Particular attention was given to the ultrastructure of primordial follicles. After morphometric evaluation, primordial follicles were numerous in controls and medroxyprogesterone therapy (28.55 ± 6.59/mm3 of ovarian cortex). After chemotherapy and medroxyprogesterone acetate, the number of follicles was slightly reduced (19.37 ± 3.41/mm3 of ovarian cortex) in contrast to the dramatic loss usually observed when protection is not given, although more follicles were atretic. Medroxyprogesterone may protect follicles only from acute, toxic effects of chemotherapy, which dramatically reduce their number and lead to sterility. Nevertheless, the quality of follicles is still impaired, and many undergo atresia, resulting in a shortened fertility period.