Follicle features in adolescent and young adult women with Hodgkin’s disease prior to chemotherapy: a preliminary report

Abstract

Treatment of Hodgkin’s disease (HD) has improved over the last two decades, but infertility is a common side effect of chemotherapy. Men with HD have an increased risk of inadequate semen quality and severe damage of fertility before treatment. The aim of this study was to investigate the possible association between the disease itself and germ-cell damage in female patients before treatment for HD. The ovarian cortex from 13 untreated women with HD was processed by light and transmission electron microscopy and compared with the ovarian cortex from the control group of 13 untreated women without HD. Histological examination of fresh ovarian cortex showed that in HD patients, follicles presented an unusual presence of clear vacuoles when compared with control group (73.7% versus 5.7%). Ultrastructural examination demonstrated that the small vacuoles fused into large autophagic vacuoles. The percentage of vacuolated follicles was higher in patients with advanced stage and bulky disease. In conclusion, this study demonstrates for the first time that significant damage to gametes occurs in women with HD. Further investigations are required to establish whether the present features should be considered a common side effect of HD. Treatment of Hodgkin’s disease (HD) has improved over the last two decades. More than 80% of patients with HD can be cured, but infertility is a common side effect of chemotherapy. Males with HD have an increased risk of inadequate semen quality before treatment. The aim of this study was to investigate the possible association between the disease itself and germ cell damage in HD female patients, before treatment. The ovarian cortex from nine adult (age range 18–37) and four adolescent (age range 14–16) untreated females with HD was processed by light microscopy and transmission electron microscope and compared with the ovarian cortex from a control group composed of 10 adult (age range 24–34) and three adolescent (age range 12–15) untreated females without HD. Histological examination of fresh ovarian cortex showed that in patients with HD the stromal cells were apparently normal, while follicles showed an unusual presence of cytoplasmic vacuolization when compared with control group (73.7% versus 5.7%). Ultrastructural examination of vacuolated oocytes demonstrated that vacuoles were circumscribed by discontinuous cell membrane and contained sparse granular-filamentous material. The percentage of vacuolated follicles was significantly higher in patients with advanced stage, but no correlation was observed with haematological and inflammation-related parameters. This preliminary report documents, for the first time, the unusual presence of vacuoles in follicles from HD patients. The mechanism of the high rate of oocyte vacuolation remains unknown and its relevant to gonadal dysfunction still remain to be elucidated in further investigation.