Fertility and gonadal function in female survivors after treatment of early unfavorable Hodgkin lymphoma (HL) within the German Hodgkin Study Group HD14 trial

In the HD14 trial, 2x BEACOPP(escalated) + 2x ABVD (2 + 2) has improved the primary outcome. Compared with 4x ABVD, this benefit might be compromised by more infertility in women. Therefore, we analyzed gonadal function and fertility. Women < 45 years in ongoing remission at least 1 year after therapy were included. Hormone parameters, menopausal symptoms, measures to preserve fertility, menstrual cycle, pregnancies, and offspring were evaluated. Three hundred and thirty one of 579 women addressed participated (57.2%) and 263 per-protocol treated patients qualified (A = ABVD: 137, B = 2 + 2: 126, mean time after therapy 42 and 43 months, respectively). Regular menstrual cycle after treatment (A: 87%, B: 83%) and time to recovery (< 12 months) were not different. Follicle-stimulating hormone and anti-Muellerian hormone were significantly better in arm A. However, pregnancies after therapy favored arm B (A: 15%, B: 26%, P = 0.043) and motherhood rates were equivalent to the German normal population. Multivariate analysis revealed prophylactic use of gonadotropin-releasing hormone (GnRH) analogues as highly significant prognostic factor for preservation of fertility (odds ratio = 12.87, P = 0.001). Severe menopausal symptoms were frequent in women >= 30 years (A: 21%, B: 25%). Hormonal levels after 2 + 2 indicate a reduced ovarian reserve. However, 2 + 2 in combination with GnRH analogues does not compromise fertility within the evaluated observation time.