To the best of our knowledge, this is the first long-term analysis confirming that GnRHa is not efficient in preventing chemotherapy-induced POF in young patients with lymphoma and did not influence future pregnancy rate. These results reopen the debate about the drug's benefit in that it should not be recommended as standard for fertility preservation in patients with lymphoma.

This study was supported by the Télévie, FNRS-FRSM and Fondation Belge contre le cancer. There are no competing interests to report.

A consistent trend for reduced reproductive potential and performance of cryopreservation strategies was observed in BRCA-mutated breast cancer patients. Independent validation of these results is needed.

A B S T R A C T PurposeTo assess the efficacy of gonadotropin-releasing hormone agonist (GnRHa) in preventing chemotherapy-induced ovarian failure in patients treated for Hodgkin or non-Hodgkin lymphoma within the setting of a multicenter, randomized, prospective trial. Patients and MethodsPatients age 18 to 45 years were randomly assigned to receive either the GnRHa triptorelin plus norethisterone (GnRHa group) or norethisterone alone (control group) concomitantly with alkylating agents containing chemotherapy. The primary end point was the premature ovarian failure (POF) rate (follicle-stimulating hormone [FSH] Ն 40 IU/L) after 1 year of follow-up. ResultsEighty-four of 129 randomly assigned patients completed the 1-year follow-up. The mean FSH values were higher in the control group than in the GnRHa group during chemotherapy; however, this difference was no longer observed after 6 months of follow-up. After 1 year, 20% and 19% of patients in the GnRHa and control groups, respectively, exhibited POF (P ϭ 1.00). More than half of patients in each group completely restored their ovarian function (FSH Ͻ 10 IU/L), but the anti-Mü llerian hormone values were higher in the GnRHa group than in the control group (1.4 Ϯ 0.35 v 0.5 Ϯ 0.15 ng/mL, respectively; P ϭ .040). The occurrence of adverse events was similar in both groups with the exception of metrorrhagia, which was more frequently observed in the control group than the GnRHa group (38.4% v 15.6%, respectively; P ϭ .024). ConclusionApproximately 20% of patients in both groups exhibited POF after 1 year of follow-up. Triptorelin was not associated with a significant decreased risk of POF in young patients treated for lymphoma but may provide protection of the ovarian reserve.J Clin Oncol 30.