Treatment of young patients diagnosed with HL is multidisciplinary and involves a team of hematologists, gynecologists, and fertility specialists, who should all keep in mind that increased disease activity could be associated with adverse pregnancy outcome.108–113 The risk of chemotherapy-induced infertility should be discussed with all newly diagnosed HL patients. A thorough evaluation of ovarian function and semen should be performed in all young HL patients. Even if the infertility risk associated with ABVD regimen is known to be low, fertility issues and preservation methods should be discussed with all patients under the age of 40 diagnosed with early stage HL before the beginning of therapy. Patients diagnosed with advanced stage HL, treated with combination chemotherapy, should also be offered fertility preservation methods prior to therapy, as well as counseling, which must be offered to all patients regarding the risks of pregnancy during treatment. Other long-term complications of chemoradiotherapy, such as secondary acute leukemia or breast cancer or thyroid disfunction, should be kept in mind when deciding in favor of fertility preservation at the initial HL diagnosis, considering the timeframe for next chemotherapy and the possible contraindication for ovarian stimulation.
Current recommendations suggest a planned pregnancy after 6–24 months following chemotherapy, considering the approximate 6 months interval for follicullar maturation and the relapse risk which is highest during the first 2 years. For the anti-CD20 monoclonal antibody rituximab, the recommendations are for contraception during treatment and no less than 12 months after the last dose. For anti-PD-1 monoclonal antibodies, strong recommendations are in favor of contraception. Still, most available data on fertility issues and pregnancy rate and pregnancy outcome are from voluntary reports, from clinical trials, or from registries, thus making clear interpretation of data difficult. Long-term follow-ups of pregnancies during chemo-, immunotherapy are scarce, and reports on pregnancies and their outcomes should be encouraged, in order to have better guidelines.
With the impressive results obtained with targeted molecules, even in the setting of relapsed/refractory disease, long-term survivors of HL will be seen. Future studies will assess the best approach regarding the use of monoclonal antibodies in frontline or relapsed settings, with single agents or combination therapy. Due to the important progress made with the addition of monoclonal antibodies, fertility issues need to be carefully studied in future trials for responding patients.
All authors have read and approved the final version of the manuscript.
The authors report no conflicts of interest in this work.
Alexandra Traila,1,2,*Delia Dima,3 Patriciu Achimas-Cadariu,1,2,*Romeo Micu1,4
1School of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania; 2Department of Surgical Oncology, Ion Chiricuta Oncology Institute, Cluj Napoca, Romania; 3Department of Hematology, Ion Chiricuta Oncology Institute, Cluj Napoca, Romania; 4Department of Human Assisted Reproduction of 1st Gynecology Clinic, Cluj Napoca, Romania
*These authors contributed equally to this work.
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