Abstract

Abstract Study question What are the reproductive outcomes in women with malignant lymphoma Hodgkins (HD) and non-Hodgkins (NH) from a single, experienced center? Summary answer 74 children were born to 43 women (28 with HD, 15 with NH) giving a live birth rate (LBR) of 81% and 72%, respectively. What is known already The risk of premature ovarian insufficiency (POI) after HD and NH is related to female age, type and dose of gonadotoxic treatment. Where ABVD regimens in HD patients and CHOEP regimens in most young NH patients, rarely results in POI and reduced fertility, treatment with BEACOPP or BEAM and stem cell transplantation seems to be associated with a much higher risk of ovarian failure. However, studies are heterogeneous and there is still a need for studies with structural follow up on repeated measurements of ovarian function markers in relation to clinical outcomes. Study design, size, duration This cohort study was conducted as a single center study at the fertility clinic in a large public Danish university hospital. Data was collected retrospectively from medical records from 1999 to 2020 and prospectively from 2020 to 2023. We included all female patients with HD (n = 63) and NH (n = 32), who were referred to our clinic for fertility preservation between 1999 and 2022. End of follow up was December 31st, 2023. Participants/materials, setting, methods Age at referral ranged from 14 to 33 years. Information about diagnoses, gonadotoxic treatment, gynecologic (including endocrine parameters) and obstetric history was retrieved from medical records. Permission to obtain retrospective data from 1999 to 2020 was given by the Danish Patient Safety Authorities (jrn 3-3013-2790/1) and prospective data collection was given by informed consent from the patients from 2020 and onwards. Main results and the role of chance 33% of patients with HD had ABVD only, and the remaining BEACOPP or other high-dose alkylating regimens. 72% of patients with NH had CHOEP, and the rest other high-dose alkylating regimens. 78/95 women had fertility preservation. Of these, 95% had ovarian tissue cryopreservation (OTC), 5% had IVF with vitrification of oocytes or embryos. Following chemotherapy 33 women (52%) with HD and 18 (56%) with NH became pregnant. Of these, 28 women with HD had 51 deliveries, and 15 with NH had 23 deliveries. The LBR was 0,81 for HD and 0,72 for NH. For HD patients, 54% of the deliveries were achieved by women who had ABVD compared to about 40% after other high-dose alkylating regimens. For NH patients, 73% of deliveries were achieved by women who had CHOEP compared to 13% after other high-dose alkylating regimens. Most pregnancies were conceived spontaneously. A total of 15/74 women had ovarian tissue transplantation (OTT). Of these, 7 women with HD became pregnant resulting in 4 deliveries, and 4 women with NH became pregnant resulting in 2 deliveries giving an overall pregnancy rate of 73% in this group of women and a LBR of 40%. Limitations, reasons for caution This study is based on information from medical records in public Danish hospitals, containing information on all deliveries. Pregnancies and deliveries outside of Denmark might therefore not be included. Furthermore, for some women the follow-up period was only one year, which could underestimate the fertility in this group of patients. Wider implications of the findings This study shows a reassuringly high rate of spontaneous pregnancies in female survivors of malignant lymphomas. Only 20% of the women have so far used their tissue stored before chemotherapy. Current results might question whether we overtreat our lymphoma patients by offering OTC to the majority Trial registration number not applicable

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