Abstract

Abstract Study question What proportion of adolescents who have cryo-preserved sperm for medical indications will have normal semen analysis after treatment and no longer require stored sperm samples? Summary answer More than half of adolescent patients with cryo-preserved sperm will not need continued storage as sperm parameters return to normal after completion of treatment. What is known already Worldwide, about 12,400 young adults are diagnosed with cancer every year. With modern treatment 80% of them will achieve a long-term cure1. Lymphomas, brain tumours, sarcomas, and carcinomas account for more than 90% of cases, for which treatment tends to be predominantly gonadotoxic. Sperm cryo-preservation prior to starting treatment is recommended by all clinical guidelines. Although there is evidence that treatment could cause prolonged azoospermia, especially alkylating or platinum-based agents, several therapy regimes seem to induce only a temporary reduction in sperm count. In some cases spermatagonial stem cells can repopulate the seminiferous tubules after chemotherapy-induced damage2. Study design, size, duration This was a retrospective cohort study on male adolescent who underwent medical sperm cryo-preservation between 1985 and 2014. The data was retrieved from a prospective held secure electronic database. Within 10 years of storage a review was carried out to ascertain if they met criteria for continued storage. A total of 323 teenagers were included in the study. Participants/materials, setting, methods In a tertiary fertility preservation centre, 323 adolescents had sperm cryopreservation before undergoing potentially gonadotoxic treatment. All patients were offered repeat semen analysis within 10 years from storage. The indication for discarding sperm within this period were analysed. The primary outcome was the proportion of patients who did not have adverse impact on sperm. Their diagnosis, treatments and outcomes including death were included in the analysis. Statistical analysis was performed using IBM SPSS Statistics. Main results and the role of chance According to WHO criteria, at time of cryo-preservation 168/323 (52%) adolescents had a normal semen analysis, 120/323 (37,1%) had oligospermia and 35/323 (10,8%) had azoospermia. For the 198 adolescents included in the final analysis, median age was 16 (IQR 15-16). Haematological cancer was the predominant group [94/198 (47%)] followed by sarcoma/osteosarcoma [58/198 (29%)]. Outcome analysis revealed that 99/198 (50%) patients had repeated semen analyses. Median time between the pre- and post-treatment analysis was 10 years (IQR 7-10). Of those who had a subsequent semen analysis, 59/99 (58,4%) showed improvement, 23/99 (22,8%) had no change and 17/99 (16.8%) revealed decline in sperm quality parameters compared to the stored sample. Post treatment, spontaneous pregnancy was reported by 16 (8%) patients. Sperm was discarded for patient demise in 35.8% (71/198) of cases and for inability to contact the patient since storage in 13.1% (26/198). Limitations, reasons for caution One limitation is the retrospective design and the relatively small number of cases included in the study. A second limitation is that although we have information of semen analysis, we did not have information on pregnancies achieved for patients with a normal semen analysis. Wider implications of the findings This is one of the largest case series of outcomes in adolescents. We can anticipate retention of fertility potential in half of the adolescents freezing sperm. A repeat semen analysis facilitates reassurance to the patients and allows discarding sperm when in remission. Patients can refreeze sperm if disease relapse occurs. Trial registration number Non applicable

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