Risk of non-reproductive cancer in men from couples conceiving through assisted reproduction: a Swedish nation-based register study

Whereas the link between impaired male fertility and risk of testicular and prostate cancer is well established, studies investigating non-reproductive cancer risk among men with impaired reproductive function are scarce and show conflicting results. The aim of the study was to compare the risk of developing non-reproductive cancers in men achieving paternity through assisted reproduction as compared to those conceiving naturally. All first-time fathers n = 1 137 829 in Sweden during the period January 1994 to December 2014 were included and followed from the time of conception until date of cancer diagnosis, death, or end of follow-up (31st of December 2014). Conception by intracytoplasmic sperm injection (ICSI) or use of donated spermatozoa was used as proxy for impaired male fertility. As controls we used males who conceived spontaneously. National register based cohort study. By linking the Swedish multigeneration register with the Swedish medical birth register (MBR), all men conceiving their 1st child between 1994 and 2014 in Sweden were identified (n = 1 181 490). Information on mode of conception was derived from the MBR or the Q-IVF register. Men with history of cancer prior to conception, missing covariate data, and those with missing information to estimate gestational age were excluded (n = 43 661). From the Swedish cancer registry data was retrieved on cancer diagnoses during follow-up. Fathers´ fertility status was based on mode of conception i.e. naturally, standard in-vitro fertilization (IVF) or ICSI. Diagnosis of any type of non-reproductive cancer according to International Classification of Diseases 7th revision (ICD-7) after the time of conception. Among 1 137 829 men, 20 142 and 14 540 achieved paternity through IVF and ICSI treatment, respectively. ICSI-fathers and those using donated spermatozoa were, as compared to those conceiving spontanouesly, at an increased risk of non-reproductive cancers (adjusted hazardo ratio (aHR) 1.3; 95%CI 1.1-1.5), foremost colon (aHR 1.7; 95%CI 1.1-2.7), rectum (aHR 1.8. 95%CI 1.1-3.0) or thyroid gland cancer (aHR 3.3; 95%CI 1.7-6.2). Men achieving paternity after ICSI treatment or by using donated spermatozoa, in other words those with most severely hampered fertility, were at increased risk of colorectal and thyroid cancer. For this subpopulation of men, an extended health check-up at the time of fertility treatment as well as at long-term follow-up, should be considered.