Risk of prostate cancer for men fathering through assisted reproduction: nationwide population based register study

Abstract

Objective To compare the risk and severity of prostate cancer between men achieving fatherhood by assisted reproduction and men conceiving naturally. Design National register based cohort study. Setting Sweden from January 1994 to December 2014. Participants 1 181 490 children born alive in Sweden during 1994-2014 to the same number of fathers. Fathers were grouped according to fertility status by mode of conception: 20 618 by in vitro fertilisation (IVF), 14 882 by intra-cytoplasmic sperm injection (ICSI), and 1 145 990 by natural conception. Main outcome measures Prostate cancer diagnosis, age of onset, and androgen deprivation therapy (serving as proxy for advanced or metastatic malignancy). Results Among men achieving fatherhood by IVF, by ICSI, and by non-assisted means, 77 (0.37%), 63 (0.42%), and 3244 (0.28%), respectively, were diagnosed as having prostate cancer. Mean age at onset was 55.9, 55.1, and 57.1 years, respectively. Men who became fathers through assisted reproduction had a statistically significantly increased risk of prostate cancer compared with men who conceived naturally (hazard ratio 1.64, 95% confidence interval 1.25 to 2.15, for ICSI; 1.33, 1.06 to 1.66, for IVF). They also had an increased risk of early onset disease (that is, diagnosis before age 55 years) (hazard ratio 1.86, 1.25 to 2.77, for ICSI; 1.51, 1.09 to 2.08, for IVF). Fathers who conceived through ICSI and developed prostate cancer received androgen deprivation therapy to at least the same extent as the reference group (odds ratio 1.91; P=0.07). Conclusions Men who achieved fatherhood through assisted reproduction techniques, particularly through ICSI, are at increased risk for early onset prostate cancer and thus constitute a risk group in which testing and careful long term follow-up for prostate cancer may be beneficial.

Clinical correlation among male infertility and overall male health: A systematic review of the literature

“…All of these were single-center retrospective surveys ( Table 1 ). Eleven studies [ 20 21 22 23 24 25 26 27 28 29 30 ] examined infertility and its association with oncological malignancies. Of these, 7 [ 21 24 25 26 27 28 29 ] of these were conducted in the US, while 4 [ 20 22 23 30 ] were from Europe (Denmark and Sweden).…”

“…Eleven studies [ 20 21 22 23 24 25 26 27 28 29 30 ] examined infertility and its association with oncological malignancies. Of these, 7 [ 21 24 25 26 27 28 29 ] of these were conducted in the US, while 4 [ 20 22 23 30 ] were from Europe (Denmark and Sweden). Eight of eleven [ 23 24 25 26 27 28 29 30 ] were single-center retrospective population-based reviews while the remaining 3 [ 20 21 22 ] were case–control cohort studies ( Table 1 ).…”

“…The quality of the identified studies was assessed independently by two reviewers (FDG, FB) using the “Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies,” provided by the National Institute of Health (NIH) [ 14 ], by assessing the potential risk for selection bias, information bias, measurement bias, or confounding (confounding includes cointerventions, differences at baseline in patient characteristics, and other issues as shown in Supplementary Table 1 ) [ 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 ]. Studies were rated as good, fair, and poor quality, where high risk of bias translated to a rating of poor quality (“−”) and low risk of bias translated to a rating of good quality (“+”).…”

Male infertility linked to risk of prostate cancer

“…Their results provide the strongest evidence to date that risk of prostate cancer may be increased in infertile men. Importantly though, a causal relation cannot be assumed 1…”

“…These authors acknowledge the limitations of their study 1. Firstly, the study did not include infertile men who were unable to father children.…”