Men who became fathers through assisted reproductive techniques were at significantly higher risk for prostate cancer and at a younger age than those who fathered children naturally, a Swedish registry study found.
The point was not to suggest that assisted reproduction itself promoted prostate cancer, but rather that infertility is somehow a risk factor. Although the study authors had no explanation for the connection, they said men seeking treatments for infertility may benefit from early prostate cancer screening.
In this population-based analysis, men who participated in intra-cytoplasmic sperm injection (ICSI) had a 64% higher risk of developing prostate cancer over the succeeding two decades compared with men who conceived naturally (HR 1.64, 95% CI 1.25 to 2.15), doctoral student Yahia Al-Jebari, of Lund University, Malmo, Sweden, and colleagues reported in The BMJ. ICSI, in which sperm are manually injected into retrieved oocytes, is typically used in the most severe forms of male infertility.
Similarly, men who conceived with the help of in vitro fertilization (in which sperm are placed with oocytes for fertilization) were at one-third greater risk of developing prostate cancer (HR 1.33, 95% CI 1.06 to 1.66) during follow-up.
Moreover, the risk of developing early prostate cancer before the age of 55 was 86% higher for men who had undergone ICSI, while IVF was associated with 51% greater risk of early onset disease.
“The main conclusion of this study, comprising virtually all men fathering a child in Sweden during two decades, is that men who achieved fatherhood through assisted reproduction had a remarkably high risk of prostate cancer,” Al-Jebari and colleagues observed. “Men undergoing assisted reproduction may merit further attention and comprise an easily accessible category of patients who may benefit from early screening.”
However, in an accompanying editorial, Aditi Sharma, MD and Channa Jayasena, MD, PhD, both from Imperial College London in England, cautioned that the study authors did not suggest a specific mechanism by which infertility could increase prostate cancer risk. Consequently, they wrote, “justifying screening for prostate cancer in all infertile men is difficult.” About 8% of men in Western countries are infertile to some degree.
Al-Jebari and colleagues analyzed registry date for 1,181,490 children born in Sweden from 1994 to 2014 to the same number of fathers. Of these, 1.7% underwent IVF while 1.3% participated in ICSI. The rest of the cohort conceived children naturally. Mean age of fathers at childbirth was 37 in both the IVF and ICSI groups, versus 33 for men conceiving naturally.
When men who had had any cancer prior to their child’s conception date were excluded, ICSI fathers were still 70% more likely to develop prostate cancer (P<0.001), and showed a nearly doubled risk of early onset disease. The IVF group with no previous cancer history also showed higher risk for overall and early-onset prostate cancer, with a smaller magnitude than with ICSI, as in the other analyses.
One limitation noted by Sharma and Jayasena was that the study did not include infertile men who were unable to father children.
“These men might be expected to have a higher risk of prostate cancer than infertile men who managed to father children,” they observed. The editorialists also pointed out that the mean age at follow-up was only 45 years, “so these findings are unlikely to quantify risk of prostate cancer over a lifetime,” they wrote.
Sharma and Jayasena did suggest possible mechanisms to explain the findings. One could be “a genetic association between microdeletions in the Y chromosome, which are known to cause severe male infertility, and genes on the same chromosome known to be associated with prostate cancer.” Another could be mutated DNA repair genes “and epigenetic and environmental modulators,” they wrote.
“Further research on the possible future complications of male infertility would be welcomed by patients and will help clinicians to counsel all infertile men about their future health,” the editorialists concluded.
Al-Jebari had no financial conflicts of interest to declare.
Neither editorialist had any conflicts of interest to disclose.