Use of Assisted Reproduction Techniques Linked to Increased Prostate Cancer Risk, Study Suggests

Men who father children through assisted reproduction techniques, either in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), may be at a higher risk of developing prostate cancer, a study shows.

Early screening for prostate cancer may also be beneficial for infertile men, according to the study, titled “Risk of prostate cancer for men fathering through assisted reproduction: nationwide population based register study” and published in The BMJ.

Both prostate cancer and male infertility are associated with androgens — the so-called male hormones — suggesting a link between the two conditions. However, previous studies reported conflicting results about whether infertility increases, decreases, or has no effect on prostate cancer risk.

This may be partly due to limited data used in these studies: “Previous studies have often had small cohorts, short follow-up times and some have been based on self-reported diagnoses,” Yvonne Lundberg Giwercman, a professor at Lund University in Sweden and co-author of the study, said in a press release.

To address these shortcomings, researchers took advantage of the large amounts of data stored in Swedish national databases. They retrieved data for 1,181,490 children born between 1994 and 2014 and the same number of fathers. They then compared prostate cancer rates between parents who conceived naturally (that is, without medical assistance) and those who used IVF or ICSI.

Assisted reproductive techniques are intended to help with conception. In IVF, sperm and egg cells are put in a dish and the sperm is allowed to fertilize the egg. In ICSI, a newer technique, a sperm cell is injected directly into an egg and the embryo is put back into the uterus.

Of the total number of fathers, 20,618 (1.7%) had children with the assistance of IVF, 14,882 (1.3%) used ICSI, and the remaining 1,145,990 (97%) conceived naturally. In Sweden, ICSI is only indicated for men who cannot conceive with the help of regular IVF, thus most infertile men are included in the ICSI group.

Results revealed that among those who used reproductive techniques, 76 (0.37%) of those in the IVF group and 54 (0.36%) who used ICSI were diagnosed with prostate cancer after conception. This represented a significantly higher rate than among those who conceived naturally, 3,216 (0.28%) of whom were diagnosed with prostate cancer after conception.

In other words, compared with those who conceived naturally, men who became fathers through IVF had a 33% higher risk of developing prostate cancer, while those who conceived through ICSI had a 64% increased risk.

Using assisted reproductive techniques was also associated with an increased risk of early-onset prostate cancer (at an age younger than 55 years) than conceiving naturally — 51% with IVF and 86% with ICSI.

Overall, using these infertility treatments was associated with a 44% greater risk of prostate cancer and a 63% higher likelihood of early-onset disease. These differences were maintained after excluding fathers diagnosed with any cancer before they conceived a child.

“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,” the team wrote.

Data also showed a trend for an association between the level of infertility and both overall and early-onset prostate cancer. In addition, fathers who conceived through ICSI and developed prostate cancer were more likely to receive androgen deprivation therapy than those conceiving naturally.

In an editorial also published in The BMJ, endocrinology experts from the U.K. said these findings “provide the strongest evidence to date that risk of prostate cancer may be increased in infertile men.”

However, the biological basis for this link is not yet clear, they cautioned. “Possibilities include 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.

“Mutations in DNA repair genes and epigenetic [changes to gene expression, not the DNA itself] and environmental modulators have also been suggested to link male infertility and prostate cancer,” they added.

According to Giwercman, looking at cancer risk over a longer period is among the team’s goals “as ICSI has only existed as a method since the 1990s. It would also be interesting to investigate factors such as socio-economical aspects, health and lifestyle factors in men seeking assisted reproduction.”