Prostate cancer risk linked to assisted reproduction techniques

A new study has revealed that the risk of prostate cancer is significantly raised among men who have become fathers via assisted reproduction techniques when compared to men who become fathers naturally. The study titled, “Risk of prostate cancer for men fathering through assisted reproduction: nationwide population based register study,” was published in the latest issue of the journal BMJ.

According to the researchers, this study reveals that men who have used these techniques to become fathers need to be screened early and adequately and monitored for symptoms of prostate cancers. They explained that both prostate cancer and infertility are fairly common among men with an incidence of 10% and 8% respectively in the West.

There have been studies that have investigated the risk of prostate cancer among infertile men. However, there are no conclusive findings in this respect.

As prostate cancer and many forms of infertility are androgen related, a possible link between them has been studied, yielding contradictory results. Studies in older men using childlessness as a proxy for infertility show that childless men have a lower risk of prostate cancer.” They added, “Previous studies have been limited by small numbers of study participants, self reported diagnoses, or short follow-up time.”
BMJ

The new study conducted by Swedish researchers looked at a comparison of the risk and severity of prostate cancer between men who conceive naturally versus men who become fathers for the first time using assisted techniques. The data on these men was gathered from all babies born in Sweden between 1994 and 2014 from the national registers (Swedish National Quality Register for Assisted Reproduction) to the same number of fathers.

The fathers of these children were divided into groups according to their fertility and mode of conception. It was noted that there were 20,618 fathers or 1.7% of the population of fathers that gave birth via in vitro fertilization (IVF), 14,882 fathers or 1.3 %  that gave birth via sperm injection (ICSI) and 1,145,990 fathers or 97% that became fathers naturally. Men who had had cancer before or who had received testosterone replacement therapy were excluded from the study.

For IVF and ICSI, the average fathers’ age was around 37 years, while the average age of fathers that conceived naturally was around 32 years. Also, the team compared the list of these fathers with the cancer registry to see how many of them developed prostate cancers within two decades of becoming fathers.

The team knew that several other factors also contributed to development of prostate cancers and statistically nullified these factors to reach a conclusion that provided an accurate association between the two events - artificial reproduction and prostate cancer. These factors included age, education level and socioeconomic status.

Results revealed that men who used IVF and ICSI to become fathers had a significantly higher risk of getting prostate cancer compared to men who became fathers naturally. Results revealed that the 0.28% or 3,244 fathers conceiving naturally developed prostate cancer compared to 77 (0.37%) and 63 (0.42%) among IVF and ICSI fathers, respectively. The risk of prostate cancer detected before the age of 55 years rose among fathers using ICSI. ICSI is typically used in men with more severe forms of infertility.

This large register based study show that men fathering children through assisted reproduction have a 30-60% increased risk of prostate cancer compared with men conceiving naturally. They have almost twice the risk of developing early onset prostate cancer, before 55 years of age. Men fathering children through assisted reproduction seem to be at higher risk for prostate cancer, so the benefits of prostate cancer screening should be considered for this.”
BMJ

The researchers added that the study should have included men who had tried and failed to become fathers despite artificial reproduction techniques. These men might have a greater risk of getting prostate cancers, they said. They also added that this study did not follow the men for lifetime and thus did not assess the lifetime risk of prostate cancers.

They concluded, “Men who achieved fatherhood through assisted reproduction techniques, particularly through ICSI, are at high 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.”

In an associated editorial in the BMJ titled, “Male infertility linked to risk of prostate cancer,” researchers have written that there may be abnormalities of the Y chromosome that may be associated with infertility as well as prostate cancer. There are minimal survival benefits associated with screening for prostate cancer, they write. They warned that positive screening might lead to overdiagnosis and overtreatment which may cause harm.

In the absence of a plausible mechanism of action or proof of causation, justifying screening for prostate cancer in all infertile men is difficult. However, 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.”
BMJ

The study was funded by Swedish Cancer Foundation, an ALF government grant, Malmö University Hospital Cancer Research Fund and the Swedish Prostate Cancer Federation, and the European Association of Urology.

Journal reference:

BMJ 2019;366:l5525 - https://www.bmj.com/content/366/bmj.l5525